Endogenous Glycosaminoglycans in Various Pathologic Plasma Samples as Measured by a Fluorescent Quenching Method.

Endogenous glycosaminoglycans (GAGs) with a similar structure to heparin are widely distributed in various tissues. A fluorescence probe, namely Heparin Red, can detect polyanionic GAGs in plasma samples. The purpose of this study is to measure endogenous GAGs in various plasma samples obtained from different pathologic states in comparison to healthy controls utilizing this method. Plasma samples were obtained from patient groups including atrial fibrillation (AF), end-stage-renal-disease (ESRD), diabetes mellitus (DM), sepsis, cancer, liver disease (LD), and pulmonary embolism (PE). Normal human plasma (NHP) was used as healthy controls. The Heparin Red kit from Red Probes (Münster, Germany) was used for the quantification of endogenous GAGs in each sample before and after heparinase I degradation. All results were compiled as group means ± SD for comparison. NHP was found to have relatively low levels of endogenous GAGs with a mean concentration of 0.06 µg/mL. The AF, ESRD, DM, and sepsis patient samples had a mean endogenous GAG concentration of 0.55, 0.72, 0.92, and 0.94 µg/mL, respectively. The levels of endogenous GAGs were highest in cancer, LD, and PE patient plasma samples with a mean concentration of 1.95, 2.78, and 2.83 µg/mL, respectively. Heparinase I degradation resulted in a decline in GAG levels in plasma samples. These results clearly show that detectable Heparin Red sensitive endogenous GAGs are present in circulating plasma at varying levels in various patient groups. Additional studies are necessary to understand this complex pathophysiology.

Differential Neutralization of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban by Andexanet Alfa as Measured by Whole Blood Thromboelastographic Analysis.

INTRODUCTION: The available oral anti-Xa agents are routinely used for the management of thrombotic disorders. A molecularly modified recombinant coagulation FXa, also known as Andexanet Alfa (AA), that has been developed as an antidote to neutralize the bleeding effects of oral FXa inhibitors, such as Apixaban and Rivaroxaban. MATERIALS AND METHODS: This study utilized thromboelastography (TEG 5000 Hemostasis System), to investigate the neutralizing effects of AA at different concentrations of oral FXa inhibitors measuring such parameters as R-Time, K-Time, Angle, and Max Amplitude (MA). Apixaban, Betrixaban, Edoxaban, and Rivaroxaban were obtained commercially in powdered form. Each of these drugs was supplemented with freshly drawn whole citrated blood at a concentration of 1 µg/mL. And subsequently mixed with AA at 50 or 100 µg/mL. RESULTS: At a concentration of 1 µg/mL, all FXa inhibitors produced variable anticoagulant effects in the order of Edoxaban > Betrixaban > Rivaroxaban > Apixaban. AA at 100 µg/mL produced a complete neutralization of these inhibitors whereas at 50 µg/mL relatively weaker neutralization as measured by various parameters. CONCLUSION: These results suggest that regardless of the variable anticoagulant effects exhibited by the FXa Inhibitors, AA at FC = 100 µg/mL fully neutralized these agents as measured by the TEG parameters. AA was shown to be more effective in neutralizing Betrixaban and least effective in Apixaban. The neutralization of various FXa inhibitors was dose and donor-dependent warranting dosage adjustment for optimal outcomes.

Post pancreaticoduodenectomy hemorrhage: A retrospective analysis of incidence, risk factors and outcome.

BACKGROUND: The operative mortality after pancreaticoduodenectomy (PD) has declined but morbidity still remains considerable. Post pancreaticoduodenectomy hemorrhage (PPH) occurs in 3-13% of patients following PD. We studied the incidence and outcomes of patients with PPH after PD to determine the associated risk factors and effect on hospital stay. METHODS: We retrospectively analyzed from a prospectively collected data of patients developing PPH following PD between January 2007 and May 2018. ISGPS definition and grading system were used. By using univariate and multivariate analyses, independent predictors of PPH were identified. RESULTS: Of the 340 patients undergoing PD, PPH occurred in 39 patients (11.5%), of whom 5 (12.8%) had Grade A, 22 (56.4%) had Grade B and 12 (30.8%) had Grade C PPH. Six (15.4%) of the 39 patients with PPH died against an overall mortality in the study population of 16 out of 340 patients (4.7%), reflecting higher mortality (P = 0.019) in patients with PPH . The independent risk factors for PPH were a high pre-operative bilirubin (mean 4.7 vs. 7.4 mg/dl, P = 0.01) and INR (mean 1.2 vs. 1.72, P = 0.024), whereas it was closely followed by but, but not significantly associated with pre-operative biliary stent placement (P = 0.09). Pancreatico-jejunostomy (PJ) leak was seen in 20.7% in non-hemorrhage group vs. 41% in hemorrhage group (P = 0.008) and was an independent risk factor for PPH. CONCLUSION: PPH occurred in 11.5% of patients and resulted in a mortality four times greater than those without a PPH. It occurred more frequently in patents with a high pre-operative serum bilirubin, INR, biliary stenting or those with a PJ leak.

Management Strategies for Patients with Hilar Cholangiocarcinomas: Challenges and Solutions.

Advances in imaging, pathology and therapy have resulted in major improvements in the management of cholangiocarcinomas; the mortality has come down and with it there has been an improved 5-year survival. Surgical resection remains the treatment of choice and reports from high volume centres have shown an increase in resectability rates, R0 resection, a decrease in mortality and an improvement in 5-year survival; however, the operative morbidity remains high, pointing towards the complexity of the management of these difficult lesions. Complete excision is also often limited by the locally advanced nature of the disease at the time of diagnosis and a proportion of patients who were earlier deemed resectable on imaging are found to have unresectable disease at the time of operation. Neoadjuvant therapy has had only a limited impact on survival. Liver transplantation is also an option in a few patients following strict criteria for selection. Since the large majority of patients are only diagnosed at the late stages of the disease palliation (endoscopic or surgical) is an important part of treatment. Portal vein embolisation and pre-operative biliary drainage have had a major impact on outcomes. Major liver resection with caudate lobe removal remains the standard operation and procedures like routine vascular resection and liver transplant should only be carried out in experienced centres. Improvements in both neo as well as adjuvant therapy may lead to a standardized protocol in the future, as well as an improvement in survival.

Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa.

Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to neutralize the effects of heparin-related drugs. This study focused on the neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a chemically synthetic pentasaccharide, fondaparinux by andexanet alfa. Whole blood clotting studies were carried out using thromboelastography (TEG) and activated clotting time (ACT). The anticoagulant profile of UFH, enoxaparin, and fondaparinux was studied using the activated partial thromboplastin time (aPTT), thrombin time (TT), and amidolytic anti-Xa, and anti-IIa methods. Thrombin generation inhibition was studied using the calibrated automated thrombogram system. Reversal of each of these agents was studied by supplementing andexanet alfa at 100 µg/mL. In the TEG, andexanet alfa produced almost a complete reversal of the anticoagulant effects of UFH and enoxaparin; however, it augmented the effects of fondaparinux. In the ACT, aPTT, and TT, UFH produced strong anticoagulant effects that were almost completely neutralized by andexanet alfa. Enoxaparin produced milder anticoagulant responses that were partially neutralized, whereas fondaparinux did not produce any sizeable effects. In the anti-Xa and anti-IIa assays, UFH exhibited partial neutralization whereas enoxaparin and fondaparinux did not show any neutralization. All agents produced varying degrees of the inhibition of thrombin generation, which were differentially neutralized by andexanet alfa. These results indicate that andexanet alfa is capable of differentially neutralizing anticoagulant and antiprotease effects of UFH and enoxaparin in an assay-dependent manner. However, andexanet alfa is incapable of neutralizing the anti-Xa effects of fondaparinux.

A Comparison Between the Comprehensive Complication Index and the Clavien-Dindo Grading as a Measure of Postoperative Outcome in Patients Undergoing Gastrointestinal Surgery-A Prospective Study.

BACKGROUND: The Clavien-Dindo (CD) grading system reports the most severe of all the postoperative complications. The comprehensive complication index (CCI) sums up all the complications in postoperative period. We compared the CCI and CD to assess which of the two was a better measure of postoperative outcomes. MATERIALS AND METHODS: Between June 2015 and December 2016, we recorded the complications using CD grading and CCI in 1000 consecutive patients in our gastrointestinal and hepatopancreaticobiliary surgery unit. The outcome variables studied were postoperative length of hospital stay (LOS), postoperative intensive care unit (ICU) stay, and time to normal activity. The results were expressed as strength of correlation and predictive accuracy of the outcome variables. RESULTS: There were 600 males and 400 female patients, with a mean age of 50.3 y. A total of 788 (78.8%) elective and 212(21.2%) emergency procedures were performed. The overall 90-day/in-hospital mortality was 7.9%. Both CD and CCI showed a good correlation with LOS (r = 0.58; P = 0.001, r = 0.57; P = 0.001), ICU stay (r = 0.62; P = 0.002, r = 0.62; P = 0.001), and time to normal activity (r = 0.48; P = 0.01; r = 0.49; P = 0.01). The accuracy of CCI to predict the LOS (area under the curve [AUC] = 0.89; P < 0.001), ICU stay (AUC = 0.85; P < 0.001), and time to normal activity (AUC = 0.76; P < 0.001) was comparable to that of CD (AUC = 0.90; P < 0.001, AUC = 0.87; P < 0.001, AUC = 0.77; P < 0.001). CONCLUSIONS: Both CD and CCI were equally accurate in measuring the postoperative outcomes and in their ability to predict the same in patients undergoing gastrointestinal and hepatopancreaticobiliary surgeries. Considering the relative ease of determination of CD, it remains a more commonly used measure for assessing the severity of complications and outcomes compared to CCI.

Brunner's gland hyperplasia: an unusual duodenal submucosal lesion seen in four patients.

Brunner's gland hyperplasia is an extremely rare benign hamartomatous lesion seen in proximal duodenum. Difficulty in diagnosing the condition pre-operatively puts the surgeon in dilemma for deciding appropriate management. We retrieved details from prospectively maintained retrospective data from January 2014 to April 2018. Four patients were identified of which three were males and one was female. Symptoms ranged from 4 days to 4 years, with abdominal pain, vomiting and malena being predominant. No patients were identified with diagnosis pre-operatively. Diagnosis was made on histopathological examination of the resected specimen and none of them were having malignant features. At a median follow up of 11 months, no patient had recurrence and were symptom free. Brunner's gland hyperplasia is a rare elusive duodenal pathology, symptomatically mimicking alarming duodenal lesions and mostly diagnosed on histopathology of specimen. Patients may harbour the lesion for long periods with little symptoms and upon treatment have good outcomes.

Penoscrotal swelling-an unusual occurrence in a patient with an anastomotic leak following ileostomy closure.

Diverting loop ileostomy is a frequently done procedure accompanying colorectal surgeries. Dreaded complication is anastomotic leak. Early identification of anastomotic leak and apt management is required for better outcomes. Most often leak presents with fever, abdominal pain, rigidity, fever and hemodynamic instability. We report a rare occurrence of penoscrotal oedema in a patient with anastomotic leak and spontaneously subsiding with drainage of leaked contents.

A Review of 2255 Emergency Abdominal Operations Performed over 17 years (1996-2013) in a Gastrointestinal Surgery Unit in India.

There is little information regarding the clinical spectrum and outcome of emergency abdominal operations from specialized units in India. We examined these in our gastrointestinal surgery and liver transplantation unit from a prospective database maintained between July 1996 and April 2013. Out of 9966 operations performed, 2255 (26%) were emergency procedures (reoperations during the same admission, e.g., for necrotizing pancreatitis were excluded). The primary outcome was 30-day postoperative mortality. The mean age of the patients was 47 years (range 1-107) and included the following age groups: 0-18 years (n = 105, 4.7%); 19-64 years (n = 1766, 78.3%), and >65 years (n = 384, 17.0%). The majority were males (1609, 71%), and there were 646 females (29%). The most common indications were small bowel emergencies (598, 26.5%), followed by pancreatic (417, 18.5%) and colonic (281, 12.5%) emergencies. Pancreatic operations were the second commonest in the adult and middle aged group. Colorectal operations were the second commonest in the geriatric age group (>65 years). Emergency operations for other conditions were: postoperative complications following elective operations 171 (7.5%), gastroduodenal bleeding or perforation in 144 (6.3%), and liver surgery in 93 patients (4.1%) patients. In the small bowel emergencies, 223 patients (37.2%) had primary diagnosis of adhesive obstruction, gangrene in 135 patients (22.5%), perforation in 121 patients (20%), and fistula in 56 patients (9.3%). Mesenteric venous thrombosis was found to be the primary cause of small bowel emergencies, either as a primary cause in gangrene or as a secondary cause in perforations and adhesions. The postoperative mortality after emergencies was 12.6% compared to 2% in elective procedures. Mortality was significantly higher in males (14%) than females (9.6%), p < 0.005. Category wise mortality was as follows: pancreatic surgery (n = 86, 20.6%), surgery for postoperative complications (n = 33, 19.3%), duodenal surgery (n = 18, 12.5%), small intestinal surgery (n = 68, 11.4%), and colonic surgery (n = 35, 12.45%). Emergency operations comprise a significant proportion of a GI surgical unit's workload. The mortality is greatest after pancreatic operations followed by those done for postoperative complications. Despite advances in surgical and postoperative care, emergency operations for abdominal emergencies are associated with mortality which is six times higher compared to elective procedures.

Limited distal duodenal resection: Surgical approach and outcomes. A case series.

INTRODUCTION: Tumours involving the duodenum are usually treated with pancreaticoduodenectomy, which may be associated with considerable morbidity. Limited distal duodenal resection, a relatively smaller procedure, can be done in some of these patients. We describe our experience with this operation for such lesions. METHODS: We retrospectively analyzed, from prospectively collected data 10 consecutive patients who underwent limited duodenal and proximal jejunal resection between March 2011 and Nov 2015. RESULTS: There were 8 males and 2 females who had a median age of 47 years. Their common presentations were abdominal pain (50%) and upper gastrointestinal bleeding (40%). Five had malignancy (adenocarcinoma: 2, neuroendocrine tumours: 2, non Hodgkin's lymphoma 1). Three had gastrointestinal stromal tumours (GISTs) and 2 had other benign tumours (lipoma 1, ectopic pancreas 1). The 30-day post-operative morbidity rate was 60% (n = 6) with mostly minor complications (Clavien grade 1 or 2). Median post-operative stay was 9 (range, 6-13) days. All ten patients were alive without recurrence after a median follow up of 26.5 months. CONCLUSION: Limited distal duodenal resection is a feasible surgical alternative to a pancreaticoduodenectomy in carefully selected patients with benign and some malignant tumours of the third and fourth part of the duodenum.

Distal Bowel Re-feeding in Patients with Proximal Jejunostomy.

BACKGROUND: Patients who have a proximal jejunostomy are difficult to manage because of their high stoma output which results in fluid and electrolyte imbalance with repeated hospital admissions and the necessity for expensive parenteral nutrition (PN). There are few reports on the use of re-feeding of the proximal effluents in this situation. METHODS: We here relate our experience with this manoeuvre in 35 patients between Jan 2010 and Feb 2016 who had stomas less than 120 cm away from the duodenojejunal flexure. RESULTS: There were 26 males and 9 females, whose median age was 47 (19-74) years. The most common indications for massive bowel resection were gangrene in 25 (71%) and intestinal perforation in 7 (20%). The median proximal and distal small bowel lengths were 45 (15-120) cm and 90 (0-240) cm respectively. The ileocaecal (IC) valve was preserved in 33 (94%) and there was only colon distally (without the ileocaecal valve) in 2 (6%) patients. Twenty-five (71%) patients required post-operative ICU care. Additional PN was required in 6 (17%) patients during their index admission with the average extra cost of treatment being 20,000 rupees. Their median hospital stay was 13 (6-60) days. Patients were discharged without intravenous (IV) lines. Eight (26%) patients required re-admission for acute renal failure which was managed conservatively. No major problems were associated with re-feeding. None of the patients required PN after discharge from hospital. Thirty (86%) patients had their stomas closed at 65 (14-224) days. Both the patients with colon only as their distal bowel remnant died. Sepsis was the cause of mortality in 4 (11%) during index admission and 3 after their discharge. On follow-up after bowel re-connection, 2 patients died after 1 and 12 months, both due to intracranial bleeding, and the overall survival was 74%. CONCLUSIONS: Patients with proximal jejunostomies can be managed with distal re-feeding. It is a cost-effective and effective substitute for PN, is associated with few problems, and has a fairly good long-term outcome.

Live donor liver transplantation for acute liver failure: A single center experience.

INTRODUCTION: Acute liver failure (ALF) is an indication for emergency liver transplantation (LT). Although centers performing only deceased donor liver transplants (DDLT) have shown improved outcomes in this situation, they still have relatively long waiting lists. An alternative would be living donor liver transplantation (LDLT), which has shown equivalent outcomes in the elective situation but there is limited evidence of its results in ALF. AIM: The purpose of this study was to assess the outcomes in patients with ALF undergoing emergency LDLT in our center in Delhi, India. METHODS: We prospectively collected data on 479 patients who underwent LT in our hospital between January 2009 and December 2015 to evaluate the outcomes of those with ALF. The ALF patients were listed for transplantation after they met the Kings' College criteria and rapid evaluation was done following a protocol consisting of three phases. Patients with grade III/IV encephalopathy were put on mechanical ventilation. Data regarding their postoperative course, morbidity, and mortality were analyzed. RESULTS: Thirty-six (7.5%) out of the 479 patients underwent emergency LT for ALF. Their mean age was 27.5 years (range 4-59 years) and the male to female ratio of 2:3. Preoperative intubation was required in 15 of 25 patients who had encephalopathy. Wilson's disease was the most common cause of ALF in children while in adults, it was acute viral hepatitis. The time interval between listing and transplantation was a mean of 36 ± 12.4 h. The mean graft to recipient weight ratio (GRWR) was 1.06 ± 0.3. The recipients were extubated postoperatively after a mean period of 2.6 days and their mean ICU stay was 6.3 days. Postoperative infection was the most common complication and required upgradation of antifungal and antibiotic treatments. Neurological complications occurred in five patients. Thirty-one of 36 (86.1%) patients survived and progressive cerebral edema and sepsis were the most common causes of mortality. Patients who died had higher model for end-stage liver disease scores, longer cold ischemia time (CIT), and higher grades of encephalopathy (though 80% patients with encephalopathy survived). There was no donor mortality. At long-term follow up of a median of 56 months, 29 (80.5%) of 36 patients were still alive. CONCLUSIONS: In our experience, LDLT is an alternative procedure to DDLT in patients with ALF and is associated with good outcomes even in patients with high grades of encephalopathy.

New scoring system for differentiating xanthogranulomatous cholecystitis from gall bladder carcinoma: a tertiary care centre experience.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, characterized by a focal or diffuse destructive inflammatory process. The importance of XGC is that it mimics gall bladder carcinoma (GBC) both preoperatively and intra-operatively, as it can present with pericholecystic infiltration, hepatic involvement and lymphadenopathy. As a result of a misdiagnosis, which is not infrequent, the patient may undergo an unnecessary radical cholecystectomy rather than only a cholecystectomy, which is associated with a greater morbidity and mortality. The main aim of the study is to formulate a simple preoperative scoring system for diagnosis of XGC which might benefit patients by avoiding radical procedures. METHODS: A retrospective study was done from all the patients who underwent gall bladder and gall bladder-related operations (benign and malignant), during a 5-year time period from 2010 to 2014 in a tertiary care centre were reviewed (n = 462). RESULTS: Initial analyses of all the clinical and imaging parameters were done. Patients with a long history of recurrent abdominal pain with leucocytosis and who on imaging are found to have a diffusely thickened gall bladder wall, cholelithiasis, choledocholithiasis and submucosal hypoattenuated nodules are likely to have XGC while those with anorexia, weight loss, focal thickening of the gall bladder wall on imaging and dense local organ infiltration are more likely to have GBC. The presence of lymph nodes on imaging and the loss of a fat plane interface between the liver and gall bladder are not differentiating factors. A scoring system was made by taking statistically significant features (n = 13) of clinical and imaging parameters in initial assessment to identify the features of XGC. The same scoring system was subsequently applied to the patients who underwent cholecystectomy to study the effectiveness and the results were reviewed. CONCLUSION: High value scores (≥11/13) helps in diagnosing XGC in preoperative setting. Hence, intra-operative frozen section analysis can be avoided in such cases to differentiate XGC and GBC. However in difficult cases with high suspicion of malignancy based on clinical experience, definitive diagnosis still remains a histopathological examination to avoid radical resection in patients who have a benign condition.

Successful Resection in a Case of Hepatocellular Carcinoma Masquerading as Hilar Cholangiocarcinoma: A Case Report.

Obstructive jaundice in the setting of a hilar mass raises strong suspicion of a cholangiocarcinoma, with diagnosis usually made on imaging. Jaundice, when present in patients with hepatocellular carcinoma, is mostly related to underlying liver disease (i.e. cirrhosis) and only rarely to diffuse tumor infiltration of liver parenchyma or hilar invasion. We report here the good outcome of a 67 year-old patient who presented with obstructive jaundice, underwent surgery and was given a diagnosis of hepatocellular carcinoma, which was made only at histopathological examination of resected specimen.

Strategies for Differentiating Gallbladder Carcinoma from Xanthogranulomatous Cholecystitis-a Tertiary Care Centre Experience.

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, characterized by focal or diffuse destructive inflammatory process. The importance of XGC is that it mimics gallbladder carcinoma (GBC) both preoperatively and intra-operatively, since it can present with pericholecystic infiltration, hepatic involvement and lymphadenopathy. As a result of this misdiagnosis which is not infrequent, the patient may need to undergo an unnecessary radical cholecystectomy rather than only a cholecystectomy which is associated with greater morbidity and mortality. Patients who underwent gallbladder and gallbladder-related operations during period of 5 years between 2010 and 2014 were reviewed (n = 462). A comparison of clinical, biochemical, radiological and operative features were made between patients with carcinoma gallbladder (n = 101) and xanthogranulomatous cholecystitis (n = 22). Patient with a long history of recurrent abdominal pain with leucocytosis and who on imaging are found to have a diffusely thickened gallbladder wall (p < 0.01), with cholelithiasis, choledocholithiasis and sub-mucosal hypoattenuated nodules (p < 0.05) are likely to have XGC while those with anorexia, weight loss, focal thickening of the gallbladder wall on imaging (p < 0.01) and dense local organ infiltration are more likely to have GBC. The presence of lymph nodes on imaging and the loss of fat plane interface between the liver and gallbladder are not differentiating factors. Differentiating XGC from GBC in preoperative setting is necessary to avoid radical procedures being done for a benign process. Certain clinical, radiological and intra-operative features aid in differentiating these benign and malignant process. However, the definitive diagnosis still remains a histopathological examination to avoid radical resection in patients who have a benign condition.