Enhanced recovery after surgery protocol enhances early postoperative recovery after pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocol is a multimodal, multidisciplinary and evidence-based approach to reduce surgical stress and enhance recovery in the postoperative period. This study aimed to analyze the outcome of ERAS protocol in patients after pancreaticoduodenectomy (PD). METHODS: A total of 50 consecutive patients with pancreatic/periampullary cancer who underwent PD between January 2016 to August 2017 were included in the study. As per the institute ERAS protocol, nasogastric tube (NGT) was removed on postoperative day (POD) 1 if output was less than 200 mL and oral sips were allowed; oral liquids were allowed on POD2; semisolid diet by POD3; abdominal drain was removed on POD 4 if output was less than 100 mL with no evidence of postoperative pancreatic fistula (POPF); normal diet was allowed on POD5. Discharge criteria on POD6 were afebrile, tolerating oral normal diet, pain free and no surgery related complications (defined as per the ISGPS definitions). RESULTS: NGT was removed on POD1 in 45 (90%) patients, abdominal drain removed by POD4 in 41 (82%) and 43 (86%) patients were discharged on POD6. There was no 30-day postoperative mortality. Three (6%) patients had delayed gastric emptying (DGE). None had postoperative hemorrhage and POPF. Readmission rate was 8%. A significant relation was found between the length of hospital stay (LOS) with age (P < 0.05) and a marginal relation between LOS and postoperative albumin (P = 0.05). CONCLUSIONS: ERAS protocol can be safely followed in the perioperative care of patients who undergo PD. Early removal of NGT and allowing oral diet restore bowel function early. ERAS decreases the LOS and postoperative complications.

The see-saw of Keap1-Nrf2 pathway in cancer.

Keap1-Nrf2 pathway is continuously involved in the cytoprotection from oxidative stress generated due to various factors either extrinsic or intrinsic in origin. This role of Nrf2 in the response to oxidative stress is well established. Following oxidative insult, Nrf2 mediates the regulation of the inducible expression of cytoprotective genes. The level and functional capacity of Nrf2 is regulated at the post-transcriptional level, mainly through its association with an actin-associated protein, Keap1. Various studies reported that any discrepancy from their routine may lead to promotion of tumor as well. So there is need to explore their role in cytoprotection and tumor promotion if any. This review is an attempt to critically analyze the available data that may lighten up the present knowledge and unveil the new regime for cancer prevention and treatment.

Heterogeneous expression of cholecystokinin and gastrin receptor in stomach and pancreatic cancer: An immunohistochemical study.

AIM: Cholecystokinin (CCK) and gastrin (Gs) are a well known trophic factor for the gastrointestinal tract and their trophic effects are shown mainly toward pancreas and stomach, respectively. Though, the exact characterization of CCK and Gs receptors subtype (cholecystokinin type A receptor [CCKAR] and cholecystokinin type B receptor/gastrin receptor [CCKBR/GR]) in stomach cancer (SC) and pancreatic cancer (PC) is still controversial and necessities further validation. SUBJECTS AND METHODS: CCKAR and CCKBR/GR expression was analyzed by immunohistochemistry in 55 SC, 25 benign gastric diseases (BGDs), 38 PC (including periampullary carcinoma), and 10 normal pancreatic tissue. The results were statistically correlated with the patient's clinical history to observe the prognostic significance if any. RESULT: CCKAR expression was detected in 18.2% of SC, 20% of BGD, 65.8% of PC, and 30.0% of normal pancreas tissue samples. The CCKBR/GR expression was detected in 58.2% of SC, 48.0% of BGD, 18.4% of PC, and 60.0% of normal pancreas tissue samples. CCKBR/GR expression was significantly high in well and moderately differentiated SC samples as compared to poorly differentiated samples. CONCLUSION: Our study showed significantly higher expression of CCKAR and down regulation of CCKBR in PC as compared to control while CCKBR/GR was detected in majority of SC samples. Thus, our study suggests that CCK and Gs receptors may have diagnostic and therapeutic implications. However, study need to be validated in significantly bigger sample size and need to be replicated in different cohorts.

Indian Council of Medical Research consensus document for the management of gall bladder cancer.

The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.All postcholecystectomy gallbladder specimens should be opened and examined carefully by the operating surgeon and be sent for histopathological examination.All "incidental" gall bladder cancers (GBCs) picked up on histopathological examination should have an expert opinion.Evaluation of a patient with early GBC should include essential tests: A computed tomography (CT) scan (multi-detector or helical) of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal and liver function tests. magnetic resonance imaging/positron emission tomography (PET)-CT are not recommended for all patients.For early stage disease (up to Stage IVA), surgery is recommended. The need for adjuvant treatment would be guided by the histopathological analysis of the resected specimen.Patients with Stage IVB/metastatic disease must be assessed for palliative e.g. endoscopic or radiological intervention, chemotherapy versus best supportive care on an individual basis. These patients do not require extensive workup outside of a clinical trial setting.There is an urgent need for multicenter trials from India covering various aspects of epidemiology (viz., identification of population at high-risk, organized follow-up), clinical management (viz., bile spill during surgery, excision of all port sites, adjuvant/neoadjuvant therapy) and basic research (viz., what causes GBC).

Human mitochondrial genome flaws and risk of cancer.

Mitochondria perform significant roles in cellular energy metabolism. Among others, these functions include free radicals generation, control of cell death, growth, development, integration of signals from mitochondria to nucleus and nucleus to mitochondria, and various metabolic pathways. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell transformation and cancer progression. Introduction of mtDNA mutations in transformed cells has been associated with increased ROS production and tumor growth. Studies reveal that increased and altered mtDNA plays a role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. This review briefly summarizes the recent progress in this field.

Epigenetic silencing of BRCA1 gene associated with demographic and pathologic factors in sporadic breast cancer: a study of an Indian population.

Breast cancer (BC) is a leading cause of cancer-related deaths among women worldwide, and this study further demonstrates that the women of Varanasi (north India) are not untouched by this fatal disease. During BC development, epigenetic activity plays a key role in silencing gene expression. Its widespread occurrence in the cancer genome could inactivate many cellular pathways including DNA repair, cell cycle control, apoptosis, cell adherence, and detoxification. In this study, our aim was to determine the penetrance of BRCA1 promoter methylation and its correlation with pathological and demographic factors in sporadic BC in an Indian population. Our analysis included 127 patients who were diagnosed with sporadic BC. Methylation-specific PCR for the BRCA1 promoter was used during the study and correlated with pathological and demographic factors. Methylation of the BRCA1 promoter was detected in 8.7% (11/127) of the tumors. Correlation of promoter methylation with demographic factors and clinicopathological markers revealed the following data: (i) BRCA1 methylation was more frequently observed in tumor samples taken from premenopausal or perimenopausal women (P=0.026), (ii) methylation of the BRCA1 promoter negatively correlated with estrogen receptor (P=0.040), progesterone receptor (P=0.013), and epidermal growth factor receptor-2 (P=0.002), (iii) the overall promoter methylation was higher in more advanced stages (P=0.036) of the disease. This study has immense implications for understanding epigenetic mechanisms in BC development. The result suggests that the epigenetic silencing of BRCA1 is uncommon and is associated with the triple-negative phenotype.

Assessment of predictive markers of response to neoadjuvant chemotherapy in breast cancer.

OBJECTIVE: To identify the predictive markers associated with chemotherapy sensitivity, especially those producing pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer. METHODS: Core needle biopsy of 50 locally advanced breast cancer patients was analysed for histopathology, grade, oestrogen receptor, progesterone receptor, HER2, Ki-67, p53, Bcl-2, and BAX before starting NACT. This was correlated with response to NACT using Response Evaluation Criteria in Solid Tumours criteria. RESULTS: The mean tumour reduction rate per chemotherapy cycle was significantly higher in BAX-positive (p = 0.01) and Bcl-2-negative (p = 0.04) tumours. BAX expression significantly (p = 0.043) correlated with a response of an at least 30% reduction in tumour size post-NACT on multivariate analysis. A significant relationship was seen between loss of Bcl-2 expression and pCR on univariate (p = 0.048) analysis. Overall, all of the above 12 parameters had 30.4% and 28.5% success in predicting clinical complete response and pCR, respectively, by the Cox and Snell formula. CONCLUSION: Of all parameters examined, only the apoptosis-related genes (Bcl-2 and BAX) seemed to exert some influence on the response to NACT, and neither by itself was sufficient to predict pCR; however, 50 patients is not sufficient to simultaneously analyse several predictive markers.

Esophageal mucosal stripping for palliation of dysphagia in advanced carcinoma of lower third esophagus diagnosed at laparotomy.

We report our novel technique, as a palliative procedure for carcinoma of the lower third esophagus, of stripping the mucosa of the esophagus with enbloc resection of cancer of the lower third esophagus with gastric pull up and cervical hand sewn esophagogastric anastomosis. This was undertaken primarily for the relief of dysphagia in locally advanced/metastatic cancer diagnosed at laparotomy. The technique has distinct advantages of being simpler, economical with minimal morbidity.