Emergency surgical intervention in acute corrosive ingestion: single-center experience from India.

BACKGROUND: Surgical intervention for acute corrosive injury is often required. It is associated with considerable morbidity and mortality. Sparce data is available on the types and timing of surgery after acute corrosive ingestion and complications associated with the same. METHODS: This is a retrospective single-center study from a tertiary care center in India. All patients who underwent surgical exploration after acute corrosive intake between January 2003 and June 2014 were enrolled in the study. Data on patients' presentation, their endoscopic findings, indications of surgery, type of surgery and post-operative follow-up was retrieved. RESULTS: Out of 170 patients who presented with acute corrosive ingestion, 24 patients (14.11%) required emergency surgery. The mean interval between ingestion and surgery was 9.92 ± 9.03 days. Presence of peritonitis was the most common indication for surgery (n = 10; 41.7%) followed by mediastinitis (n = 7; 29.2%). A total of 17 resectional and 7 non-resectional procedures were performed. Thirteen (54%) patients succumbed to their illness post-operatively due to multi-organ failure (n = 9), refractory shock (n = 3) or pulmonary thromboembolism (n = 1). Patients with early surgery (≤7 days) after corrosive ingestion had similar mortality compared to patients with late surgery (>7 days) (50% versus 67%; P = 0.30). Of the 11 surviving patients, eight patients (72%) underwent successful reconstructive surgery on follow-up. CONCLUSIONS: Emergency surgery after corrosive ingestion carries high morbidity and mortality. However, after the initial stormy acute phase, majority of patients can undergo successful reconstructive surgery on follow-up.

Hemorrhage complicating the course of severe acute pancreatitis.

BACKGROUNDS/AIMS: The course of severe acute pancreatitis (SAP) complicated by hemorrhage is associated with poor outcome. METHODS: Twenty-four (13%) out of 183 cases of SAP had hemorrhagic complications- 12 intraabdominal & 12 intraluminal, 13 had major & 11 had minor and 16 had de-novo & 8 post-surgical bleeding. The mean duration of pancreatitis prior to bleeding was 27±27.2 days. RESULTS: Predictors of haemorrhage on univariate analysis were delayed admission (0.037), more than one organ failure (p=0.008), presence of venous thrombosis (p=0.033), infective necrosis (0.001) and systemic sepsis - bacterial (0.037) & fungal (p=0.032). On multivariate analysis infected necrosis (OR=11.82) and presence of fungal sepsis (OR=3.73) were the significant factors. Patients presenting with more than one organ failure and bacterial sepsis had borderline significance on multivariate analysis. Need for surgery (50% vs. 12.6%), intensive care stay (7.4±7.9 vs. 5.4±5.2 days) and mortality (41.7% vs. 10.7%) were significantly higher in patients who suffered haemorrhage. Seven of the 13 with major bleeding had pseudoaneurysms-4 were embolized, 4 needed surgery including 1 embolization failure. Seven with intraabdominal bleeding required surgical intervention, 2 had successful embolization and 3 had expectant management. CT severity index and surgical intervention, were significantly associated with intraabdominal bleeding. Organ failure, presence of pseudoaneurysm and surgical intervention were associated with major bleeding. CONCLUSIONS: Hemorrhage in SAP was associated with increased morbidity and mortality. Infected necrosis accentuated the degradation of the vessel wall, which predispose to hemorrhage. Luminal bleeding may be indicative of erosion into the adjacent viscera by the pseudoaneurysm.

Treatment strategies for bleeding from gastroduodenal artery pseudoaneurysms complicating the course of chronic pancreatitis-A case series of 10 patients.

We analyzed our experience with management of gastroduodenal artery (GDA) pseudoaneurysms associated with chronic pancreatitis using a multidisciplinary approach. We treated 10 patients with GDA pseudoaneurysms (all men, aged 24-62 year) who underwent treatment during April 1998 to December 2016. All had presented with recent hematemesis and/or melena. Hemodynamically, stable patients were initially subjected to transcatheter embolization or radiologically guided thrombin injection. Recurrence of bleeding within 48 h was taken as failure. Emergency surgery was done for hemodynamic instability and recurrent bleeding, and elective surgery was carried out as per specific indications. Ten interventional procedures were performed in nine patients, while one was directly subjected to surgery. Angioembolization was done in five patients (with success in four) and thrombin injection in five patients (including one with embolization failure; with success in three). Six patients underwent surgery, two on emergency basis, for hemodynamic instability and recurrent bleeding in one each, and four for definitive treatment of pancreatitis/associated complication. One patient died while the other nine survived and well with no recurrence of bleeding during follow up (6 months to 10 years). Management of GDA pseudoaneurysms requires a multidisciplinary approach. Pseudoaneurysms with narrow neck are suitable for thrombin injection while those with wide neck should be subjected to angioembolization. Emergency surgical treatment is reserved for non-surgical failures, and choice between trans-ductal or trans-cystic approach is based on the location of the aneurysm.

Isolated splenic metastasis from clear cell renal carcinoma - A case report.

BACK GROUND: Metastatic deposits in spleen are rare owing to its physiological functions and sharp angle of splenic artery with coelic axis. CASE REPORT: We report a case of a 53year old male with clear cell carcinoma of left kidney. Isolated splenic metastasis was detected on a follow up PET CT scan 2 months post radical nephrectomy. Splenectomy was performed; histopathology confirmed multiple metastatic lesions within the spleen CONCLUSION: Timely treatment of isolated metastasis in case of renal cell carcinoma carries good prognosis.

Alterations in K-ras, APC and p53-multiple genetic pathway in colorectal cancer among Indians.

The incidence of colorectal cancer (CRC) is increasing rapidly in Asian countries during the past few decades, but no comprehensive analysis has been done to find out the exact cause of this disease. In this study, we investigated the frequencies of mutations and expression pattern of K-ras, APC (adenomatosis polyposis coli) and p53 in tumor, adjoining and distant normal mucosa and to correlate these alterations with patients clinicopathological parameters as well as with the survival. Polymerase chain reaction (PCR)-restriction digestion was used to detect mutations in K-ras and PCR-SSCP (Single Strand Conformation Polymorphism) followed by DNA sequencing was used to detect mutations in APC and p53 genes. Immunohistochemistry was used to detect the expression pattern of K-ras, APC and p53 proteins. The frequencies of mutations of K-ras, APC and p53 in 30 tumor tissues samples were 26.7 %, 46.7 % and 20 %, respectively. Only 3.3 % of tumors contained mutations in all the three genes. The most common combination of mutation was APC and p53 whereas mutation in both p53 and K-ras were extremely rare. There was no association between the mutations and expression pattern of K-ras, APC and p53 (p>0.05). In Indians, the frequency of alterations of K-ras and APC is similar as in Westerns, whereas the frequency of p53 mutation is slightly lower. The lack of multiple mutations in tumor specimens suggests that these genetic alterations might have independent influences on CRC development and there could be multiple alternative genetic pathways to CRC in our present study cohort.

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.

Comparison of neutral and positive enteral contrast media for MDCT enteroclysis.

OBJECTIVE: To compare neutral and positive enteral contrast media for MDCT enteroclysis (MDCTE) in various small bowel diseases. MATERIALS AND METHODS: 40 patients with suspicion of small bowel diseases were divided randomly into two equal groups. In one group, water was used as neutral enteral contrast and in other group, 2% water soluble iodinated contrast was used as positive enteral contrast. All MDCTE were done on a 16-slice multidetector row CT unit. The findings of MDCTE were compared with the standards of reference. RESULTS: There were 12 cases of abdominal tuberculosis (30%), 5 cases of bowel masses (12%), 4 cases of Crohn's disease (10%), 3 cases of small bowel adhesions (7%), 2 cases of midgut volvulus (5%), 2 cases of segmental enteritis (5%) and 12 of all cases (30%) were normal. There was no statistically significant difference between neutral and positive enteral contrast with regards to bowel distention, contrast reflux and evaluation of duodenum. Abnormal bowel wall enhancement was appreciated only with use of neutral enteral contrast (n=12). Evaluation of ileocaecal junction was possible in all 20 patients (100%) with positive enteral contrast but in only 17 patients (85%) with neutral enteral contrast. Overall sensitivity and specificity of MDCTE with use of neutral contrast medium (100 and 88% respectively) was greater for evaluation of small bowel diseases, when compared to MDCTE using positive enteral contrast medium (92.8 and 83.3% respectively). CONCLUSIONS: Water is a good enteral contrast medium for MDCT enteroclysis examination and allows better evaluation of abnormal bowel wall enhancement. Ileocaecal junction evaluation is better with positive enteral contrast medium.

Port catheter fracture and migration in Internal Jugular Vein.

BACKGROUND: Central venous access devices for chemotherapy are being used extensively in patients with cancer. Spontaneous fracture and migration of the catheter is uncommon. We present the uncommon occurrence of a fracture and spontaneous migration of the fragment into the internal jugular vein as a delayed complication of a central venous access catheter implanted for chemotherapy administration. CASE REPORT: A patient with Ewing's sarcoma of the humerus with metastasis in the lungs underwent placement of a totally implantable venous access device. The port was in place for 1 year. The patient presented with pain in the right side of the neck. A chest X-ray demonstrated complete transection of the catheter and migration of the catheter fragment in the internal jugular vein. Both the migrated catheter fragment and the proximal part of the catheter were retrieved surgically. He had an uneventful recovery. CONCLUSIONS: Catheter fracture remains a potential complication, which must be recognized and treated promptly. Periodic chest imaging is recommended for detection and timely removal of the catheter.

Pancreatic choledochal fistula complicating acute pancreatitis.

BACKGROUND: Biliary tract involvement in acute necrotizing pancreatitis is rare. CASE REPORT: We report a case of a 53-year-old man who had a pancreatic choledochal fistula complicating acute necrotizing pancreatitis. The fistula was suspected at computed tomography and confirmed at surgery. The patient underwent necrosectomy, cholecystectomy and proximal biliary diversion. He is well at 1-year follow-up. CONCLUSIONS: Simultaneous presence of air in the biliary tree and pancreatic collection is highly suggestive of a pancreaticobiliary fistula. Pancreatic necrosectomy and proximal biliary diversion resulted in closure of the fistula.

A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival.

BACKGROUND: Smad4 is the common mediator of the tumor suppressive functions of TGF-beta. Smad6 and Smad7 are the antagonists of the TGF-beta pathway. This study investigates the differential protein expressions of Smad4, Smad6 and Smad7 in tumor as compared to normal tissue of pancreatic ductal adenocarcinoma (PDAC) and compares them with clinicopathological parameters and patient survival. RESULTS: There was a significant difference in protein expressions of Smad4 (p = 0.0001), Smad6 (p = 0.0015) and Smad7 (p = 0.0005) protein in tumor as compared to paired normal samples. Loss of Smad7 expression correlated significantly with tumor size (r = 0.421, p < 0.036) and margin status (r = 0.431; p < .032). Patients with moderate to high Smad4 protein expression had a better survival (median survival = 14.600 ± 2.112 months) than patients with absent or weak Smad4 protein expression (median survival = 7.150 ± 0.662). In addition, advanced disease stage correlated significantly with poor prognosis. CONCLUSION: Loss of Smad4 significantly correlated with poor survival of PDAC patients. In the cases where Smad4 is expressed, Smad6 inhibition is possibly a novel mechanism for Smad4 inactivation. Smad7 has a role in pathobiology of PDAC. Further investigation in the roles of Smad6 and Smad7 would help in the identification of novel therapeutic targets for PDAC.

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.

Adult intussusception in Northern India.

BACKGROUND: Adult intussusception is infrequently encountered in Asians. The diagnosis is often late because of the variable presentation. The optimal treatment is not universally agreed upon. PURPOSE: To determine the causes and management of this uncommon entity in India. METHODS: A retrospective review of patients with postoperative diagnosis of intussusception between March 2003 and March 2008 was conducted in a tertiary care centre in North India. Data relating to diagnosis, treatment and histopathology was analyzed. RESULTS: Twenty-seven patients, aged 15-72 years with 28 intussusceptions were studied. Four patients (14.29%) had acute presentation, 16 (57.14%) subacute and 7 (25%) had chronic symptoms. The most common type of intussusception was enteroenteric. A diagnosis of intussusception on contrast enhanced computed tomogram was made in 84% and a lead point was identified in 89%. A causative factor could be identified in 89% (25 out of 28 intussusceptions) which was malignant in 37% and benign in 48%. The most common underlying malignant lesions were adenocarcinoma (50%), and lymphoma (25%). Among benign lesions, small bowel polyps were the most common (57%). All cases underwent surgical intervention. Bowel resection was performed in 89%. There was no mortality. CONCLUSION: Our series highlights a high frequency of a demonstrable cause of intussusception in a tropical country. Overall our results are similar to those reported from other countries. Resection of the involved bowel is recommended because of high incidence of underlying pathology.

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.

Anticoagulant-induced intramural hematoma of the jejunum.

BACKGROUND: Spontaneous intramural intestinal hematoma in patients on oral anticoagulation therapy is rare. MATERIALS AND METHODS: Case report. RESULTS: We report a spontaneous intramural jejunal hematoma presenting with small bowel obstruction in a patient who was on oral anticoagulation therapy with acitrom following aortic valve replacement. Contrast-enhanced computed tomography of the abdomen showed findings of intramural hematoma. The patient was successfully managed conservatively. CONCLUSION: Abdominal pain and abnormal coagulation profile in patients on oral anticoagulants should alert the clinician to consider intramural hematoma. Early diagnosis is essential, as patients are successfully managed conservatively with good outcome.

Aberrant promoter methylation of p16 in colorectal adenocarcinoma in North Indian patients.

AIM: To investigate p16 gene methylation and its expression in 30 patients with sporadic colorectal adenocarcinoma in a North Indian population. METHODS: Methylation specific polymerase chain reaction was used to detect p16 gene methylation and immunohistochemistry was used to study the p16 expression in 30 sporadic colorectal tumors as well as adjoining and normal tissue specimens. RESULTS: Aberrant promoter methylation of p16 gene was detected in 12 (40%) tumor specimens, whereas no promoter methylation was observed in adjoining and normal tissue. Immunohistochemistry showed expression of p16 protein in 26 (86.6%) colorectal tumors whereas complete loss of expression was seen in 4 (13.3%) and reduced expression was observed in 12 (40%) tumors. In the adjoining mucosa, expression of p16 was in 11 (36.6%) whereas no clear positivity for p16 protein was seen in normal tissue. There was a significant difference in the expression of p16 protein in tumor tissue and adjoining mucosa (P < 0.001). The methylation of the p16 gene had a significant effect on the expression of p16 protein (P = 0.021). There was a significant association of methylation of p16 gene with the tumor size (P = 0.015) and of the loss/reduced expression of p16 protein with the proximal site of the tumor (P = 0.047). Promoter methylation and expression of p16 had no relation with the survival of the patients (P > 0.05). CONCLUSION: Our study demonstrated that promoter hypermethylation of the p16 gene results in loss/reduced expression of p16 protein and this loss/reduced expression may contribute to tumor enlargement.

The role of non-operative strategies in the management of severe acute pancreatitis.

CONTEXT: Non-operative strategies are gaining preference in the management of patients with severe acute pancreatitis. OBJECTIVE: The present study was undertaken to evaluate the efficacy of a non-operative approach, including percutaneous drainage, in the management of severe acute pancreatitis. DESIGN: Prospective study. SETTING: Tertiary care centre in India. PATIENTS: Fifty consecutive patients with severe acute pancreatitis were managed in an intensive care unit. INTERVENTIONS: The patients were initially managed conservatively. Those with 5 cm, or more, of fluid collection having fever, leukocytosis or organ failure underwent percutaneous catheter drainage using a 10 Fr catheter. Those not responding underwent a necrosectomy. Depending on the outcome of their supportive care, the patients were divided into three groups: those responding to intensive care, those needing percutaneous catheter drainage and those requiring surgical intervention. Twelve patients were managed conservatively (Group 1) while 24 underwent percutaneous catheter drainage (Group 2), 9 of whom were not operated (Group 2a) and 15 of whom underwent necrosectomy (Group 2b). Fourteen patients were operated on directly (Group 3). MAIN OUTCOME MEASURES: Hospital stay, intensive care unit stay, and mortality. RESULTS: Among patients requiring surgery, the patients in Group 2b had a shorter intensive care unit stay (22.1±11.1 days) as compared to the patients in Group 3 (25.0±15.6 days) and a longer interval to surgery, 30.7±8.9 days versus 25.4±8.5 days. However, these differences did not reach statistical significance (P=0.705 and P=0.133, respectively). The two groups did not differ in terms of mortality (5/15 versus 3/14; P=0.682). CONCLUSION: The use of percutaneous catheter drainage helped avoid or delay surgery in two-fifths of the patients with severe acute pancreatitis.

Potential role of CXCL10 in the induction of cell injury and mitochondrial dysfunction.

Chemokines have been known to play a critical role in pathogenesis of chronic pancreatitis and acinar cell death. However, the role played by one of the CXC chemokines: CXCL10 in regulation of acinar cell death has remained unexplored. Hence, this study was designed to assess the role of CXCL10 promoting apoptosis in ex vivo cultured acinar cells. Primary human pancreatic acinar cell cultures were established and exposed to varying doses of CXCL10 for different time intervals. Apoptotic induction was evaluated by both qualitative as well as quantitative analyses. Various mediators of apoptosis were also studied by Western blotting, membrane potential (Psim) and ATP depletion in acinar cells. Analysis of apoptosis via DNA ladder and cell death detection - ELISA demonstrated that CXCL10 induced 3.9-fold apoptosis when administrated at an optimal dose of 0.1 mug of recombinant CXCL10 for 8 h. Quantitative analysis using FACS and dual staining by PI-annexin showed increased apoptosis (48.98 and 53.78% respectively). The involvement of upstream apoptotic regulators like pJNK, p38 and Bax was established on the basis of their increased expression of CXCL10. The change of Psim by 50% was observed in the presence of CXCL10 in treated acinar cells along with enhanced expression of Cytochrome C, apaf-1 and caspase 9/3 activation. In addition, ATP depletion was also noticed in CXCL10 stimulated acinar cells. CXCL10 induces cell death in human cultured pancreatic cells leading to apoptosis and DNA fragmentation via CXCR3 signalling. These signalling mechanisms may play an important role in parenchymal cell loss and injury in pancreatitis.

Traumatic Transection of Pancreas at the Neck: Feasibility of Parenchymal Preserving Strategy.

BACKGROUND: To assess the feasibility and safety of a pancreas preserving operative technique in the management of isolated complete pancreatic neck transection following blunt abdominal trauma. METHODS: Two patients with isolated blunt fracture of the pancreatic neck underwent pancreas preserving procedure comprising of oversewing of the proximal pancreas and Roux-en-Y pancreatico jejunostomy to the distal remnant. A feeding jejunostomy tube was placed for postoperative nutritional support in these patients. Both patients received subcutaneous octreotide 300 µg/day. RESULTS: Their ages ranged from 15 years to 20 years, mode of injury was bicycle handle-bar injury (n = 2). Both had pancreatic transection at neck in the line of superior mesenteric vessels. One had ascites. These patients had pancreas parenchyma preserving surgery - internal drainage of the left remnant in a Roux-en-Y jejunal loop. The postoperative course was uneventful in these and both are well on follow-up. CONCLUSIONS: Pancreas preserving strategy - suture of head side of pancreas and an internal drainage of left remnant with a Roux-en-Y jejunal loop is feasible and safe and should be considered in selected cases. Substantial amount of normal pancreatic parenchyma is preserved.

Pancreas preserving total duodenectomy for complex duodenal injury.

CONTEXT: To assess the feasibility and safety of a pancreas-preserving total duodenectomy in the management of severe duodenal injury caused by abdominal trauma. CASE REPORT: Two patients with both extensive injury of the duodenum and diffuse peritonitis underwent pancreas preserving total duodenectomy at our tertiary care centre. These two young male patients (age 20 and 22 years) presented 2 days and 6 hours respectively following blunt abdominal trauma. The duodenum was almost completely separated from the pancreas. Ampulla was seen as a button on the pancreas. Following total duodenectomy, reconstruction was performed by suturing the jejunum to the head of the pancreas anteriorly and posteriorly away from the ampulla (invagination of the pancreas into the jejunum). There were no complications attributable to the procedure. Both patients are well on follow up. CONCLUSION: A Pancreas-preserving total duodenectomy offers a safe alternative to the Whipple procedure in managing complex duodenal injury. This procedure avoids unnecessary resection of the adjacent pancreas and anastomosis to undilated hepatic and pancreatic ducts.