Abeezar I. Sarela

Expression of the antiapoptosis gene, Survivin, predicts death from recurrent colorectal carcinoma

BACKGROUND/AIMS Inhibition of programmed cell death (apoptosis) is associated with increased tumour aggressiveness, and expression ofSurvivin, an antiapoptosis gene, in colorectal carcinomas may provide important prognostic information. PATIENTS/METHODS Expression of Survivin messenger RNA was evaluated by reverse transcription-polymerase chain reaction in 144 colorectal carcinomas and 86 adjacent histologically normal mucosa samples from patients for whom long term follow up data were available. RESULTS Survivintranscripts were detected in a significantly greater proportion of carcinomas (63.5%) than normal mucosa samples (29.1%; p<0.001). The prevalence of Survivin expression was independent of advancing pathological stage. Death due to recurrent cancer following curative resection was predicted independently by tumour expression of Survivin (hazard ratio (HR) 2.60; 95% confidence interval (95% CI) 1.17–5.75) and lymph node metastases (HR 2.38; 95% CI 1.21–4.70). On stage wise analysis, the predictive value of Survivin expression was limited to patients with stage II colorectal carcinomas; those with Survivin negative tumours had a five year survival rate of 94.4% compared with 44.8% for patients withSurvivin positive tumours (p=0.004, log rank test). CONCLUSION In patients with stage II colorectal carcinomas,Survivin expression provides prognostic information that may have important therapeutic implications.

Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma.

Survivin is unique for its expression in human malignancies but not in normal adult cells. It has been implicated in sensitisation to chemotherapy and as a prognostic marker in several common cancers. Immunohistochemistry for Survivin, P53 and BCL-2 expression as well as cell proliferative index (Ki-67) and apoptosis index (TUNEL) was conducted on 52 pancreatic and 12 ampullary adenocarcinomas. Survivin was detected in the cytoplasm of carcinoma cells in 46 (88%) of pancreatic tumours. P53 and BCL-2 were detected in 54% and 12% of pancreatic tumours, respectively. Proliferative index was 26.2±10.5% and apoptosis index was 1.38±0.69%. Prevalence of Survivin expression was significantly higher in P53-positive than in P53-negative cases (P=0.05) but was not associated with BCL-2 expression. Incrementally higher weighted scores of Survivin expression were associated with increased proliferative index (P=0.001). Furthermore, there was linear correlation between increased proliferative index and higher apoptosis index (P<0.001). Surprisingly, higher scores of Survivin expression were associated with increased apoptosis index (P=0.007). Survival characteristics were not influenced by Survivin, P53 or BCL-2 expression, apoptosis index or proliferative index. Ampullary carcinoma showed Survivin expression in 83% of cases. However, unlike pancreatic carcinoma, there was no correlation between Survivin and P53 expression or proliferative index. In conclusion, Survivin is expressed in the majority of pancreatic adenocarcinomas and correlates with both cellular proliferation and apoptosis. Molecular manipulation of Survivin expression may enhance chemotherapy and radiation therapy for pancreatic cancer.

Immunohistochemical detection of the anti-apoptosis protein, survivin, predicts survival after curative resection of stage II colorectal carcinomas.

Background:This study examined the role of Survivin protein, a novel inhibitor of apoptosis, in determining prognosis after curative resection of stage II colorectal carcinomas.Methods: Expression of Survivin, P53, and BCL-2 was evaluated immunohistochemically in stage II colorectal carcinomas from 49 patients who were followed for up to 9 years after operation. The Cox proportional hazards regression model was used to examine the predictive value of several covariates.Results: The patients comprised 33 men and 16 women with a median age of 71 years. There were 32 colonic and 17 rectal cancers comprising 40 T3 and nine T4 primary tumors. Survivin was expressed in 30 (61.2%), P53 in 30 (61.2%), and BCL-2 in 21 (42.9%) tumors. Expression of Survivin was independent of P53 or BCL-2 expression and histopathological characteristics of the tumor. The 5-year survival rate of patients with Survivin-positive tumors was significantly lower than that of patients with Survivin-negative tumors (52.5% vs. 94.1%, respectively; P = .01). On multivariate analysis, expression of Survivin (Hazard Ratio [HR] = 9; P = .03), and rectal origin of cancer (HR = 3; P = .05) were the only factors which independently predicted an increased risk of death from recurrent cancer.Conclusion: Survivin expression within the tumor can identify patients with stage II colorectal carcinoma who are at increased risk of death from recurrent disease and might particularly benefit from adjuvant therapy.

Long-term follow-up after laparoscopic sleeve gastrectomy: 8–9-year results

BACKGROUND Laparoscopic sleeve gastrectomy (LSG) has rapidly gained popularity as a definitive bariatric procedure despite the sparse long-term follow-up data. On the basis of extensive experience with the open Magenstrasse and Mill operation, we began practice of LSG in 2000. The objective of the present study was to analyze 8-9 years of our follow-up data for LSG at a university hospital in the United Kingdom. METHODS From January 2000 to December 2001, 20 patients underwent LSG. A 32F bougie was used for calibration in all cases. RESULTS The preoperative median body mass index was 45.8 kg/m(2) (range 35.8-63.7), and 9 patients (45%) were superobese (body mass index ≥ 50 kg/m(2)). For LSG as a definitive bariatric procedure, 8-9-year follow-up data were available for 13 patients. Of the remainder, 4 patients underwent revision surgery and 3 were lost to follow-up after 2 years. For the entire cohort, the median excess weight loss (EWL) was 73% (range 13-105%) at 1 year, 78% (range 22-98%) at 2 years, 73% (range 28-90%) at 3 years, and 68% (range 18-85%) at 8 or 9 years (P = .074). Of the 13 LSG-only patients with 8-9 years of follow-up, 11 (55% of the starting cohort) had >50% EWL at 8 or 9 years. No significant difference was found in the initial body mass index between the LSG-only patients with >50% EWL and others (45.9 kg/m(2), range 35.8-59.4 versus 45.7 kg/m(2), range 38.9-63.7, respectively; P = .70). The LSG-only patients with >50% EWL had a marginally significantly greater EWL at 1 year compared with the others (76%, range 48-103% versus 45%, range 13-99%, respectively; P = .058). CONCLUSION At 8-9 years of follow-up, 55% of patients had >50% EWL from LSG as a definitive bariatric procedure.

Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family.

An intrinsic component of colorectal carcinogenesis may be the capacity to activate regenerative responses simultaneously with inhibition of apoptosis. Since apoptosis is known to be inhibited in colorectal cancer, this study sought evidence for the activation of the REG family of genes which are considered to be activated during regeneration of intestinal mucosa. Transcripts for the REG gene were found in 53% of colorectal cancers and for the PAP gene in 60% of colorectal cancers, by RT-PCR. Using in situ hybridization, the REG transcripts were found to be present in the tumour cells themselves rather than inflammatory or stromal cells. There were no significant correlations between the expression of these two genes and tumour stage, age or sex of the patient population or tumour site. However, in patients with non-metastatic disease who underwent ostensibly curative surgery, the expression of REG alone and co-expression of REG with PAP had a highly significantly adverse effect on survival. These data provide support for the concept that, in some tumours, carcinogenesis involves a regenerative process which co-exists with apoptotic inhibition and may provide a valuable selective indicator of the need for adjuvant therapy in those patients with early-stage colorectal cancer whose disease is destined to recur after curative surgery.

Anastomotic Leakage after Esophagectomy for Cancer: A Mortality-Free Experience

BACKGROUND Leakage is a serious complication of esophagectomy and is historically associated with high mortality. This study aimed to describe the morphology and strategies for clinical management of leakage after esophagectomy. STUDY DESIGN A database prospectively maintained from July 2002 to July 2005 at a referral unit for foregut cancer was used to identify patients with leakage of saliva or gastrointestinal contents after esophagectomy and reconstruction with stomach. Contrast swallow was routinely performed on postoperative day 7. Leakage was diagnosed and classified by well-defined criteria. RESULTS There were 99 men and 27 women, yielding an institutional volume of 42 esophagectomies per year. There was no in-hospital mortality from any cause. Actual 1-year survival was 87%. An Ivor Lewis operation was performed on 103 patients (82%); 4 patients had leakage within 5 days of operation and all had immediate rethoracotomy. An additional 8 patients with Ivor Lewis operation had leakage after day 5, and this was detected by contrast swallow in only 3 patients; 2 patients had no intervention, 4 patients had radiology-guided drainage, 1 had thoracoscopy, and 1 had rethoracotomy. Leakage was from the actual esophagogastric anastomosis in eight patients, from the linear gastric staple line in three patients, or from gastric necrosis in one patient. Twenty-three patients had a transhiatal or three-stage operation; leakage was from the actual anastomosis in five patients or gastric necrosis in one patient. CONCLUSIONS After Ivor Lewis esophagectomy, leakage was from the actual anastomosis in two-thirds of patients or from the gastric conduit in the remaining one-third. Prompt reoperation is recommended for early postoperative leakage. Most patients with leakage after day 5 can be treated nonoperatively.

Bone marrow micrometastases predict early post-operative recurrence following surgical resection of oesophageal and gastric carcinoma

AIM Tumour cells in the bone marrow of patients with gastrointestinal cancer may detect patients at higher risk of disease recurrence and death following potentially curative surgery. METHODS Immunocytochemistry using the monoclonal antibody Ber-EP4, which detects tumour cells from squamous and adenocarcinomas was used. In preliminary spiking experiments to define sensitivity, tumour cells were detected in blood at 10(3)/ml. Bone marrow samples from 74 patients with oesophago-gastric cancer and from 14 control patients was examined. RESULTS 27 (36.5%) patients with cancer and one control patient had stained cells present in their bone marrow at the time of resection. During the follow up period (mean 14 months), relapse and disease-specific death were commoner in patients whose marrow contained tumour cells. Multivariate analysis confirmed bone marrow micrometastasis as an independent prognostic variable for both recurrence and survival. CONCLUSIONS Bone marrow immunocytochemistry using Ber-EP4 may identify those patients at highest risk of early relapse following RO resection of oesophageal or gastric cancer.

Comparison of early outcomes for laparoscopic ventral hernia repair between nonobese and morbidly obese patient populations

BackgroundObesity predisposes to incisional herniation and increased the incidence of recurrence after conventional open repair. Only sparse data on the safety and security of laparoscopic ventral hernia repair (LVHR) for morbidly obese patients are available. This study compared the incidence of perioperative complications and early recurrence after LVHR between morbidly obese and non–morbidly obese patients.MethodsThe case records of consecutive patients who underwent LVHR between December 2002 and August 2007 were reviewed. Patients with a body mass index (BMI) lower than 35 kg/m2 were compared with morbidly obesity patients who had a BMI of 35 kg/m2 or higher.ResultsThe study included 168 patients (87 men) with a median age of 55 years (range, 24–92 years). Two conversions to open repair (1.2%) were performed, both for non–morbidly obese patients. Of the 168 patients, 42 (25%) were morbidly obese (BMI range, 35.0–58.0 kg/m2) and 126 (75%) were non–morbidly obese (BMI range, 15.5–34.9 kg/m2). The groups showed no significant differences in age, gender, number or size of fascial defects, operative time, length of hospital stay, or incidence of perioperative complications. At a median follow-up period of 19 months (range, 6–62 months), 20 patients (12%) had recurrent hernias. The incidence of recurrence was significantly associated with the size of the fascial defect and the size of the mesh, but not with morbid obesity.ConclusionNo significant difference in the incidence of perioperative complications or recurrence after LVHR was observed between the morbidly obese patients and the non–morbidly obese patients.

The candidate tumour suppressor gene, ING1, is retained in colorectal carcinomas.

ING1 plays a critical role in regulating cell cycle progression and susceptibility to apoptosis. The present study aimed to investigate allelic deletion of, and mutations within, the ING1 gene in colorectal carcinomas. Genomic DNA was extracted from 29 sporadic colorectal carcinomas and samples of adjacent normal mucosa. Losses of heterozygosity of two polymorphic dinucleotide repeat markers close to the ING1 locus at chromosome 13q32-34 were analysed. Single-stranded conformational polymorphisms of polymerase chain reaction amplified regions within the coding sequence of ING1 were examined. Microsatellite instability was noted in 5 (17%) colorectal carcinomas; this confirms selection of a subject sample representative of the population. Neither losses of heterozygosity nor changes in electrophoretic mobility of single-stranded polymerase chain reaction products were detected in any colorectal carcinoma. Thus, in common with tumour suppressor genes such as RB and BRCA2 on chromosome 13q, ING1 appears to be retained intact in colorectal carcinomas.

An international perspective on interest in a general surgery career among final-year medical students

BACKGROUND The level of interest in general surgery among US seniors has been declining; however, it may be perceived as a more attractive career outside the United States. METHODS A survey was developed and distributed to students at medical schools in 8 countries. Results were analyzed to determine whether interest in general surgery was related to sex of the respondent or economic standing of the country. RESULTS We noted differences in the level of interest in general surgery, ranging from 8% in Italy to 58% in India. As in the United States, there was a difference in the level of interest between sexes, with a male preponderance. Students from economically less developed countries expressed a greater interest in general surgery compared with students from countries with high development. CONCLUSIONS Our study suggested the level of interest for general surgery may depend on the sex and the location of the student. Further comparison studies may suggest means to stimulate student interest in the field.