Jai Dev Wig

Major molecular markers in pancreatic ductal adenocarcinoma and their roles in screening, diagnosis, prognosis, and treatment.

Pancreatic cancer is notorious for its late presentation, early and aggressive local invasion, metastatic potential, and poor outcome. It presents at a clinically advanced stage that precludes the possibility of surgical resection in most cases and shows constitutive resistance to chemotherapy and radiotherapy in others. As a result, mortality from this disease parallels its incidence rates. Recent breakthroughs in the molecular biology of pancreatic cancer have assisted in translational research, giving hope for individualized therapy and better disease management. Molecular biology tools are guiding early diagnosis, the assessment of prognosis, and isolation of novel, more effective therapeutic targets. This review discusses the signature mutations of pancreatic cancer, implications of these mutations to pancreatic cancer biology, their linked pathways, and recent advances in their understanding as biomarkers as diagnostic, prognostic, and therapeutic tools in dealing with this disease.

Endoscopic balloon dilation in caustic-induced chronic gastric outlet obstruction

BACKGROUND The standard treatment of caustic-induced gastric outlet obstruction (GOO) is surgery. There are only a few reports in the medical literature on endoscopic balloon dilation (EBD) for caustic-induced GOO. OBJECTIVE To study the short-term and long-term response of EBD in patients with caustic-induced GOO. SETTING Tertiary-care center in India. DESIGN Retrospective analysis of data. PATIENTS Of the 49 patients with caustic-induced GOO seen by us between January 1998 and December 2003, 41 were treated by EBD. Thirty-seven patients had consumed an acid and 4 had consumed an alkali a mean (SD) of 19.5 +/- 14.5 weeks earlier. EBD was performed every 3 weeks by using through-the-scope balloons under endoscopic guidance. INTERVENTION The balloon was negotiated across the narrowed segment and inflated for 60 seconds by using a pressure gun. Balloons of incremental diameters, up to a maximum of 3 sizes, were used in each sitting. The end point of dilation was 15 mm, after which patients were assessed for recurrence. The patients were observed until August 2007. RESULTS All 41 patients (23 men; mean [SD] age 29.6 +/- 8.5 years) could be successfully taken for EBD. Thirty-nine patients underwent successful repeated dilations, which required a mean (SD) of 5.8 +/- 2.6 dilations (range 2-13) to achieve the end point of 15 mm. All 39 patients were followed up for an average (SD) of 35.4 +/- 11.1 months (range 18-58 months). The mean (SD) size of the first dilator was 8.2 +/- 0.6 mm (range 8-10 mm). One patient had a perforation and was subjected to antrectomy; another patient had pain every time he received EBD; he also had surgery. Other complications were minor: self-limiting pain (n = 8) or bleeding (n = 7). CONCLUSIONS EBD is a safe, effective, and long-lasting alternative to surgery for caustic-induced GOO.

Bacteriology of infection in severe acute pancreatitis.

CONTEXT Severe acute pancreatitis is associated with high mortality with infectious complications being the most common cause of mortality. OBJECTIVE To analyze the prevalence and characteristics of pancreatic and extrapancreatic infection in patients with severe acute pancreatitis. DESIGN Prospective study over a one-year period. PATIENTS Fifty-one consecutive patients with severe acute pancreatitis. Setting Tertiary care centre, Northern India. MAIN OUTCOME MEASURES The presence of pancreatic and extrapancreatic infections were noted in consecutive patients with severe acute pancreatitis and their effect on disease outcome was assessed. RESULTS Pancreatic infection was noted in 19 (37.3%) patients; 14 (27.5%) patients had monomicrobial and 5 (9.8%) patients had polymicrobial infections. In the first week of hospitalization, all positive 6/6 (100%) cultures grew Escherichia coli, in the second week 5/8 (62.5%) grew Escherichia coli while after the second week, 2/5 (40.0%) cultures grew Escherichia coli. A total of 32 (62.7%) patients had evidence of extrapancreatic infections, with 53 positive cultures. Fifteen (29.4%) patients had monomicrobial infections while 17 (33.3%) had polymicrobial infections. The most common site was blood together with intravenous site with 21 positive cultures in 16 patients. Staphylococcus aureus was most commonly isolated in the blood cultures. There was a statistically significant increase in mortality with pancreatic (P=0.003) and extrapancreatic (P=0.041) infections. The antibiotic sensitivity pattern showed that most of the bacteria were sensitive to beta lactum antibiotics, aminoglycosides and imipenem. CONCLUSION Pancreatic infections are more often monomicrobial with a shift from gram-negative to gram-positive as the pancreatitis progressed. Extrapancreatic infections are more often polymicrobial; most commonly, the blood stream is invaded by gram-positive bacteria.

Efficacy of serum nitric oxide level estimation in assessing the severity of necrotizing pancreatitis

Background: The role of nitric oxide in the pathophysiology of necrotizing pancreatitis is unclear. Methods: In a prospective study, the clinical course of 40 patients diagnosed as having acute necrotizing pancreatitis was followed using computed tomography severity score (CTSS) and serial APACHE II scoring. The serum nitric oxide levels in the form of reactive nitrogen intermediates (RNI) were estimated on admission and on day 3. Occurrence of complications, need for intervention, incidence of organ failure, and outcome were noted. The efficacy of CTSS, APACHE II scores, and RNI levels in predicting morbidity and mortality was assessed. The correlation between CTSS, APACHE II scores, and RNI levels was studied. Results: The study group showed significantly higher levels of RNI as compared with the control group (159.1 vs. 106.0 nmol/ml, p < 0.05). The RNI levels were not affected by the occurrence of local complications or distant-organ failure. The RNI levels on admission were significantly higher in the subset of patients who developed bacterial sepsis (195.5 vs. 134.7 nmol/ml, p < 0.05). The RNI levels on admission in the non-survivors were higher as compared with those of the survivors (216.0 vs. 140.1 nmol/ml, p < 0.05).There was a significant positive correlation between the RNI levels and the CTSS in these patients (p < 0.05). There was no correlation between RNI levels and APACHE II scores. Conclusions: Acute necrotizing pancreatitis is associated with raised serum nitric oxide levels at its early stage. Patients with higher serum nitric oxide levels are at a significantly higher risk of sepsis and mortality.

Prevalence and outcome of fungal infection in patients with severe acute pancreatitis

Background and Aim:  To study the prevalence of risk factors and outcome of fungal infections in patients with severe acute pancreatitis.

Prognostic Significance of Micropapillary Pattern in Pure Mucinous Carcinoma of the Breast

Breast carcinoma with micropapillary architecture is associated with aggressive behavior. Similar micropapillary pattern in pure mucinous carcinoma has been noticed and has been shown to convey poor prognosis. In this study 17 cases of pure mucinous carcinoma of the breast seen during a 10-year period have been reviewed, with special reference to micropapillary pattern. Diffuse micropapillary pattern was seen in 6 of 17 cases of mucinous carcinoma of the breast and demonstrated reverse polarity immunostaining pattern with “Epithelial Membrane Antigen.” In all cases, the tumor cells showed grade I morphology, and no lymph node metastases were noticed. All the tumors except 1 expressed strong estrogen and progesterone receptor expression, however, all the cases were negative for Her-2/neu expression. In this present study, mucinous carcinomas with micropapillary pattern showed a low nuclear grade, higher incidence of hormone receptor positivity, and lower incidence of Her-2/neu similar to mucinous carcinomas without micropapillary pattern, thus explaining their indolent behavior.

OUTCOME AFTER PANCREATIC NECROSECTOMY: TRENDS OVER 12 YEARS AT AN INDIAN CENTRE

Background:  Pancreatic necrosectomy for necrotizing pancreatitis is a formidable operation. There are limited data from the Indian subcontinent regarding outcome and recent trends in management.

Closed lesser sac lavage in the management of pancreatic necrosis.

Background and Aim:  Surgery for pancreatic necrosis complicating acute severe pancreatitis carries a high risk of morbidity and mortality. We evaluated the efficacy of necrosectomy and closed lesser sac lavage as a method of management of pancreatic necrosis.

SMAD4 genetic alterations predict a worse prognosis in patients with pancreatic ductal adenocarcinoma.

Objectives The present study screened the SMAD4 gene in an Indian population of patients with pancreatic ductal adenocarcinoma (PDAC) for the presence of homozygous deletions and mutations. The effect of these genetic alterations on Smad4 protein expression and patient survival was also evaluated. Methods This study was conducted on surgically resected paired normal and tumor tissue samples of 25 consecutive patients with PDAC. The SMAD4 gene was screened for alterations by polymerase chain reaction and polymerase chain reaction–single-strand conformation polymorphism, followed by sequencing. The log-rank test was applied for survival analysis. Results The SMAD4 gene was altered in 8 (32%) of the 25 cases, 3 cases (12%) by homozygous deletion, and 5 cases (20%) by mutations in the C-terminal MH2 domain. Eighty percent of the total mutations were located in the mutational hotspot, mutation cluster region, present within the C-terminal MH2 domain. Mutations did not always result in the complete absence of protein expression. SMAD4 genetic alterations significantly correlated with poor prognosis (5 vs 10 months, log-rank test; P = 0.001). Conclusions Most SMAD4 mutations are located in the mutational hotspot, mutation cluster region, present within MH2 domain. SMAD4 mutations affect Smad4 protein expression to different extents, depending on their location within the gene. SMAD4 gene alterations predict a worse outcome for patients with PDAC.

Comparative evaluation of nasoenteral feeding and jejunostomy feeding in acute corrosive injury: a retrospective analysis

BACKGROUND Nutritional support in corrosive injury patients is traditionally achieved through total parenteral nutrition (TPN) or jejunostomy feeding (JF). There are no reports of nasoenteral tube feeding in patients with corrosive ingestion. OBJECTIVE We report our experience with nasoenteral tube feeding (NETF) and compare the outcome of these patients with those undergoing JF. SETTING Tertiary medical center in North India. DESIGN AND INTERVENTION The records of 53 and 43 patients with severe acute corrosive injury who underwent NETF and JF, respectively, were reviewed. All had received a 50-kcal/kg, 2-g/kg protein homogenized liquid diet for 8 weeks. A contrast study was performed at 8 weeks, and body weight and serum albumin levels were recorded at hospitalization and at 8 weeks. MAIN OUTCOME MEASUREMENTS Change in weight and serum albumin at 8 weeks and stricture development rate. RESULTS Strictures developed in 41 (80.39%) and 36 (83.72%) patients in the NETF and JF groups, respectively. Development of esophageal stricture (P = .71) and gastric stenosis (P = .89) was comparable in the 2 groups. No significant changes in serum albumin and weight were noted at 8 weeks in either group. The complication rate was lower in the NETF group compared with the JF group. Although all of the patients in the NETF group had a patent lumen, 5 in the JF group had total obstruction precluding endoscopic intervention. LIMITATIONS Retrospective study design. CONCLUSION NETF is as effective as JF in maintaining nutrition in patients with severe corrosive injury. The stricture development rate is similar, but nasoenteral tube placement provides a lumen for dilatation should a tight stricture develop.