Management of patients at the hepatopancreatobiliary unit of a London teaching hospital during the COVID-19 pandemic.

To mitigate COVID-19-related shortage of treatment capacity, the hepatopancreatobiliary (HPB) unit of the Royal Free Hospital London (RFHL) transferred its practice to independent hospitals in Central London through the North Central London Cancer Alliance. The aim of this study was to critically assess this strategy and evaluate perioperative outcomes. Prospectively collected data were reviewed on all patients who were treated under the RFHL HPB unit in six hospitals between November 2020 and October 2021. A total of 1541 patients were included, as follows: 1246 (81%) at the RFHL, 41 (3%) at the Chase Farm Hospital, 23 (2%) at the Whittington Hospital, 207 (13%) at the Princess Grace Hospital, 12 (1%) at the Wellington Hospital and 12 (1%) at the Lister Hospital, Chelsea. Across all institutions, overall complication rate were 40%, major complication (Clavien-Dindo grade ≥ 3a) rate were 11% and mortality rates were 1.4%, respectively. In COVID-19-positive patients (n = 28), compared with negative patients, complication rate and mortality rates were increased tenfold. Outsourcing HPB patients, including their specialist care, to surrounding institutions was safe and ensured ongoing treatment with comparable outcomes among the institutions during the COVID-19 pandemic. Due to the lack of direct comparison with a non-pandemic cohort, these results can strictly only be applied within a pandemic setting.

Radiological tumor density and lymph node size correlate with survival in resectable adenocarcinoma of the pancreatic head: A retrospective cohort study.

INTRODUCTION: Tumors within the pancreatic head show a variable density and enhancement on computerized tomography (CT). The relationship between the radiological appearance of pancreatic adenocarcinoma on CT and survival remains unclear. The aim of this study was to evaluate the relationship between the tumor density on CT and survival. We also evaluated the correlation between lymph node (LN) size and overall survival in patients undergoing pancreaticoduodenectomy for head of pancreas adenocarcinoma. MATERIALS AND METHODS: Case records of patients undergoing pancreaticoduodenectomy for the adenocarcinoma of pancreas head, between 2005 and 2009, were evaluated. CT was interpreted to document tumor density - Hounsfield unit (HU) and LN size of enlarged LNs. Histology was analyzed to review tumor differentiation and LN status. Survival was correlated with LN size and tumor density (HU). RESULTS: Increasing tumor density was significantly associated with an adverse outcome (P = 0.042, hazard ratio [HR] 1.034, 1.002-1.067 95% confidence interval [95% CI]). Patients with well-differentiated tumors had significantly lower tumor density as compared to moderately differentiated tumors (39.00 ± 26.00 vs. 71.31 ± 21.03 HU, P = 0.005). LN size more than 1 cm irrespective of LN status strongly correlated with the survival and was found to be an important prognostic factor (19.37 ± 2.71 months vs. 27.44 ± 2.74 months; P = 0.025; HR 2.70; 1.09-6.68 95% CI). CONCLUSION: Increasing pancreatic tumor density and the lymph nodal size of more than 1 cm are strong predictors of unfavorable overall survival for resectable adenocarcinoma of the pancreatic head. Further studies are required to identify the value of these proposed prognostic factors.

Redefining the R1 resection for pancreatic ductal adenocarcinoma: tumour lymph nodal burden and lymph node ratio are the only prognostic factors associated with survival.

INTRODUCTION: The presence of positive nodal disease (LND) and the number of lymph nodes involved (LNB) are known to be significant prognostic markers for resected adenocarcinoma of the pancreas. In addition, the ratio of the number of involved nodes to the number of nodes resected known as the lymph node ratio (LNR) is emerging as an important prognostic marker. The role of the resection margin (RM) as presently defined (R1 ≤ 1 mm) is unclear as results differ based on the dataset. The aim of this study was to assess the impact of nodal disease and a redefined RM on outcome. MATERIAL AND METHODS: Retrospective analysis of pancreatic head resections for adenocarcinomas from 2003-2009. The RM was re-analysed based on tumour clearance and categorized into: histopathological evidence of a tumour; ≤ 0.5 mm, ≤ 1 mm, ≤ 1.5 mm, or ≤ 2.0 mm of the actual surgical resection margin. The impact of histopathological variables on cancer-specific survival (CSS) and disease-free survival (DFS) was analysed. RESULTS: LND, LNB and LNR were independent prognostic markers for CSS (P = 0.048, 0.003, 0.016) but, did not influence DFS. A LNR < 0.143 was associated with a higher CSS [38.16 ± 4.69 versus 20.59 ± 2.20 months, P = 0.0042, hazard ratio (HR) 3.74 (95% confidence interval (CI) 1.52-9.23)]. An R1 RM was not associated with CSS or DFS on multivariate analysis, irrespective of the distance. LNB and LNR maintained independent significance irrespective of the size of the RM. CONCLUSION: LNB and LNR are the only prognostic factors for CSS in patients with pancreatic head adenocarcinoma, but do not predict recurrence. Microscopic RMs does not seem to influence the outcome even when redefined. Further prospective studies are indicated to substantiate these findings.

Splanchnic vein thrombosis in severe acute pancreatitis: a 2-year, single-institution experience.

OBJECTIVES: This study aimed to determine current practice in the management and outcome of splanchnic vein thrombosis complicating acute pancreatitis (AP). METHODS: An audit of prospectively collected data for all patients presenting with AP was conducted. Patients with splanchnic vein thrombosis were grouped according to vessel involvement and whether or not systemic anticoagulation was administered. RESULTS: Of 127 consecutive patients admitted with AP, 20 had splanchnic venous thrombosis; in all cases the thrombosis was associated with a severe attack of AP. Involvement of the splenic vein (SV), portal vein (PV) and superior mesenteric vein (SMV) was observed in 14, 10 and three patients, respectively. Involvement of more than one vessel was observed in six patients (SV and PV in four patients; SMV and SV in one patient; all three veins in one patient). Thromboses were colocalized with collections in 19 patients. Only four patients received systemic anticoagulation. Resolution of thrombosis was observed in six patients over a median of 77 days. No significant differences were observed in recanalization rates following anticoagulation (P= 0.076). No complications associated with systemic anticoagulation occurred. One patient developed liver failure associated with progressive PV thrombosis and one patient died. CONCLUSIONS: Splanchnic vein thrombosis is a relatively common observation in severe AP and is associated with pancreatic necrosis and peripancreatic collections. Recanalization is observed in almost a third of patients, irrespective of whether or not they receive systemic anticoagulation.

Successful management of gastrointestinal haemorrhage associated with ischaemic colonic ulceration in acute pancreatitis with video assisted retroperitoneal debridement.

CONTEXT: Colonic involvement is an uncommon but potentially lethal complication of severe acute pancreatitis and has received little attention in the surgical literature. Such complications can range from localized colonic pathology to widespread ischaemic pancolitis. Treatment options have historically been limited to resection of the affected segment. CASE REPORT: We describe the successful role of video assisted retroperitoneal pancreatic debridement in the management of two cases presenting with major gastrointestinal haemorrhage due to localised colonic ulceration on the background of acute necrotising pancreatitis. CONCLUSION: Video assisted retroperitoneal debridement should be considered early in the management of local colonic complications associated with severe acute necrotising pancreatitis.

Pancreatic actinomycosis as a cause of retroperitoneal fibrosis in a patient with chronic pancreatitis. Case report and literature review.

CONTEXT: Chronic alcoholic pancreatitis is a debilitating disease that is often complicated by pseudotumoral changes of the pancreas, retroperitoneal fibrosis, and pancreatic cancer. Actinomycosis is an uncommon intra-abdominal infection and its association with chronic pancreatitis has been rarely reported. CASE REPORT: We present a case of a patient with progressive long standing chronic pancreatitis who develops pseudo-tumoural changes and retroperitoneal fibrosis associated with actinomycosis. CONCLUSION: This is a rare presentation of actinomycosis, posing a diagnostic challenge to the clinician, with important therapeutic implications.

Transsulfuration pathway defects and increased glutathione degradation in severe acute pancreatitis.

Glutathione depletion is a consistent feature of the progression of mild to severe acute pancreatitis. In this study, we examined the temporal relationship between cysteine, homocysteine, and cysteinyl-glycine levels; total reduced erythrocyte glutathione; gamma-glutamyl transpeptidase activity; and disease severity. Initially, cysteine concentration was low, at levels similar to those of healthy controls. However, glutathione was reduced whilst cysteinyl glycine and gamma-glutamyl transpeptidase activity were increased in both mild and severe attacks. As the disease progressed, glutathione and cysteinyl glycine were further increased in mild attacks and cysteine levels correlated with homocysteine (r = 0.8, P < 0.001) and gamma-glutamyl transpeptidase activity (r = 0.75, P < 0.001). The progress of severe attacks was associated with glutathione depletion, reduced gamma-glutamyl transpeptidase activity, and increased cysteinyl glycine that correlated with glutathione depletion (r = 0.99, P = 0.01). These results show that glutathione depletion associated with severe acute pancreatitis occurs despite an adequate cysteine supply and could be attributed to heightened oxidative stress coupled to impaired downstream biosynthesis.

The SPINK1 N34S variant is associated with acute pancreatitis.

OBJECTIVE: Acute pancreatitis (AP) is a disease whose pathogenesis remains largely obscure. Genetic research has focussed attention upon the role of the pancreatic protease/protease inhibitor system. The aim of this study was to investigate the prevalence of genetic variants of the trypsin inhibitor, SPINK1, in acute pancreatitis. METHODS: We genotyped 468 patients with AP and 1117 healthy controls for SPINK1 alterations by single-strand conformation polymorphism analysis and by melting curve analysis using fluorescence resonance energy transfer probes. RESULTS: The c.101A>G (p.N34S) variant was detected in 24/936 alleles of patients and in 18/2234 alleles of healthy controls (odds ratio=3.240; 95% confidence interval: 1.766-5.945; P<0.001). In the UK patients, the mean age of patients with N34S was 11.9 years younger compared with N34S negative patients (P=0.023), but this was not apparent in the German patients. Allele frequencies for the c.163C>T (p.P55S) variant did not differ between patients and controls. CONCLUSION: The SPINK1 N34S variant is associated with acute pancreatitis. This supports the importance of premature protease activation in the pathogenesis of AP and suggests that mutated SPINK1 may predispose certain individuals to develop this disease.

Prognostic utility of postoperative C-reactive protein for posthepatectomy liver failure.

HYPOTHESIS: C-reactive protein (CRP) is an acute-phase protein produced by the liver. We hypothesize that an early dampened CRP response after major liver resection is of prognostic importance in predicting posthepatectomy liver failure (PHLF). DESIGN: Serum CRP levels were determined on postoperative days 1, 3, and 7 in patients undergoing liver resection (stratified into minor [/=5 segments]). Correlations were made with indices of PHLF (hyperbilirubinemia, coagulopathy, ascites, and encephalopathy), multi-organ dysfunction syndrome, sepsis, and death. SETTING: Division of Hepatobiliary and Transplant Surgery, Leeds Teaching Hospitals National Health Service Trust, England. PATIENTS: One hundred thirty-eight individuals who underwent liver resection. MAIN OUTCOME MEASURES: Sepsis, PHLF, and mortality. RESULTS: A total of 138 liver resections (39 minor, 51 standard, and 48 extended) were included. Median serum CRP levels on day 1 were significantly lower after extended liver resection (28 mg/L; range, 5-119 mg/L [to convert to nanomoles per liter, multiply by 9.524]) compared with standard resection (41 mg/L; range, 5-85 mg/L) and minor resection (51 mg/L; range, 8-203 mg/L; chi(2) = 19; P < .001). Similar differences were observed on day 3 (chi(2) = 27; P < .001). Postoperative day 1 CRP levels were significantly lower in patients developing PHLF (hyperbilirubinemia, P = .001; ascites, P < .001; coagulopathy, P = .002; and encephalopathy, P < .001) or multiorgan dysfunction syndrome (P = .009) or who died (P = .01). Day 1 serum CRP levels and extent of resection were independent predictors of PHLF in multivariate analysis. CONCLUSION: The early dampened CRP response after major liver resection may reflect poor hepatic reserve that could have prognostic utility.

Carcinoma of the body of pancreas in evolution: an aggressive disease affecting younger patients?

CONTEXT: Pancreatic body carcinoma has a poor prognosis with advanced disease at presentation. Recent experience at multidisciplinary team (MDT) meetings suggests increasing prevalence. OBJECTIVE: Our aim was to determine if introduction of MDT meetings has affected the natural history of this disease. DESIGN: Retrospective diagnostic and survival data were collected from 1995 to 2006 at two large teaching hospitals, and divided into pre- and post 2003 groups (based on MDT introduction). PARTICIPANTS: Thirty-one patients with pancreatic body carcinoma (median age at diagnosis 72 years; range 43-87 years). RESULTS: Commonest symptoms at presentation were abdominal pain and weight loss. Eight patients (25.8%) were diagnosed pre MDT (median age 71.5 years, range: 60-87 years) and 23 patients (74.2%) were diagnosed post MDT (median age 67 years, range: 43-85 years; P=0.299 vs. pre MDT). There was a significantly (P=0.024) greater prevalence of more advanced tumours post MDT (stage IV: 15/23, 65.2%) than pre MDT (stage IV: 2/8, 25.0%). Neither tumour markers nor liver biochemistry differentiated tumour stage. Best supportive care was offered to 16 patients (51.6%) while 12 patients (38.7%) were suitable for chemotherapy: 2 out of 8 pre MDT (25.0%) and 10 out of 23 (43.5%) post MDT (P=0.433). For stage III tumours, post MDT patients tended to be younger (median 59 years vs. 74.5 years, P=0.042). Survival was not significantly increased after MDT introduction but chemotherapy offered significant survival benefit on multivariate analysis (P=0.042; hazard ratio: 0.39, 95% CI: 0.16-0.97). CONCLUSION: The trend is towards increased prevalence of pancreatic body cancer and more advanced disease at presentation. Chemotherapy was associated with a survival benefit, although the introduction of the MDT has not significantly altered disease management.

Serum macrophage migration inhibitory factor is an early marker of pancreatic necrosis in acute pancreatitis.

OBJECTIVE: To determine if 24-hour blood concentrations of macrophage migration inhibitory factor (MIF), soluble CD14, and CD163 receptors could predict complications associated with acute pancreatitis (AP). SUMMARY BACKGROUND DATA: Soluble receptor proteins derived from the macrophage-monocyte lineage potentiate the inflammatory cytokine response early in AP. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention. METHODS: Patients with AP (amylase >5 times normal) were recruited within 24-hour of onset of pain. Peripheral blood was analyzed for MIF, sCD163, and sCD14 levels and levels correlated with CRP, APACHE-II score, and clinical disease severity (Atlanta criteria); subclassified as multiorgan dysfunction (MOF), pancreatic necrosis (PN >30% on contrast CT), and death. RESULTS: In total, 64 patients with AP (severe, 19: 8 had MOF alone, 7 both PN and MOF, 2 PN without MOF, and 2 single-organ failures with local septic complications) were recruited. Both sCD14 and MIF concentrations were elevated in patients with severe attacks (P = 0.004 and P < 0.001 respectively), and patients who developed MOF (P = 0.004 and P < 0.001). However, only serum MIF was significantly raised in patients who subsequently developed PN (median, 92.5 ng/mL; IQR, 26-181 vs. 31.1 ng/mL; IQR, 5-82, P < 0.001), independently of MOF (P = 0.01). Multivariate analysis demonstrated serum MIF as an independent predictor of PN (P = 0.01; OR = 2.73; 95% CI, 2.72-2.74). CONCLUSION: The prognostic utility of 24-hour plasma MIF concentration in predicting PN has major clinical and healthcare resource implications. Its mechanistic pathway may afford novel therapeutic interventions in clinical disease by using blocking agents to ameliorate the systemic manifestations of AP.

Pancreatico-duodenectomy for complicated groove pancreatitis.

OBJECTIVES: Groove pancreatitis (GP) describes a form of segmental pancreatitis, which affects the pancreatic head at the interface with the duodenum, and is frequently associated with ectopic pancreatic tissue in the duodenal wall. We present a series of symptomatic patients with complicated GP who underwent pancreaticoduodenectomy, and review the diagnostic challenges, imaging modalities, pathological features and clinical outcome of this rare condition. PATIENTS AND METHODS: This was a prospective case base study of clinical, radiological and pathological data collected between the years 2000 and 2005 on patients diagnosed with severe GP--confirmed by histopathological examination following pancreaticoduodenectomy. RESULTS: In total 11 patients were included, presenting with chronic abdominal pain (n=11), gastric outlet obstruction (n=5) and jaundice (n=1). Exocrine dysfunction with associated weight loss (median > 9 kg) was present in 10 patients, and type 2 diabetes in 2 patients. Radiological imaging (CT/MRCP/EUS) provided complementary investigations and correlated well with classic histopathological findings (duodenal wall thickening, mucosal irregularity and Brunner's gland hyperplasia, duodenal wall cysts and pancreatic heterotropia). Following pancreaticoduodenectomy (median follow-up period 52 weeks) all patients experienced significant pain alleviation and weight gain (average 3 kg at 2 months). CONCLUSION: Pancreaticoduodenectomy is associated with significant improvements in weight gain and alleviates the chronic pain associated with severe GP.

Characterization of malignant pancreatic cystic lesions in the background of chronic pancreatitis.

CONTEXT: Cystic lesions of the pancreas in association with chronic pancreatitis are a diagnostic and therapeutic challenge. OBJECTIVE: The aim of the study was to study clinical and radiological features that may differentiate between benign and malignant cystic lesions of the pancreas and examine the indications for surgery in these patients. DESIGN: Retrospective case note study. PATIENTS: Patients with concomitant cystic lesions of the pancreas and chronic pancreatitis stated in radiology reports between 1995 and 2005. RESULTS: Thirty-one patients were identified with alcohol-related chronic pancreatitis with a median age of 53 years (range: 27-82 years). Eight patients (26%) had deranged liver function tests and four (13%) presented a raised CA 19.9. Radiological features of cystic lesions of the pancreas included median cyst size of 3 cm (range: 0.8-10 cm), solitary cyst in 28 patients (90%) and multi-loculated in 3 patients (10%). Dilatation of the main pancreatic duct was seen in seven cases (23%). Overall, 12 patients (39%) underwent surgery, 13 patients (42%) were managed with radiological follow-up, five patients (16%) were managed conservatively and one patient (3%) was treated with chemotherapy for advanced malignancy. Overall, three cases (10%) of this series had malignant cystic lesions of the pancreas. Malignant cystic lesions of the pancreas are associated with deranged liver function tests, elevated CA 19.9, and are larger solitary cysts on imaging. CONCLUSION: The differentiation between benign and malignant cystic lesions of the pancreas remains a diagnostic challenge, although malignant cysts tend to be solitary and larger. The high prevalence of malignancy merits an aggressive approach to follow-up and early surgical intervention.

Endoscopic ultrasound guided transgastric stenting of traumatic pancreatic pseudocyst.

CONTEXT: Although there exists multiple modalities of managing traumatic pancreatic pseudocysts it remains a diagnostic and therapeutic challenge. We report herein a case that was successfully managed by endoscopic ultrasound guided transgastric stent placement. CASE REPORT: A 28-year-old female jockey presented with abdominal pain after being kicked by a horse. Computerised tomography and magnetic resonance imaging revealed pancreatitis which resolved with conservative treatment. She proceeded to develop a pancreatic pseudocyst demonstrated on a magnetic resonance cholangiopancreatogram. This was managed by transgastric placement of two double pigtail stents into the pseudocyst by endoscopic ultrasound guidance. Rapid recovery followed with the patient remaining well on follow up. CONCLUSIONS: EUS guided transgastric stent placement for drainage of pancreatic pseudocysts is recommended particularly if they are in close proximity to the stomach.

Genetic polymorphisms of GSTT1, GSTM1, GSTP1, MnSOD, and catalase in nonhereditary chronic pancreatitis: evidence of xenobiotic stress and impaired antioxidant capacity.

Epidemiological studies have demonstrated a variety of potential environmental factors that may alter susceptibility to chronic pancreatitis (CP) through oxidative/xenobiotic stress; however, a direct causal and mechanistic role has not been established. We aimed (1) to determine the prevalence of functional genetic polymorphisms in the antioxidant enzymes, glutathione S-transferase GSTM-1, GSTP-1, and GSTT-1, manganese superoxide dismutase, and catalase in CP and (2) to reveal evidence of oxidative stress in patients with CP by measuring whole-blood glutathione redox status. In total, 122 patients with CP (75 alcohol-induced [A1CP], 33 idiopathic [ICP], and 13 hereditary) and 245 age- and sex-matched controls were recruited. The prevalence of the functional GSTT-1 genotype (GSTT-1*A) was significantly higher in CP (88.5%) compared to healthy controls (76%; chi2 = 7.26, P = 0.007). Stratification to disease etiology demonstrated that the GSTT-1*A genotype was also significantly more prevalent among patients with ICP (94%; P = 0.02; 95% CI, 0.04-9.16) but not in those with A1CP. In 22 patients with stable CP, the whole-blood glutathione concentration (median [IQR]: 72 micromol/L [21-181 micromol/L]) and the glutathione redox ratio (GSH/GSSG) (median [IQR]: 9 (3-77]) were significantly reduced compared to those in 20 healthy volunteers (median [IQR]: 815 micromol/L [679-1148 micromol/L], P < 0.001, and 96 [52-347], P = 0.005, respectively). We conclude that the GSTT-1 functional genotype is associated with ICP. Evidence of altered glutathione redox status suggests that this disease modification may be a consequence of oxidative stress or the bioactivation of xenobiotics.

Clinical presentation and delayed treatment of cholangitis in older people.

Acute cholangitis is more common in older people, and increasing age is a determinant of morbidity and mortality, as is early biliary decompression by ERCP. This study aims to identify factors that may contribute to delays in the diagnosis and treatment of older people with acute cholangitis. Case notes of 122 patients (45 aged < 75 years, 77 > 75 years) with a final diagnosis of acute cholangitis who underwent ERCP were reviewed for presenting clinical features (pain, jaundice, rigors, fever, falls, incontinence, confusion), liver function tests, blood count, and the interval from admission to diagnosis, ultrasonography, and ERCP. The most common symptom at presentation was abdominal pain (81%), followed by jaundice (55%). These symptoms were no less common in older patients. Charcot's triad was present in only 15.6% of young and 18.8% of older patients. Jaundice was not detected in 16% of significantly hyperbilirubinemic older patients, but only the presence of functional symptoms was associated with significant diagnostic delay (median, 1 day [range: 0-11] vs. 9.5 days [3-25]; P< 0.001) and delay in performing ERCP (median: 4 days [0-24] vs. 16.5 days [2-29], P< 0.001). Overall mortality was 10%, and the incidence of septic shock was similar in both groups. Charcot's classical triad is infrequent in patients suffering from acute cholangitis. Given the greater difficulty assessing jaundice in older people and the confounding effect of falls, incontinence, and confusion, a routine policy of liver function tests, with further investigation of abnormal results in such presentations, may reduce delays in diagnosing and treating acute cholangitis.

Soluble CD14 receptor expression and monocyte heterogeneity but not the C-260T CD14 genotype are associated with severe acute pancreatitis.

OBJECTIVE: Soluble CD14 is derived from a membrane glycoprotein, and it enhances endothelial cytokine responses to lipopolysaccharide. We studied the role of soluble CD14 in the pathogenesis of the systemic inflammatory response associated with acute pancreatitis, to determine whether altered expression was due to a functional C-260T polymorphism in the CD14 promoter gene or altered monocyte heterogeneity. DESIGN: Prospective case-matched study. SETTING: Tertiary pancreatic treatment unit in the United Kingdom. SUBJECTS: Patients with pancreatitis and controls. INTERVENTIONS: DNA from 117 patients with pancreatitis (34 severe) and 263 controls underwent CD14 genotyping using restriction fragment length polymorphism-polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: Peripheral venous blood samples at 24 and 72 hrs after the onset of abdominal pain were analyzed for sCD14 levels. Isolated peripheral blood mononuclear cells were phenotyped for CD14/CD16 receptor expression using immunofluorescence flow cytometry. Disease severity was assessed using Atlanta criteria, Acute Physiology Scores, and C-reactive protein.Soluble CD14 levels were higher in severe (24-hr median, 66.6 ng/mL; 72-hr median, 72.2 ng/mL) compared with mild attacks (24-hr median, 50.7 ng/mL; 72-hr median, 49.7 ng/mL, p < .001), although the latter was similar to controls (median, 51 ng/mL). Furthermore, soluble CD14 levels correlated with Acute Physiology Scores (p < .001) and C-reactive protein (p = .01).Peripheral blood mononuclear cells CD14++ (p = .008), CD14+/16+ (p = .003), and CD16++ (p = .015) receptor densities were all increased in severe attacks at 24 hrs. Early CD14+/16+ receptor density correlated with sCD14 (p < .001), Acute Physiology Scores (p < .001), and C-reactive protein (p = 0.006). The CD14 genotype prevalence in acute pancreatitis was similar to controls and failed to correlate with any variables studied. CONCLUSIONS: Increased soluble CD14 expression is associated with the systemic inflammatory response to acute pancreatitis and an expansion of the proinflammatory CD14+/CD16+ monocyte subset. Its targeted disruption may afford some benefit in preventing the development of systemic complications.

Association of antioxidant enzyme gene polymorphisms and glutathione status with severe acute pancreatitis.

BACKGROUND & AIMS: Genetic variations in antioxidant metabolism may explain varying biological responses to acute pancreatitis (AP). We studied the contribution of oxidative stress to the pathogenesis of severe pancreatitis by examining the prevalence of functional gene polymorphisms of antioxidant enzymes and evidence of heightened oxidative stress. METHODS: DNA from 320 patients with AP (90 severe) and 263 controls was genotyped for glutathione S-transferase (Mu-1 [M-1], theta-1 [T-1], and pi-1 [P-1: Ile-105Val]), manganese superoxide dismutase (Ala-9Val), and catalase (C-260T) polymorphisms. Erythrocyte reduced glutathione (GSH) concentration was determined 24 and 72 hours after the onset of pain in 46 patients (11 severe). Disease severity was assessed using Atlanta clinical criteria, Acute Physiology Scores (APS), and peak serum C-reactive protein levels. RESULTS: The functional GSTT-1*A genotype was more prevalent in severe (96%) compared with mild attacks of AP (78%; odds ratio [OR], 5.9; 95% confidence interval [CI ], 2-17; P < 0.0001) and controls (76%; OR, 6.6; 95% CI, 2.3-18.7; P < 0.0001). Compared with null genotype, GSTT-1*A was associated with higher peak C-reactive protein levels (184 vs. 94 g/dL; P = 0.0005) and APS (24 hours, P = 0.04; 48 hours, P = 0.015). Reduced glutathione (GSH) at 24 hours was lower in mild (median, 382 nmol/g) and severe attacks (median, 407 nmol/g) compared with controls (median, 3685 nmol/g; P < 0.001). Levels increased at 72 hours in mild (P = 0.012) but not severe attacks and inversely correlated with APS (r = -0.49; P = 0.04). CONCLUSIONS: The functional GSTT-1*A genotype was associated with severe attacks of pancreatitis. Heightened oxidative stress characterized by glutathione depletion may be of importance in mediating the progression from mild to severe pancreatitis.