Colorectal carcinoma is one of the most common cancers and one of the leading causes of cancer-related death in the United States. Pathologic examination of biopsy, polypectomy and resection specimens is crucial to appropriate patient managemnt, prognosis assessment and family counseling. Molecular testing plays an increasingly important role in the era of personalized medicine. This review article focuses on the histopathology and molecular pathology of colorectal carcinoma and its precursor lesions, with an emphasis on their clinical relevance.

/pdf/colorectal-carcinoma-pathologic-aspects-iun914la98.pdf

Colorectal carcinoma: Pathologic aspects

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment

Background: Although high-risk mutations in identified major susceptibility genes (DNA mismatch repair genes and MUTYH) account for some familial aggregation of colorectal cancer, their population prevalence and the causes of the remaining familial aggregation are not knownMethods: We studied the families of 5,744 colorectal cancer cases (probands) recruited from population cancer registries in the United States, Canada, and Australia and screened probands for mutations in mismatch repair genes and MUTYH We conducted modified segregation analyses using the cancer history of first-degree relatives, conditional on the proband's age at diagnosis We estimated the prevalence of mutations in the identified genes, the prevalence of HR for unidentified major gene mutations, and the variance of the residual polygenic componentResults: We estimated that 1 in 279 of the population carry mutations in mismatch repair genes (MLH1 = 1 in 1,946, MSH2 = 1 in 2,841, MSH6 = 1 in 758, PMS2 = 1 in 714), 1 in 45 carry mutations in MUTYH, and 1 in 504 carry mutations associated with an average 31-fold increased risk of colorectal cancer in unidentified major genes The estimated polygenic variance was reduced by 30% to 50% after allowing for unidentified major genes and decreased from 33 for age <40 years to 05 for age ≥70 years (equivalent to sibling relative risks of 51 to 13, respectively)Conclusions: Unidentified major genes might explain one third to one half of the missing heritability of colorectal cancerImpact: Our findings could aid gene discovery and development of better colorectal cancer risk prediction models Cancer Epidemiol Biomarkers Prev; 26(3); 404-12 ©2016 AACR

/pdf/prevalence-and-penetrance-of-major-genes-and-polygenes-for-2020x9ogqs.pdf

Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer

Background:Esophageal atresia (EA) is one of the most common congenital digestive anomalies. With improvements in surgical techniques and intensive care treatments, the focus of care of these patients has shifted from mortality to morbidity and quality-of-life issues. These children face gas

/pdf/espghan-naspghan-guidelines-for-the-evaluation-and-treatment-ifmeqgvo2g.pdf

ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.

Germline point mutations in the SMAD4 and BMPR1A genes have been reported in around 40% of patients with juvenile polyposis syndrome (JPS). We performed mutation analysis in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. By direct sequencing of the two genes we identified point mutations in 30 patients (46% of typical JPS). Using MLPA we detected large genomic SMAD4 or BMPR1A deletions in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Thus, screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. Mutation analysis of the PTEN gene in the remaining 41 SMAD4 and BMPR1A mutation negative cases uncovered a point mutation in two patients (5%). We identified a strong genotype-phenotype correlation regarding gastric polyposis, gastric cancer, and hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) in JPS patients: SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) compared to patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without gastric polyps (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, HHT was also diagnosed clinically. In many JPS patients with identified germline mutation, the documented histologic findings encompassed a wide distribution of different polyp types, comparable to that described in hereditary mixed polyposis syndromes (HMPS).

/pdf/high-proportion-of-large-genomic-deletions-and-a-genotype-16ktjmfpoo.pdf

High proportion of large genomic deletions and a genotype–phenotype update in 80 unrelated families with juvenile polyposis syndrome

Aim: Report of a series of 12 cases of juvenile polyposis coli. Methods: The study period was from 1995 to 2005. All the patients were treated by total colectomy with rectal mucosectomy and endorectal ileoanal pullthrough with or without ileal pouch formation. Covering ileostomy was avoided in all the cases. Time taken for the surgery, postoperative complications and continence were documented. Results: The mean operating time was 4.2 h (range: 4-5 h). The mean duration of hospital stay was 16.3 days (range: 15-18 days). The most common postoperative complication was pouchitis and perianal excoriation. Initially, all the patients were passing stools at an interval of 2 h, and after 3 weeks, the frequency has reduced to 6-8 stools per day. In the follow-up after 3 months, the frequency was 3-5 per day with minimal soiling. Conclusions: Single-stage total colectomy with rectal mucosectomy and endorectal ileoanal pull-through without covering ileostomy and pouch formation is a safe and definitive treatment for juvenile polyposis coli if the patient selection is appropriate.

Juvenile polyposis syndrome

Congenital tracheoesophageal fistula (TEF) with esophageal atresia (EA) is not an uncommon disease of newborns. Several classifications have been advocated for predicting the outcomes of these patients but all are physiological and concentrated on associated medical condition that influences survival. We emphasize a new classification on the basis of gap between two esophageal pouches to define the magnitude of surgical problems in the primary repair and correlate them with the outcomes in terms of anastomotic leak, esophageal stricture and mortality, keeping other prognostic factors constant. A total of 50 cases of congenital TEF with EA were included and all underwent primary esophageal anastomosis after the ligation of TEF. The gap between the two pouches was meticulously measured intraoperatively using a vernier caliper before the ligation of TEF, and patients were divided into four groups on the basis of gap length. Group A, where gap length was >3.5 cm (ultralong), group B where gap length was 2.1-3.5 cm (long gap), group C where gap length was >1 cm but not more than 2 cm (intermediate group) and group D, where the gap between two esophageal pouches was 1 cm or less (short gap). The incidence of anastomotic leak was 80, 50, 28, 10.5% and the incidence of esophageal stricture was 100, 75, 22.5, 19% after successful primary repair, respectively, in groups A, B, C and D. The mortality was highest in group A (80%) followed by group B (50%) and 22% in group C and least 15.6% in group D. The incidences of esophageal leak and mortality were found to be statistically significant. This classification which is based on easily measurable criteria provides a useful method to predict morbidity, long-term outcome and mortality of EA with TEF surgery.

/pdf/prognosis-of-congenital-tracheoesophageal-fistula-with-346kmmt33q.pdf

Prognosis of congenital tracheoesophageal fistula with esophageal atresia on the basis of gap length.

The aim of this study was to characterize a successful approach for the management of infants with long-gap esophageal atresia (EA) with tracheoesophageal fistula (TEF). The goal was to preserve the native esophagus and minimize the incidence of esophageal anastomotic leaks using fibrin glue as a sealant over the esophageal anastomosis. A total of 52 patients were evaluated in this study. Only patients in whom, gap between the two ends of the esophagus was ≥ 2 cm were selected during January 2005 to January 2007. Patients were divided in two groups on the basis of block randomization. Group A comprised the patients in whom fibrin sealant was used as reinforcement on a primary end-to-end esophageal anastomosis; in group B, fibrin glue was not used. The two groups were compared in terms of esophageal anastomotic leak (EL), postoperative esophageal stricture (ES), and mortality. The statistical analysis was done using Fisher’s exact test and the chi-squared test. The number of anastomotic leaks in group A (glue group) was about one-fifth that in group B (no glue group). The incidence of ES was almost twice as high in group B as in group A. The mortality rate was almost threefold higher in group B (no-glue group). The higher incidence of EL and ES in group B compared to group A was statistically significant. Thus, fibrin glue when used as an adjunct to esophageal anastomosis for primary repair of long-gap EA with TEF appears safe in the clinical setting and may lower the chances of esophageal leak and anastomosis-site strictures. Hence, it can diminish the mortality and morbidity of these patients.

/pdf/role-of-fibrin-glue-as-a-sealant-to-esophageal-anastomosis-qqwvlgycaf.pdf

Role of fibrin glue as a sealant to esophageal anastomosis in cases of congenital esophageal atresia with tracheoesophageal fistula.

Buts: La fistule tracheo-oesophagienne congenitale avec atresie de l'oesophage (TEF avec EA) n'est pas une malformation rare du nouveau-ne. L'approche classique pour la reparation de TEF avec EA est une thoracotomie droite avec une approche extra-pleurale, ligature de la veine azygos, identification et ligature de la fistule tracheo-oesophagienne, identification du cul de sac superieur de l'oesophage et anastomose termino-terminale. Cette etude est realisee pour apprecier si la ligature de la veine azygos est necessaire durant la reparation de TEF avec EA. Methodes: Nous avons etudie 50 cas dans les 2 dernieres annees (janvier 2003 janvier 2005). Pour 25 enfants (groupe A). La reparation etait faite avec preservation de la veine azygos alors que 25 enfants (groupe B) etaient operes avec une approche classique avec ligature et section de la veine azygos. Les resultats postoperatoires sont compares dans les 2 situations. Resultats: Les infections pulmonaires postoperatoires etaient plus frequentes chez les enfants operes avec l'approche classique (56% dans le groupe B et 12% dans le groupe A) et ceci est significatif. Les complications a type de fistule anastomotiques etaient, elles, legerement plus hautes dans le groupe B, mais ceci n'etait pas significatif. La mortalite etait similaire dans les 2 cas. Les bebes du groupe A etaient hemodynamiquement plus stable que ceux du groupe B. Conclusion: La preservation de la veine azygos maintient un drainage veineux normal du mediastin et diminue la stase thoracique postoperatoire et les complications a type de pneumonie ainsi la veine azygos doit etre preservee autant que possible.

Is Ligation of Azygos Vein Necessary in Primary Repair of Tracheoesophageal Fistula with Esophageal Atresia

Anorectal malformations are one of the most common congenital defects. This study is conducted to evaluate the result of single stage anterior sagittal anorectovaginoplasty (ASARVP) in cases of vestibular anus (AVF) in neonatal age group without thorough gut preparation. All the patients of AVF admitted during 2003-2006 were included in this study. Single stage ASARVP was done in these patients without preparing the bowel in the lithotomy position, the fistula was freed and sufficient length of anorectum was dissected and vagina was separated. Midline incision at the proposed anal site was made, then a plane was dissected between the muscle complex going anteriorly. The mobilized anorectum was pulled to the proposed anal site and proper anoplasty was done. The results were evaluated for duration of surgery, need of bowel preparation, commencement of feed and hospital stay and follow-up (assessment of continence and anal dilatation). A total of 27 patients were included in our study. All patients were less than 1-month-old. Operative time ranges from 50 to 70 min. Bowel preparation was not needed. Per oral feed was started after 48 h in all patients and average duration of hospital stay was 3- 4 days. Postoperative regular anal dilatation was commenced after 1 week of operation. Continence results according to Kelly's method were good in 70%, fair in 21% and poor 9%. Single-stage anorectovaginoplasty in neonates has a good result in cases of AVF and avoids the need of bowel preparation.

A. N. Gangopadhyaya

Papers

Juvenile polyposis syndrome

Prognosis of congenital tracheoesophageal fistula with esophageal atresia on the basis of gap length.

Role of fibrin glue as a sealant to esophageal anastomosis in cases of congenital esophageal atresia with tracheoesophageal fistula.

Is Ligation of Azygos Vein Necessary in Primary Repair of Tracheoesophageal Fistula with Esophageal Atresia

Single stage repair of anovestibular fistula in neonate.