Clusterin is upregulated by erastin, a ferroptosis inducer and exerts cytoprotective effects in pancreatic adenocarcinoma cells.

Ferroptosis is a novel form of cell death, which is distinguished from apoptosis and necrosis, and characterized by accumulation of lipid-based reactive oxygen species (ROS) in an iron-dependent manner. Erastin, a small molecule, was widely reported to trigger ferroptosis in various kinds of cancer cells, including pancreatic cancer cells by inducing ROS accumulation. However, how erastin treatment exerts cytotoxicity is not still fully understood. In this study, the effects of erastin in causing pancreatic cancer cell death via inducing ferroptosis and apoptosis are investigated. As expected, erastin treatment caused ROS accumulation, increase in iron concentration and non-apoptotic cell death, which is different from that of induced by apoptosis inducer, staurosporine. Interestingly, erastin treatment caused the upregulation of clusterin, which contributes to the regulation of malignant behaviors of pancreatic cancer, including preventing apoptosis and inducing chemoresistance. Without erastin treatment, overexpressed clusterin significantly promoted cell proliferation, which is consistent with its cytoprotective roles. After erastin treatment, overexpressed clusterin decreased erastin-induced ROS accumulation and cell death. By measuring iron concentration, reduced glutathione (GSH) and glutathione peroxidase 4 (GPX4), it is revealed that clusterin caused resistance to erastin-induced ferroptosis potentially via maintaining the enzymatic activity of GPX4, without disturbing GSH amount. Thus, ferroptosis inducer, erastin, may crosstalk with apoptotic cell death via regulating clusterin, indicating a more complex regulatory network between ferroptosis and apoptosis.

MEX3A knockdown inhibits the development of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDA) is one of the most serious causes of death in the world due to its high mortality and inefficacy treatments. MEX3A was first identified in nematodes and was associated with tumor formation and may promote cell proliferation and tumor metastasis. So far, nothing is known about the relationship between MEX3A and PDA. METHODS: In this study, the expression level of MEX3A in PDA tissues was measured by immunohistochemistry. The qRT-PCR and western blot were used to identify the constructed MEX3A knockdown cell lines, which was further used to construct mouse xenotransplantation models. Cell proliferation, colony formation, cell apoptosis and migration were detected by MTT, colony formation, flow cytometry and Transwell. RESULTS: This study showed that MEX3A expression is significantly upregulated in PDA and associated with tumor grade. Loss-of-function studies showed that downregulation of MEX3A could inhibit cell growth in vitro and in vivo. Moreover, it was demonstrated that knockdown of MEX3A in PDA cells promotes apoptosis by regulating apoptosis-related factors, and inhibits migration through influencing EMT. At the same time, the regulation of PDA progression by MEX3A involves changes in downstream signaling pathways including Akt, p-Akt, PIK3CA, CDK6 and MAPK9. CONCLUSIONS: We proposed that MEX3A is associated with the prognosis and progression of PDA,which can be used as a potential therapeutic target.

World Health Organization grading classification for pancreatic neuroendocrine neoplasms: a comprehensive analysis from a large Chinese institution.

BACKGROUND: Pancreatic neuroendocrine neoplasms (p-NENs) are a group of highly heterogeneous tumors with distinct clinicopathological features and long-term prognosis. In 2017, in order to better stratify patients into prognostic groups and predicting their outcomes, World Health Organization (WHO) officially updated its grading system for p-NENs which distinguished these neoplasms among Grading 1 (G1) pancreatic neuroendocrine tumors (p-NETs), G2 p-NETs, G3 p-NETs and G3 pancreatic neuroendocrine carcinomas (p-NECs). However, this new grading classification for p-NENs has not yet been rigorously validated. METHODS: Data of patients who were surgically treated and histopathologically diagnosed as p-NENs at West China Hospital of Sichuan University from January 2002 to December 2018 were retrospectively collected and analyzed according the novel WHO 2017 grading classification. RESULTS: We eventually enrolled 480 eligible patients with p-NENs in our present study, in which 150 patients with WHO 2017 G1 p-NETs, 158 with G2 p-NETs, 64 with G3 p-NETs and 108 with G3 p-NECs were identified. The estimated 5-year overall survival for patients with G1 p-NETs, G2 p-NETs, G3 p-NETs and G3 p-NECs was 75.8, 58.4, 35.1 and 11.1%, with a median survival time of 85.3mons, 67.4mons, 51.3mons and 26.8mons, respectively. Patients with G2 p-NETs present notably worse survival than those with G1 p-NETs (P = 0.03). Survival of G3 p-NETs were significantly worse than that of G1 p-NETs or G2 p-NETs (P < 0.001, P = 0.023, respectively), as well as that when comparing G3 p-NECs with G1 p-NETs or G2 p-NETs (P < 0.001, P < 0.001, respectively). Patients with G3 p-NECs showed statistically shorter survival than those with G3 p-NETs (P < 0.001). Both WHO 2017 and 2010 grading criteria could be independent predictor for the OS of p-NENs (P = 0.016, P = 0.022; respectively). The 95% confidence intervals of WHO 2017 grading classification (0.983-9.454) was slightly smaller than that of WHO 2010 criteria (0.201-13.374), indicating a relatively more accurate predicting ability for the prognosis of p-NENs. CONCLUSION: The WHO 2017 grading classification for p-NENs could successfully allocate patients into four groups with distinct clinical features and significant survival differences, which might be superior to the WHO 2010 criteria for its better prognostic stratification and more accurate predicting ability.

Short-term outcomes and risk factors for pancreatic fistula after pancreatic enucleation: A single-center experience of 142 patients.

BACKGROUND: Enucleation is increasingly used for benign or low-grade pancreatic neoplasms. Enucleation preserves the pancreatic parenchyma as well as decreases the risk of long-term endocrine and exocrine dysfunction, but may be associated with a higher rate of postoperative pancreatic fistula (POPF). The aim of this study was to assess short-term outcomes, in particular, POPF. METHODS: Data were collected retrospectively from all 142 patients who underwent pancreatic enucleation between 2009 and 2014 in our institution were analyzed. RESULTS: Lesions were most frequently located in the head and uncinate process of the pancreas (60.6%), and the most common types were neuroendocrine neoplasms (52.1%). Overall morbidity was 66%, mainly due to POPF (53.5%), and severe morbidity was only 8.4%, including one death (0.7%). Clinical POPF (Grade B or C) occurred in 22 patients (15.5%). Independent risk factors for clinical POPF were age ≥60 years, an episode of acute pancreatitis, and cystic morphology. Tumor size, coverage, histological differentiation, and prolonged operative time were not associated with the risk of POPF. CONCLUSIONS: Enucleation is a safe and feasible procedure for benign or low-grade pancreatic neoplasms. The rate of clinical POPF is acceptable, and clinical POPF occurs more frequently in elderly patients (≥60 years of age), patients with cystic neoplasms, or patients with an episode of acute pancreatitis.

Undifferentiated (spindle cell) pancreatic carcinoma: a case report with osteochondroid differentiation.

CONTEXT: Undifferentiated (spindle cell) carcinomas of the pancreas are rare anaplastic variants of pancreatic ductal adenocarcinoma with a frequency of 2% of pancreatic exocrine tumors. Their clinicopathological features are limited and obtained by few previously case reports. We report a case of undifferentiated pancreatic carcinoma with a rare focal osteochondroid differentiation. CASE REPORT: A sixty-six-year-old woman was admitted to our hospital for abdominal pain and nonspecific nausea for almost 40 days. Imaging studies revealed a well-defined cystic-solid mass with heterogeneous density involving the tail of the pancreas. We performed an en bloc distal pancreatectomy with splenectomy for radical excision, as well as regional lymphadenectomy. The resected specimen revealed a 4.0×5.0 cm exophytic clear-bordered neoplasm of the tail of the pancreas containing necrotic and calcified areas, without splenic invasion. The lymph node involvement was not detected (0/5) and the surgical margins were negative. Microscopy showed pleomorphism with giant cells, spindle-shaped cells with anaplasia, and osteochondroid differentiation. A diagnosis of undifferentiated (spindle cell) carcinoma of the pancreas with focal osteochondroid differentiation was made. The patient declined chemotherapy and extended lymphadenectomy. She suffered from liver and lymph nodes metastasis 9 months after surgery, and she subsequently died 4 months later due to high tumor burden. CONCLUSIONS: Undifferentiated pancreatic carcinoma with osteochondroid differentiation is rare but associated with extremely poor prognosis. It should be included in the differential diagnosis of pancreatic mass lesions.

Is laparoscopic approach for pancreatic insulinomas safe? Results of a systematic review and meta-analysis.

BACKGROUND: No consensus exists as to whether laparoscopic treatment for pancreatic insulinomas (PIs) is safe and feasible. The aim of this meta-analysis was to assess the feasibility, safety, and potential benefits of laparoscopic approach (LA) for PIs. The abovementioned approach is also compared with open surgery. METHODS: A systematic literature search (MEDLINE, EMBASE, Cochrane Library, Science Citation Index, and Ovid journals) was performed to identify relevant articles. Articles that compare the use of LA and open approach to treat PI published on or before April 30, 2013, were included in the meta-analysis. The evaluated end points were operative outcomes, postoperative recovery, and postoperative complications. RESULTS: Seven observational clinical studies that recruited a total of 452 patients were included. The rates of conversion from LA to open surgery ranged from 0%-41.3%. The meta-analysis revealed that LA for PIs is associated with reduced length of hospital stay (weighted mean difference, -5.64; 95% confidence interval [CI], -7.11 to -4.16; P < 0.00001). No significant difference was observed between LA and open surgery in terms of operation time (weighted mean difference, 2.57; 95% CI, -10.91 to 16.05; P = 0.71), postoperative mortality, overall morbidity (odds ratio [OR], 0.64; 95% CI, 0.35-1.17; P = 0.14], incidence of pancreatic fistula (OR, 0.86; 95% CI, 0.51-1.44; P = 0.56), and recurrence of hyperglycemia (OR, 1.81; 95% CI, 0.41-7.95; P = 0.43). CONCLUSIONS: Laparoscopic treatment for PIs is a safe and feasible approach associated with reduction in length of hospital stay and comparable rates of postoperative complications in relation with open surgery.

Pancreatic injuries in earthquake victims: what have we learnt?

OBJECTIVE: To analyze the clinical characteristic and management of patients with pancreatic injuries from the Wen-Chuan and Lu-Shan earthquakes. METHODS: We retrospectively reviewed 39,784 patients from the Wen-Chuan earthquake and 1489 from the Lu-Shan earthquake. The demographics, clinical data, treatment strategies, and outcomes of patients with pancreatic injuries were recorded and compared between survivors of the two earthquakes. RESULTS: Pancreatic injury occurred only in a small proportion (0.2%) in patients with trauma on admission, and most (61%) patients had Grades I-II pancreatic injuries. Blunt trauma was the leading cause of pancreatic trauma. Most patients (95%) suffered multiple injuries, of which chest injuries (61%) were the most common. Elevated serum amylase levels were observed in 50 (86%) of 58 patients, and computed tomography (CT) identified pancreatic injuries in 32 (80%) of 40 patients. A significantly higher rate (p = 0.043) of pancreatic complication was present in patients with Grade III and IV injuries (38%) than in those with Grade I and II injuries (18%). Forty patients were initially treated by conservative management with 6 (15%) requiring delayed operations. Four (67%) pancreatic complications and 2 (33%) deaths occurred in patients with delayed operations. CONCLUSIONS: Repeated serum amylase analysis, CT, and laparoscopic exploration were reliable diagnostic modalities to diagnose pancreatic injury. Conservative management was safe in patients with Grade I and II injuries. Delayed operation, especially for Grade III patients, resulted in increased morbidity and mortality.

Does modified Braun enteroenterostomy improve alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy?

BACKGROUND: The safety of pancreaticoduodenectomy has improved significantly. However, alkaline reflux gastritis and marginal ulcer are two substantial problems after pancreaticoduodenectomy. AIMS: To identify whether Child reconstruction with a modified Braun enteroenterostomy decreases the incidence of alkaline reflux gastritis and marginal ulcer after pancreaticoduodenectomy better than Roux-en-Y reconstruction. METHODS: Data on 57 consecutive patients who underwent standard pancreaticoduodenectomy between January 1, 2008 and January 31, 2012 were collected prospectively. Data on early and late complications of the Child reconstruction with a modified Braun enteroenterostomy and Roux-en-Y were gathered. The risk factors of alkaline reflux gastritis and marginal ulcer were also investigated by using univariate and multivariate analyses. RESULTS: Twenty-five patients received Roux-en-Y and 32 underwent Child reconstruction with a modified Braun enteroenterostomy. Early complications after the two reconstruction methods were insignificant. Significant differences in terms of later postoperative morbidity (P = 0.01) and change in body mass index (P = 0.03) were found 12 months after pancreaticoduodenectomy. No significant difference for alkaline reflux gastritis was observed between the two methods (14.8 vs. 28.6 %, P = 0.24). Marginal ulcer occurred significantly lower in patients with the modified reconstruction than in those with Roux-en-Y reconstruction (11.1 vs. 47.6 %, P = 0.01). Peptic ulcer history, diabetes mellitus, and reconstruction type had a significant effect on marginal ulcer formation. CONCLUSIONS: Child reconstruction with a modified Braun enteroenterostomy offers an advantage with respect to marginal ulcer after standard pancreaticoduodenectomy, potentially decreasing the incidence of alkaline reflux gastritis as effectively as Roux-en-Y reconstruction.

Standard versus extended pancreaticoduodenectomy in treating adenocarcinoma of the head of the pancreas.

OBJECTIVES: To compare the postoperative complications and survival of standard pancreatoduodenectomy (SPD) and extended pancreatoduodenectomy (EPD) in patients with resectable adenocarcinoma of the head of the pancreas. METHODS: Between January 1994 and December 2011, 165 patients with biopsy-proven adenocarcinoma of the pancreatic head were treated in West China Hospital, among whom 93 underwent SPD and 72 had EPD. Complications and survival after the surgery were analyzed retrospectively. RESULTS: The median operation time of the EPD group was longer compared with the SPD group (375 minutes vs.310 minutes, P<0.01), the volume of blood transfusion was larger (700 mL vs.400 mL, P<0.05), while the median hospital stay (13.5 days vs.12 days, P=0.79) and the total complication rates were comparable (34.7% vs.32.4%, P=0.93). The total recurrence rates of the SPD and EPD groups were not significantly different (52.7% vs. 43.1%, P=0.83). No significant differences were found between the SPD and EPD groups in 1-year (81.7% vs. 86.1%), 3-year (38.7% vs. 43.1%), 5-year (16.7% vs. 19.4%), and median survivals (19.8 months vs. 23.2 months, P= 0.52). CONCLUSION: The postoperative complications and survival donot differ significantly between SPD and EPD.

Prognostic role and predictors of lymph node involvement in pancreatic neuroendocrine tumors.

PURPOSE: To define the prognostic role of lymph node involvement (LNI) in patients with pancreatic neuroendocrine tumors (PNETs) and identify predictors of LNI using a comprehensive multifactor analysis focusing on preoperative radiological features. METHODS: This study included 236 patients with preoperative computed tomography who underwent radical surgical resection of PNETs at our hospital between 2009 and 2019. Univariate and multivariable logistic regression analyses were performed to investigate the risk factors associated with LNI and tumor recurrence. The disease-free survival (DFS) rates with and without LNI were compared. RESULTS: Forty-four of the 236 patients (18.6%) had LNI. Biliopancreatic duct dilatation (odds ratio [OR], 2.295; 95% confidence interval [CI], 1.046-5.035; p = 0.038), tumor margin (OR, 2.189; 95% CI, 1.034-4.632; p = 0.041), and WHO grade (G2: OR, 2.923; 95% CI, 1.005-8.507; p = 0.049; G3: OR, 12.067; 95% CI, 3.057-47.629; p < 0.001) were independent risk factors of LNI in PNETs. Multivariable analysis showed that LNI (OR, 2.728; 95% CI, 1.070-6.954; p = 0.036), G3 (OR, 4.894; 95% CI, 1.047-22.866; p = 0.044), and biliopancreatic duct dilatation (OR, 2.895; 95% CI, 1.124-7.458; p = 0.028) were associated with PNET recurrence in patients after surgery. Patients with LNI had a significantly worse DFS than those without LNI (3-year DFS: 85.9 vs. 96.7%; p < 0.001; 5-year DFS: 65.1 vs. 93.9%; p < 0.001). CONCLUSION: LNI was associated with decreased DFS. Biliopancreatic duct dilatation, irregular tumor margins, and grades G2 and G3 were independent risk factors for LNI.

Clinicopathological features and long-term prognosis of purely cystic pancreatic neuroendocrine tumors: A single-center experience.

BACKGROUND: Pancreatic neuroendocrine tumors (pNETs) are heterogenous neoplasms, of which the prognosis varies widely. Purely cystic pancreatic neuroendocrine tumors (C-pNETs) are a small subset of pNETs in which data are extremely rare. This study aimed to compare clinicopathological and long-term survival differences between C-pNETs and solid pNETs (S-pNETs). METHODS: A retrospective review of 242 patients with pNETs underwent resection in our institution from 2009 to 2019 was conducted. Demography characteristics, clinicopathological features and long-term outcomes of them were analyzed. RESULTS: Sixteen out of 242 patients (6.6%) were identified as C-pNETs. Compared with S-pNETs, C-pNETs were more frequently non-functional (75% vs 45%, P = 0.02), and the median tumor diameter of C-pNETs was smaller (36 mm vs. 47 mm, P = 0.001). And the accuracy of preoperative diagnosis of C-pNETs was significantly lower (31% vs 78%, P = 0.001). Of note, the majority of C-pNETs were well-differentiated with G1 (81% vs 35%, P = 0.001). And there were no G3 (0 vs 7%, P = 0.001) in C-pNETs. No T4 stage or R1/R2 surgical margin detected in C-pNETs. And only one C-pNETs (6%) had regional lymph node metastasis (N) or synchronous distant metastasis (M). Additionally, only one patient with C-pNETs (6%) suffered tumor recurrence, compared with 24 (13%) for S-pNETs. And survival analysis showed the patients with C-pNETs seemed to be with better disease-free survival (P = 0.26). CONCLUSION: C-pNETs are rare subtype with possibly less aggressive behavior comparing with their solid counterparts. Recurrence and tumor-related death still occurs in patients with resected C-pNETs, although they tend to be with more favorable prognosis.

The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.

OBJECTIVES: Both cachexia and sarcopenia have been considered adverse predictors for prognosis in patients with pancreatic cancer; although sarcopenia and cachexia share some similarities, they are still defined as distinct nutritional conditions. We aimed to explore the differential impacts of sarcopenia and cachexia on prognosis for pancreatic ductal adenocarcinoma (PDAC) patients following radical excision. METHODS: From January 2015 to May 2022, 614 patients undergoing surgery for PDAC were retrospectively included. Sarcopenia was defined as the L3 total skeletal muscle index below 52.4 cm2 /m2 (men) and 38.5 cm2 /m2 (women). Cachexia was classified according to the following criteria: involuntary weight loss >5% over the past 6 months, or weight loss >2% and BMI <20 kg/m2 , or weight loss >2% and sarcopenia. RESULTS: Of the 614 patients included in the analysis, 62% and 48% were diagnosed with sarcopenia and cachexia, respectively. Kaplan-Meier analysis showed that sarcopenia and/or cachexia were significantly associated with worse overall survival (OS) rather than worse recurrence-free survival (RFS). Moreover, Cox regression analysis revealed that cachexia rather than sarcopenia was an adverse factor for OS in all PDAC patients. For poorly differentiated PDAC, both cachexia and sarcopenia were significantly associated with shorter OS. However, for moderately/well-differentiated PADC, cachexia was an independent factor for adverse OS, but not sarcopenia. CONCLUSIONS: Sarcopenia and cachexia have different effects on OS for PDAC patients undergoing radical excision. This difference may provide some important information for preoperative management.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

BACKGROUND: Islet amyloid deposition and reduced ß-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. AIM: To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. METHODS: We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional ß-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of ß-cell area, α-cell area and amyloid deposits. RESULTS: Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). CONCLUSION: In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

Central pancreatectomy for benign or borderline lesions of the pancreatic neck: a single centre experience and literature review.

BACKGROUND/AIMS: To investigate the effectiveness and safety of central pancreatectomy. METHODOLOGY: We retrospectively studied 44 cases that underwent central pancreatectomy (CP), 55 patients who underwent distal pancreatectomy (DP), and 62 patients who underwent pancreatoduodenectomy (PD) for their benign or borderline pancreatic lesions; as well as the different management styles for pancreatic stumps in CP. RESULTS: The duration of surgery and length of hospital stay were shorter in the CP group than that of PD group, and blood loss was also less in CP group. There were no differences between the CP and DP groups in duration of surgery, length of hospital stay, and blood loss. The incidence of common surgical complications was higher in the PD group. There were more pancreatic fistulas (grade B/C) in CP and PD groups compared to that of the DP group. New onset or worsening of diabetes occurred only in the CP and PD groups at 4.8% and 10.9%, respectively. A pancreaticogastrostomy for distal pancreatic stumps reduced the incidence of pancreatic fistula (p=0.038). Duct-to-mucosa anastomosis had less pancreatic fistula than invagination anastomosis (p=0.017). There was no difference in incidence of pancreatic fistula between pancreaticojejunostomy and oversewing of proximal pancreatic stumps (p=0.601). CONCLUSIONS: CP is an available and safe operation for benign or borderline lesions located in the pancreatic neck. A pancreaticogastrostomy for distal pancreatic stumps or duct-to-mucosa anastomosis may reduce the risk of pancreatic fistula.

Serum matrix metalloproteinase-9 is an early marker of pancreatic necrosis in patients with severe acute pancreatitis.

BACKGROUND/AIMS: To study the ability of matrix metalloproteinase-9 (MMP-9) to predict pancreatic necrosis (PN) in patients with severe acute pancreatitis (SAP). METHODOLOGY: From July 1, 2010 to December 31, 2010 patients diagnosed with SAP were included (n=35). Serum MMP-9, CRP and IL-6 were analyzed on days 1, 3, 5 and 7 of hospitalization to determine if they could predict the development of pancreatic necrosis. RESULTS: Of the 35 patients included, 12 (34.3%) had evidence of PN. Admission MMP-9 concentrations were significantly higher in patients with PN compared to subjects without PN (13.1±4.0 vs. 7.5±3.8, p<0.05). Receiver operating characteristic curves for PN revealed an area under the curve of 0.832 for admission MMP-9 (95% confidence interval 0.696-0.967, p=0.001). Elevated concentrations of MMP-9 on admission for pancreatic necrosis =9.35mg/L yielded a positive predictive value of 90.9% with a sensitivity of 91.7% and a specificity of 69.6%. Binary logistic regression indicated that MMP-9 was significantly associated with pancreatic necrosis (Odds ratios 25.1, 95% confidence interval 2.7-234.2; p=0.005). CONCLUSIONS: An elevation in serum MMP-9 within the first 24 hours of disease is strongly associated with the development of pancreatic necrosis. This finding may have important clinical implications and requires further investigation.

Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats.

BACKGROUND: Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model. METHODS: Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro. RESULTS: Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10(-3)-10(-1) mg/100 µL), and interferon gamma (10(-2)-10(-1) µg/100 µL) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10(-1) µg/100 µL, P<0.05, 10(-2)-10(-3) µg/100 µL, P>0.05) and a time-dependent manner (P<0.05). CONCLUSIONS: Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.

Prospects and applications of enucleation in solid pseudopapillary neoplasms of the pancreas.

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade, malignant neoplasms that are mostly seen in young women in the second and third decades of life and are quite uncommon in children. Standard resection for benign and borderline neoplasms of the pancreas is associated with a substantial risk of postoperative morbidity and long-term functional impairment, whereas enucleation leads to less morbidity and preserves healthy parenchyma as well as exocrine and endocrine function. Enucleation of SPNs has been increasingly reported to be feasible and safe for preserving the normal physiological function of the pancreas, especially in teenagers and children. This review summarizes findings published in recent years on the enucleation of SPNs as well as potential future developments and directions. Enucleation has undoubtedly come to stay as an alternative surgical procedure for SPNs. However, many questions remain unresolved, and future directions toward the best surgical indication, the prevention and intervention of complications, especially pancreatic fistula, intraoperative resection margin safety assessment, and long-term oncology prognosis remain to be evaluated and should be explored in future clinical trials.