Establishment of a novel prognostic signature based on an identified expression profile of integrin superfamily to predict overall survival of patients with colorectal adenocarcinoma.

The abnormal expression of integrin superfamily members commonly related to kinds of malignancies. However, the role of integrins in predicting the prognosis of cancers is still little known, especially for colorectal cancer that is one of the leading causes of cancer-related death. RNA-seq data and clinical features of colorectal adenocarcinoma (COAD) patients were derived from The Cancer Genome Atlas (TCGA), used to analyze the expression pattern and genomic alterations of integrin genes in the COAD cohort. Unsupervised hierarchical clustering divided COAD patients into two clusters (clusters 1 & 2), and we observed that patients in cluster 2 with high expressions of most integrin genes had worse clinical features and shorter overall survival (a median OS: 67.25 months vs 99.93 months, p = 0.012), compared to those in cluster 1. Combined with univariate Cox regression analysis, Pearson Correlation Coefficients (PCC), and Principal Component Analysis (PCA), an integrin-related signature was established, including ITGA1, ITGA5, ITGA7, ITGA11, ITGAX, ITGAM, ITGB1, and ITGB5. And the AUC values for OS at 1, 3, and 5 years was 0.61, 0.59, and 0.56, further demonstrating the predicting capacity of our signature. Furthermore, overexpression of which also significantly correlated with poorer prognosis of colon cancer patients in a separate validation cohort, GSE17536 (p < 0.05). Meanwhile, the AUC values for OS in the validation cohort at 1, 3, and 5 years was 0.62, 0.59, and 0.59. Additionally, enrichment analysis indicated significant differences between cluster 1 and cluster 2 in the biological processes of cell adhesion, signal transduction, extracellular matrix, immune system, and in tumor microenvironment (TME), which were crucial to the progression of tumor. The findings supplied compelling evidence that our signature could be a novel prognostic biomarker for COAD patients, and these genes had the potential to be therapeutic targets.

Pancreas-Preserving Total Duodenectomy: A Systematic Review.

BACKGROUND: The management of the pancreas in patients with duodenal trauma or duodenal tumors remains a controversial issue. Pancreas-preserving total duodenectomy (PPTD) requires a meticulous surgical technique. The most common indication is familial duodenal adenomatous polyposis (FAP). The aims of this study are to carry out a systematic review of the literature on the indications for PPTD and to highlight the risks and benefits compared with other more aggressive procedures. SUMMARY: A systematic literature review was performed following PRISMA recommendations of studies published in PubMed, Embase, and Cochrane library until May 2019. Thirty articles describing 211 patients were chosen. The mean age was 48 years. The surgical indication in 75% of patients was FAP. The mean operating time was 329 min and mean intraoperative bleeding 412 mL. Postoperative morbidity rate was 49.7% (76% Clavien-Dindo 97.8%. Key Messages: PPTD is indicated for patients with benign and premalignant duodenal lesions without involvement of the pancreatic head. It is a feasible procedure offering an alternative to other more aggressive procedures in selected patients. Mortality is below 1.5%.

Survival outcomes after surgical management of sporadic or familial adenomatous polyposis associated duodenal cancer.

BACKGROUND: Duodenal cancer is the second most common cause of cancer death in familial adenomatous polyposis (FAP) patients. In this study, we compare oncologic outcomes between sporadic and FAP-associated duodenal cancer. METHODS: In this retrospective study, all patients who underwent surgeries between 2000 and 2014 for either sporadic or FAP duodenal cancer were identified. The patients were grouped based on diagnoses and perioperative and survival outcomes were compared. RESULTS: A total of 56 patients with duodenal cancer (43 sporadic, 13 FAP) who underwent surgery were identified. Pancreatoduodenectomy (PD) was the most common procedure performed. The overall median survival was 7.5 years (1 year: 92%; 5 years: 58.1%). FAP patients had earlier tumor, node, and metastasis stage, less margin involvement, less perineural, and angiolymphatic invasion but had a comparable survival to sporadic patients. The median survival for FAP duodenal cancer was 7.4 vs 9.6 years for sporadic (P = .97) with similar utilization of adjuvant chemotherapy. Although not statistically significant, PD had an improved median survival compared to segmental duodenal resection (SDR) (9.6 years for PD vs 3.6 years for SDR, P = .17). Non-periampullary location and presence of positive lymph nodes were significant predictors of mortality on multivariate analysis. CONCLUSIONS: FAP duodenal cancer has no survival advantage compared to sporadic duodenal cancer despite an improved stage of resection with extraampullary lesions having a worse survival.

Long-term clinical outcomes and follow-up status in Japanese patients with familial adenomatous polyposis after radical surgery: a descriptive, retrospective cohort study from a single institute.

PURPOSE: Data on long-term outcomes of familial adenomatous polyposis (FAP) are unclear in Japan because a nationwide registry system is lacking. We assessed overall survival, incidence of neoplasms, fecal incontinence, and postoperative follow-up status of patients with FAP treated surgically in our hospital. METHODS: In total, 154 patients with FAP who underwent radical surgery from 1981 to 2017 in our department were available for the questionnaire. Sixty-five patients, 36 of whom were followed at our hospital, were assessed using clinical records and the questionnaire. RESULTS: The median follow-up time was 187 months (interquartile range, 93.5-296 months). The median age at surgery was 36 years (range, 12-69 years). The 5-, 10-, 15-, and 20-year overall survival rate was 100%, 98%, 95%, and 89%, respectively. All five deaths were caused by diseases other than colorectal cancer. FAP-related neoplasms comprised 23 colorectal cancers, five duodenal cancers, three gastric cancers, five thyroid cancers, two ileal pouch cancers, and nine desmoid tumors. The incidence of desmoid tumors was significantly associated with the operation date. The duration from radical surgery to neoplasm onset significantly differed by neoplasm type. Forty-five of 54 patients (excluding those who died or underwent ileostomy) developed fecal incontinence (median Wexner score of 8). Surgical procedures involving hand-sewn sutures with rectal mucosal stripping were significantly associated with fecal incontinence and the Wexner score. Fifty-eight of the 60 surviving patients underwent follow-up examinations. CONCLUSION: Overall survival was favorable. Fecal incontinence depended on the surgical procedures. Most patients continued to receive follow-up examinations. TRIAL REGISTRATION: No. 3112 by Institutional Review Board of Hyogo College of Medicine.

Acarbose improved survival for Apc+/Min mice.

Acarbose blocks the digestion of complex carbohydrates, and the NIA Intervention Testing Program (ITP) found that it improved survival when fed to mice. Yet, we do not know if lifespan extension was caused by its effect on metabolism with regard to the soma or cancer suppression. Cancer caused death for ~80% of ITP mice. The ITP found rapamycin, an inhibitor to the pro-growth mTORC1 (mechanistic target of rapamycin complex 1) pathway, improved survival and it suppressed tumors in Apc+/Min mice providing a plausible rationale to ask if acarbose had a similar effect. Apc+/Min is a mouse model prone to intestinal polyposis and a mimic of familial adenomatous polyposis in people. Polyp-associated anemia contributed to their death. To address this knowledge gap, we fed two doses of acarbose to Apc+/Min mice. Acarbose improved median survival at both doses. A cross-sectional analysis was performed next. At both doses, ACA fed mice exhibited reduced intestinal crypt depth, weight loss despite increased food consumption and reduced postprandial blood glucose and plasma insulin, indicative of improved insulin sensitivity. Dose-independent and dose-dependent compensatory liver responses were observed for AMPK and mTORC1 activities, respectively. Only mice fed the high dose diet exhibited reductions in tumor number with higher hematocrits. Because low-dose acarbose improved lifespan but failed to reduced tumors, its effects seem to be independent of cancer. These data implicate the importance of improved carbohydrate metabolism on survival.

SATB1 Expression of Colorectal Adenomatous Polyps is Higher than that of Colorectal Carcinomas.

"Special AT-rich sequence-binding protein-1" (SATB1) is a global genome organizer and is found to have effects on carcinogenesis and progression of various malignancies including colorectal carcinoma (CRC). We aimed to investigate the expression of SATB1 in CRC and colorectal adenomatous polyps (CAP), the correlation between clinicopathologic parameters, and overall survival. We examined 227 CRCs and 129 CAPs. SATB1 protein expression was evaluated by immunohistochemistry. We found higher SATB1 expression in adenomatous epithelium than in CRC tissues (55.0% vs. 42.7%, respectively) (P<0.05). None of the adjacent normal colorectal mucosa stained positive in CRC cases, and only one of the adjacent normal mucosa of the CAP cases was positive. SATB1 expression of left-sided CRC was higher than that of right-sided CRC (46.3% vs. 28.6%, respectively) (P<0.05), and SATB1 expression of conventional adenocarcinomas was higher than that of mucinous carcinomas (45.5% vs. 6.3%, respectively) (P<0.05). SATB1 expression was higher in CAPs consisting of high-grade dysplasia than in polyps with low-grade dysplasia (77.8% vs. 51.4%) (P<0.05). SATB1 expression did not correlate with patients' overall survival. In conclusion, due to the higher expression of SATB1 in CAP than in CRC, we think SATB1 may have a role in the early stages of carcinogenesis of CRCs. This is the first study investigating SATB1 expression in CAPs. Besides this is the first report that shows different SATB1 expressions in conventional colorectal adenocarcinoma and mucinous carcinoma, and also in right-sided and left-sided CRC. Our results, with supporting new studies, can provide SATB1 as a possible candidate for targeted therapy for CRC patients.

Comparison of pancreas-sparing duodenectomy (PSD) and pancreatoduodenectomy (PD) for the management of duodenal polyposis syndromes.

BACKGROUND: Familial adenomatous polyposis affects primarily the colon but can also involve other locations within the gastrointestinal tract, including the duodenum. The aim of this study was to describe a single center experience with pancreas-sparing duodenectomy for familial adenomatous polyposis and to compare outcomes with pancreatoduodenectomy performed for duodenal polyp disease. PATIENTS AND METHODS: A retrospective review of a prospectively maintained database identified patients who had undergone pancreas-sparing duodenectomy during the period 2001 to 2016. This population was matched 1:1 with a cohort of patients undergoing pancreatoduodenectomy for duodenal adenomas, both sporadic and familial, during the same time period. Baseline demographics and perioperative (short- and long-term) outcomes were compared. RESULTS: A total of 88 patients were included; 44 in each group. The pancreas-sparing duodenectomy cohort was younger (52.6 vs 64.3 years; P < .001) and more patients had undergone prior colectomy (100% vs 32%; P < .001) or additional prior abdominal surgery (27% vs 9% (P < .001). Median operative times were greater for pancreatoduodenectomy (391 vs 460 min; P = .002). There was no difference in any of the early postoperative complications. There was 1 30-day mortality in the pancreatoduodenectomy group secondary to aspiration. Late acute pancreatitis was more common after pancreas-sparing duodenectomy (16% vs 0%; P = .012) and exocrine pancreatic insufficiency was more common after pancreatoduodenectomy (30% vs 11%; P = .034). CONCLUSION: Pancreas-sparing duodenectomy is a reasonable option for duodenal cancer prophylaxis in familial adenomatous polyposis with high-risk features. The perioperative safety profile is comparable to pancreatoduodenectomy done for similar indications, and pancreas-sparing duodenectomy has a favorable long-term with a lesser incidence of exocrine impairment.

Curative and Prophylactic Surgery of Young-onset Colorectal Cancer in Inherited Syndromes: A 15-Year Monocentric Retrospective Experience.

BACKGROUND/AIM: Although genoproteomic and clinicopathological knowledge on Lynch syndrome (LS) and familial adenomatous polyposis (FAP) has notably increased during the past two decades and even though surgery represents the mainstay of treatment for both conditions, as of 2019, the surgical choice in terms of timing and procedure still appears controversial in the absence of definitive guidelines. MATERIALS AND METHODS: Data were retrospectively analyzed of patients with colorectal cancer (CRC) surgically treated at our Institution between 1st January 2003 and 31st December 2018. Particular attention was given to patients with LS and FAP ≤45 years of age (young-onset CRC); for this category of patients, the surgical procedures performed were compared in terms of benefits and disadvantages. RESULTS: A total of 1,878 primary CRCs were submitted to major surgery; young-onset malignancies accounted for 3.8% of all CRCs. Thirteen young-onset inherited CRCs were surgically removed from 11 patients with LS and two with FAP. Segmental colectomy and restorative proctocolectomy were the procedures most frequently performed in young patients with LS and FAP, respectively. CONCLUSION: In the light of our retrospective results, we highlight the need for randomized controlled trials comparing the surgical options for LS- and FAP-related CRC developing in young patients. Defining the advantages and risks of each surgical option is of the utmost importance in order to improve prognosis of such patients and establish unanimous recommendations.

Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran.

CONTEXT: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder. Colorectal cancer (CRC) has been implicated as the most common cause of death in FAP patients, especially in those with coexisting CRC at initial diagnosis (FAP-CRC). AIM: We aimed to determine the survival rate of FAP-CRC and the factors affecting FAP-CRC survival. SETTING AND DESIGN: This was a retrospective cohort FAP study conducted in northwest Iran. SUBJECTS AND METHODS: From 2006 to 2016, 51 FAP-CRC individuals were selected from among 4588 CRC patients. STATISTICAL ANALYSIS: A Student's t-test, life table method, log-rank tests, a Kaplan-Maier survival curve, and Cox regression analysis were performed and a value of P < 0.05 was set as statistically significant. RESULTS: A total of 51 FAP-CRC patients were selected, (30 males and 21 females), with a mean age of 42.2 years at diagnosis. The most common presenting symptom was abdominal pain and the most common primary tumor site was the rectum. The 1-, 5- and 10-year overall survival rates were 76%, 59%, and 52%, respectively. Factors affecting the FAP-CRC survival rate, namely, sex, age at CRC diagnosis, and extracolonic manifestations showed no significant differences. The difference in 5-year survival rates between patients with colon and rectal cancers was significant (75% vs. 33%, P = 0.02). The survival rate was significantly higher among patients with disease Stages I and II than those in disease Stages III and IV (P = 0.001). 5-year survival rates in patients with ileal pouch-anal anastomosis and ileorectal anastomosis were 71% and 78%, respectively (P = 0.001). There was an interesting difference in survival between FAP and attenuated FAP (P = 0.01). In cox regression analysis, distant metastasis was a significant predictor of survival (P = 0.001). CONCLUSIONS: Long-term survival from FAP-CRC remains poor; therefore, early-stage detection and the choice of an appropriate surgical method can improve survival in such patients.

Diagnóstico de Cáncer Colorrectal en paciente con sospecha de Poliposis Adenomatosa Familiar / Diagnosis of colonrectal cancer in patient with suspicion of Familial Adenomatous Polyposis

Familial adenomatous polyposis (FAP) is a rare, hereditary disease whose main characteristic is the presence of a large number of polyps in the colon and rectum, which, in the absence of timely treatment, 100% progresses to colorectal cancer. The early diagnosis of this condition is the pillar of the prevention of complications. We present the case of a patient with a low digestive tract syndrome, without previous diagnosis, who after a careful review of clinical and family history, the diagnosis of PAF and later colorectal cancer, is reached. A review of the literature on current advances and recommendations on this disease is made.

Síndrome de Turcot / Turcot´s syndrome

RESUMEN Se presenta a una paciente de 27 años de edad, con varios ingresos en el Hospital Provincial Clínico Quirúrgico Docente “José Ramón López Tabrane”, de Matanzas. Por presentar clínica compatible con pólipos de colon, corroborados por videocolonoscopia, diagnosticados en marzo de 2015. Posteriormente reingresa a los 14 meses por convulsiones, al inicio generalizado y luego limitado al hemicuerpo derecho, cefalea universal y vómitos. Falleció a los 23 días de su ingreso, en los antecedentes patológicos familiares destaca madre fallecida a los 52 años por cáncer de colon y hermana a los 21 años por neoplasia maligna colorectal (AU).

ABSTRACT The case of a female patient, aged 27 years is presented. She was in-patient in the Teaching Clinical Surgical Provincial Hospital “José Ramón López Tabrane”, of Matanzas for several times presenting clinical characteristics compatible polyps in the colon, corroborated by video colonoscopy, and diagnosed in March 2015. She was readmitted 14 months later because of convulsions, generalized firstly and lately limited to the right side of the body, universal headache and vomits. She died 23 days after the admittance. The family history shows that her mother died when she was 52, due to colon cancer and her sister died at twenty one due to colorectal malignant neoplasia (AU).

Síndrome de Turcot / Turcotꞌs syndrome

RESUMEN Se presenta a una paciente de 27 años de edad, con varios ingresos en el Hospital Provincial Clínico Quirúrgico Docente “José Ramón López Tabrane”, de Matanzas. Por presentar clínica compatible con pólipos de colon, corroborados por videocolonoscopia, diagnosticados en marzo de 2015. Posteriormente reingresa a los 14 meses por convulsiones, al inicio generalizado y luego limitado al hemicuerpo derecho, cefalea universal y vómitos. Falleció a los 23 días de su ingreso, en los antecedentes patológicos familiares destaca madre fallecida a los 52 años por cáncer de colon y hermana a los 21 años por neoplasia maligna colorectal (AU).

ABSTRACT The case of a female patient, aged 27 years is presented. She was in-patient in the Teaching Clinical Surgical Provincial Hospital “José Ramón López Tabrane”, of Matanzas for several times presenting clinical characteristics compatible polyps in the colon, corroborated by video colonoscopy, and diagnosed in March 2015. She was readmitted 14 months later because of convulsions, generalized firstly and lately limited to the right side of the body, universal headache and vomits. She died 23 days after the admittance. The family history shows that her mother died when she was 52, due to colon cancer and her sister died at twenty one due to colorectal malignant neoplasia (AU).

Association of Sulindac and Erlotinib vs Placebo With Colorectal Neoplasia in Familial Adenomatous Polyposis: Secondary Analysis of a Randomized Clinical Trial.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. Objective: To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. Design, Setting, and Participants: Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. Interventions: Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. Main Outcomes and Measurements: The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. Results: Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009). Conclusion and Relevance: In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum. Trial Registration: clinicaltrials.gov Identifier: NCT01187901.

Desmoid Tumours of the extremity and trunk. A retrospective study of 44 patients.

BACKGROUND: Desmoid-type fibromatosis (DF) is a aggressive (myo)fibroblastic neoplasm with an infiltrative growth and a tendency to local recurrence. Resection of the tumour and/or radiation were proposed as principal treatment. The aim of this retrospective study was to analyze the local control rates focusing on the effect of surgical margins and radiotherapy. METHODS: From 1981 to 2014, 44 patients had been treated. Fifty four therapies had been applied, in 50 cases surgery +/- radiation therapy, NSAIDs or chemotherapy. In 4 cases a conservative approach was chosen. Thirty seven patients had primary, 17 recurrent disease. Endpoint was either local recurrence (LR), progression of residual disease or rare non-metastatic secondary lesions at the same extremity. RESULTS: The mean age was 39,4 years. In 17 cases a R0, in 27 a R1 and in 6 cases a R2 resection was achieved. Four patients were treated conservatively. All together in 21 cases radiotherapy, in 5 NSAIDs, in 3 imatinib and in 2 cases each tamoxifen or chemotherapy had been applied. The median follow-up was 119 months. 5-year recurrence free survival after resection was 78%. 10 (20.4%) patients developed LR between 5 and 42 months after therapy. Recurrent disease was a negative factor on LR. Margins, radiotherapy, sex, or size of the tumour had no significant impact on LR. Patients younger than 40 years had a significant higher risk of LR. CONCLUSIONS: Surgical margins are less important than keeping function. Radiotherapy might be an option in unresectable lesions, the role of adjuvant radiotherapy is controversially discussed.

Tailored surgical treatment of duodenal polyposis in familial adenomatous polyposis syndrome.

BACKGROUND: To review our experience in patients undergoing operative treatment for duodenal polypoisis associated with familial adenomatous polyposis with an emphasis on operative approach and long-term outcomes. METHODS: Duodenal polypoisis associated with familial adenomatous polyposis patients undergoing operative treatment were studied retrospectively excluding patients with preoperative duodenal cancer. RESULTS: Of 767 patients in the database, 63 (8.2%) patients underwent operative treatment: 42 (67%) pancreas-sparing duodenectomy, 15 (24%) pancreatoduodenectomy, and 6 (9.5%) segmental duodenal resection; the majority for Spigelman stages III and IV polyposis. Overall 9.6% had adenocarcinoma postoperatively (28.6% in the pancreatoduodenectomy group; P = .01). The proportion of Spigelman stages III and IV with cancer were 9.5% and 6.5%, respectively. Pathologic upgrade to cancer in patients with low grade dysplasia and high-grade dysplasia on preoperative biopsy was 5.7% and 6.7%, respectively (P = .13). At a median follow-up of 16 years, 7.7% needed a second duodenal polypoisis associated with familial adenomatous polyposis-related operation. Progression to high grade dysplasia or cancer in the stomach occurred in 15.4% of patients. Median overall survival and recurrence-free survival was at least 16 years and 15.6 years. No significant group-based differences were noted on follow-up. CONCLUSION: The majority of patients with duodenal polypoisis associated with familial adenomatous polyposis can achieve long-term, cancer-free survival with organ-preserving approaches (pancreas-sparing-duodenectomy and segmental-duodenal-resection) with survival not dependent on the type of resection.

Postoperative outcome and quality of life after surgery for FAP-associated duodenal adenomatosis.

INTRODUCTION: Prophylactic colon surgery has increased life expectancy of familial adenomatous polyposis patients. Extracolonic manifestations are life limiting, above all duodenal adenomas. Severe duodenal adenomatosis or cancer may necessitate pancreas-preserving total duodenectomy or partial pancreatico-duodenectomy, mostly after previous proctocolectomy and often after limited local resections of duodenal adenomas. Scarce information on long-term postoperative outcome and quality of life after surgery for duodenal adenomatosis is available. Aim of the present study was to analyze perioperative and long-term outcome after PD and PPTD for FAP-associated duodenal adenomatosis, including QoL and recurrence of adenomas in the neoduodenum after PPTD. MATERIAL, METHODS AND PATIENTS: Thirty-eight patients, 27 after pancreas-preserving duodenectomy and 11 after partial pancreaticoduodenectomy, were included. RESULTS: Pancreas-preserving total duodenectomy was associated with shorter operation time and less blood loss than partial pancreatico-duodenectomy. Clinically relevant pancreatic fistula occurred in 31.5%. In-hospital mortality was 5.3%. Long-term follow-up revealed recurrent pancreatitis after pancreas-preserving total duodenectomy in 22% of patients, two (7.4%) required re-operation. Recurrent adenomatosis was detected in 26% of patients. Quality of life was comparable to the German normal population after both surgical procedures. Patients with postoperative complications showed worse results than those without complications. Disease-specific 10-year survival rate with respect to duodenal adenomatosis was 100%. CONCLUSION: Surgery for FAP-associated duodenal adenomatosis and cancer can be carried out with reasonable morbidity rates despite previous proctocolectomy. Long-term outcome, quality of life, and survival rates are favorable.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-ß (ERß). The expression of ERß isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. METHODS: This study aimed to investigate the expression levels of the ERß1, ERß2, ERß4 and ERß5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. RESULTS: Decreased expression of ERß isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p < 0.001). In FAP patients, ERß1 and ERß5 isoforms showed significant down-expression in polyps (p < 0.001) compared with matched normal tissues. However, no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERß isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERß was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p < 0.05). In sporadic colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERß1 and ERß5 expression levels were associated with better disease-free survival (p = 0.002). CONCLUSION: These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Major hereditary gastrointestinal cancer syndromes: a narrative review.

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.

[Differential indications for ileoanal pouch anastomosis : Ulcerative colitis, familial adenomatous polyposis, synchronous colorectal cancer - Crohn's disease, constipation]. / Differenzialindikation zur ileoanalen Pouchanlage : Colitis ulcerosa, FAP, multilokuläres kolorektales Karzinom ­ M. Crohn, Obstipation.

Ileoanal pouch anastomosis is the procedure of choice for patients with drug refractory ulcerative colitis, indeterminate colitis and familial adenomatous polyposis (FAP). In selected patient groups this procedure is a treatment option for patients with Crohn's disease, hereditary nonpolyposis colorectal cancer (HNPCC), synchronous colorectal cancer and for severe colorectal constipation refractory to conservative drug treatment. The pouch procedure provides the opportunity to avoid a permanent ileostomy. The majority of surgeons prefer the ileal J­pouch as the construction is the easiest to perform and complications and dysfunction rates are low. Due to functional reasons most pouch surgeons favor a circular stapled ileoanal pouch anastomosis. The more radical proctocolectomy can produce sensory defects in the anal canal with subsequent soiling and incontinence. Studies have shown that even after proctocolectomy residual rectal mucosa was found in the anal canal. Therefore, the functionally important anorectal transitional zone should be preserved if possible. Ulcerative colitis can be "healed" with proctocolectomy; however, pouchitis can still occur in one third of the patients. Patients must be informed about the risk of pouchitis and a multidisciplinary monitoring and treatment strategy must be available. In Crohn's disease the ileoanal pouch survival rate of 80% in the long-term follow-up is surprisingly good despite an increased postoperative complication rate. The anal pouch anastomosis is the standard operation in patients with drug refractory ulcerative colitis, indeterminate colitis and FAP. Synchronous colorectal cancer, HNPCC and severe therapy refractive constipation represent rare indications for proctocolectomy where decisions must be made on an individual basis.

Dispelling misconceptions in the management of familial adenomatous polyposis.

Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.