Serum Human Epididymis Protein-4 (HE4) - A novel Approach to Differentiate Malignant Frombenign Breast Tumors.

BACKGROUND: The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. METHODS: Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. RESULTS: A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. CONCLUSION: Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.

Rate of colorectal neoplasia in patients with Hodgkin lymphoma.

AIM: Survivors of Hodgkin lymphoma (HL) are at increased risk of breast, lung, thyroid, stomach, pancreatic and colon cancer. There is limited information on the utility of endoscopic screening for colon cancer. We aimed to describe the adenoma detection rate (ADR) in patients with HL to determine the appropriate timing of colonoscopy screening. METHOD: We retrospectively studied patients with HL who underwent colonoscopy between 2000 and 2017. RESULTS: A total of 251 patients underwent colonoscopy. Eighty (32%) patients had 151 colonic polyps. Thirty per cent of the polyps exhibited high-grade dysplasia, and invasive colon adenocarcinoma was found in 10 patients. Patients with the nodular sclerosing subtype of HL had a significantly lower ADR than others (P = 0.002). The ADR was 5% in patients younger than 35 years (n = 64), 23% in patients between 35 and 40 years of age (n = 22), 39% in patients between 40 and 50 years of age (n = 51) and 46% in patients older than 50 years (n = 114).

Reconstruction in head-and-neck cancers - analysis of the learning curve.

BACKGROUND: Oral cancers are some of the most common cancers in India. Most patients present with locally advanced disease requiring extensive resection resulting in large defects. Reconstruction of these defects plays a major role in restoring form and function to these patients, as well as enabling the delivery of adjuvant therapy on time. AIM OF THE STUDY: The aim of this study was to analyze the learning curve involved in microvascular surgery. MATERIALS AND METHODS: A retrospective analysis of the case records of all patients of oral cancers, who underwent resection and reconstruction between January 2008 and December 2012 at our institute, was done. Demographic, clinical, and pathological data were collected and analyzed. Statistical analysis was done using the SPSS software. RESULTS: The operative time and the postoperative ventilation (7.8 h and 3.7 days, respectively) were significantly higher than those for pedicled flaps (3.6 h and 1.4 days, respectively). Both these variables reached statistical significance with P < 0.05 and < 0.04. The hospital stay was also statistically significantly longer for patients who underwent free-flap reconstruction (17.9 days vs. 7.9 days; P < 0.05). The number of reexplorations were higher in the free-flap group (31), when compared to the pedicled flap group (9). However, partial flap loss was higher in the pedicled flap subset when compared to the free-flap group. The complications significantly dropped after the performance of 30-40 free flaps. CONCLUSION: There is a steep learning curve in microvascular surgery, but the cosmetic and functional outcomes outweigh the complications.

Endoscopic resection is cost-effective compared with laparoscopic resection in the management of complex colon polyps: an economic analysis.

BACKGROUND AND AIMS: Endoscopic resection (ER) is an efficacious treatment for complex colon polyps (CCPs). Many patients are referred for surgical resection because of concerns over procedural safety, incomplete polyp resection, and adenoma recurrence after ER. Efficacy data for both resection strategies are widely available, but a paucity of data exist on the cost-effectiveness of each modality. The aim of this study was to perform an economic analysis comparing ER and laparoscopic resection (LR) strategies in patients with CCP. METHODS: A decision analysis tree was constructed using decision analysis software. The 2 strategies (ER vs LR) were evaluated in a hypothetical cohort of patients with CCPs. A hybrid Markov model with a 10-year time horizon was used. Patients entered the model after colonoscopic diagnosis at age 50. Under Strategy I, patients underwent ER followed by surveillance colonoscopy at 3 to 6 months and 12 months. Patients with failed ER and residual adenoma at 12 months were referred for LR. Under Strategy II, patients underwent LR as primary treatment. Patients with invasive cancer were excluded. Estimates regarding ER performance characteristics were obtained from a systematic review of published literature. The Centers for Medicare & Medicaid Services (2012-2013) and the 2012 Healthcare Cost and Utilization Project databases were used to determine the costs and loss of utility. We assumed that all procedures were performed with anesthesia support, and patients with adverse events in both strategies required inpatient hospitalization. Baseline estimates and costs were varied by using a sensitivity analysis through the ranges. RESULTS: LR was found to be more costly and yielded fewer quality-adjusted life-years (QALYs) compared with ER. The cost of ER of a CCP was $5570 per patient and yielded 9.640 QALYs. LR of a CCP cost $18,717 per patient and yielded fewer QALYs (9.577). For LR to be more cost-effective, the thresholds of 1-way sensitivity analyses were (1) technical success of ER for complete resection in <75.8% of cases, (2) adverse event rates for ER > 12%, and (3) LR cost of <$14,000. CONCLUSIONS: Our data suggest that ER is a cost-effective strategy for removal of CCPs. The effectiveness is driven by high technical success and low adverse event rates associated with ER, in addition to the increased cost of LR.

Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre.

BACKGROUND: In contrast to the consistent evidence for obesity and colorectal cancer (CRC) risk, the impact of obesity in CRC patients is less clear. In a well-characterised cohort of CRC patients, we prospectively evaluated class I and class II obesity with survival outcomes. METHODS: The CRC patients (N=634) were followed from the date of diagnosis until disease progression/first recurrence (progression-free survival (PFS)) or death (overall survival (OS)). Body mass index (BMI) was calculated from reported usual weight prior to diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic, treatment, and lifestyle factors. RESULTS: Over a median follow-up of 4 years, 208 (33%) patients died and 235 (37%) recurred or progressed. Class II obesity, as compared with either overweight or normal weight, was associated with an increased risk of death (HR and 95% CI: 1.55 (0.97-2.48) and 1.65 (1.02-2.68), respectively), but no clear association was observed with PFS. In analyses restricted to patients who presented as stages I-III, who reported stable weight, or who were aged <50 years, obesity was associated with a significant two- to five-fold increased risk of death. CONCLUSIONS: In CRC patients evaluated at a large cancer centre, severely obese patients experienced worse survival outcomes independent of many other factors.

Endoscopic closure of acute esophageal perforations.

Esophageal leak is a life-threatening problem that can result from spontaneous rupture of the esophagus, cancer, anastomotic dehiscence after surgery, or as a complication of endoscopy. During the last decade, developments in the minimally invasive endoluminal approach to the management of esophageal leaks include utilization of endoscopy not only for diagnosis but also for closure of leaks with clips or sutures, bypass of the leaks with stents, and/or endoluminal drainage of mediastinal infection. The aim of this review is to summarize recent advances and the principles of endoscopic management of acute esophageal perforations.

Safety and efficacy of donepezil hydrochloride in patients with mild to moderate Alzheimer's disease: Findings of an observational study.

BACKGROUND: Alzheimer's disease (AD), a progressive brain disorder, is the most common cause of dementia among the elderly. Donepezil hydrochloride is a potent, reversible, and highly selective inhibitor of acetylcholinesterase (AChE). It is chemically distinct from other cholinesterase (ChE) inhibitors which are effective in the treatment of AD. OBJECTIVES: To evaluate the safety and efficacy of donepezil hydrochloride therapy over a 12 weeks period in patients with mild to moderate AD in Indian population. MATERIALS AND METHODS: In this post-marketing study, patients with mild to moderate AD received oral donepezil hydrochloride 5 mg/day for 4 weeks followed by 10 mg/day for 8 weeks. Patients were assessed 4 times weekly for cognition on 'Mini Mental Status Examination (MMSE) scale', and function on 'Activities of Daily Living (ADL) index'. Clinicians and caregivers assessment of safety and efficacy was assessed on a 5-point rating scale. RESULTS: One hundred and seventy two of one hundred and eighty two patients completed 12 weeks of study period. MMSE score significantly improved (P<0.0001) from 16.72 at baseline to 19.77 after 12 weeks, and there was significant improvement (P<0.05) in ADL index in 13 of 17 domains after 12 weeks. Caregivers and clinicians rated the therapy as very good to good in >80% and >90% patients, respectively. Adverse events were consistent with the known pharmacological and safety profile of donepezil. CONCLUSIONS: Donepezil is well tolerated in Indian patients with mild to moderate AD with significant improvement in cognition and function.

Predictors of colorectal cancer following a negative colonoscopy in the Medicare population.

BACKGROUND: The incidence of colorectal cancer following a normal colonoscopy in the Medicare population is not known. METHODS: A 5% national sample of Medicare enrollees from 1996 to 2005 was used to identify patients undergoing complete colonoscopy. A colonoscopy not associated with any procedure (e.g., biopsy, polypectomy or fulguration) was defined as a negative colonoscopy. Patients with history of inflammatory bowel disease, colorectal cancer or death within 12 months of colonoscopy were excluded. A multivariable model was constructed to evaluate the factors associated with a new diagnosis of colorectal cancer in the period from 12 to 120 months following the negative colonoscopy. RESULTS: Among 200,857 patients (mean age 74 years, 61% female, 92% White) with a negative colonoscopy, the incidence of colorectal cancer was 1.8 per 1,000 person-years. The incidence rate for matched follow-up periods decreased from 2.0/1,000 person-years for patients undergoing colonoscopy during 1996-2000 to 1.2/1,000 person years during 2001-2005. Multivariate analysis revealed a significant regional variation in the incidence of colorectal cancer following a negative colonoscopy. The incidence was higher in patients >85 years, males and patients who underwent a negative colonoscopy by a non-gastroenterologist or endoscopist in the lowest volume quartile. On stratified analyses, endoscopist volume was a significant predictor for non-gastroenterologists only. CONCLUSIONS: The specialty and experience of the endoscopist are significant predictors of the incidence rate of colorectal cancer in Medicare patients with a negative colonoscopy.

Bowel preparation and colonoscopy technique to detect non-polypoid colorectal neoplasms.

Colonoscopy is considered the gold standard for colon cancer screening. In a recent study, however, 0.3% to 0.9% patients developed colorectal cancer within 3 years after removal of adenomas. Some reasons for the development of interval colorectal cancers include missed or incompletely removed lesions during the initial colonoscopy. Non-polypoid colorectal neoplasms are a potential contributor to the pool of missed lesions because they can be easily missed as a result of inadequate colon preparation or examination technique. This article discusses the methods that are useful to improve the quality of bowel preparation and examination technique.

Endoscopic sutured closure of a gastric natural orifice transluminal endoscopic surgery access gastrotomy compared with open surgical closure in a porcine model. A randomized, multicenter controlled trial.

BACKGROUND AND STUDY AIMS: In natural orifice transluminal endoscopic surgery (NOTES) procedures it is essential to be able to perform secure closure of the access perforation. The aim of this study was to compare endoscopically sutured closure of a gastric access gastrotomy using the tissue apposition system (TAS), with closure via laparotomy in a randomized multicenter study. METHODS: A total of 32 pigs (18 - 42 kg) were used in this study. The gastric NOTES access was created using a needle knife and a 20-mm balloon. Following transgastric pelvic peritoneoscopy, the endoscope was withdrawn into the stomach. The animals were then randomized to endoscopic closure or laparotomy with surgical closure. Procedure time, recovery time, and weight gain were measured. At necropsy, adhesions, abscesses or peritonitis were recorded. RESULTS: Of the 32 pigs, 29 survived 14 days without complications. All endoscopic and all open surgical closures were secure at postmortem. On average two suture pairs were used for endoscopic closure. Surgical closure was quicker (12.5 vs. 20.1 minutes). Recovery time and postoperative weight gain were similar for both groups. Two pigs in the endoscopic group died: one of gastric dilatation, without leakage from the gastrotomy; another was euthanized due to rectal prolapse. In the laparotomy group one pig was euthanized after 7 days due to abdominal wound dehiscence. At necropsy there were significantly more intra-abdominal adhesions in the laparotomized group. CONCLUSION: This randomized controlled study of endoscopic and surgical closure of a gastrotomy made for transperitoneal access for NOTES procedures suggests that both techniques are comparable in technical closure rates, postoperative recovery, and prevention of peritonitis. There were fewer adhesions in the endoscopic group.

Endoscopic management of gastrointestinal leaks.

Endoscopic closure of gastrointestinal perforations, fistulas, and anastomotic dehiscence is technically feasible. Endoluminal closure of the instrumental perforations of the gastrointestinal tract can be accomplished immediately after the recognition of perforation, while avoiding the delay of arranging surgery and the trauma associated with thoracotomy or laparotomy. In addition, endoscopic closure should be considered in patients with anastomotic dehiscence and chronic fistulas as this may avoid the risk associated with reoperation. The outcome of closure depends on the technical expertise in the proper selection and use of various endoluminal closure options. Training of the endoscopists in the use of this novel technology will enhance the quality of care of our patients.