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.

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.

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.

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.

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.

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.

A comparative study of scalpel and surgical diathermy incision in elective operations of head and neck cancer.

OBJECTIVE: The aim of the study was to assess the outcome of patients following use of scalpel or surgical diathermy in elective skin incision of head and neck cancer. MATERIALS AND METHODS: 80 patients undergoing surgery for various head and neck cancers were analyzed retrospectively from Jan 2002 to May 2005 and divided into two groups, matched for age, sex, stage and histopathology according to the method used to perform incision, i.e., scalpel or surgical diathermy. Blood loss, total operative time, blood transfusions, wound related complications and cosmetic assessments of the scar were compared. RESULTS: The two groups did not differ significantly in relation to patients or wound characteristics in terms of total operative time and quantity of blood transfusions. There was significantly less blood loss in the diathermy group compared with the scalpel group. There was no difference between the groups in wound complications and cosmetic results before discharge and at 1-month follow-up. CONCLUSIONS: There is no change in wound complication rate and scar formation even after application of heat during use of surgical diathermy. Therefore, surgical diathermy is safe and as effective as scalpel during elective skin incision of head and neck cancer.

An evolution of clinical application of inferior pedicle based rectus abdominis myocutaneous flap for repair of perineal defects after radical surgery for cancer.

The inferior epigastric artery based rectus abdominis myocutaneous flap (RAMF) is one of the most versatile flaps used to bridge gaps in the perineum and groin, in the reconstruction of vagina after radical resections for cancer and in selected patients with benign and non-healing perineal lesions. Its use for reconstruction after Abdomino-perineal resection was first described in 1984. This review attempts to summarize the anatomic-technical aspects of inferiorly based RAMF and its applications.

Nd:YAG laser therapy of carcinoma lip (stage I squamous cell carcinoma): a retrospective evaluation.

OBJECTIVE: To asses the efficacy of Nd:YAG laser for stage I squamous cell carcinoma of the lip. To the authors' knowledge this is the first reported study on this subject. STUDY DESIGN: Retrospective study design involving treatment of 46 patients of either sex of stage I squamous cell carcinoma of lip over a 10-year period in a single tertiary care university teaching hospital with Nd:YAG laser. METHODS: Nd:YAG laser ablation of lesions in lip was carried out in all the patients on an OPD basis with prior consent. A regular follow-up was maintained for a period of 5 years. A negative biopsy at the end of one month and one year was considered a treated case. The tabulated data was analysed statistically by "Kaplan Meier" method and "Log Rank" test. Also cosmetic and functional results were assessed by any sign of flow away after filling the oral cavity with water and postoperative integrity of facial nerve in accordance with "House Brackmann" classification. RESULTS: In this series of 46 patients, 35 patients were disease free at the end of 3 years and this number further declined to 29 at the end of 5 years with 4 deaths and 2 more patients lost to follow-up. The statistical evaluation by Kaplan Meier method gives us an overall 5-year survival rate of 88.14% with a mean survival of 58 months. Further 8 patients required repeat laserization either for residual or recurrence of lesion. Also 2 patients had a lymph node metastasis during the follow-up period. Thus, by applying Kaplan Meier method recurrence-free survival (RFS) and disease-free survival was found to be 85.1% (mean: 55 months) and 73.34% (mean: 57 months respectively. Interestingly on applying Log Rank test it was observed that the site of the lip involvement, i.e. whether upper or lower had no influence on disease-free survival. It was also observed that history of tobacco intake did not influence the disease free survival either (Log Rank Test). Moreover the cosmetic results were excellent and with no significant complication observed. CONCLUSION: The results reported here support the use of Nd:YAG laser for treatment of Stage I squamous cell carcinoma of lip in accordance with principles of minimal invasive and morbid surgery.

Significance of Her-2/neu protein over expression in Indian breast cancer patients.

BACKGROUND: Racial disparity in presentation and outcome of breast cancer is established but cause is unexplained. Many studies show various molecular markers for racial differences in the prognosis of breast cancer. There is scarcity of data on prognostic significance of HER-2/neu in Indian breast cancer. AIMS AND OBJECTIVE: To know incidence and prognostic significance of HER-2/neu expression in Indian patients. To correlate HER-2/neu Expression with other prognostic markers and ER/PR Receptor status. MATERIAL AND METHODS: 112 consecutive patients with breast cancer attending the Department of Surgical Oncology from March 1997 to March 2000 were included in this study. The clinical data along with ER/PR status, follow up data and HER-2/neu expression examined by immuno-histochemical method was recorded. STATISTICAL ANALYSIS: Data was analyzed by univariate and multivariate analysis for all prognostic factors. Significance was calculated by using Chi square test and survival analysis by using Kaplan Meier survival curve. RESULTS: The median age of 112 patients was 46.56 (±9.55) years. HER-2/neu over expression was present in 46.37%. Significant correlation was found between HER-2/neu over expression and lymph node status, grade of tumor and ER/PR receptor status. Median follow up period of 23 months. There was significant tumour free survival advantage (p < 0.01) and overall survival advantage (p < 0.001) in patients with HER-2/neu negative expression. CONCLUSION: HER-2/neu oncogene over expression is higher (46.37%) among Indian patients in comparison to 25-30% shown in most western literature. HER-2/neu oncogene over expression significantly correlates with grade, lymph node involvement, ER/PR status and also affects survival.

Effect of prevailing local treatment options of breast cancer on survival outside controlled clinical trials: experience of a specialist breast unit in North India.

BACKGROUND: This study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients' survival, and discusses the most suitable method within available resources. METHODS: The study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow-up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow-up was 6 years. RESULTS: Overall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%). CONCLUSIONS: Several types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.