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وهنا على وهن وفصاله في عامين أن اشكر لي

يرصالم إلي كيدالول14( و(

MOHAMMED V DE RABAT FACULTE DE MEDECINE ET DE PHARMACIE - RABAT

DOYENS HONORAIRES : 1962 – 1969 : Professeur Abdelmalek FARAJ 1969 – 1974 : Professeur Abdellatif BERBICH 1974 – 1981 : Professeur Bachir LAZRAK 1981 – 1989 : Professeur Taieb CHKILI 1989 – 1997 : Professeur Mohamed Tahar ALAOUI 1997 – 2003 : Professeur Abdelmajid BELMAHI 2003 - 2013 : Professeur Najia HAJJAJ – HASSOUNI ADMINISTRATION : Doyen

Professeur Mohamed ADNAOUI Vice-Doyen chargé des Affaires Académiques et estudiantines

Professeur Brahim LEKEHAL Vice-Doyen chargé de la Recherche et de la Coopération

Professeur Toufiq DAKKA Vice-Doyen chargé des Affaires Spécifiques à la Pharmacie

Professeur Jamal TAOUFIK Secrétaire Général

Mr. Mohamed KARRA

1 - ENSEIGNANTS-CHERCHEURS MEDECINS ET PHARMACIENS

PROFESSEURS : DECEMBRE 1984 Pr. MAAOUNI Abdelaziz Médecine Interne – Clinique Royale Pr. MAAZOUZI Ahmed Wajdi Anesthésie -Réanimation Pr. SETTAF Abdellatif Pathologie Chirurgicale

NOVEMBRE ET DECEMBRE 1985 Pr. BENSAID Younes Pathologie Chirurgicale JANVIER, FEVRIER ET DECEMBRE 1987 Pr. LACHKAR Hassan Médecine Interne Pr. YAHYAOUI Mohamed Neurologie

DECEMBRE 1989 Pr. ADNAOUI Mohamed Médecine Interne –Doyen de la FMPR Pr. OUAZZANI Taïbi Mohamed Réda Neurologie

JANVIER ET NOVEMBRE 1990 Pr. HACHIM Mohammed* Médecine-Interne Pr. KHARBACH Aîcha Gynécologie -Obstétrique Pr. TAZI Saoud Anas Anesthésie Réanimation FEVRIER AVRIL JUILLET ET DECEMBRE 1991 Pr. AZZOUZI Abderrahim Anesthésie Réanimation- Doyen de FMPO Pr. BAYAHIA Rabéa Néphrologie Pr. BELKOUCHI Abdelkader Chirurgie Générale Pr. BENCHEKROUN Belabbes Abdellatif Chirurgie Générale Pr. BENSOUDA Yahia Pharmacie galénique Pr. BERRAHO Amina Ophtalmologie

Pr. BEZAD Rachid Gynécologie Obstétrique Méd. Chef Maternité des Orangers

Pr. CHERRAH Yahia Pharmacologie Pr. CHOKAIRI Omar Histologie Embryologie Pr. KHATTAB Mohamed Pédiatrie Pr. SOULAYMANI Rachida Pharmacologie- Dir. du Centre National PV Rabat

Pr. TAOUFIK Jamal Chimie thérapeutique V.D à la pharmacie+Dir. du CEDOC +

Directeur du Médicament DECEMBRE 1992 Pr. AHALLAT Mohamed Chirurgie Générale Doyen de FMPT Pr. BENSOUDA Adil Anesthésie Réanimation Pr. CHAHED OUAZZANI Laaziza Gastro-Entérologie Pr. CHRAIBI Chafiq Gynécologie Obstétrique

Pr. EL OUAHABI Abdessamad Neurochirurgie Pr. FELLAT Rokaya Cardiologie Pr. GHAFIR Driss* Médecine Interne Pr. JIDDANE Mohamed Anatomie Pr. TAGHY Ahmed Chirurgie Générale Pr. ZOUHDI Mimoun Microbiologie MARS 1994 Pr. BENJAAFAR Noureddine Radiothérapie Pr. BEN RAIS Nozha Biophysique Pr. CAOUI Malika Biophysique

Pr. CHRAIBI Abdelmjid Endocrinologie et Maladies Métaboliques Doyen de la FMPA

Pr. EL AMRANI Sabah Gynécologie Obstétrique Pr. EL BARDOUNI Ahmed Traumato-Orthopédie Pr. EL HASSANI My Rachid Radiologie Pr. ERROUGANI Abdelkader Chirurgie Générale – Directeur du CHIS-Rabat Pr. ESSAKALI Malika Immunologie Pr. ETTAYEBI Fouad Chirurgie Pédiatrique Pr. HASSAM Badredine Dermatologie Pr. IFRINE Lahssan Chirurgie Générale Pr. MAHFOUD Mustapha Traumatologie – Orthopédie Pr. RHRAB Brahim Gynécologie –Obstétrique Pr. SENOUCI Karima Dermatologie MARS 1994 Pr. ABBAR Mohamed* Urologie Directeur Hôpital My Ismail Meknès Pr. ABDELHAK M’barek Chirurgie – Pédiatrique Pr. BENTAHILA Abdelali Pédiatrie Pr. BENYAHIA Mohammed Ali Gynécologie – Obstétrique Pr. BERRADA Mohamed Saleh Traumatologie – Orthopédie Pr. CHERKAOUI Lalla Ouafae Ophtalmologie Pr. LAKHDAR Amina Gynécologie Obstétrique Pr. MOUANE Nezha Pédiatrie MARS 1995 Pr. ABOUQUAL Redouane Réanimation Médicale Pr. AMRAOUI Mohamed Chirurgie Générale Pr. BAIDADA Abdelaziz Gynécologie Obstétrique Pr. BARGACH Samir Gynécologie Obstétrique Pr. DRISSI KAMILI Med Nordine* Anesthésie Réanimation Pr. EL MESNAOUI Abbes Chirurgie Générale Pr. ESSAKALI HOUSSYNI Leila Oto-Rhino-Laryngologie Pr. HDA Abdelhamid* Cardiologie Inspecteur du Service de Santé des FAR Pr. IBEN ATTYA ANDALOUSSI Ahmed Urologie

Pr. OUAZZANI CHAHDI Bahia Ophtalmologie Pr. SEFIANI Abdelaziz Génétique Pr. ZEGGWAGH Amine Ali Réanimation Médicale DECEMBRE 1996 Pr. AMIL Touriya* Radiologie Pr. BELKACEM Rachid Chirurgie Pédiatrie Pr. BOULANOUAR Abdelkrim Ophtalmologie Pr. EL ALAMI EL FARICHA EL Hassan Chirurgie Générale Pr. GAOUZI Ahmed Pédiatrie Pr. MAHFOUDI M’barek* Radiologie Pr. OUZEDDOUN Naima Néphrologie Pr. ZBIR EL Mehdi* Cardiologie DirecteurHôp.Mil. d’Instruction Med V Rabat NOVEMBRE 1997 Pr. ALAMI Mohamed Hassan Gynécologie-Obstétrique Pr. BEN SLIMANE Lounis Urologie Pr. BIROUK Nazha Neurologie Pr. ERREIMI Naima Pédiatrie Pr. FELLAT Nadia Cardiologie Pr. KADDOURI Noureddine Chirurgie Pédiatrique Pr. KOUTANI Abdellatif Urologie Pr. LAHLOU Mohamed Khalid Chirurgie Générale Pr. MAHRAOUI CHAFIQ Pédiatrie Pr. TOUFIQ Jallal Psychiatrie Directeur Hôp.Ar-razi Salé Pr. YOUSFI MALKI Mounia Gynécologie Obstétrique NOVEMBRE 1998 Pr. BENOMAR ALI Neurologie Doyen de la FMP Abulcassis Pr. BOUGTAB Abdesslam Chirurgie Générale Pr. ER RIHANI Hassan Oncologie Médicale Pr. BENKIRANE Majid* Hématologie JANVIER 2000 Pr. ABID Ahmed* Pneumo-phtisiologie Pr. AIT OUAMAR Hassan Pédiatrie Pr. BENJELLOUN Dakhama Badr.Sououd Pédiatrie Pr. BOURKADI Jamal-Eddine Pneumo-phtisiologie Directeur Hôp. My Youssef Pr. CHARIF CHEFCHAOUNI Al Montacer Chirurgie Générale Pr. ECHARRAB El Mahjoub Chirurgie Générale Pr. EL FTOUH Mustapha Pneumo-phtisiologie Pr. EL MOSTARCHID Brahim* Neurochirurgie Pr. MAHMOUDI Abdelkrim* Anesthésie-Réanimation Pr. TACHINANTE Rajae Anesthésie-Réanimation Pr. TAZI MEZALEK Zoubida Médecine Interne

NOVEMBRE 2000

Pr. AIDI Saadia Neurologie Pr. AJANA Fatima Zohra Gastro-Entérologie Pr. BENAMR Said Chirurgie Générale Pr. CHERTI Mohammed Cardiologie Pr. ECH-CHERIF EL KETTANI Selma Anesthésie-Réanimation Pr. EL HASSANI Amine Pédiatrie - Directeur Hôp.Cheikh Zaid Pr. EL KHADER Khalid Urologie Pr. EL MAGHRAOUI Abdellah* Rhumatologie Pr. GHARBI Mohamed El Hassan Endocrinologie et Maladies Métaboliques Pr. MDAGHRI ALAOUI Asmae Pédiatrie Pr. ROUIMI Abdelhadi* Neurologie DECEMBRE 2000 Pr.ZOHAIR ABDELLAH * ORL Pr. BALKHI Hicham* Anesthésie-Réanimation Pr. BENABDELJLIL Maria Neurologie Pr. BENAMAR Loubna Néphrologie Pr. BENAMOR Jouda Pneumo-phtisiologie Pr. BENELBARHDADI Imane Gastro-Entérologie Pr. BENNANI Rajae Cardiologie Pr. BENOUACHANE Thami Pédiatrie Pr. BEZZA Ahmed* Rhumatologie Pr. BOUCHIKHI IDRISSI Med Larbi Anatomie Pr. BOUMDIN El Hassane* Radiologie Pr. CHAT Latifa Radiologie Pr. DAALI Mustapha* Chirurgie Générale Pr. DRISSI Sidi Mourad* Radiologie Pr. EL HIJRI Ahmed Anesthésie-Réanimation Pr. EL MAAQILI Moulay Rachid Neuro-Chirurgie Pr. EL MADHI Tarik Chirurgie-Pédiatrique Pr. EL OUNANI Mohamed Chirurgie Générale Pr. ETTAIR Said Pédiatrie - Directeur Hôp. d’EnfantsRabat Pr. GAZZAZ Miloudi* Neuro-Chirurgie Pr. HRORA Abdelmalek Chirurgie Générale Pr. KABBAJ Saad Anesthésie-Réanimation Pr. KABIRI EL Hassane* Chirurgie Thoracique Pr. LAMRANI Moulay Omar Traumatologie Orthopédie Pr. LEKEHAL Brahim Chirurgie Vasculaire Périphérique Pr. MAHASSIN Fattouma* Médecine Interne Pr. MEDARHRI Jalil Chirurgie Générale Pr. MIKDAME Mohammed* Hématologie Clinique

Pr. MOHSINE Raouf Chirurgie Générale Pr. NOUINI Yassine Urologie - Directeur Hôpital Ibn Sina Pr. SABBAH Farid Chirurgie Générale Pr. SEFIANI Yasser Chirurgie Vasculaire Périphérique Pr. TAOUFIQ BENCHEKROUN Soumia Pédiatrie

DECEMBRE 2002 Pr. AL BOUZIDI Abderrahmane* Anatomie Pathologique Pr. AMEUR Ahmed * Urologie Pr. AMRI Rachida Cardiologie Pr. AOURARH Aziz* Gastro-Entérologie Pr. BAMOU Youssef * Biochimie-Chimie Pr. BELMEJDOUB Ghizlene* Endocrinologie et Maladies Métaboliques Pr. BENZEKRI Laila Dermatologie Pr. BENZZOUBEIR Nadia Gastro-Entérologie Pr. BERNOUSSI Zakiya Anatomie Pathologique Pr. BICHRA Mohamed Zakariya* Psychiatrie Pr. CHOHO Abdelkrim * Chirurgie Générale Pr. CHKIRATE Bouchra Pédiatrie Pr. EL ALAMI EL Fellous Sidi Zouhair Chirurgie Pédiatrique Pr. EL HAOURI Mohamed * Dermatologie Pr. FILALI ADIB Abdelhai Gynécologie Obstétrique Pr. HAJJI Zakia Ophtalmologie Pr. IKEN Ali Urologie Pr. JAAFAR Abdeloihab* Traumatologie Orthopédie Pr. KRIOUILE Yamina Pédiatrie Pr. MABROUK Hfid* Traumatologie Orthopédie Pr. MOUSSAOUI RAHALI Driss* Gynécologie Obstétrique Pr. OUJILAL Abdelilah Oto-Rhino-Laryngologie Pr. RACHID Khalid * Traumatologie Orthopédie Pr. RAISS Mohamed Chirurgie Générale Pr. RGUIBI IDRISSI Sidi Mustapha* Pneumo-phtisiologie Pr. RHOU Hakima Néphrologie Pr. SIAH Samir * Anesthésie Réanimation Pr. THIMOU Amal Pédiatrie Pr. ZENTAR Aziz* Chirurgie Générale

JANVIER 2004 Pr. ABDELLAH El Hassan Ophtalmologie Pr. AMRANI Mariam Anatomie Pathologique Pr. BENBOUZID Mohammed Anas Oto-Rhino-Laryngologie Pr. BENKIRANE Ahmed* Gastro-Entérologie Pr. BOULAADAS Malik Stomatologie et Chirurgie Maxillo-faciale Pr. BOURAZZA Ahmed* Neurologie Pr. CHAGAR Belkacem* Traumatologie Orthopédie Pr. CHERRADI Nadia Anatomie Pathologique Pr. EL FENNI Jamal* Radiologie Pr. EL HANCHI ZAKI Gynécologie Obstétrique Pr. EL KHORASSANI Mohamed Pédiatrie Pr. EL YOUNASSI Badreddine* Cardiologie Pr. HACHI Hafid Chirurgie Générale Pr. JABOUIRIK Fatima Pédiatrie Pr. KHARMAZ Mohamed Traumatologie Orthopédie Pr. MOUGHIL Said Chirurgie Cardio-Vasculaire Pr. OUBAAZ Abdelbarre * Ophtalmologie Pr. TARIB Abdelilah* Pharmacie Clinique Pr. TIJAMI Fouad Chirurgie Générale Pr. ZARZUR Jamila Cardiologie JANVIER 2005 Pr. ABBASSI Abdellah Chirurgie Réparatrice et Plastique Pr. AL KANDRY Sif Eddine* Chirurgie Générale Pr. ALLALI Fadoua Rhumatologie Pr. AMAZOUZI Abdellah Ophtalmologie Pr. AZIZ Noureddine* Radiologie Pr. BAHIRI Rachid Rhumatologie Directeur Hôp. Al Ayachi Salé Pr. BARKAT Amina Pédiatrie Pr. BENYASS Aatif Cardiologie Pr. DOUDOUH Abderrahim* Biophysique Pr. EL HAMZAOUI Sakina * Microbiologie Pr. HAJJI Leila Cardiologie (mise en disponibilité Pr. HESSISSEN Leila Pédiatrie Pr. JIDAL Mohamed* Radiologie Pr. LAAROUSSI Mohamed Chirurgie Cardio-vasculaire Pr. LYAGOUBI Mohammed Parasitologie Pr. RAGALA Abdelhak Gynécologie Obstétrique Pr. SBIHI Souad Histo-Embryologie Cytogénétique Pr. ZERAIDI Najia Gynécologie Obstétrique

AVRIL 2006

Pr. ACHEMLAL Lahsen* Rhumatologie Pr. AKJOUJ Said* Radiologie Pr. BELMEKKI Abdelkader* Hématologie Pr. BENCHEIKH Razika O.R.L Pr. BIYI Abdelhamid* Biophysique Pr. BOUHAFS Mohamed El Amine Chirurgie - Pédiatrique Pr. BOULAHYA Abdellatif* Chirurgie Cardio – Vasculaire. Pr. CHENGUETI ANSARI Anas Gynécologie Obstétrique Pr. DOGHMI Nawal Cardiologie Pr. FELLAT Ibtissam Cardiologie Pr. FAROUDY Mamoun Anesthésie Réanimation Pr. HARMOUCHE Hicham Médecine Interne Pr. HANAFI Sidi Mohamed* Anesthésie Réanimation Pr. IDRISS LAHLOU Amine* Microbiologie Pr. JROUNDI Laila Radiologie Pr. KARMOUNI Tariq Urologie Pr. KILI Amina Pédiatrie Pr. KISRA Hassan Psychiatrie Pr. KISRA Mounir Chirurgie – Pédiatrique Pr. LAATIRIS Abdelkader* Pharmacie Galénique Pr. LMIMOUNI Badreddine* Parasitologie Pr. MANSOURI Hamid* Radiothérapie Pr. OUANASS Abderrazzak Psychiatrie

Pr. SAFI Soumaya* Endocrinologie Pr. SEKKAT Fatima Zahra Psychiatrie Pr. SOUALHI Mouna Pneumo – Phtisiologie Pr. TELLAL Saida* Biochimie Pr. ZAHRAOUI Rachida Pneumo – Phtisiologie DECEMBRE 2006 Pr SAIR Khalid Chirurgie générale Dir. Hôp.Av.Marrakech

OCTOBRE 2007 Pr. ABIDI Khalid Réanimation médicale Pr. ACHACHI Leila Pneumo phtisiologie Pr. ACHOUR Abdessamad* Chirurgie générale Pr. AIT HOUSSA Mahdi * Chirurgie cardio vasculaire Pr. AMHAJJI Larbi * Traumatologie orthopédie Pr. AOUFI Sarra Parasitologie Pr. BAITE Abdelouahed * Anesthésie réanimation Directeur ERSSM Pr. BALOUCH Lhousaine * Biochimie-chimie Pr. BENZIANE Hamid * Pharmacie clinique Pr. BOUTIMZINE Nourdine Ophtalmologie Pr. CHERKAOUI Naoual * Pharmacie galénique

Pr. EHIRCHIOU Abdelkader * Chirurgie générale Pr. EL BEKKALI Youssef * Chirurgie cardio-vasculaire Pr. EL ABSI Mohamed Chirurgie générale Pr. EL MOUSSAOUI Rachid Anesthésie réanimation Pr. EL OMARI Fatima Psychiatrie Pr. GHARIB Noureddine Chirurgie plastique et réparatrice Pr. HADADI Khalid * Radiothérapie Pr. ICHOU Mohamed * Oncologie médicale Pr. ISMAILI Nadia Dermatologie Pr. KEBDANI Tayeb Radiothérapie Pr. LALAOUI SALIM Jaafar * Anesthésie réanimation Pr. LOUZI Lhoussain * Microbiologie Pr. MADANI Naoufel Réanimation médicale Pr. MAHI Mohamed * Radiologie Pr. MARC Karima Pneumo phtisiologie Pr. MASRAR Azlarab Hématologie biologique Pr. MRANI Saad * Virologie Pr. OUZZIF Ez zohra * Biochimie-chimie Pr. RABHI Monsef * Médecine interne Pr. RADOUANE Bouchaib* Radiologie Pr. SEFFAR Myriame Microbiologie Pr. SEKHSOKH Yessine * Microbiologie Pr. SIFAT Hassan * Radiothérapie Pr. TABERKANET Mustafa * Chirurgie vasculaire périphérique Pr. TACHFOUTI Samira Ophtalmologie Pr. TAJDINE Mohammed Tariq* Chirurgie générale Pr. TANANE Mansour * Traumatologie-orthopédie Pr. TLIGUI Houssain Parasitologie Pr. TOUATI Zakia Cardiologie

DECEMBRE 2008 Pr TAHIRI My El Hassan* Chirurgie Générale MARS 2009

Pr. ABOUZAHIR Ali * Médecine interne Pr. AGADR Aomar * Pédiatrie Pr. AIT ALI Abdelmounaim * Chirurgie Générale Pr. AIT BENHADDOU El Hachmia Neurologie Pr. AKHADDAR Ali * Neuro-chirurgie Pr. ALLALI Nazik Radiologie Pr. AMINE Bouchra Rhumatologie Pr. ARKHA Yassir Neuro-chirurgie Directeur Hôp.des Spécialités Pr. BELYAMANI Lahcen* Anesthésie Réanimation Pr. BJIJOU Younes Anatomie Pr. BOUHSAIN Sanae * Biochimie-chimie

Pr. BOUI Mohammed * Dermatologie Pr. BOUNAIM Ahmed * Chirurgie Générale Pr. BOUSSOUGA Mostapha * Traumatologie-orthopédie Pr. CHTATA Hassan Toufik * Chirurgie Vasculaire Périphérique Pr. DOGHMI Kamal * Hématologie clinique Pr. EL MALKI Hadj Omar Chirurgie Générale Pr. EL OUENNASS Mostapha* Microbiologie Pr. ENNIBI Khalid * Médecine interne Pr. FATHI Khalid Gynécologie obstétrique Pr. HASSIKOU Hasna * Rhumatologie Pr. KABBAJ Nawal Gastro-entérologie Pr. KABIRI Meryem Pédiatrie Pr. KARBOUBI Lamya Pédiatrie Pr. LAMSAOURI Jamal * Chimie Thérapeutique Pr. MARMADE Lahcen Chirurgie Cardio-vasculaire Pr. MESKINI Toufik Pédiatrie Pr. MESSAOUDI Nezha * Hématologie biologique Pr. MSSROURI Rahal Chirurgie Générale Pr. NASSAR Ittimade Radiologie Pr. OUKERRAJ Latifa Cardiologie Pr. RHORFI Ismail Abderrahmani * Pneumo-Phtisiologie OCTOBRE 2010 Pr. ALILOU Mustapha Anesthésie réanimation Pr. AMEZIANE Taoufiq* Médecine Interne Pr. BELAGUID Abdelaziz Physiologie Pr. CHADLI Mariama* Microbiologie Pr. CHEMSI Mohamed* Médecine Aéronautique Pr. DAMI Abdellah* Biochimie- Chimie Pr. DARBI Abdellatif* Radiologie Pr. DENDANE Mohammed Anouar Chirurgie Pédiatrique Pr. EL HAFIDI Naima Pédiatrie Pr. EL KHARRAS Abdennasser* Radiologie Pr. EL MAZOUZ Samir Chirurgie Plastique et Réparatrice Pr. EL SAYEGH Hachem Urologie Pr. ERRABIH Ikram Gastro-Entérologie Pr. LAMALMI Najat Anatomie Pathologique Pr. MOSADIK Ahlam Anesthésie Réanimation Pr. MOUJAHID Mountassir* Chirurgie Générale Pr. NAZIH Mouna* Hématologie Pr. ZOUAIDIA Fouad Anatomie Pathologique DECEMBRE 2010 Pr.ZNATI Kaoutar Anatomie Pathologique

MAI 2012 Pr. AMRANI Abdelouahed Chirurgie pédiatrique Pr. ABOUELALAA Khalil * Anesthésie Réanimation

Pr. BENCHEBBA Driss * Traumatologie-orthopédie Pr. DRISSI Mohamed * Anesthésie Réanimation Pr. EL ALAOUI MHAMDI Mouna Chirurgie Générale Pr. EL KHATTABI Abdessadek * Médecine Interne Pr. EL OUAZZANI Hanane * Pneumophtisiologie Pr. ER-RAJI Mounir Chirurgie Pédiatrique Pr. JAHID Ahmed Anatomie Pathologique

Pr. MEHSSANI Jamal * Psychiatrie Pr. RAISSOUNI Maha * Cardiologie

* Enseignants MilitairesFEVRIER 2013 Pr.AHID Samir Pharmacologie Pr.AIT EL CADI Mina Toxicologie Pr.AMRANI HANCHI Laila Gastro-Entérologie Pr.AMOR Mourad Anesthésie Réanimation Pr.AWAB Almahdi Anesthésie Réanimation Pr.BELAYACHI Jihane Réanimation Médicale Pr.BELKHADIR Zakaria Houssain Anesthésie Réanimation Pr.BENCHEKROUN Laila Biochimie-Chimie Pr.BENKIRANE Souad Hématologie Pr.BENNANA Ahmed* Informatique Pharmaceutique Pr.BENSGHIR Mustapha * Anesthésie Réanimation Pr.BENYAHIA Mohammed * Néphrologie Pr.BOUATIA Mustapha Chimie Analytique et Bromatologie Pr.BOUABID Ahmed Salim* Traumatologie orthopédie Pr BOUTARBOUCH Mahjouba Anatomie Pr.CHAIB Ali * Cardiologie Pr.DENDANE Tarek Réanimation Médicale Pr.DINI Nouzha * Pédiatrie Pr.ECH-CHERIF EL KETTANI Mohamed Ali Anesthésie Réanimation Pr.ECH-CHERIF EL KETTANI Najwa Radiologie Pr.EL FATEMI NIZARE Neuro-chirurgie Pr.EL GUERROUJ Hasnae Médecine Nucléaire Pr.EL HARTI Jaouad Chimie Thérapeutique Pr.EL JAOUDI Rachid * Toxicologie Pr.EL KABABRI Maria Pédiatrie Pr.EL KHANNOUSSI Basma Anatomie Pathologique Pr.EL KHLOUFI Samir Anatomie Pr.EL KORAICHI Alae Anesthésie Réanimation Pr.EN-NOUALI Hassane * Radiologie Pr.ERRGUIG Laila Physiologie Pr.FIKRI Meryem Radiologie

Pr.GHFIR Imade Médecine Nucléaire Pr.IMANE Zineb Pédiatrie Pr.IRAQI Hind Endocrinologie et maladies métaboliques Pr.KABBAJ Hakima Microbiologie Pr.KADIRI Mohamed * Psychiatrie Pr.MAAMAR Mouna Fatima Zahra Médecine Interne Pr.MEDDAH Bouchra Pharmacologie Pr.MELHAOUI Adyl Neuro-chirurgie Pr.MRABTI Hind Oncologie Médicale Pr.NEJJARI Rachid Pharmacognosie Pr.OUBEJJA Houda Chirugie Pédiatrique Pr.OUKABLI Mohamed * Anatomie Pathologique Pr.RAHALI Younes Pharmacie Galénique Pr.RATBI Ilham Génétique Pr.RAHMANI Mounia Neurologie Pr.REDA Karim * Ophtalmologie Pr.REGRAGUI Wafa Neurologie Pr.RKAIN Hanan Physiologie Pr.ROSTOM Samira Rhumatologie Pr.ROUAS Lamiaa Anatomie Pathologique Pr.ROUIBAA Fedoua * Gastro-Entérologie Pr SALIHOUN Mouna Gastro-Entérologie Pr.SAYAH Rochde Chirurgie Cardio-Vasculaire Pr.SEDDIK Hassan * Gastro-Entérologie Pr.ZERHOUNI Hicham Chirurgie Pédiatrique Pr.ZINE Ali* Traumatologie Orthopédie

AVRIL 2013 Pr.EL KHATIB MOHAMED KARIM * Stomatologie et Chirurgie Maxillo-faciale MAI 2013 Pr.BOUSLIMAN Yassir Toxicologie

MARS 2014 Pr. ACHIR Abdellah Chirurgie Thoracique Pr.BENCHAKROUN Mohammed * Traumatologie- Orthopédie Pr.BOUCHIKH Mohammed Chirurgie Thoracique Pr. EL KABBAJ Driss * Néphrologie Pr. EL MACHTANI IDRISSI Samira * Biochimie-Chimie Pr. HARDIZI Houyam Histologie- Embryologie-Cytogénétique Pr. HASSANI Amale * Pédiatrie Pr. HERRAK Laila Pneumologie Pr. JANANE Abdellah * Urologie Pr. JEAIDI Anass * Hématologie Biologique

PROFESSEURS AGREGES : DECEMBRE 2014 Pr. ABILKASSEM Rachid* Pédiatrie Pr. AIT BOUGHIMA Fadila Médecine Légale Pr. BEKKALI Hicham * Anesthésie-Réanimation Pr. BENAZZOU Salma Chirurgie Maxillo-Faciale Pr. BOUABDELLAH Mounya Biochimie-Chimie Pr. BOUCHRIK Mourad* Parasitologie Pr. DERRAJI Soufiane* Pharmacie Clinique Pr. DOBLALI Taoufik* Microbiologie Pr. EL AYOUBI EL IDRISSI Ali Anatomie Pr. EL GHADBANE Abdedaim Hatim* Anesthésie-Réanimation Pr. EL MARJANY Mohammed* Radiothérapie Pr. FEJJAL Nawfal Chirurgie Réparatrice et Plastique Pr. JAHIDI Mohamed* O.R.L Pr. LAKHAL Zouhair* Cardiologie Pr. OUDGHIRI NEZHA Anesthésie-Réanimation Pr. RAMI Mohamed Chirurgie Pédiatrique Pr. SABIR Maria Psychiatrie Pr. SBAI IDRISSI Karim* Médecine préventive, santé publique et Hyg. AOUT 2015 Pr. MEZIANE Meryem Dermatologie Pr. TAHRI Latifa Rhumatologie JANVIER 2016

Pr. BENKABBOU Amine Chirurgie Générale Pr. EL ASRI Fouad* Ophtalmologie Pr. ERRAMI Noureddine* O.R.L Pr. NITASSI Sophia O.R.L JUIN 2017 Pr. ABI Rachid* Microbiologie Pr. ASFALOU Ilyasse* Cardiologie

Pr. KOUACH Jaouad* Gynécologie-Obstétrique Pr. LEMNOUER Abdelhay* Microbiologie Pr. MAKRAM Sanaa * Pharmacologie Pr. OULAHYANE Rachid* Chirurgie Pédiatrique Pr. RHISSASSI Mohamed Jaafar CCV Pr. SABRY Mohamed* Cardiologie Pr. SEKKACH Youssef* Médecine Interne Pr. TAZI MOUKHA Zakia Gynécologie-Obstétrique AVRIL 2014

Pr.ZALAGH Mohammed ORL

Pr. BOUAYTI El Arbi* Médecine préventive, santé publique et Hyg. Pr. BOUTAYEB Saber Oncologie Médicale Pr. EL GHISSASSI Ibrahim Oncologie Médicale Pr. OURAINI Saloua* O.R.L Pr. RAZINE Rachid Médecine préventive, santé publique et Hyg. Pr. ZRARA Abdelhamid* Immunologie

* Enseignants Militaires 2 - ENSEIGNANTS-CHERCHEURS SCIENTIFIQUES

PROFESSEURS/Prs. HABILITES

Pr. ABOUDRAR Saadia Physiologie Pr. ALAMI OUHABI Naima Biochimie-chimie Pr. ALAOUI KATIM Pharmacologie Pr. ALAOUI SLIMANI Lalla Naïma Histologie-Embryologie Pr. ANSAR M’hammed Chimie Organique et Pharmacie Chimique Pr .BARKIYOU Malika Histologie-Embryologie Pr. BOUHOUCHE Ahmed Génétique Humaine Pr. BOUKLOUZE Abdelaziz Applications Pharmaceutiques Pr. CHAHED OUAZZANI Lalla Chadia Biochimie-chimie Pr. DAKKA Taoufiq Physiologie Pr. FAOUZI Moulay El Abbes Pharmacologie Pr. IBRAHIMI Azeddine Biologie moléculaire/Biotechnologie Pr. KHANFRI Jamal Eddine Biologie Pr. OULAD BOUYAHYA IDRISSI Med Chimie Organique Pr. REDHA Ahlam Chimie Pr. TOUATI Driss Pharmacognosie Pr. ZAHIDI Ahmed Pharmacologie

Mise à jour le 10/10/2018 Khaled Abdellah

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DEDICATIONS

Dear God:

A big part of me always revolved around my faith and relationship

with you and so choosing this proficiency I devote my work and

self to your worshipness

and the help of others in the name of your love. Most of my strength and persistence,

I draw from your affection and benediction. I believe in your divine assistance

in everything that i ever did or will do and I am deeply grateful for all

the blessings you’ve granted me with. Today I devote myself to humanity

in your name. Praise be to Allah.

My Mother Hafida Nassiri:

I don’t think I have ever tried putting into words the way I feel about you.

You ingrained in me the love of knowledge from a very young age and made

sure there were no limits to my dreams, even when that meant me telling everyone in

primary school that all what’s left for me to become a doctor was being inside an

operating room. I grew up admiring the magnificent selfless woman that you are:

managing your passion for teaching and the love and care you have for your family.

You have always supported my decisions and your prayers enlighten my path as my

main aspiration will always be to make you proud.

I love you more than words can say.

My Father Larbi Essangri:

Being your daughter connotes growing in the shadow of a man who worked

hard, regardless of all to give the best possible life for his children and so it’s only

natural to strive for success. You raised us in an affluence of love and affection,

and made sure we were reminded of how strong and beautiful we are.

You oversaw that we knew our worth and grew up to be independent and

your faith in each one of my steps will always incite me to be better.

I love you.

My Brother Yassine:

Apart from being my bigger brother, you were always a good confident

and supported me through everything (apart from when we had occasional war times).

Your are the most kind hearted and affectionate man and i can never properly

express how glad i am to be your sister. I can make your life hard sometimes

but that’s what siblings are for. I will always have your back. I love you.

My Sister Hiba:

I cannot write about you without mentioning first that no matter

how grown up you are you will always be my baby sister and that no matter

how close or far we are, the love and care I have for you is bigger.

You’ve allowed me to grow a lot in the past few years and for that I thank you.

I admire the fighter and ambitious “young” woman that you are and believe

you will have the brightest future. I will always have your back. I love you.

My Grandmothers Yema and Jedda:

I would like to dedicate this work to the hard work and not so easy

lives you have led. My respect and admiration for you in endless.

To the Memory of my Grandfathers:

To Bassidi: I can still recall the writing lecons and struggle you had

to get me to hold my pencil properly, as well as your speeches about

the importance of doing Good to others. You were an amazing role model

and part of me will always be the values you taught me. May your soul rest in peace.

To my grandfather Ahmed Essangri: This work is the representation of my love and

recognition. May your soul rest in peace.

To the Nassiri and Essangri families:

To my uncles and aunts, the dear ones who were able to make it and the ones

who wished to be here, I dedicate this work to each one of you. Accept this work

as a symbol of my love and recognition.

My best friend: soukaina al hadrati

It’s been 10 years and we made it without killing each other! Our friendship

had its ups and downs but we always managed to find our way back and

I know that following our dreams is scary and may mean not having the

life we imagined (us growing old somewhere and never having a THIRD)

but I am SURE we will manage… and you know how sure I can be about things.

I love you. You will always be my person.

Nouha Labassi:

To the dear friend, the sister, the smart and the strong person

that you are and that I deeply admire. Your friendship means a lot to me.

I will always be grateful for the guidance, affection and support I received from

you and walid. I love you dearly.

Youssef Aadi:

Do not get overly excited because i wrote your name. I didn’t. This is an illusion…

To the memory of the best night shifts that put you in my way

(and me in yours of course).I applaud your goodness as a person and as a doctor.

I love you buddy.

Nada El kadiri:

No matter how far apart we are, you always hold a special place in my heart.

Your friendship is something I hold on to profoundly. I love you.

Ollie Mae Nicoll:

To the Slilou of my cafe creme … although I drink my coffee black and sugarless like my soul now. With 6142km apart we still manage to be part of almost

everything in each others lives (and you manage to encourage all my crazy ideas). This is a reminder of how much your friendship means to me. I love you.

PS: yes i researched the distance to look extra smart; this is a thesis after all -

Kholoud Salahuddin Afifi:

There is some telepathic soul connection going on here, which we’re sure of just as much as I am sure that in some other life you were my twin. I admire the

strong person that you are and can’t wait to see you. Thank you for being my dear friend.

Ilias belkhairi:

Who would have thought that sitting next to you as a punishment would lead to such long and great friendship and that I can brag about having a childhood

friend now? You mean a lot to me. Thank you for always being there and to our bright futures.

Kholoud Houssaini:

To the newest bird and most natural connection: I look forward to the future of our friendship… To growth, soul searching and bright futures.

Sara Bortolani :

La circostanze hanno voluto che io non potessi vederti proclamata neurologa e che tu non possa vedere me nel giorno della mia laurea. Ma guardaci. Siamo diventate

grandi ! A noi due che saremo sempre sorelle. Ti voglio bene.

To Chaymae Al hadrati & Imad eddine chahboun:

For being the good friends and almost family

To Lyn abu sidu

To my friends and collegues:

Youssef Garda, Hamza Labiad, Basma Lahmer, Maha El Ouadi,

Amine Chibani, Nassima Belhaj …

To the great moments we shared and the bright futures that lie ahead.

ACKNOWLEDGEMENT

To general surgery professor Amine souadka:

Director of thesis

In this past year, having been able to learn from you gave me the opportunity

to absorb the energy, passion and encouragement you spread around as a professor,

researcher and mostly role model; and for that i am deeply honored. I could never

thank you enough for taking me under your wing, giving me the amazing

opportunities you did and somehow unconditionally believing in me. The knowledge

you passed on to me allowed me to grow so much and become a better version of myself

as a person and researcher and I can only wish to be able to follow your example.

I profoundly thank you for having my best interest and success in mind and could

never fairly phrase how much your support means to me. My respect and admiration

for you are beyond words and I am most proud to have you as my mentor.

To general surgery professor and head

of digestive oncological surgery Mohcine Raouf:

President of thesis

I would like to express my admiration to the amazing research project

and great learning opportunities as well the great work environment in your

department. I am very honored by your presence as president of my thesis jury.

To general surgery professor Mohammed

Anass Majbar: Jury of thesis

Foremost, I would like to express how honored I am for being able to carry

on with the research project you started; I also would like to express my respect

and admiration for your amazing work and expertise. I thank you for doing me the

honor of being part of my thesis jury and judging my merit to carry the title

of Medical Doctor.

To gastroenterology professor Leila amrani:

Jury of thesis

I thank you for doing me the honor of being part of my thesis jury

and judging my merit to carry the title of Medical Doctor.

Please accept the expression of my deep esteem.

To general surgery professor El malki Hadj Omar:

Jury of thesis

I thank you for doing me the honor of being part of my thesis jury

to evaluate my work and judge my merit to carry the title of Medical Doctor.

Please accept my utmost respect and my consideration.

ILLUSTRATIONS

LIST OF FIGURES

Figure 1: Number of new cases and deaths in 2018 linked to cancers ..................................................3

Figure 2 : Age standardized incidence rates of colorectal cancer in the male population worldwide ...3

Figure 3 : Age standardized incidence rates of colorectal cancer in the male population worldwide ...4

Figure 4: Sagittal view of the sigmoid colon, the rectum and anal canal showing the sacral and

anorectal flexures ................................................................................................................................6

Figure 5: Sagittal view of the rectum and anal canal showing the angle variation of the anorectal

flexure when the EAS and puborectalis are contracted or relaxed .......................................................7

Figure 6: Coronal view showing the upper, middle and lower portions of the rectum and the anal

canal ...................................................................................................................................................8

Figure 7 : Sagittal view showing the anatomic and surgical anal canal ................................................9

Figure 8: Coronal view showing the anal sphincter complex and levator ani complex ...................... 12

Figure 9: Pelvic view of the levator muscles demonstrating its four main components: puborectalis,

pubococcygeus, iliococcygeus, and coccygeus (From Gordon PH, Nivatvongs S [eds]: Principles and

practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999, Quality Medical Publishing, p

18.) ................................................................................................................................................... 13

Figure 10: Sagittal view showing the rectum’s peritoneal covering and nearby organs in male and

female............................................................................................................................................... 14

Figure 11: transversal view showing the pelvic fascia in their relationship with the mesorectum [41]

......................................................................................................................................................... 17

Figure 12: Sagittal view showing the pelvic fascia (From Gordon PH, Nivatvongs S [eds]: Principles

and practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999, Quality Medical

Publishing, p 10.) .............................................................................................................................. 18

Figure 14 : sagittal view showing the lines of mesorectal excision .................................................... 20

Figure 15: Coronal view of the low rectum showing the nearby structures at the limits of mesorectal

excision ............................................................................................................................................ 20

Figure 16: Anorectal arterial blood supply. (From Gordon PH, Nivatvongs S [eds]: Principles and

practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999, Quality Medical Publishing, p

24.) ................................................................................................................................................... 21

Figure 17: Anorectal venous drainage. (From Gordon PH, Nivatvongs S [eds]: Principles and

practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999, Quality Medical Publishing,

p 30.) ................................................................................................................................................ 22

Figure 18: Lymphatic drainage of rectum and anal canal from Gordon PH, Nivatvongs S [eds]:

Principles and practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999, Quality

Medical Publishing, p 32. .................................................................................................................. 23

Figure 19: Nerve supply of the rectum and anal canal. ...................................................................... 24

Figure 20: the limits of excision for a rectal tumor ........................................................................... 26

Figure 21 : The Wexner score ........................................................................................................... 34

Figure22: The VAIZEY score .......................................................................................................... 35

Figure 23: The LARS score .............................................................................................................. 36

Figure 23: The American Association of Orthopaedic Surgeons (AAOS) Cross-cultural adaptation

protocol ............................................................................................................................................ 40

Figure 24: Patient selection flowchart ............................................................................................... 45

Figure 25: Bland–Altman plot with 95% limits of agreement illustrating the difference between

LARS scores at the first and second test. ........................................................................................... 54

Figure 26 : Bland–Altman plot with 95% limits of agreement illustrating the difference between

WEXNER scores at the first and second test. .................................................................................... 55

Figure 27 : Boxplot showing the LARS total score median values according to rectal

tumor location................................................................................................................................... 60

Figure 28 : Boxplot showing the LARS total score median values according to anastomosis type .... 60

Figure 29 : Boxplot showing the LARS total score median values according to radiochemotherapy . 61

Figure 30 : Boxplot showing the LARS total score median values according to the type of mesorectal

excision ............................................................................................................................................ 61

Figure 31 : Boxplot showing the WEXNER total score median values according to rectal tumor

location ............................................................................................................................................. 62

Figure 32 : Boxplot showing the WEXNER total score median values according to anastomosis

type .................................................................................................................................................. 63

Figure 33 : Boxplot showing the WEXNER total score median values according to

radiochemotherapy ........................................................................................................................... 63

Figure 34: Boxplot showing the WEXNER total score median values according to type of

mesorectal excision ........................................................................................................................... 64

Figure 35 : Scatter plot showing the correlation between the WEXNER and LARS scores .............. 65

LISTE OF TABLES

Table I : Clinical and demographic characteristics of patients. .......................................................... 52

Table II : Agreement levels of the LARS categories and score items between the test and retest ...... 54

Table III : Agreement levels of the WEXNER score items between the test and retest ...................... 56

Table IV: Convergent validity of the LARS score ............................................................................ 57

Table V : Convergent validity of the WEXNER score ...................................................................... 58

Table V : Literature review results of the available international validations of the LARS and

WEXNER ....................................................................................................................................... 68

SUMMARY INTRODUCTION ................................................................................................................1

I. SURGICAL ANATOMY : ...............................................................................................5

❖ Rectum: ....................................................................................................................5

❖ Anal canal : ..............................................................................................................8

❖ Anal sphincter : ...................................................................................................... 10

-Internal anal sphincter :............................................................................................. 10

- External anal sphincter :........................................................................................... 10

- The conjoined longitudinal muscle : ........................................................................ 11

❖The pelvic floor : ....................................................................................................... 12

❖Rectum and peritoneum : ........................................................................................... 13

❖The Pelvic fascia: ...................................................................................................... 15

❖The Rectal spaces : .................................................................................................... 16

❖Rectum and mesorectum : .......................................................................................... 19

❖Rectum vasculature : ................................................................................................. 21

- Arterial Supply: ....................................................................................................... 21

- Venous Drainage: .................................................................................................... 22

-Lymphatic Drainage: ................................................................................................ 23

- Nerve supply: .......................................................................................................... 24

II.-SURGICAL MANAGEMENT OF RECTAL CANCER : ............................................. 25

❖Low anterior resection (LAR) : .................................................................................. 25

❖Principles of the resection : ........................................................................................ 26

❖Surgical steps : .......................................................................................................... 27

❖Types of anastomoses: ............................................................................................... 28

III.-PATHOPHYSIOLOGY OF THE LAR: ...................................................................... 29

❖Normal continence :................................................................................................... 29

❖Incontinence : ............................................................................................................ 30

IV.-THE LOW ANTERIOR RESECTION SYNDROME : ................................................ 32

V.-INCONTINENCE ASSESSMENT TOOLS : ............................................................... 32

❖The Jorge- wexner score : .......................................................................................... 33

❖The vaizey score : ...................................................................................................... 34

❖The LARS score : ...................................................................................................... 35

METHODOLOGY: .............................................................................................................. 38

I.-QUESTIONNAIRE ELABORATION : ......................................................................... 41

❖Translation: ............................................................................................................... 41

❖Back-translation: ....................................................................................................... 41

❖Pre-test: ..................................................................................................................... 41

II.-PATIENT REPORTED OUTCOME MEASURES : ..................................................... 42

❖LARS score: .............................................................................................................. 42

❖Wexner score : ........................................................................................................... 42

❖EORTC QLQ-C30: .................................................................................................... 43

III.-PARTICIPANTS SAMPLING AND DATA COLLECTION: ..................................... 44

IV.-PSYCHOMETRIC PROPERTIES: ............................................................................. 46

❖Reliability : ................................................................................................................ 46

-Internal consistency: ................................................................................................. 46

- Test - retest : ............................................................................................................ 46

❖Validity : ................................................................................................................... 47

- Convergent validity: ................................................................................................ 47

- Discriminant validity : ............................................................................................. 48

V.-STATISTICAL ANALYSIS: ....................................................................................... 48

VI.-INTERNATIONAL DATABASE AND ETHICS CONSIDERATIONS: .................... 49

RESULTS ........................................................................................................................... 50

I.-TRANSLATION : ......................................................................................................... 51

II.-PATIENTS CLINICAL AND DEMOGRAPHIC CHARACTERISTICS : .................... 51

III.-RELIABILITY : ......................................................................................................... 53

❖Internal consistency : ................................................................................................. 53

❖Test-retest: ................................................................................................................. 53

-LARS reliability : ..................................................................................................... 53

-WEXNER reliability:................................................................................................ 55

IV.-VALIDITY:................................................................................................................ 57

❖Convergent validity : ................................................................................................. 57

-LARS score : ............................................................................................................ 57

-WEXNER score: ...................................................................................................... 58

❖Discriminant validity : ............................................................................................... 59

-LARS discriminant validity: ..................................................................................... 59

-WEXNER discriminant validity:............................................................................... 62

V.-CORRELATION BETWEEN THE LARS AND WEXNER: ........................................ 65

DISCUSSION ..................................................................................................................... 66

I.-PRIOR VALIDATIONS OF THE LARS AND WEXNER SCORE : .............................. 67

II.-MEAN FOLLOW UP TIME : ....................................................................................... 69

III.-RELIABILITY : ......................................................................................................... 69

❖Internal consistency: .................................................................................................. 69

❖Test-retest reliability: ................................................................................................. 70

IV. VALIDITY : ............................................................................................................... 70

❖Convergent validity : ................................................................................................. 70

❖Divergent validity : ................................................................................................... 71

❖Correlation between low anterior resection syndrome questionnaires: ........................ 73

CONCLUSION ................................................................................................................... 74

ABSTRACT ........................................................................................................................ 76

APPENDIX ......................................................................................................................... 80

REFERENCES ................................................................................................................... 91

1

INTRODUCTION

2

Colorectal cancer is a critical global health issue with 1 849 518 (10.2%)

new cases and 880 792 (9.2%) deaths in 2018. It’s the third most commonly

diagnosed malignancy and the second leading cause of cancer-related deaths in

the world. [1] Its burden is expected to increase by 60% to more than 2.2 million

new cases and 1.1 million cancer deaths by 2030 [2,3] ) Similarly, the number of

deaths in subjects with rectal cancer has been projected to rise by 71.5% until

2035.

These numbers are the result of population growth and aging, [2,3]

alongside being the reflection of already established risk factors of CRC such as

high BMI, physical inactivity, smoking, alcohol consumption, diets rich in red

and processed meat, artificially sweetened foods, and salt, with minimal intake

of fruits and vegetables [4]. In fact, colorectal cancer is being increasingly

considered one of the clearest markers of epidemiological and nutritional

transition, with increasing incidence rates of this cancer among others, offsetting

infection-related cancers in countries undergoing societal and economic

changes. Moreover, the incidence of CRC in younger individuals aged under 50

is progressively rising, accounting for up to 11% of all male CRCs, 10% of all

female CRCs, and 7% of all CRCs occurring before 40 years of age. [5];[6].

Opposingly to the aforementioned facts, CRC linked death rate showed

declining trends in the past years [7] mirroring the effects of preventive

strategies such as early detection [8] , colonoscopy [9] , polypectomy [10] as

well as the improvements in perioperative care,chemotherapy and radiotherapy

throughout the adoption of multidisciplinary management [11]

3

In Morocco, colorectal cancer is the second most frequent digestif cancer

after stomach cancer, the tenth most frequent cancer for male patients and the

sixth most frequent for female patients in Casablanca. [12]

Figure 1: Number of new cases and deaths in 2018 linked to cancers

Figure 2 : Age standardized incidence rates of colorectal

cancer in the male population worldwide

4

Figure 3 : Age standardized incidence rates of colorectal cancer in the male population worldwide

Survival rates for colorectal cancer have been improving, with 5-year survival rate for patients at the early stage of CRC (stages I and II) above 60% and up to 10% for patients beyond stage III when distant metastases have already occurred. [13] This has been attributed to the multimodal management of rectal cancer which involves a multidisciplinary team of cancer specialists with expertise in gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology. [14] Notwithstanding the enhanced oncological outcome and long term survival rate, this lengthened survivorship is also correlated to deteriorating anorectal function, impaired physical functioning and everyday life multiple disease- and treatment-related symptoms such as pain, bowel dysfunction, and fatigue which negatively affect psychological, emotional, social, and role functioning through fear, anxiety, sleep disruption, and depression making it therefore pivotal to assess and attempt to improve the quality of life of CRC patients. [15]

5

Almost 80% of patients having undergone sphincter preserving surgery report a set of symptoms including difficulty emptying the bowel, faecal urgency and faecal incontinence, all encompassed by the term : low anterior resection syndrome (LARS). Bryant and al suggested a definition that is “disordered bowel function after rectal resection, leading to a detriment in quality of life” [16]

This syndrome previously thought to be transient, is shown to persist for years after resection, hence the crucial need to include the LARS among the adverse effects and as a part of the surgical outcome assessment. Accordingly, many tools have been developed to measure the degree of LARS and make this complex syndrome amenable to discussion, namely the LARS and WEXNER scores. These questionnaires, as with more traditional health-care assessment tools need to be tested for reliability and validity.

I. SURGICAL ANATOMY :

❖ Rectum:

The rectum is the most distal portion of the large intestine, bound

superiorly by the transition from the sigmoid colon and converging at the level

of the dentate line into the anal canal distally. This transition is marked by the

cessation of the mesocolon, coalescence of taenia coli, loss of appendices

epiploicae and the fusion of the surgical mesocolon. The rectum has a length

varying from 12 to 15 cm and is devided into two segments, the first being the

rectal ampulla, which is known for it’s expansion from 8 to 16cm according to

varying filling states, and the second being the anal canal.

6

The rectum can also be divided into an upper, middle, and lower portion

located at a distance of 15-12cm, 11-7 cm and 6-0 cm respectfully.

Its course is marked by two anterior-posterior flexures, the first following

the concavity of the sacrum as the sacral flexure and the second coursing

anteriorly as the anorectal flexure. This latter presents at an angle of 90° at rest,

whereas with voluntary squeeze of the EAS and puborectalis muscle, the angle

becomes more acute (70° ) in order to close off the anal canal and maintain

continence. It’s during defecation that it widens to 110-130° as the puborectalis

and EAS relax in order to straighten out the anorectal junction, allowing stool to

pass through. [20]

Figure 4: Sagittal view of the sigmoid colon, the rectum and anal canal showing the sacral and anorectal flexures

7

Figure 5: Sagittal view of the rectum and anal canal showing the angle variation of the

anorectal flexure when the EAS and puborectalis are contracted or relaxed

Additionally the rectum presents three lateral curvatures - superior inferior

and middle oriented respectfully to the right and left. Each of these curves

presents on the inside a transverse sickle-shaped luminal fold: the valves of

Houston, the rectal folds or the semi-lunar transverse folds; the middle fold

being the most prominent one. This latter also called the kohlrasch’s valve,

marks the anterior peritoneal reflection which is about 7-9 cm above the anal

verge in men and 5-7.5 cm in women. These folds contribute significantly to the

support of the weight of the fecal matter and therefore the prevention of fecal

incontinence. [21]

8

Figure 6: Coronal view showing the upper, middle and lower portions

of the rectum and the anal canal

❖ Anal canal :

The anatomical anal canal measures approximately 2 cm and extends from

the dentate line to the anal verge with two thirds above the pectinate line and

one third below it. It is surrounded by the IAS, EAS, and the puborectalis

muscle.

Another definition of the anal canal was suggested by Milligan and

Morgan, measuring the “surgical” anal canal from the anal verge to the anorectal

ring (levator ani) with a length of 4.4 cm and 4.5 cm in men and women

respectively.[22] This definition is useful in a physiologic and surgical manner

9

as this longer anal canal begins at a region with higher intraluminal pressure

(end of the ampulla), thereby correlating better to digital, sonographic and

manometric examination. [23–25]

Transitionning to the anal canal, the epithelium from the rectum (columnar

epithelium) becomes a squamous epithelium (also called anal mucosa) with the

transition line marked by the dentate line. This squamous epithelium is none

keratinizing above the anal verge and pigmented and keratinized with skin

appendages below it (eg, hair, sweat glands, and sebaceous glands). It’s located

in the midportion of the anal canal and contains anal crypts or colomns at the

base of which are anal glands and anal papillae. More inferiorly are the anal

valves which are transverse folds of the mucosa containing vascular cushions

(expansions of vascular tissue within the mucosa) which can expand to form a

seal that aids in maintaining resting anal tone and promoting continence.

Figure 7 : Sagittal view showing the anatomic and surgical anal canal [26]

10

❖ Anal sphincter :

The anal sphincter complex consists of the internal anal sphincter (IAS),

external anal sphincter (EAS), puborectalis sling, and longitudinal rectal muscle

which layer up from inside to outside as the anal mucosa, smooth muscle IAS

layer, fat-containing intersphincteric space with conjoined longitudinal muscle

layer, and outer striated EAS muscle layer. [27,28]

Internal anal sphincter :

As the rectum inserts into the pelvic diaphragm, the inner circular muscle

of the rectum becomes the IAS being 2-3 cm long and 5-8mm thick with an

increasing thickness near the anal verge. The IAS terminates at 1 cm proximal to

the distal edge of the EAS. The innervation is due to both intrinsic myogenic

[29] and extrinsic autonomic neurogenic properties [30,31] insured by the

inferior pelvic plexus and splanchnic nerves (S2–4). This provides a natural

barrier to the involuntary loss of stool through its ability to maintain a

continuous state of partial contraction and only relax in response to rectal

distension.

The IAS is palpable through digital examination as a rigid cylinder,

particularly when the striated EAS is completely relaxed.[28,32]

External anal sphincter :

The EAS is the expansion of the levator ani muscles and surrounds the anal

canal, IAS, and conjoined longitudinal muscle in a cylindrical conformation. It

is approximately 2.7 cm high, but is anteriorly shorter in women being

approximately 1.5 cm, and extends approximately 1 cm beyond the internal

sphincter.

11

The nerve supply is bilaterally insured by the inferior rectal branch of the

pudendal nerve (S2, S3) and the perineal branch of the fourth sacral nerve (S4).

Unlike other skeletal muscles that are inactive at rest, the EAS along with the

pelvic floor muscles maintains continuous unconscious resting electrical tone

[33]. This special activity is due to a reflex arc made up of stretch receptors in

both levator ani muscles and the anal sphincters, through an afferent neurone to

the cauda equina and an efferent motor neurone to the muscles[34]. This resting

tone varies to the intra-abdominal pressure and the Valsalva maneuver as well as

through voluntary contraction for a short period.[35] In fact it can contract to

more than double the resting tone of the anus when stimulated and is responsible

for the anal canal’s squeeze pressure[36]

The conjoined longitudinal muscle :

The CLM, also called the longitudinal anal muscle, has been described as a

vertical layer of muscular tissue within the intersphincteric space between the

IAS and the EAS. It begins at the anorectal ring as an extension of the

longitudinal rectal muscle fibers and descends caudally where it’s joined by

striated muscle fibres from the puborectalis, hence the term “conjoined”

longitudinal muscle. The fibro-elastic tissue of the longitudinal layer is

continuous with the fibro-elastic network outside the sphincter to the perianal

skin forming the corrugator cutis ani, which constitutes an intra-sphincteric

fibro-elastic network passing through the external sphincter. [28,32]

12

Figure 8: Coronal view showing the anal sphincter complex

and levator ani complex [37]

❖ The pelvic floor :

The pelvic floor is an intricate composite of muscles, fascia, and ligaments

that functions to provide support to the pelvic organs. It consists of the levator

ani muscles that lie within the endopelvic fascia superiorly, the perineal

membrane inferiorly, and the perineal body beneath it providing additional

support to the anal sphincter.

The levator ani consists of four major muscles namely pubococcygeus,

ileococcygeus, ischiococcygeus and puborectalis with distinct muscle fascicle

orientation for the three which contribute to the maintain of a constant resting

and closing off the anal sphincter [38]. The urogenital hiatus is an opening in

this muscular complex through which passes the rectum [39].

13

On the other hand, the perineal body is made out of the intersection of the

striated external anal sphincter (EAS), superficial transverse perinei, deep

transverse perinei, and bulbospongiosus muscles all functionning in purse string

morphology. [32]

Figure 9: Pelvic view of the levator muscles demonstrating its four main components:

puborectalis, pubococcygeus, iliococcygeus, and coccygeus (From Gordon PH, Nivatvongs S [eds]: Principles and practice of surgery for the colon, rectum and anus, ed 2, St Louis,

1999, Quality Medical Publishing, p 18.)

❖ Rectum and peritoneum :

The rectum is the continuation of the sigmoid colon as it loses its

mesentery, becoming entirely free on its posterior aspect.The peritoneum covers

the upper two-thirds of the rectum anteriorly and only the upper third laterally.

The lower third of the rectum is entirely devoid of peritoneal covering. The

peritoneum covering the upper third of the rectum is reflected onto the pelvic

sidewalls to form the pararectal fossa and onto the seminal vesicles in the male

and vagina in the female to form the rectovesical and rectovaginal pouch

respectively.

14

Figure 10: Sagittal view showing the rectum’s peritoneal covering

and nearby organs in male and female

15

❖ The Pelvic fascia:

- Fascia propria of the rectum (FPR): As the lower third of rectum is not

covered by peritoneum, it is enveloped, along with the mesorectum, by a “sock”

shape fascial layer which is removed as an entire package during mesorectal

excision. It fuses with the endopelvic fascia and the presacral fascia

respectively.

- Endopelvic fascia : covers the floor and sidewalls of the pelvis as well as

the origin of the levator ani muscles.

- Presacral fascia: covers the posterior aspect of the mesorectum anteriorly

to the sacrum as well as the promontory In the posterior midline descending

along into the pelvis and spreading anteriorly and laterally.

- Denonvilliers’ Fascia : separates the mesorectum anteriorly from the rest

of the pelvic organs, namely the bladder, seminal vesicles, vasa deferentia,

ureters and prostate and both neurovascular (genitourinary) bundles in men and

the vagina as well as the genitourinary neurovascular bundles in women.

- Waldeyer’s fascia or retro-sacral fascia: this fascia is a subject of

controversy in anatomical texts between considering it a fascia or a ligament. It

is described as the thickening of the presacral fascia that descends to meet the

mesorectal fascia about 3-5 cm from the anorectal junction and which dissection

is important to the full mobilization of the rectum.

- Parietal fascia : is the lateral extension of the Denonvilliers’ fascia and it

separates the mesorectal compartment from the lateral pelvic wall. It also

adheres to the presacral fascia and encases the hypogastric nerves and the pelvic

splanchnic nerves, which run through the lateral pelvic walls.

16

- lateral rectal ligaments: these fibrous formations are subject of

controversy as many anatomists disagree about not only their position but also

their existence while others think of them as lateral condensations of the

endopelvic fascia.

Surgical implications of rectal fascia:

Separation of the mesorectum and parietal fascia must be done with caution

as any violation of the mesorectal fascia predisposes to tumor local recurrence

while the violation of parietal pelvic fascia may result in injury of the presacral

venous plexus. Accordingly, the dissection should be done on the avascular

“yellow side of the white”.

Moreover, the recognition and dissection of the rectosacral fascia close to

its anchoring on the rectal wall increases the mobility of the distal rectum and

ensures dissection along the correct plane.

Dissecting close to the denonviller’s fascia or the rectogenital septum is

linked with great risk of neurovascular involvement as it contains small nerve

fibers and vessels which could result in some degree of urogenital

dysfunction.[40]

❖ The Rectal spaces :

- Retrosacral space: separates the rectal and pelvic fascia and extends

down to the pelvic floor.

- Presacral space: separates the parietal pelvic fascia and the sacrum and

contains the origin of parasympathetic pelvic splanchnic nerves as

well as the medial and lateral sacral arteries.

17

- Retro-rectal space: an avascular nerve free space separating the

waldeyer’s fascia and rectal fascia along the surface of the sacrum,

which plays a pivotal role in the dorsal mobilisation of the rectum

during the TME.

Figure 11: transversal view showing the pelvic fascia in their relationship

with the mesorectum [41]

18

Figure 12: Sagittal view showing the pelvic fascia (From Gordon PH, Nivatvongs S [eds]:

Principles and practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999,

Quality Medical Publishing, p 10.)

Figure 13: Midsagittal section showing the perirectal fascia and spaces

19

Figure 14: transversal view at the level of the midrectum showing the lateral ligaments

❖ Rectum and mesorectum :

The mesorectum is the remnant of the embryological hindgut mesentery,

and consists of a cut of connective tissue and fat that surround the rectum

enveloped within the mesorectal fascia and in some areas by the peritoneum. It

is bulkier posteriorly with variable thickness. The mesorectum logges the

epirectal and pararectal lymph nodes as long as the superior rectal vessels being

thereby the earliest and most frequent ones that might be involved when tumor

spread occurs.[42,43] This structure represents an important principle in rectal

cancer surgery as successful outcome depends on the removal of the rectum with

an intact mesorectum.[44] Between the mesorectal fascia and parietal pelvic

fascia is an avascular areolar tissue plane, demonstrated surgically as the ‘Holy

Plane of Heald’ and allows a histopathological landmark for comparison of

quality of surgical resection. [45,46]

20

Figure 13 : sagittal view showing the lines of mesorectal excision [47]

Figure 14: Coronal view of the low rectum showing the nearby structures

at the limits of mesorectal excision [48]

21

❖ Rectum vasculature :

Arterial Supply:

The superior rectal artery, emerging from the inferior mesenteric artery.

The middle rectal arteries, originating from the internal iliac arteries,

supply to distal rectum and proximal anal canal. The presence of these arteries is

variable.

The inferior rectal arteries arise from the internal pudendal artery, which is

a branch of the internal iliac artery.

These arteries traverse the ischioanal fossa on both sides of the anal canal

feeding the sphincter muscles. Intramural collaterals exist between the superior

and inferior rectal arteries at the level of the dentate line in the submucosa. [49]

Figure 15: Anorectal arterial blood supply. (From Gordon PH, Nivatvongs S [eds]:

Principles and practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999,

Quality Medical Publishing, p 24.)

22

Venous Drainage:

Blood returns from the rectum and anal canal into either the portal or

systemic systems. Most of the blood from the rectum drains into the superior

hemorrhoidal vein that ultimately drains into the portal system via the inferior

mesenteric vein. The lowermost portion of the rectum and the anal canal drain

into the internal iliac veins directly through the middle rectal veins and the

inferior rectal veins.

Figure 16: Anorectal venous drainage. (From Gordon PH, Nivatvongs S [eds]:

Principles and practice of surgery for the colon, rectum and anus, ed 2, St Louis, 1999,

Quality Medical Publishing, p 30.)

23

Lymphatic Drainage:

Mainly following the arterial supply, the rectum drains via the superior

rectal lymphatics to the inferior mesenteric lymph nodes in the retroperitoneum

and laterally to the internal iliac nodes along the middle and inferior rectal

vessels through the ischioanal fossa. Lymph drainage from below the dentate

line drains to the inguinal nodes.

Figure 17: Lymphatic drainage of rectum and anal canal from Gordon PH,

Nivatvongs S [eds]: Principles and practice of surgery for the colon, rectum and anus,

ed 2, St Louis, 1999, Quality Medical Publishing, p 32.

24

Nerve supply:

Rectum and anal canal are supplied by superior, middle and inferior rectal

plexuses. The parasympathetic fibers of this synapse have their postganglionic

neurons in the myenteric plexus of the rectum wall. Also fibers ascend from

inferior hypogastric plexus to superior hypogastric and aortic plexus to reach

inferior mesenteric plexus which innervates descending and sigmoid colon by

traveling up along left colonic wall.

Figure 18: Nerve supply of the rectum and anal canal.

25

II. SURGICAL MANAGEMENT OF RECTAL CANCER :

Successful resection of rectal cancer is technically challenging due to the

complex anatomy within the pelvis and risk of urinary and sexual dysfunction.

Patient characteristics, such as a narrow android pelvis or increased visceral fat,

represent further difficulties as well.

Prior to surgery, determination of patient’s fitness and general status is

primordial. In addition to that, it is important to assess for metastatic disease

through imaging of the chest, abdomen, and pelvis and measure the carcino-

embryonic antigen (CEA). This will also allow staging of the tumor and

determining the CRM in addition to planning neoadjuvant treatment and

resection. Use of infection-prevention measures and deep venous prophylaxis is

standard for these major procedures.

❖ Low anterior resection (LAR) :

LAR is defined as resection of the rectum with total or partial mesorectal

excision and colo-rectal or -anal anastomosis which will be sometimes protected

by a temporary stoma. Total mesorectal excision exploits an embryologic

avascular perimesorectal plane to extract a cylindrical specimen of rectum and

mesorectum. Preservation of nerves critical to normal sexual and bladder

function is a hallmark of the technique.

26

Figure 19: the limits of excision for a rectal tumor

❖ Principles of the resection :

- Tumor in the rectosigmoid flexure or upper rectum (above 12 cm): The

rectum and mesorectum are divided 5 cm below the tumor. Avoid coning from

the mesorectal fascia to the bowel (the total mesorectum must be resected in all

5 cm). A small remnant of the mesorectum is spared.

- Tumor at level 8-12 cm: Bowel and mesorectum is resected 5 cm below

the tumor which means TME for all practical purposes.

- Tumor at 5 to 9 cm: total mesorectal excision all the way to the pelvic

floor. Adequate distance on the bowel wall < 1 cm.

27

❖ Surgical steps :

- Incision: As good visualization is crucial to safe completion of all

portions of the procedure. A midline incision is usually accomplished starting

from above the umbilicus to allow complete mobilization of the splenic flexure

with extension up to the pubis.

- Colon mobilization and mesenteric vessel ligation: For the anterior

resection, a sigmoid colon mobilization is required, as well as the mobilization

of the descending colon and full splenic flexure to allow tension free

anastomosis. The inferior mesenteric artery is considered the key starting point

to good anatomical dissection as it is ligated along with the inferior mesenteric

vein and the superior rectal artery. The sigmoid colon is examined and divided

at the chosen point, carefully cleansed, wrapped with a piece of gauze and

tucked under the abdominal wall.

- Rectum mobilization: Pelvic dissection starts and proceeds

circumferentially. Posteriorly, dissection is carried past the tip of the coccyx,

with division of the rectosacral ligament. Lateral extension carries the plane

between the superior hypogastric plexus and the mesorectum. As lateral

dissection proceeds inferiorly, meticulous maintenance of a plane is required as

straying medially from the plane in this region may compromise the

circumferential margin and produce bleeding from mesorectal vessels, while

straying laterally may injure the nerves of the hypogastric plexus and/or cause

bleeding from the pelvic sidewall. Following the plane anteriorly, dissection

proceeds through Denonvilliers’ fascia or the rectogenital septum between the

mesorectum and prostate and seminal vesicles or posterior wall of the vagina.

28

Further mobilization of the rectum is attained by dividing the areolar tissue

between the fascia propria of the rectum and the fascia of the pelvic sidewall

namely the endopelvic fascia.

- Anastomosis: For pelvic anastomosis an adequate length of free colon is

required which if not reached after the mobilization of the splenic flexure and

IMA, could be attained by dividing the IMV. The preservation of the marginal

artery is paramount to constructing a proper low anastomosis without tension

and with good blood supply. Clamping off the proximal end of bowel and

dissection is performed then stapling devices are used to make the anastomosis

which will be thoroughly evaluated, first by examining the integrity of the

anastomotic doughnuts and then by air insufflation. [50–53]

❖ Types of anastomoses:

- End-end colorectal anastomosis, also called straight anastomosis.

- Side-end colorectal anastomosis without reservoir.

- Side-end anastomosis with reservoir and a blind loop around 5 cm

long.

- End-end coloanal anastomosis, colon is sutured to the dentate line.

29

III. PATHOPHYSIOLOGY OF THE LAR:

❖ Normal continence :

Continence is a physiological phenomenon that relies on a multitude of

factors. Normally feces are transferred into rectum by colonic propulsive

contractions. Rectal distension evokes the recto-anal inhibitory reflex which

occurs when acute rectal distention with flatus or feces reflexly inhibits the

internal anal sphincter, thus allowing a sample of rectal contents into the upper

anal canal. [54] This contact with the sensitive transitional mucosa allows the

differentiation between different states of fecal matter and flatus, enabling the

subject to safely pass flatus. Concurrently, the external anal sphincter will

maintain the resting anal tone, thereby preventing defecation either voluntary or

through the increase of the intra-abdominal pressure.

Any loss of this refinement may contribute to imperfections of continence

sometimes found following low anterior resection.

Furthermore the puborectalis muscle, supplied by the pudendal nerve, plays

an important role too by maintaining and modifying the anorectal angle.

Another important element is the ability of the anorectal margins to

distinguish between rectal gas, liquid or solid stool throughout the input coming

through the sacral dorsal roots, which will allow not only that but also the

monitoring of filing states and contraction level of the rectum [55,56] .

Incontinence thereby can be provoked by a multitude of mechanisms.

30

❖ Incontinence :

The LAR syndrome is caused by a multitude of mechanisms among which

is: IAS dysfunction, decrease in anal canal sensation, disappearance of the

rectoanal inhibitory reflex (RAIR), disruption in local reflexes between the anus

and the neorectum, and reduction in rectal reservoir capacity and compliance.

Anal sphincter damage :

Whether the incontinence is passive (unconscious leakage) or active (feeling of urgency and an impending leakage) allows us to estimate the damaged part. In fact the external anal sphincter is responsible of conscious leakage and reduction in maximum squeeze pressures, whereas the internal anal sphincter dysfunction is often passive and associated with mean anal resting pressure perturbations. [55,56] Anatomic studies have shown that sympathetic nerves supplying the IAS course intersphincterically, and as a result are likely to be injured in LAR for rectal cancer, affecting function. [57] In addition to that, the differences in IAS pressure before and after surgery have been proven to be a major contributive to LAR syndrome. [58]

Decreased anal canal sensation :

Many studies addressed the role of decreased anal canal sensation and inability to distinguish between the different states of feceal matter in the LAR through comparing groups of patients after LAR with and without incontinence, and demonstrated lower anal canal sensitivity at the dentate line in patients with incontinence. [59]

Neorectum and anastomosis:

After rectal excision and formation of a neorectum, the volume of what used to be the faeces reservoir is reduced and so is the capacity to contain stool.

Additionally the type of anastomosis and the use of a conventional end-to-end colorectal or coloanal anastomosis have been proven to be responsible of

31

urgency and incontinence, which can be avoided by the use of alternative configurations such as side-to-end anastomosis, the colonic pouch, and the transverse coloplasty.

Furthermore, the amount of force required to distend the rectal wall, also

referred to as the compliance, is altered in the neorectum causing bowel

urgency, frequency, and incontinence.

Recto-anal inhibitory reflex :

The compliance of the neorectum plays an important role in the recto-anal

inhibitory reflex (RAIR) which is described as transient relaxation of the IAS in

response to rectal dilation. If the defecation is inconvenient, the contraction of

the external anal sphincter is maintained and retrograde rectal peristalsis moves

stool out of distal rectum which has to remain constantly empty, except for

during defecation. [60] [61] The RAIR has been studied in preoperative and

postoperative patients with symptoms of LAR syndrome, showing this reflex to

be an independent predictor of poor 12-month function after LAR.

Colonic and neorectal motility:

Many studies have shown that after anterior resection and radiotherapy,

small irregular waves (spastic waves) were noted at the site of the neorectum.

These contractions are thought to be responsible of stool mass movement and

therefore symptoms of faecal leakage, urgency, and multiple evacuations.[62]

Preoperative radiotherapy and chemotherapy:

It has been noted through many studies that the use of preoperative

radiotherapy has been linked to worse frequency and severity of faecal

incontinence compared to patients who did only go through surgery. [63]

32

IV. THE LOW ANTERIOR RESECTION SYNDROME :

The LAR represents a major complication of low anterior resection in

rectal cancer patients as it is composed of a variety of symptoms ranging from

partial and occasional to total incontinence with increased frequency and

urgency, or constipation and incomplete emptying. This syndrome is associated

with negative impact on the quality of life and is subject to a multitude of

assessment tools most of which incorporate the same parameters, including the

nature of incontinence (flatus, liquid seepage, liquid incontinence, solid

incontinence), the incontinence type (active awareness, passive non-awareness,

urge incontinence), the quantity of loss, the frequency of incontinence episodes,

and accompanying complaints such as abdominal/pelvic pain and obstructed

defecation.

V. INCONTINENCE ASSESSMENT TOOLS :

Objective assessement of the anal function includes anorectal manometry,

electrophysiologic study, and endoanal ultrasonography but they do not measure

the incontinence. Measuring symptoms of incontinence is directly dependant on

the patient’s experience and perception of the disease implications on his or her

life. [64][65] Accordingly, a variety of instruments have been used to attempt

quantifying these complaints into an objective scale through giving values to

some aspects of incontinence. These instruments vary between descriptive

measures, impact measures, and severity measures. Among these, severity

measures are more commonly used in clinical practice. On the other hand

scoring systems can either rely on a grading system which correlates a value to

33

specific types of incontinence in an ordinal way or adopt a summary scoring

system. In fact, the latter is thought to enable better differentiation between

groups of patients and levels of incontinence as it takes into account various

aspects of incontinence such as type, frequency, and contribution to severity and

computes the summary scores by adding up the values for each category.

The use of these tools in any context other than the one it was created in

entails besides translation, proper transcultural adaptation and validation,

predominantly due to the racial and cultural differences encountered in disease

perception, expression and responsiveness to treatment either between different

backgrounds or for immigrant populations in the same community. Furthermore,

the use of a multitude of instruments will only aggravate the lack of consensual

understanding and management and acquiring unified methods will facilitate

multinational and multicultural research projects. [17–19][66]

Consequently a variety of these scores have been translated and validated

into different languages.

❖ The Jorge- wexner score :

Also called the Cleveland Clinic score, this widely applied fecal

incontinence instrument was developed in 1993 is nonetheless the least

validated among all incontinence scores with only a few transcultural

adaptations none of which are related to colorectal surgery. [64,67] It examines

the frequency of three types of fecal incontinence (solid, liquid, and gas) and

their consequences (pad wearing and lifestyle alteration). For each item, the five

frequency options range from never (score 0) through to always (meaning at

least once per day; score 4). The total score is the sum of the item scores, and

ranges from 0 (perfect continence) to 20 (complete incontinence). [68]

34

Figure 20 : The Wexner score

❖ The vaizey score :

Built on the Wexner score while incorporating three modifications; first of

which is an urgency item (lack of ability to defer defecation for 15 min) with a

response options of no (score 0) and yes (score 4). Secondly, an item on

antidiarrheal drugs (use of constipation medicines) was added, with a yes and no

response as well and variating scores going from (score 0) to (score 2)

respectively. Lastly, it was thought that pad wearing should not be given the

same emphasis as the incontinence items and consequently the response options

and scoring of the pad wearing item were adjusted to no (score 0) and yes (score

2). The total score ranges from 0 (perfect continence) to 24 (complete

incontinence). [69].

35

Figure21: The VAIZEY score

❖ The LARS score :

The LARS score was developed from and validated on a nationwide cohort

of 961 Danish patients who received curative low anterior resection with or

without radiotherapy for non-disseminated rectal cancer in Denmark between

2001 and 2007. In addition to the Danish version, the LARS has been validated

36

into 24 languages (English, French, German, Chinese…). This questionnaire

relies on the recurrence of the symptom/ episodes through assessing the

frequency of emptying, incontinence (liquid, gas), and other symptoms such as

urgency and incomplete voiding. The response score values are based on the

impact of the particular symptom/frequency combination on QOL. Among the

assessed elements, urgency and clustering are the items with the highest

response score values, indicating the effect of these factors on the patient’s

QOL. [70]

Figure 22: The LARS score

37

Presently, the Wexner score is the most widely applied fecal incontinence

instrument to date.[71] Likewise, the LARS score is one of the most

internationally validated low anterior resection syndrome assessment tools. Yet,

these scores have never been compared together nor have they been validated

into Arabic making the spectrum of their association or complementarity

unexplored in medical research, and their possible use in arabe nations, and

morocco more specifically, out of reach.

The aim of this study was to translate and validate the LARS and

WEXNER questionnaires, in our Moroccan Arabic context and compare both

scores, as the universal low anterior resection syndrome assessment tools.

38

METHODOLOGY

39

Despite the availability of validated fecal incontinence assessment tools,

researchers continue to develop their own methods, diluting the quality of rectal

cancer research and aggravating the absence of universal understanding and

evaluation of low anterior resection syndrome. On these grounds, we designated

the two most widely used scores, namely the LARS and WEXNER for our

Arabic Moroccan validation.

In the past decades, the situation in clinical research has become more

complex with healthcare professionals becoming more aware of the effects of

new drugs or surgical procedures on health related quality of life. Subsequently,

the tangible and objective assessment of health status was no longer sufficient;

thus sustaining the elaboration of patient reported outcome measures.

The development of a questionnaire is firstly based on determining all domains reflecting the impact of the affection on their health and quality of life.

This could either be done through a literature review or by including the process

of deciding which dimensions matter most. A first draft is drawn, which can also

include questions from other scores that are thought to be most representative. A

committee of experts will discuss each question and a second draft will be

concluded. This latter should be discussed with a sample of patients and modified accordingly. [70]

The cross-cultural adaptation is the process of producing equivalence

between source and target, based on content and according to predetermined

stages. A protocol is provided by the American Association of Orthopaedic

Surgeons (AAOS) which includes initial translation, synthesis of the translation,

back translation and the decision of experts committee with documentation of all of the steps and encountered discrepancies. [72]

40

Figure 23: The American Association of Orthopaedic Surgeons (AAOS) Cross-cultural adaptation protocol

41

I. QUESTIONNAIRE ELABORATION :

❖ Translation:

We were granted permission from the original authors of the WEXNER score, whilst the LARS score authors were out of reach. The original versions were translated to Moroccan Arabic dialect by two independent professional translators, one of which had no prior awareness of the concepts being examined in the questionnaire. Both translators discussed the translations until a final consensual version was reached. The translations aimed at conceptual equivalence rather than a word-for-word translation and the process followed the recommendations of the WHO and the European Organisation for Research and Treatment of Cancer (EORTC)[73,74]

❖ Back-translation:

Back-translation is a process of validity checking that makes sure that the translated version is reflecting the same item content as the original version. A third translator, who wasn’t familiar with the original English version, back translated the agreed Arabic version to English. Afterwards, the two Arabic versions were checked for differences and a final version was formed.

❖ Pre-test:

This is the final stage of the adaptation process and it aims to pretest the questionnaire on subjects from the target population. Each subject completes the questionnaire and further discussion is made on what he or she thought was meant by each questionnaire item and the chosen response. This ensures that the adapted version is still retaining its equivalence in an applied situation. The distribution of responses is examined to look for a high proportion of missing items or single responses.

42

II. PATIENT REPORTED OUTCOME MEASURES :

❖ LARS score:

All participants received the LARS score (Appendix 3), which was first

developed for a population of Danish colorectal cancer patients than translated

and validated to different versions. This score consists of five items:

“incontinence for flatus,” “incontinence for liquid stool,” “frequency of bowel

movements,” “clustering of stools” and “urgency”; all elements that have a high

correlation to the quality of life of the patients. Each item has three to four

response choices that are assigned with different score values. The third item has

four choices, including “>7 times per day,” “4 to 7 times per day,” “1 to 3 times

per day,” and “less than once per day,” assigned with values of 4, 2, 0, and 5

respectively. All the other four items have three choices, including “no, never,”

“yes, less than once per week,” and “yes, at least once per week,” and are

assigned with the values of 0, 4, and 7 for the first item; 0, 3, and 3 for the

second item; 0, 9, and 11 for the fourth item; and 0, 11, and 16 for the fifth item,

respectively.

The total score ranges from 0 to 42 and is categorized into three different

groups: 0 to 20 points - no LARS, 21 to 29 points - minor LARS and 30 to 42

points - Major LARS. [70]

❖ Wexner score :

All participants received the WEXNER score (Appendix 1). The

questionnaire consists of five questions: three about anal incontinence (gas,

liquid, and solid), a coping mechanism (pad wear), and a lifestyle question

(alteration). The respondents were asked to rate the frequency of stool loss,

43

frequency of use of a coping mechanism, and the frequency of lifestyle

alteration through the use of quantifiers (0 = never, 1 = rarely, 2 = sometimes, 3

= usually, 4 = always). The final score indicates the severity of incontinence,

ranging from 0 (no incontinence) to 20 (complete incontinence). [68]

❖ EORTC QLQ-C30:

When either the LARS score or the WEXNER score were originally

developed, the impact of colorectal surgery on patients was weighted according

to the correlation between each symptom and QoL. It is therefore relevant to

determine whether a similarly high correlation can be found when applying

these scores to Moroccan rectal cancer patients. Consequently, the convergent

validity in this study was determined by computing the correlations between the

LARS score and the European Organization for Research and Treatment of

Cancer (EORTC) QLQ-C30 [75]

The QLQ-C30 includes five functional subscales (i.e., physical functioning,

role functioning, emotional functioning, cognitive functioning, and social

functioning), three symptom subscales (i.e., fatigue, nausea and vomiting, and

pain), a global QoL subscale, and six single symptom items (i.e., dyspnea,

insomnia, appetite loss, constipation, diarrhea, and financial difficulties).

With regards to the scoring instructions for this instrument, a high score

represented a high QoL or a high level of functioning for the global QoL

subscale and functional subscale. Opposingly, for a symptom subscale/item the

higher the score, the more severe the symptom is.[76]

44

III. PARTICIPANTS SAMPLING AND DATA COLLECTION:

The patients for our study were retrospectively and prospectively selected

based on predetermined inclusion criteria on the period extending from January

2012 to March 2019. Demographic, clinical and pathological data was selected

from the data basis of the National Oncology Institute of Rabat and the Private

Oncology Clinic of Professor Abdelilah Souadka. Based on earlier validation

studies, 100 patients were needed for the validation of LARS [68] and

WEXNER scores [70].The questionnaire was given to patients during their day

clinic check up and those among them who could not read received help from an

interviewer whose mission was to solemnly read the questions and answers to

choose from. Questionnaires were also presented to patients who could not show

up to the day clinic over telephone interviews. The responses were collected

from March 12th 2019 to October 8th 2019. The average interview time was

computed.

Our non-inclusion criteria included:

- Patients who underwent abdomino-perineal amputation.

- Patients who underwent pseudo-continent perineal colostomy.

- Permanent stoma.

Our eligibility Criteria included:

- Patients aged 18 years and older

- Diagnosis of rectal adenocarcinoma through colonoscopy and

pathological evaluation

- Curative surgery

45

- Low anterior resection with total or partial mesorectal excision with

or without temporary stoma and a minimum interval of 6 months

after stoma reversal by October first 2019 to insure restitution of

normal bowel function.

- Voluntary participation in this study and written consent.

Consequently our exclusion criteria included:

- Dementia or any form of cognitive dysfunction

- Inability to speak moroccan arabic dialect

- A history of inflammatory bowel disease or any disease with bowel

function impairment namely, Crohn's disease, irritable bowel

syndrome, ulcerative colitis or others.

Figure 24: Patient selection flowchart

46

IV. PSYCHOMETRIC PROPERTIES:

The process of psychometric properties assessment aims to demonstrate the

consistency of the tool and reproducibility of its results as well provide enough

proof establishing this measure fulfills its initial vocation through validity. As a

result, reliability and validity are key elements to revealing the good

psychometric properties of any health reported outcome measure.

❖ Reliability :

Reliability of a measure refers to the ability of a questionnaire to determine

that a measurement yields reproducible and consistent results either on

different occasions, by different observers, or by similar or parallel tests .

Reliability analysis includes internal consistency reliability, split-half reliability

and test-retest.

Internal consistency:

Relies on examining the complementary nature of items by searching for

contradictions and measurement errors. There are a number of ways to calculate

these correlations, namely Cronbach’s alpha, Kuder–Richardson, or split halves.

In our case, to evaluate internal consistency, Cronbach’s alpha coefficient was

calculated for the generic score and all domains of the LARS and WEXNER

scores. A high positive value for Cronbach’s alpha refers to the extent to which

it is a consistent measure of a concept and a minimum value of 0,7 is required.

Test - retest :

Reproducibility is measured by the administration of the test on two

different occasions separated by an interval of time. We randomly selected a

group of 42 patients to repeat the assessment after an interval of 2 to 4 weeks

47

weeks from the first test. Patients who experienced any significant change in

bowel function between the first and the second test were excluded from the

test–retest analysis. The correlation between the numerical value of the LARS

score at the first and second test was assessed by intraclass correlation

coefficient. The difference between the numerical value of the LARS score at

the 2 tests was tested by means of the Student t test. Furthermore, for each of the

5 individual questions of the score, the agreement between the first and second

response was explored by means of computing the percentage of perfect,

moderate, and no agreement. A perfect agreement was assigned when

participants ticked off exactly the same category at the first and second test,

moderate agreement was assigned when responses differed by only 1 category,

and no agreement was assigned when responses differed by 2 or 3 categories at

the 2 tests.

❖ Validity :

Convergent validity:

The process of validating an assessment tool refers to the accumulation of

evidence that indicates the degree to which the measures represent what they

were intended to. One way of achieving validity is through the use of other types

of analyses which rely on the presence of other tools of the same or with similar

attributes. This approach is described by the convergent validity which we tested

by comparing the results from the LARS and WEXNER scores to those of the

EORTC QLQ-C30, specifically the functional scales and the diarrhea symptom

scale, as it is the most relatable symptom for the low anterior resection

syndrome.

48

Discriminant validity :

Another method is by linking the attribute we are measuring to some other

attribute by a hypothesis or construct, which is the construct or discriminant

validity. This latter examines the difference between two or more populations

that are already expected to have differing amounts of the assessed property and

then testing this hypothetical construct by applying our instrument to the

samples. We primarily hypothesized that the LARS and WEXNER scores will

differentiate between the bowel functions of patients with different demographic

and clinical features such as sex, age, length of postoperative period (time since

stoma-free rectal resection surgery or reversal surgery of temporary stoma),

distance of the tumor from the anal verge, radiation therapy, extent of

mesorectal excision, prior temporary stoma and post operative complications.

V. STATISTICAL ANALYSIS:

Demographic and clinical variables were analyzed by using descriptive

statistics. Internal consistency for the questionnaire was assessed using

Cronbach’s alpha coefficient. When assessing the test-retest reliability, the

Spearman correlation coefficient was used because the both scores at the first

and second surveys are non-normally distributed. Moreover, the concordance for

each item between the first and second surveys was described according to the

frequency of perfect, moderate and no agreement. The correlations between the

LARS score and the subscales of the EORTC QLQ were evaluated by using

Spearman's correlations. All p values <0.05 were considered statistically

significant. All statistical analyses were performed using IBM SPSS Statistics

(version 22).

49

VI. INTERNATIONAL DATABASE AND ETHICS

CONSIDERATIONS:

The transcultural adaptation has been approved and published in the

international clinical trials database under the title: Validation of the Moroccan

Arabic Version of the Low Anterior Resection Syndrome (LARS) and Wexner

Score of Continence Among Rectal Cancer Patients (MA_LARSWEX) and the

number: NCT04128657.

This study was approved by the biomedical ethics committee of the faculty

of medicine in Rabat (Number: 99/19). Signed informed consent was obtained

from all patients. [77]

50

RESULTS

51

I. TRANSLATION :

The English version of the LARS and WEXNER scores was successfully

translated to Moroccan Arabic after discussion and agreement on all

discrepancies. The final version is shown in appendix.

II. PATIENTS CLINICAL AND DEMOGRAPHIC

CHARACTERISTICS :

In the period from January 2012 to March 2019, we identified a total of 735

patients operated on for rectal neoplasms among which 347 patients met our

inclusion criteria and 3 were excluded for debilitating affections. 120 patients

were out of reach and 80 patients had deceased. Only 1 patient refused to

respond to the measurement tool. A total of 143 patients were deemed eligible

and responded to the questionnaire with a response rate of 99%. The mean

interview time was 7 minutes.

Among the 143 responders, 66(46.2%) were female and 77(53.8%) were

male patients. The mean age was 58.15 ± 13.23 years with 16.8% of our patients

younger than 45years. We categorized tumor location into upper, middle and

lower rectum, with the percentages of 40.6%, 42.7% and 16.8% respectively.

59.4% of our patients received neoadjuvant chemoradiotherapy compared to

40.6% who didn’t. Adjuvant chemotherapy was administered to 63.6%.

Concerning surgery, 115 (80.4%) patients had colorectal and 28 (19.6%)

coloanal anastomosis. 49% of our patients benefited from partial mesorectal

excision and 51% had total mesorectal excision. 5 patients had anastomotic

fistulas and 2 patients received surgery due to complications.

52

Variables Description

Mean follow up time 37,25 months

Age (years) ● Mean age ● <45years ● >45years

58.15 ± 13.23

24(16,8%) 117(81,8%)

Sexe ● Female ● Male

66 (46.2%) 77 (53.8%)

Tumor location (cm) ● Upper rectum (10-15) ● Middle rectum (5-10) ● Low rectum (0-5)

58 (40.6%) 61 (42.7%) 24(16.8%)

Neoadjuvant chemoradiotherapy ● No ● Yes

85 (59.4%) 58 (40.6%)

Anastomosis type ● Colorectal ● Coloanal

115 (80.4%) 28(19.6%)

Type of mesorectal excision ● Partial ● Total

70 (49%) 74(51%)

Anastomotic fistula ● Yes ● No

5 (3.5%)

138 (96.5%)

Adjuvant chemotherapy ● Yes ● No

91 (63.6%) 52(36.4%)

Reintervention for complications ● Yes ● No ● Unavailable

2 (1.4%)

140 (97.9%) 1 (0.7%)

Table I : Clinical and demographic characteristics of patients.

53

III. RELIABILITY :

❖ Internal consistency :

The LARS score showed a cronbach alpha at 0,66 which, although not

equivalent to good reliability and consistency, is quite close to the required score

of > 0.7. On the other hand, the Wexner score showed excellent internal

consistency with cronbach alpha at 0,91.

❖ Test-retest:

A total of 42 patients were asked to complete the LARS and wexner scores

twice. The median period between the two tests is 2 weeks.

LARS reliability :

The differences between the first and the second numerical values of both

LARS tests are established by the means of a Bland Altman plot with 95% limits

of agreement.

The degree of agreement between the initial test and the retest for each of

the five LARS score items and the LARS category (no, minor, major LARS), is

presented in the table: 85.6% of the patients remained in the same category,

7.1% differed by one category and the same proportion differed by two

categories. The interclass correlation showed good reliability (ICC=0.88).

54

Figure 25: Bland–Altman plot with 95% limits of agreement illustrating the difference between LARS scores at the first and second test.

Agreement level

Perfect (%) Moderate (%) None (%)

LARS category 85.6% 7.1% 7.1%

Item 1 90.4% 7.1% 2.3%

Item 2 99.9% 0 (0) 0 (0)

Item 3 88.6% 7.1% 4.7%

Item 4 85.6% 7.1% 7.1%

Item 5 76.16% 7.1% 16.6%

Table II : Agreement levels of the LARS categories and score items between

the test and retest

55

WEXNER reliability:

Similarly to the aforementioned, differences between the first and the

second numerical value of the WEXNER score is established by the means of a

Bland Altman plot with 95% limits of agreement. Additional reliability is

demonstrated through measuring the degree of agreement between the initial test

and the retest for each of the five WEXNER score items with the percentage of

perfect fit between the first and second test 88%, 83.3%, 92.8%, 97.5% and 69%

respectively for the five items. The interclass correlation between the two tests

showed excellent reliability with an ICC = 0,944.

Figure 26 : Bland–Altman plot with 95% limits of agreement illustrating the difference between WEXNER scores at the first and second test.

56

Agreement level

Perfect (%) Moderate (%) None (%)

Item 1 88% 2.3% 9.5%

Item 2 83.3% 0 (0) 16.6%

Item 3 92.8% 7.14% 0 (0)

Item 4 97.5% 2.3% 0 (0)

Item 5 69% 9.5% 21.4%

Table III : Agreement levels of the WEXNER score items between the test and retest

57

IV. VALIDITY:

❖ Convergent validity :

LARS score :

The LARS score showed statistically significant negative correlation with

each one of the five EORTC QLQ-C3o functional scales as well as a positive

correlation with the diarrhea symptom scale.

Dimensions of QLQ-

C3o

Total score of the LARS

R value P value

Global QLQ -0,409 <0,001

Physical functioning -0,119 0,158

Role functioning

-0,185 0,027

Emotional functioning -0,278 0,001

Cognitive functioning -0,279 0,001

Social functioning -0,279 0,001

Diarrhea 0,461 <0,001

Table IV: Convergent validity of the LARS score

58

WEXNER score:

The WEXNER score showed statistically significant negative correlation

with each one of the five EORTC QLQ-C3o functional scales except for the

physical functioning scale. Statistically significant positive correlation was also

demonstrated with the diarrhea symptom.

Dimensions of QLQ-C3o

Total score of the WEXNER

R value P value

Global health status -0,438 <0,001

Physical functioning -0,217 0,009

Role functioning -0,266 0,001

Emotional functioning -0,286 0,001

Cognitive functioning -0,279 <0,001

Social functioning -0,297 <0,001

Diarrhea 0,497 <0,001

Table V : Convergent validity of the WEXNER score

59

❖ Discriminant validity :

Both the LARS and WEXNER scores were able to discriminate between

patients according to their tumor location, type of anastomosis, type of

mesorectal excision and chemoradiotherapy treatment.

LARS discriminant validity:

Comparison of the LARS score on the basis of rectal location was

noteworthy (p <0,001) differentiating low rectal, middle and upper rectal

locations with median scores of 23,5 , 25 and 5.

Likewise, coloanal anastomosis had a median score of 29,5 compared to 5

for colorectal anastomosis (P<0,001).

As to the type of mesorectal excision, those with partial mesorectal

excision had better scores than those with total mesorectal excision with median

scores of 5 and 21 respectively (P<0,001).

Patients who received radiotherapy treatment had a median score of 25

which is higher than those who did not receive this therapy 5. (P <0,001).

60

Figure 27 : Boxplot showing the LARS total score median values according to rectal tumor location

Figure 28 : Boxplot showing the LARS total score median values according to anastomosis type

61

Figure 29 : Boxplot showing the LARS total score median values according to radiochemotherapy

Figure 30 : Boxplot showing the LARS total score median values according to the type of mesorectal excision

62

WEXNER discriminant validity:

The wexner score had also good discriminant validity with statistically

significant differences in the median scores ranging from 8,5, 3 and 0 for low ,

middle and upper rectum locations (P <0,001).

Furthermore, coloanal and colorectal anastomosis differed in their median

scores varying from 9 and 0 (P=0,001).

Likewise partial mesorectal excision had better median scores of 0

compared to those with total mesorectal excision with a median of 4 (P<0,001)

Patients who received radiotherapy had worse median score 9 compared to

those who didn't, who had a median score of 0 (P<0,001).

Figure 31 : Boxplot showing the WEXNER total score median values according to rectal tumor location

63

Figure 32 : Boxplot showing the WEXNER total score median values according to anastomosis type

Figure 33 : Boxplot showing the WEXNER total score median values according to radiochemotherapy

64

Figure 34: Boxplot showing the WEXNER total score median

values according to type of mesorectal excision

65

V. CORRELATION BETWEEN THE LARS AND WEXNER:

We examined the correlation between the total scores of the LARS and

Wexner questionnaires and observed statistically significant positive correlation

between the two with a correlation coefficient above 0,7.

Figure 35 : Scatter plot showing the correlation between the WEXNER

and LARS scores

66

DISCUSSION

67

The low anterior resection syndrome is a well known adverse effect to

rectal cancer surgery, with a varying incidence between 60 to 90% and studies

reporting ongoing symptoms up to 12 months in 25% of these cases [78]

Consequently effective measurement of bowel dysfunction is paramount to

capturing the treatment burden which in turn is bound to the psychometric

strength of the instrument. Reliability and validity are essential psychometric

properties for any measure. [79]

I. PRIOR VALIDATIONS OF THE LARS AND WEXNER

SCORE :

We conducted a research on all the previously validated versions of the

LARS and WEXNER questionnaires. The LARS has been validated into 24

languages among which 14 are published; other versions are still in the process

of validation and thus not yet published, namely the french, malysian, Hebrew,

Korean and polish. Conversely, the WEXNER score is by far less validated than

any of the other assessment tools for low anterior resection and fecal

incontinence.

68

Language of validation Number of patients Correlated tools

LARS INTERNATIONAL VALIDATIONS

Netherlands [80] 165 patients 1 quality of life question

German [81] 801 patients

1 quality of life question Spanish [81]

Sweden [81]

Danmark [81]

China [82] 102 patients EORTC QLQ-C30 questionnaire and EORTC QLQ-C29 questionnaire.

Japan [83] 136 patients 1 quality of life question

Lithuania [84] 111 patients wexner score

Slovenia [85] 100 patients 1 quality of life question

Portugese [86] 154 patients EORTC QLQ-C30

Russia [87] - -

Greece [88] 112 patients EORTC QLQ-C30 questionnaire and EORTC QLQ-C29 questionnaire

English [89] 451 patients EORTC QLQ-C30 questionnaire

Norwegian [90] 961 patients -

WEXNER VALIDATIONS

Turkey [91] 60 patients FIQL questionnaire

Brazil [92] 50 woman anal manometric examination

Table VI : Literature review results of the available international validations

of the LARS and WEXNER

FIQL: Fecal incontinence quality of life

69

II. MEAN FOLLOW UP TIME :

The mean follow-up time was 55.5 months in the original LARS score

development research (Emmertsen and Laurberg). Other subsequent validation

studies included relatively shorter periods such as the Lithuanian and Chinese

validations with follow up periods of 35.2 months and 17.9 months respectively.

In our study the mean follow up period was 37,25 months in order to

discriminate between the bowel functions of patients with short or long

postoperative periods as well as to have a visibility on the possible stabilization

of these symptoms after a certain period.

III. RELIABILITY :

❖ Internal consistency:

The Wexner score showed excellent internal consistency as in the turkish

[91] and brazilian validations [92].

We attempted the internal consistency assessment of the LARS through

cronbach alpha which yielded in a coefficient slightly lower than the acceptable

level of 0,70. In fact the cronbach’s alpha has been subject to some criticism as

to the relationship between longer scales and higher alpha coefficients. [93] This

could be an explanation for our findings, particularly in the shortage of

cronbach’s alpha use in the previous international validations of this

questionnaire.

70

❖ Test-retest reliability:

To determine the test-retest reliability of the score, 43 patients were chosen

and readministered the questionnaire after a between tests of up to 4 weeks. We

considered this interval to be appropriate, as it avoids not only the influence of

the first survey but also changes in the bowel function of patients.

Results on test-retest reliability for both the LARS and WEXNER score

showed good reliability and high proportions of moderate and high agreement

which exceeded 85% compared to only a few patients showing no agreement

which was the case in many other international studies. [94-96} The LARS

score has already been internationally established as a reliable assessment tool,

this is sustained by our findings as it showed good intraclass correlation

(ICC=0,88). The WEXNER score showed excellent reliability. (ICC= 0,94).

IV. VALIDITY :

❖ Convergent validity :

The original version of the LARS as well as various other validations tested

the convergent validity by adding 1 quality of life related question : “Overall,

how much does your bowel function affects your quality of life” (Not at all/A

little/Some/ A lot). However, the original author Emertson et al suggested

correlating the LARS score with other quality of life scores. We thereby tested

the convergent validity of the EORTC QLQ-C30 which demonstrated

statistically significant correlation with all functional scales and the diarrhea

symptom scale.

71

In fact, observed association has been reported between many of the scales

of the EORTC QLQ-C30 and the LARS. [97] The validation of the chinese

version tested this association as well, showing significant correlation except for

the cognitive functioning scale. [98]

On the other hand, the WEXNER score has been correlated in other studies

to manometric measurement values between female patients with fecal

incontinence and other with no continence problems showing Overall, showing

significant correlation between pressure measurement and total scores. We

tested the WEXNER score convergent validity with the EORTC QLQ-C30,

which manifested a significant correlation with diarrhea and with 5 out of the 6

functional scales; the correlation with physical functioning scale not being

statistically significant

❖ Divergent validity :

Taken the large burden of the low anterior resection syndrome , as a major

countereffect of an unavoidable course of treatment, studies have tried to

investigate risk factors of this complication which could be either avoided or

taken into consideration when dealing with sphincter preserving surgery. [100]

accordingly, proportions of low anterior resection syndrome increase on the

condition of radiotherapy, low tumor position and female gender. In the same

manner, the divergent validity analysis of the WEXNER score showed it allows

distinguishing between the level of tumor, the type of anastomosis, the type of

mesorectal excision and radiotherapy.

72

When the initial version of the LARS score was developed, it was

hypothesized that patients receiving radiotherapy and patients with low tumors

(0–5 cm from the anal verge) would have higher scores as well as patients

receiving a TME compared to PME.

Indeed when examining the capacity of our Moroccan version to

discriminate between groups of patients we were able to distinguish between

patients with total and partial mesorectal excision, this latter being associated

with lower median scores. Furthermore, we categorized tumor locations in

ranges varying from 0-5cm, 5-10cm and 10-15cm for low, middle and upper

rectum respectively; accordingly patients with low and middle rectum locations

showed higher scores. Equally, patients who benefited from coloanal

anastomosis had higher LARS scores than those with colorectal anastomosis. In

fact a level of anastomosis at 5 cm has been found to be a good predictor of

Major LARS which corresponded to a tumor level of around 7 cm from the anal

verge. [99]

Adjuvant radiotherapy effect on functional outcome has been thoroughly

studied, showing that neoadjuvant therapy, either short-course radiotherapy or

long-course chemoradiotherapy, increased the risk of Major LARS. [101] Rectal

capacity and high-pressure length have also been linked to the same category.

[100]

Our divergent validity analysis found a correlation between

Chemoradiotherapy and higher total LARS score.

Moreover, studies showed women in the age group 50-79 to have a higher proportion of Major LARS. In our contexte, age and sex were not determinant of the LARS score. Young age is a subject of controversy in literature with prior

73

studies showing either its correlation to a high LARS score [101] or the independence of the two elements, as in the Chinese and Lithuanian study. Sex presented an impact in litterature with female patients proven to have a worse functional outcome.

❖ Correlation between low anterior resection syndrome questionnaires:

Fecal incontinence is the central focus of bowel dysfunction with many assessment tools; the study and correlation of these could be a first step towards the standardisation of these reporting methods.

In the Brazilian version wexner score validation, correlation between fecal Incontinence Quality of Life questionnaire and the wexner was tested and demonstrated a significant correlation.

The LARS score has been as well positively correlated to the COREFO questionnaire for incontinence and the MSKCC-BFI questionnaire. We tested the correlation between the LARS score and the WEXNER score, which resulted in a statistically significant positive correlation (>0,7). The similarities between these scores therefore outweigh the differences, sustaining thereby the complementarity relationship between the two, specifically as one assesses fecal incontinence in general while the other revolves around the low anterior resection syndrom more precisely.

Our study has some limitations such as the retrospective observational aspect when selecting the patients. Taking the high level of illiteracy, it was not possible for the patients to complete the questionnaire solely but either with the help of an interviewer who was reading the questions or through phone communications. The number of patients involved was also a limitation.

74

CONCLUSION

75

The Moroccan version of the LARS and WEXNER score have good

psychometric properties and can therefore be used for bowel function evaluation

in colorectal cancer patients in Morocco. Needless to say, having a tangible

method to the assessment of the low anterior resection syndrome will allow the

identification of patients in need of further care. Furthermore, this will ease the

future formulation of universal solutions and quality of life optimization for

colorectal cancer patients. The relationship between the LARS and WEXNER

scores showed good complementarity as one is specific to low anterior resection

syndrome and the other assesses the anal incontinence more generally.

76

ABSTRACT

77

ABSTRACT

Title: Transcultural adaptation and validation of a Moroccan arabic dialect version of the

continence scores LARS and WEXNER in colorectal cancer patients.

Author: ESSANGRI HAJAR

Key words: Quality of life, Rectal Neoplasms, Sphincter sparing surgery, Wexner score,

LARS score.

Introduction : We aimed to demonstrate the good psychometric properties of the

moroccan arabic version of continence scores LARS and WEXNER.

Materials and methods: The LARS and wexner scores were translated into arabic

according to forward and back-translation procedures. The questionnaire was administered to

a total of 143 patients with a subgroup of 42 patients taking the test twice for test-retest

reliability. Internal consistency was examined through cronbach’s alpha. Both questionnaires

were correlated to the EORTC QLQ-C30 questionnaire for convergent validity assessment.

Discriminant validity was demonstrated through proving their ability to differentiate patients

on the basis of different clinical and pathological criteria.

Results: The LARS and Wexner score demonstrated respectively close to acceptable (

0.66) and excellent (0.91) internal consistency. The level of agreement between the test and

retest was established by the means a Bland Altman plot with 95% limits of agreement. The

percentage of patients remaining in the same category was of 85.6% for the LARS and 88%

for the WEXNER score. The LARS score showed significant negative correlation with the

QLQ-C30 functional scales. As to the WEXNER score, negative correlation was established

with all functional scales except for the physical functioning. Both scores were positively

correlated to the diarrhea symptom scale and were able to detect differences according to

tumor location, Chemoradiotherapy and type of anastomosis. The LARS and WEXNER

scores positively correlated with a coefficient at 0.76.

Conclusion: The moroccan arabic version of the LARS and Wexner scores have good

psychometric properties and can be in continence assessment in clinical and research settings.

78

RÉSUMÉ Titre: Adaptation transculturelle et validation d’une version arabe dialectal marocaine des

scores de continence LARS et WEXNER chez les patients suivis pour cancer colorectal.

Auteur: ESSANGRI HAJAR

Mots cles: Qualite de vie, Cancer rectal, chirurgie conservatrice du sphincter, score de

Wexner, score de LARS.

Introduction : Notre étude vise à analyser les propriétés psychométriques de la

version arabe dialectale marocaine des scores de continence LARS et WEXNER.

Materiel et methodes: La traduction des scores de LARS et WEXNER a été faite

selon les normes de traduction et contre-traduction. 143 patients ont répondu au questionnaire

avec un sous-groupe de 42 patients l’ayant refait une deuxième fois afin d’examiner la

fiabilité test retest. La consistance interne a été démontrée par mesure du coefficient alpha de

cronbach. La corrélation de chacun des deux scores avec le questionnaire de qualité de vie

QLQ-C30 de l’EORTC a permis de tester la validité convergente, la validité discriminante a

quant à elle été prouvée par leur capacité à distinguer des groupes de patients cliniquement et

pathologiquement différents.

Résultats: La consistance interne est proche de l’acceptable pour le LARS (0,66)

tandis qu’elle est excellente pour le WEXNER (0,91). La concordance dans le temps entre les

deux tests est appréciée à travers le graphique de Bland Altman avec un accord à 95%. Le

pourcentage de patients faisant partie de la même catégorie entre les deux tests est de 85,6%

pour le LARS et de 88% pour le WEXNER. L’analyse des dimensions fonctionnelles du

QLQ-C30 est statistiquement signifiante avec corrélation négative, sauf pour l’échelle de

fonctionnement physique concernant le WEXNER. Les deux scores ont montré une

corrélation positive pour le symptôme de diarrhée ainsi qu’une aptitude à différencier les

sous-groupes de patient selon le siège de la tumeur, l’administration de radiochimiothérapie et

enfin le type d'anastomose. La corrélation entre les deux scores LARS et WEXNER est

positive avec un coefficient de 0,76.

Conclusion: La version arabe marocaine des scores LARS et Wexner a des propriétés

psychométriques valides et peut être utilisée comme outil d'évaluation autant dans la pratique

que dans la recherche.

79

ملخص

األقلمة و التطبیق عبر الثقافات للنسخة العربیة المغربیة لتقییم التبرز الالإرادي (الرس) ( ویكسنر ).: العنوان

: ھاجر السنكري المؤلف

ة، تقییم ویكسنیر، تقییم الرس. جودة الحیاة، سرطان المستقیم، الجراحة المحافظة على العضلة العاصر :الكلمات األساسیة

تھدف دراستنا إلى تحلیل الخصائص السیكومتریة للنسخة العربیة المغربیة لتقییم التبرز الالإرادي (الرس) : المقدمة

( ویكسنر ).

:المناھج

ا لمعاییر الترجمة والترجمة المضادة. تم إستجواب 143تمت ترجمة تقییمي الرس و ویكسنر وفق مع تقدیم مریضا

مریضا لمراجعة الموثوقیة عبر طریقة اإلختبار و إعادة اختبار. تم إثبات االتساق 42االستبیان لمجموعة فرعیة مكونة من

الداخلي من خالل قیاس معامل ألفا كرونباخ كما اعتمدنا دراسة االرتباط بین كل من المعیارین و استبیان جودة الحیاة

EORTC QLQ-C30 صدق التقاربي. مكنت قدرة المعیارین على التمییز بین مجموعات من المرضى ذوي إلثبات ال

خواص سریریة و عالجیة مختلفة من إثبات الصدق التمییزي.

: النتیجة

لمعیار ویكسنیر. تم تقدیر 0.91) في حین أنھ ممتاز بنسبة 0.66االتساق الداخلي بالنسبة لالرس شبھ مقبول بالنسبة (

٪. نسبة المرضى الذین ضلوا في 95بدرجة إتفاق Bland Altmanفي الوقت بین االختبارین من خالل مخطط االتفاق

٪ للویكسنیر. تم إثبات الصدق التقاربي بالبرھنة عن وجود عالقة 88٪ لالرس و 85.6نفس الفئة بین االختبارین تبلغ

بإستثناء تقارب QLQ-C30الوظیفیة لتحلیل جودة الحیاة لـ سلبیة ذات داللة إحصائیة للمعیار ین مع كافة المقاییس

الویكسنیر مع مقیاس األداء البدني. أظھر كال المقیاسین على وجود عالقة تقاربیة إیجابیة مع مقیاس اإلسھال. تم إثبات

الورم ،العالج الصدق التمییزي من خالل قدرة المعیارین على التمییز بین مجموعات فرعیة من المرضى وفقا لموقع

.0.76اإلشعاعي وكذلك نوع المفاغرة. العالقة بین المعیارین الرس و ویكسني إیجابیة بمعامل

:الخاتمة

إثبات الخصائص السیكومتریة للنسخة العربیة المغربیة لتقییم التبرز الالإرادي الرس و ویكسنر سوف یمكن من

لبحث الطبي.استعمالھا في كل من اإلجراءات السریریة وا

80

APPENDIX

81

82

83

EORTC QLQ-C30 (version 3)

تایخصنا نعرفو شي حوایج علیك و على صحتك. من فضلك جاوب على ھاد األسئلة و اختار الجواب اللي یناسبك. ما كاینش شي جواب صحیح أو غالط. المعلومات اللي غادي تعطي غادي تبقى سریة.

سمیتك:

تاریخ االزدیاد ( النھار, الشھر, العام ):

تاریخ دیال الیوم ( النھار, الشھر, العام ):

واش تایجیك شي مشكل مني تادیر شي خدمة بحال تھز شي شانطة أو قفة تقیلة: .1

o نھائیا o غیر شویا o مرة مرة o بزاف

واش تاتعیا فاش تا تمشى بزاف: .2

o نھائیا o غیر شویا o مرة مرة o بزاف

فاش تا تمشى ھي شویا خارج الدار:واش تاتعیا .3

o نھائیا o غیر شویا o مرة مرة o بزاف

واش تاتحتاج تبقى فالفراش أو تكلس فاش كاتكون فالدار: .4

o نھائیا o غیر شویا o مرة مرة o بزاف

84

واش تاتحتاج شي واحد یعاونك فالماكال، فاللباس، فالغسیل، باش تمشي لمرحاض (بیت الما): .5o نھائیا o غیر شویا o مرة مرة o بزاف

فالسیمانا اللي فاتت :

واش حسیتي براسك ما قادرش دیر الخدمة دیالك أو الشغاالت دیال كل نھار: .6o نھائیا o غیر شویا o مرة مرة o بزاف

واش حسیتي براسك ما قادرش دیر الھوایات دیالك: .7

o نھائیا o غیر شویا o مرة مرة o بزاف

واش جاك ضیق فالتنفس: .8

o نھائیا o غیر شویا o مرة مرة o بزاف

الحریق:واش جاك .9

o نھائیا o غیر شویا o مرة مرة o بزاف

85

واش حتاجیتي ترتاح: .10o نھائیا o غیر شویا o مرة مرة o بزاف o

واش عندك شي مشكل فالنعاس: .11o نھائیا o غیر شویا o مرة مرة o بزاف

واش كنتي حاس براسك مرخي (ضعیف): .12o نھائیا o غیر شویا o مرة مرة o بزاف

واش نقصاتلك الشھیة: .13

o نھائیا o غیر شویا o مرة مرة o بزاف

واش تتحس بالترویعا: .14

o نھائیا o غیر شویا o مرة مرة o بزاف

واش تقییتي (ردیتي) .15

o نھائیا o غیر شویا o مرة مرة o بزاف

86

واش كنتي مقبوط (معصوم) .16o نھائیا o غیر شویا o مرة مرة o بزاف

:فالسیمانا اللي فاتت

واش كانت كرشك جاریة (طایحة علیك الكرش): .17o نھائیا o غیر شویا o مرة مرة o بزاف

ان:واش كنتي عی .18

o نھائیا o غیر شویا o مرة مرة o بزاف

واش لحریق كان كیأثرعلى الشغاالت دیالك دیال كال نھار: .19

o نھائیا o غیر شویا o مرة مرة o بزاف

واش جاك شي مشكل فالتركیز فاش كاتقرا شي جورنال أو فاش كتفرج فالتیلیفیزیون: .20

o نھائیا o غیر شویا o مرة مرة o بزاف

87

واش حسیتي براسك معصب: .21o نھائیا o ویاغیر ش o مرة مرة o بزاف

واش حسیتي براسك مقلق: .22

o نھائیا o غیر شویا o مرة مرة o بزاف

واش حسیتي براسك منفعل (كتقلق دغیا): .23

o نھائیا o غیر شویا o مرة مرة o بزاف

واش حسیتي براسك مكتئب (مغموم): .24

o نھائیا o غیر شویا o مرة مرة o بزاف

واش كان عندك مشكل تتفكر شي حوایج (مشكل النسیان): .25

o نھائیا o شویا غیر o مرة مرة o بزاف

واش ھاد المرض دیالك أو الدوا اللي تاتخد أثر على عالقتك مع العائلة: .26

o نھائیا o غیر شویا o مرة مرة o بزاف

88

واش ھاد المرض دیالك أو الدوا اللي تاتخد أثر على عالقتك مع الناس: .27

o نھائیا o غیر شویا o مرة مرة o بزاف

بب لیك فمشاكل فالمصروف (مشاكل مادیة):واش ھاد المرض دیالك أو الدوا اللي تاتخد س .28

o نھائیا o غیر شویا o مرة مرة o بزاف

: 7إلى 1بالنسبة لألسئلة اللي جایة اختار الجواب اللي یناسبك من

شحال تقییم (تعطي) صحتك فالسیمانا اللي فاتت: .29

1 2 3 4 5 6 7

ممتاز ضعیف

ا اللي فاتت:شحال تقییم (تعطي) الجودة دیال حیاتك فالسیمان .30 1 2 3 4 5 6 7

ممتاز ضعیف

89

LARS SCORE واش كیوقع لیك شي مرات لي كتقدرش تتحكم في النفس؟ .31

o .ال، حتا مرة o .أیھ، قل من مرة وحدة في األسبوع o .أیھ، على األقل مرة في األسبوع

واش كیوقع لیك شي مرات لي كیفلت لیك الخروج جاري؟ .32

o .ال، حتا مرة o ن مرة وحدة في األسبوع.أیھ، قل م o .أیھ، على األقل مرة في األسبوع

شحال من مرة كتدیر الخروج؟ .33

o .اكثر من سبعة دیال المرات في الیوم o دیال المرات في الیوم. ٧حتا ل ٤ما بین o دیال المرات في الیوم. ٣ما بین مرة حتال o .اقل من مرة وحدة في الیوم

مرات في الساعة؟ ٢ك على األقل واش شي مرات خاصك تدیر الخروج دیال .34o .ال، حتا مرة o .أیھ، قل من مرة وحدة في األسبوع o .أیھ، على األقل مرة في األسبوع

واش شي مرات كتزیر فالخروج دیالك لدرجة انك خاصك تجري للمرحاض؟ .35

o .ال، حتا مرة o .أیھ، قل من مرة وحدة في األسبوع o .أیھ، على األقل مرة في األسبوع

90

WEXNER SCORE واش كیوقع لیك شي مرات لي كیفلت لیك الخروج قاصح؟ .36

o .ال، حتا مرة o .قل من مرة وحدة في الشھر o .قل من مرة وحدة في األسبوع، و أكثر من مرة وحدة في الشھر o .قل من مرة وحدة في الیوم، و أكثر من مرة وحدة في األسبوع o .على األقل مرة وحدة في الیوم

ع لیك شي مرات لي كیفلت لیك الخروج جاري؟واش كیوق .37

o .ال، حتا مرة o .قل من مرة وحدة في الشھر o .قل من مرة وحدة في األسبوع، و أكثر من مرة وحدة في الشھر o .قل من مرة وحدة في الیوم، و أكثر من مرة وحدة في األسبوع o .على األقل مرة وحدة في الیوم

لیك النفس؟ واش كیوقع لیك شي مرات لي كتفلت .38

o .ال، حتا مرة o .قل من مرة وحدة في الشھر o .قل من مرة وحدة في األسبوع، و أكثر من مرة وحدة في الشھر o .قل من مرة وحدة في الیوم، و أكثر من مرة وحدة في األسبوع o .على األقل مرة وحدة في الیوم

واش كتحتاج تدیر الخروق؟ .39

o .ال، حتا مرة o ھر.قل من مرة وحدة في الش o .قل من مرة وحدة في األسبوع، و أكثر من مرة وحدة في الشھر o .قل من مرة وحدة في الیوم، و أكثر من مرة وحدة في األسبوع o .على األقل مرة وحدة في الیوم

واش ھادشي عندو تأثیر سلبي على نمط الحیاة دیالك؟ .40

o .ال، حتا مرة o .قل من مرة وحدة في الشھر o األسبوع، و أكثر من مرة وحدة في الشھر.قل من مرة وحدة في o .قل من مرة وحدة في الیوم، و أكثر من مرة وحدة في األسبوع o .على األقل مرة وحدة في الیوم

91

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PHYSICIAN’S OATH

At the time of being admitted as a member of the medical profession: I solemnly

promise that I will devote my life to serve humanity.

I will give to my teachers the respect and gratitude that is their due.

I will practice my profession with conscience and dignity.

The health of my patient will be my first consideration.

I will not betray the secrets that are confided in me.

I will maintain by all the means in my power, the honour and the noble

traditions of the medical profession.

My colleagues will be my brothers.

I will not permit considerations of religion, nationality, race, party politics

or social standing to intervene between my duty and my patient.

I will maintain the utmost respect for human life from the time of

conception. Even under threat,

I will not use my medical knowledge contrary to the laws of humanity.

I make these promises solemnly, freely and upon my honour

بسم ا الرمحان الرحيم

العظيم با أقسم

عالنية: د ع أ الطبية نة امل عضوة قبو ا ف يتم ال ظة ال عالنية:ذه د ع أ الطبية نة امل عضوة قبو ا ف يتم ال ظة ال ذه

.سانية دمة ي حيا أكرس سانية.بأن دمة ي حيا أكرس بأن

با م ل ف وأع ي أساتذ م أح باوأن م ل ف وأع ي أساتذ م أح ستحقونھ.وأن الذي ستحقونھ.ميل الذي ميل

.ول د مر ة جاعلة وشر ي ضم من بوازع ن م أمارس ول.وأن د مر ة جاعلة وشر ي ضم من بوازع ن م أمارس وأن

. إ ودة سراراملع أف ال .وأن إ ودة سراراملع أف ال وأن

.الطب نة مل يلة الن والتقاليد الشرف ع وسائل من لدي ما ل ب أحافظ الطب.وأن نة مل يلة الن والتقاليد الشرف ع وسائل من لدي ما ل ب أحافظ وأن

. إخوة طباء سائر أعت .وأن إخوة طباء سائر أعت وأن

ا أي بدون نحومرضاي بواج أقوم اوأن أي بدون نحومرضاي بواج أقوم .وأن اجتما أو أوسيا عر أو وط أو .عتباردي اجتما أو أوسيا عر أو وط أو عتباردي

.ا شأ منذ سانية ياة ا ام اح ع حزم ل ب أحافظ ا.وأن شأ منذ سانية ياة ا ام اح ع حزم ل ب أحافظ وأن

.ديد من القيت ما م سان يضربحقوق بطرق الطبية ي معلوما أستعمل ال ديد.وأن من القيت ما م سان يضربحقوق بطرق الطبية ي معلوما أستعمل ال وأن

. با اختيارومقسمة امل عن د ع أ ذا ل .ب با اختيارومقسمة امل عن د ع أ ذا ل ب

يد ش أقول ما ع .وهللا