Expression Profile of KRAS and p16 in Periampullary Cancer.

Activating point mutations in codons 12, 13, and 61 of the KRAS gene and loss of p16 expression, a tumor suppressor gene, are common genetic alterations in periampullary cancer (PAC). The present study explores expression profile of KRAS and p16 genes in PAC and its prognostic relevance. A total of 50 patients with PAC who underwent potentially curative pancreaticoduodenectomy were included in the study. Formalin-fixed, paraffin-embedded tissue samples were analyzed for point mutations in codons 12 and 13 of KRAS and codon 9 of p16 using polymerase chain reaction. KRAS mutation in codon 12/13 was found in 32 (64%) and loss of p16 expression in 36 (72%) cases. KRAS mutation was significantly associated with higher grade, higher pathological tumor (pT) stage, lymphovascular invasion (LVI), perineural invasion (PNI), and pathological lymph nodes (pN) involvement on univariate analysis. On multivariate analysis, significant association of KRAS remained with higher grade (p = 0.031), pT stage (p = 0.09), and LVI (p = 0.028). On univariate analysis, loss of p16 expression was significantly associated with higher grade, pN involvement, LVI, PNI, and pT stage whereas on multivariate analysis, statistical significant association of p16 was found with higher grade of tumor only (p = 0.04). Patients with KRAS mutation had significantly (p = 0.018) worse disease-free survival (DFS) whereas no significant association was found in overall survival (OS). Loss of p16 expression had no association with either DFS or OS. The presence of p16 and KRAS alterations in patients with PAC suggests aggressive tumor biology. KRAS mutations confer a significantly poor DFS in PAC.

Octreotide and postoperative pancreatic fistula after pancreaticoduodenectomy: What we know so far? A narrative review.

Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made. Further filters were applied in the search "Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021," and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.

An outbreak investigation of acute Diarrheal Disease, Nagpur District, Maharashtra, India.

BACKGROUND: Acute diarrheal disease (ADD) accounts for 12 million cases and 1216 deaths annually in India. On July 13, 2016, an ADD outbreak was reported from Sawargaon village from Nagpur district, Maharashtra. OBJECTIVE: The outbreak was investigated to describe the epidemiology and suggest control and preventive measures. METHODS: A case was defined as a person experiencing at least one loose stool in Sawargaon village between July 9, 2016, and July 31, 2016. We searched for cases by enhanced passive surveillance. We collected stool samples for bacterial culture and tested water from multiple water sources for fecal coliforms. We also reviewed sanitary practices and rainfall data. RESULTS: A total of 889 cases were identified, with 51% female, 280 hospitalizations (31%), and two deaths. The median age was 27 years (range 6 months to 90 years). Cases started on July 9, a week after heavy rains. District authorities started chlorination of water sources on July 13 and cases declined soon after. Two of nine stool samples tested positive for Vibrio cholera O1 serogroup. Of the 18 water samples collected, 16 (88%) samples from multiple sources, including wells, hand pumps, and taps, were positive for fecal coliforms. Of 1,885 households in the village, 450 (24%) households had no toilets and open defecation was commonly observed in the nearby river bed. CONCLUSIONS: This ADD outbreak was likely associated with drinking contaminated groundwater, which probably occurred after heavy rainfall in an area of open defecation. We recommended providing chlorinated drinking water, promoting safe sanitation practices, including building more public and private toilets, and enhancing diagnostic laboratory capacity.

Assessment of Exocrine Function of Pancreas Following Pancreaticoduodenectomy.

Pancreatic exocrine insufficiency (PEI) is a common long-term complication after pancreaticoduodenectomy (PD) and is observed in 23-80% of patients. As the postoperative mortality after PD has substantially decreased, it warrants more attention on the diagnosis and treatment of functional long-term consequences after PD. These include PEI and endocrine insufficiency that can result in significant nutritional impairment and often adversely impacts quality of life (QOL) of the patient. A PubMed search was performed for articles using key words "pancreatic exocrine insufficiency"; "pancreaticoduodenectomy"; "quality of life after pancreaticoduodenectomy"; "stool elastase"; "direct, indirect tests for pancreatic exocrine insufficiency"; "pancreatic enzyme replacement therapy." Relevant studies were shortlisted and analyzed. This review summarizes relevant studies addressing PEI following PD. We also discuss functional changes after PD, risk factors and predictive factors for postoperative PEI, clinical symptoms, direct and indirect tests for estimation of PEI, pancreatic enzyme replacement therapy (PERT), and QOL after pancreatic resection for malignancy. It was found that significant PEI occurs in most patients following PD. Fecal elastase 1 is an easy indirect test and should be performed routinely in both symptomatic and asymptomatic patients after PD. PERT should be considered in every patient after PD with the aim to improve the QOL and perhaps even their long time survival.

Oncological benefits of postoperative radiotherapy in node-negative early stage cancer of the oral cavity with isolated perineural invasion.

Perineural invasion has been widely regarded as a poor prognostic factor in cancer of the oral cavity, but adjuvant treatment based only on this is still debatable. We have made an effort to address the question in a retrospective analysis of data from 2009-15 of patients with early node-negative cancers of the oral cavity. Patients with perineural invasion were divided into those who were treated with radiotherapy and those who were not. The records of a total of 169 patients were analysed, and 118 were given adjuvant radiotherapy and 51 were not. The median (range) duration of follow up was 45 (26-86) months. Of 169 patients, 47 (28%) developed recurrence, 28 in the treated, and 19 in the untreated, group. There was a significant disease-free survival benefit for adjuvant treatment (p = 0.047) but no overall survival benefit (p = 0.54). We conclude that adjuvant radiotherapy should be considered for patients with perineural invasion, even in early cancers of the oral cavity.

Outcome of 150 Consecutive Blumgart's Pancreaticojejunostomy After Pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is the most feared complication after pancreaticoduodenectomy (PD) that leads to intra-abdominal abscess, sepsis, or bleeding and remains the single most important source of morbidity and mortality after PD. To minimize this dreaded complication, various surgical techniques and modifications of pancreaticoenteric reconstruction have been proposed. However, still POPF does occur even in experienced hands. We herein describe the outcome of 150 post PD patients who underwent duct-to-mucosa (DM) pancreaticojejunostomy (PJ) using a special technique, Blumgart's "through & through" U transpancreatic sutures. The technique is described in detail. Postoperative octreotide and metoclopramide were used in all patients for 3 days. An enhanced recovery (ERAS) protocol was followed in a subset of patients. All patients were ASA grade 1 and had adenocarcinoma of the periampullary region/pancreatic head and underwent standard pylorus resecting PD after due optimization. Eighty-eight (58.7%) patients had pancreatic duct < 3 mm and pancreatic texture was soft to very soft in 112 (74.6%) patients. There was only one International Study Group of Pancreatic Surgery (ISGPS) grade C POPF with concomitant hemorrhage. Five patients developed ISGPS grade B and two grade C, delayed gastric emptying (DGE). There was no 30-day mortality. The average length of hospital stay was 7.3 ± 4.2 days with a median of 6 days in the ERAS subset of patients. Blumgart's "through & through" DMPJ technique is very helpful in reducing the POPF and other complications even in high-risk pancreas (i.e., soft with a small pancreatic duct) and is easy to learn and perform.

A gland of diverse pathology and unpredictable behaviour: our experience of primary submandibular gland malignancies.

Submandibular gland tumours are relatively uncommon tumours and demonstrate diverse histological types and a variable prognosis. The aim of this study was to analyze our experience with submandibular malignancies over a period of 6 years (January 2009 to December 2015). Patient data from the 6-year period were reviewed retrospectively and 51 patients with submandibular malignancies were identified. Demographic data, clinicopathological details, treatment received, complications, and follow-up were recorded. The mean age of the 51 patients at presentation was 49.1 years. They were followed up for a mean 20.3 months. Nine of 47 patients (19.1%) developed distant metastasis during follow-up, while only three (6.4%) developed local recurrence. Disease-free survival at 2 years was 69.7% and overall survival at the end of 2 years was 77.8%. Actuarial 5-year survival was 57.8% when all subtypes were considered. The overall mean time to recurrence was 10 months (6-24 months). Nodal positivity was the only prognostic factor that was significant on multivariate analysis, while age, sex, perineural invasion, and grade were not. With advances in surgical and radiotherapy techniques, loco-regional control rates have improved greatly; however, effective adjuvant treatment to prevent systemic relapse is still lacking.

Co-existence of Diffuse Serous Cystadenoma and Pancreatic Neuroendocrine Tumor.

Diffuse serous cystic neoplasm (SCN) associated with pancreatic neuroendocrine tumor (PNET) is a rare finding reported previously in only three patients to the best of our knowledge. We herein present one such interesting report of a diffuse serous cystic adenoma (SCA) and co-existent PNET in a 25-year old lady who presented with abdominal pain for past 6 months. A triple-phase pancreatic protocol computed tomography (CT) scan revealed multiple cysts involving the entire pancreas. The cysts were thin walled, ranging from 2 to 8 cm in width, with no calcification or central scar that was confirmed at laparotomy. A frozen section revealed a neuroendocrine tumor and she underwent total pancreatectomy. Diffuse SCA with co-existent PNET infiltrating nerve bundles of the pancreatic parenchyma was made upon histopathology further verified by chromogranin-A immunostaining. The patient is insulin dependent and doing well at 2 years of follow-up. The origin of endocrine tumors from multipotent ductular stem cells has been suggested.

Role of telerehabilitation in patients following total knee arthroplasty: Evidence from a systematic literature review and meta-analysis.

Introduction Increased physical activity and functional ability are the goals of total knee replacement surgery. Therefore, adequate rehabilitation is required for the recovery of patients after discharge from hospital following total knee arthroplasty (TKA). This systematic literature review aimed to evaluate the effectiveness of home telerehabilitation in patients who underwent TKA. Methods Studies published in the English language between 2000 and 2014 were retrieved from Embase, PubMed, and Cochrane databases using relevant search strategies. Two researchers independently reviewed the studies as per the Cochrane methodology for systematic literature review. We considered telerehabilitation sessions as those that were conducted by experienced physiotherapists, using videoconferencing to patients' homes via an internet connection. The outcomes assessed included: knee movement (knee extension and flexion); quadriceps muscle strength; functional assessment (the timed up-and-go test); and assessment of pain, stiffness, and functional capacity using the Western Ontario and McMaster Universities Osteoarthritis Index and visual analogue scale for pain. Results In total, 160 potentially relevant studies were screened. Following the screening of studies as abstracts and full-text publications, six primary publications (four randomized controlled trials, one non-randomized controlled trial, and one single-arm trial) were included in the review. Patients experienced high levels of satisfaction with the use of telerehabilitation alone. There was no significant difference in change in active knee extension and flexion in the home telerehabilitation group as compared to the control group (mean difference (MD) -0.52, 95% CI -1.39 to 0.35, p = 0.24 and MD 1.14, 95% CI -0.61 to 2.89, p = 0.20, respectively). The patients in the home telerehabilitation group showed improvement in physical activity and functional status similar to patients in the conventional therapy group. Discussion The evidence from this systematic literature review demonstrated that telerehabilitation is a practical alternative to conventional face-to-face rehabilitation therapy in patients who underwent TKA.

Molecular Aberrations in Periampullary Carcinoma.

Periampullary carcinomas are a group of rare lesions around the ampulla of Vater including distal bile duct and duodenum and are very different from pancreatic ductal adenocarcinoma clinically and pathologically, but the molecular alterations in these tumours are less known. Genetic alterations of the KRAS oncogenes, tumour suppressor genes p53, p16 and MADH4 (SMAD4/DPC4) and genome maintenance genes (MLHI, MSH2) are commonly altered in pancreatic adenocarcinoma and have also been described in periampullary cancers, although at lower frequencies. To understand the molecular characteristics of non-pancreatic periampullary carcinomas, ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. KRAS mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42-52%), biliary (22-23%) and duodenal cancers (32-35%). Mutations are also found in tumour suppressor genes (p53) and are associated with transformation of adenomas and low-grade carcinomas into high-grade carcinomas. Loss of DPC4 occurs late in ampullary carcinogenesis. This study summarizes the current knowledge in molecular aberrations in non-pancreatic periampullary cancers.

Chylous Ascites in Advanced Gallbladder Cancer.

Chylous ascites is a very rare occurrence in a patient with gallbladder cancer (GBC), and only six cases have been reported. We report here one such case in a 55-year-old lady who presented to us with upper abdominal pain for 6 months. A polypoidal gallbladder mass with minimal liver invasion but with multiple subcentimeter pericholedochal, common hepatic, mesenteric, and para-aortic lymph nodes was found on contrast-enhanced computed tomography scan. At laparotomy, the abdomen had milky fluid with engorged beaded lymphatics all over the small intestine. The abdomen was closed over a drain after a lymph node biopsy and collection of the ascetic fluid for analysis. Histopathology confirmed metastatic adenocarcinoma in the lymph node. The triglyceride levels in the ascetic fluid were elevated to 817.00 mg/dl. The patient was put on medium-chain triglyceride diet and a diuretic and recovered well. She was discharged when drain output was nil. Chylous ascites could be a result of abdominal malignancy, post surgery, cirrhosis, and disseminated infections like tuberculosis and filariasis. Treatment is primarily conservative and includes paracentesis/drainage of the peritoneal cavity supplemented by fasting, total parenteral nutrition, and/or diet modification with medium-chain triglyceride diet.

Carcinoma of the Ampulla of Vater Associated with Annular Pancreas.

Carcinoma of the ampulla of Vater associated with annular pancreas is a rare entity. Only seven cases have been reported so far in the English literature. We herein report one such case in a 42-year-lady who presented with progressively increasing jaundice and pain in the upper abdomen for past 2 months. A magnetic resonance cholangiopancreaticography (MRCP) and MRI revealed an annular pancreas with an ampullary mass and a dilated CBD. An upper gastrointestinal endoscopic biopsy from the ampullary mass revealed a moderately differentiated adenocarcinoma. She was diagnosed as having annular pancreas with periampullary cancer that was subsequently confirmed at laparotomy. Histological examination confirmed a complete annular pancreas with a 2 cm × 2 cm moderately differentiated adenocarcinoma of the ampulla of Vater. The management, however, remains as in any case of periampullary malignancy. This highlights the importance that obstructive jaundice in an adult patient presenting with annular pancreas may be associated with a coexisting periampullary malignancy.

Free radicals hasten head and neck cancer risk: A study of total oxidant, total antioxidant, DNA damage, and histological grade.

BACKGROUND: Free radicals such as reactive oxygen species (ROS), which induce oxidative stress, are the main contributors to head and neck carcinogenesis (HNC). The present study was conducted with the aim to assess the oxidant/antioxidant status and DNA damage analysis in head and neck cancer/control patients. MATERIALS AND METHODS: This prospective study was conducted on 60 patients with biopsy-proven HNC and 17 patients of head and neck disease (HND). The total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined by novel automatic colorimetric methods from tissue homogenate. DNA damage analysis was determined by single cell gel electrophoresis (SCGE). RESULTS: The mean age of the study cohort was 46.65 ± 14.84 years for HNC patients, while it was 49.41 ± 13.00 years for HND patients. There were no significant differences found between the two groups with respect to demographic presentation except tobacco addiction. The association between oxidative stress parameters and DNA damage analysis with study group revealed the following. (A) DNA damage - tissue homogenate TOS and OSI were significantly higher in HNC subjects than in HND (16.06 ± 1.78 AU vs 7.86 ± 5.97 AU, P < 0.001; 53.00 ± 40.61 vs 19.67 ± 21.90, P < 0.01; 7.221 ± 5.80 vs 2.40 ± 2.54, P < 0.01, respectively), while TAS was significantly decreased. (B) Aggressive histological features were identified, more commonly with higher TOS and lower TAS [probability (P) = 0.002, relative risk (RR) = 11.838, 95% confidence interval CI = 2.514-55.730 and P = 0.043, RR = 0.271, 95% CI = 0.077-0.960, respectively]. CONCLUSION: The increase in free radicals may be the event that led to the reduction of antioxidant status in HNC, thus explaining the oxidative damage of DNA and the severity of disease. Increased OSI represents a general mechanism in its pathogenesis.

Analysis of wedge resection of gallbladder bed and lymphadenectomy on adequate oncologic clearance for gallbladder cancer.

BACKGROUND: Surgery (R0 resection) is the mainstay of treatment of gallbladder cancer (GBC) as GBC is relatively resistant to currently known chemotherapy and radiotherapy regimens. AIM: to assess if wedge resection of the gallbladder bed achieves an adequate oncological clearance in GBC (namely T1 and T2) and some T3 GBC with minimal liver infiltration. PATIENTS AND METHODS: Patients with GBC who underwent radical cholecystectomy (en bloc cholecystectomy, wedge resection of the gallbladder fossa with a ≥2 cm rim of nonneoplastic liver tissue, and regional lymph node dissection) between October 2012 and June 2015 after obtaining informed consent. RESULTS: Of thirty patients, mean age of 52 years, 5 had T1b, 13 T2, and 12 T3 GBC. R0 resection was achieved in all thirty GBC patients. Hepatic invasion was found in seven patients. The depth of hepatic invasion ranged from 0 to 9 mm. Follow-up ranged from a minimum of 12 to 43 months. Nineteen (63%) patients had N0 and 11 (37%) had N1 GBC. Total lymph node (TLND) count ranged from 1 to 12/patient with a median of 3. There was no local recurrence or systemic relapse of the disease. CONCLUSION: Wedge resection of the gallbladder bed achieves an adequate oncological clearance in early GBC. TLND counts remain poor even after a thorough standard lymph node dissection for resectable GBC.

Text-message reminders increase uptake of routine breast screening appointments: a randomised controlled trial in a hard-to-reach population.

BACKGROUND: There is a need for interventions to promote uptake of breast screening throughout Europe. METHODS: We performed a single-blind randomised controlled trial to test whether text-message reminders were effective. Two thousand two hundred and forty women receiving their first breast screening invitation were included in the study and randomly assigned in a 1 : 1 ratio to receive either a normal invitation only (n=1118) or a normal invitation plus a text-message reminder 48 h before their appointment (n=1122). FINDINGS: In the intention-to-treat analysis, uptake of breast screening was 59.1% among women in the normal invitation group and 64.4% in the text-message reminder group (χ(2)=6.47, odds ratio (OR): 1.26, 95% confidence intervals (CI): 1.05-1.48, P=0.01). Of the 1122 women assigned to the text-message reminder group, only 456 (41%) had a mobile number recorded by their GP and were thereby sent a text. In the per-protocol analysis, uptake by those in the control group who had a mobile number recorded on the GP system was 59.77% and by those in the intervention group who were sent a reminder 71.7% (χ(2)=14.12, OR=1.71, 95% CI=1.29-2.26, P<0.01). INTERPRETATION: Sending women a text-message reminder before their first routine breast screening appointment significantly increased attendance. This information can be used to allocate resources efficiently to improve uptake without exacerbating social inequalities.

Tobacco addiction augments obesity and carcinogenesis: Matter of concern for Indian patients.

PURPOSE: Life-style and tobacco addiction is the major risk factors for cancer progression in all over the world. Knowledge gaps between tobacco addiction, obesity and cancer in Indian patients brought an interdisciplinary group of investigators together to discuss the present study. PATIENTS AND METHODS: We calculated the body mass index (BMI) of all the patients (N = 927) who were diagnosed with cancer for its treatment. National Institutes of Health (NIH) criteria were used to categorize the patients. All the patients of this disease could be contacted in person to find out the history of the disease. RESULTS: The frequency of addiction in urban cancer patient was found to be about 53.3% and in a rural area it was only 33.7%. Tobacco addiction was independently associated with younger age of cancer patient (odds ratio [OR] 2.242; 95% Confidence interval (CI) 1.653-3.042), obese (OR 7.433; 95% CI 3.746-14.750), overweight (OR 4.676; 95% CI 3.381-6.468) and advanced stage of cancer (OR 11.950; 95% CI 5.283-27.030). CONCLUSION: Tobacco consumption appears to be a major contributor to cancer in younger age with elevated BMI in India. Rapid changes in diet and life-style, increase in tobacco consumption appear to be strongly associated with the carcinoma in this middle-income country.

Prospects of nano-material in breast cancer management.

Breast cancer evaluation and early diagnosis are core complexity worldwide and an ambiguity for scientists till date. Nano-materials are innovative tools for rapid diagnosis and therapy, which may induce an immense result in the field of oncology. Their exceptional size-dependent properties make them special and superior materials and quite indispensable in several fields of the human activities. The major obstacle in finding cure for malignant breast cancer is to increase in development of resistances for tumors to the therapeutic treatments. The widespread mammo-graph particle is being developed by nations to diagnosis disease in primitive stage to decline the mortality rates caused by breast carcinoma. The advancement of nano-particle based diagnostic tools facilitates in evaluation and provides encouraging development in breast cancer therapeutics. In this compact review, efforts have been made to compose the current advancements in the area of functional nano-particles. Furthermore, in vivo and in vitro applications of nano-materials in breast cancer management are also discussed.

Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India.

Breast cancer is the most common neoplasm affecting women in the western world with an average frequency of 1 in 11, developing the malignancy and it is second most common cancer in India. Variations in serum levels of biochemical parameters especially alkaline phosphatase (ALP) changes may be of great help in diagnosis of breast carcinoma. Serum ALP activity was assayed in 388 histopathologically proven breast cancer patients using spectrophotometric methods and monitored association with cancer stages. Breast cancer is a female-biased disease and our study was conducted in a group of female patients with mean age of 48.67 ± 8.32 years. A significant increase in levels of ALP (809.65 ± 145.97 IU/L) was observed in stage IV of the disease. The logistic regression study gave a significant result (P < 0.001) when we compared the group of ALP level (>500 IU/L) with metastatic presentation. The present study besides being cost effective suggested the usefulness of ALP in differentiating breast cancer stages and metastasis.