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ObjectiveTo investigate the influencing factors for chronic pancreatitis （CP） complicated by pancreatogenic portal hypertension （PPH）， and to establish a predictive model. MethodsA retrospective analysis was performed for the clinical data of 99 patients with CP complicated by PPH who were hospitalized in The First Affiliated Hospital of Kunming Medical University， Chuxiong Yi Autonomous Prefecture People’s Hospital， Wenshan People’s Hospital， and Puer People’s Hospital from January 2017 to December 2022， and these patients were enrolled as PPH group. The incidence density sampling method was used to select 198 CP patients from databases as control group. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Least Absolute Shrinkage and Selection Operator （LASSO） regression model was used to identify the potential predictive factors for CP complicated by PPH， and the predictive factors obtained were included in the multivariate Logistic regression analysis to obtain independent risk factors， which were used to establish a nomogram prediction model. The receiver operating characteristic （ROC） curve， the calibration curve， and the Hosmer-Lemeshow goodness-of-fit test were used to perform internal validation of the model， and the clinical decision curve was used to assess the clinical practicability of the model. ResultsThere were significant differences between the two groups in sex， history of recurrent acute pancreatitis attacks， acute exacerbation of CP， bile duct stones， peripancreatic fluid accumulation， pseudocysts， pulmonary infection， elevated C-reactive protein （CRP）， elevated procalcitonin， fibrinogen （FIB）， neutrophil-lymphocyte ratio （NLR）， gamma-glutamyl transpeptidase， total bilirubin， direct bilirubin， low-density lipoprotein （LDL）， serum amylase， D-dimer， and serum albumin （all P<0.05）. The predictive variables obtained by the LASSO regression analysis included sex， recurrent acute pancreatitis attacks， bile duct stones， peripancreatic fluid accumulation， pulmonary infection， pseudocysts， CRP， NLR， FIB， and LDL. The multivariate Logistic regression analysis showed that sex （odds ratio ［OR］=2.716， P<0.05）， recurrent acute pancreatitis attacks （OR=2.138， P<0.05）， peripancreatic fluid accumulation （OR=2.297， P<0.05）， pseudocysts （OR=2.805， P<0.05）， and FIB （OR=1.313， P<0.05） were independent risk factors for CP complicated by PPH. The above factors were fitted into the model， and the Bootstrap internal validation showed that the nomogram model had an area under the ROC curve of 0.787 （95% confidence interval： 0.730 — 0.844）， and the calibration curve was close to the reference curve. The Hosmer-Lemeshow goodness-of-fit test showed that the model had a good degree of fitting （χ2=7.469， P=0.487）. The clinical decision curve analysis showed that the prediction model had good clinical practicability. ConclusionMale sex， recurrent acute pancreatitis attacks， peripancreatic fluid accumulation， pseudocysts， and FIB are independent risk factors for CP complicated by PPH， and the nomogram model established has good discriminatory ability， calibration， and clinical practicability.
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Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.
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Dyspepsia is a common group of clinical symptoms and can be classified into organic and functional dyspepsia. Patients with chronic pancreatitis （CP） often have the symptoms of dyspepsia such as fatty diarrhea， abdominal distention， and abdominal pain， and most patients have pancreatic exocrine insufficiency （PEI）， which belongs to organic dyspepsia. In clinical practice， the diagnosis of PEI and dyspepsia requires a comprehensive assessment of clinical manifestations， nutritional status， and pancreatic exocrine function， and an individualized treatment regimen should be developed based on such factors. However， some patients with normal exocrine function may have the symptoms of dyspepsia， and the diagnosis and treatment of such patients are still difficulties in clinical practice. This article reviews the advances in the diagnosis and treatment of dyspepsia in CP patients.
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Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.
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Objective:To observe and compare the clinical characteristics between post-chronic pancreatitis diabetes mellitus(PPDM-C)patients and type 2 diabetes mellitus(T2DM).Methods:Data of 142 cases of CP patients confirmed in Shanghai Pudong New Area Gongli Hospital from January 2018 to December 2021 were collected, all the patients were divided into CP group without diabetes mellitus ( n=60) and PPDM-C group with diabetes mellitus ( n=82) based on whether with or without diabetes mellitus. And 82 cases T2DM without CP (T2DM group, n=82) hospitalized simultaneously were collected as control group. The age, sex, body mass index, onset characteristics, laboratory examination indicators at admission (fasting blood glucose, glycosylated hemoglobin, blood creatinine, and alanine transaminase), imaging characteristics of the pancreas (pancreatic atrophy, multiple calcifications of the pancreas, pancreatic duct stones, pancreatic duct dilation, and pancreatic duct obstruction), and treatments and efficacy of diabetes were recorded. Results:Compared with T2DM group, PPDM-C group had lower body mass index (22.2 kg/m 2vs 24.6 kg/m 2), and glycosylated hemoglobin levels (7.34% vs 9.20%) (all P values <0.001), higher alanine transaminase levels (33.00 U/L vs 18.65 U/L, P =0.021). And they had more upper abdominal pain, nausea, vomiting, weight loss and diarrhea symptoms. In addition, they had less use of combination of insulin and hypoglycemic drugs to control blood glucose. And compared with CP group, PPDM-C group had higher body mass index (22.06 kg/m 2vs 21.18 kg/m 2), higher glycosylated hemoglobin levels (7.34% vs 5.70%), higher fasting blood-glucose levels (7.91 mmol/l vs 5.31 mmol/l), higher alanine transaminase levels (33.00 U/L vs 26.50U/L), and their differences were statistically significant (all P values <0.05). And they had higher incidence of pancreatic atrophy, multiple calcifications in the pancreatic duct and pancreatic duct obstruction (all P values <0.05). Conclusions:PPDM-C patients are more likely to experience digestive system symptoms such as abdominal pain than T2DM patients, while their pancreatic malfunction is more likely to occur compared to CP patients. More attentions to PPDM-C associated clinical manifestations, biochemical and imaging changes could identify patients at potential risk for early diagnosis and treatment earlier.
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Objective:To compare the efficacy of endoscopy and surgery in chronic pancreatitis.Methods:CNKI, CBM, Wanfang, PubMed, Cochrane Library, Embase and Web of Science were searched to compared endoscopy and surgery for the clinical efficacy of chronic pancreatitis. Literatures were searched from the establishment of the database to August 14, 2022. Compared pain relief, clinical response to initial treatment, complications, endocrine/exocrine insufficiency, length of hospital stay and mean number of procedures between the two groups. Manager 5.4.1 software was used for data analysis. Odds ratio ( OR) or weighted mean difference ( WMD) was calculated with 95% confidence interval (95% CI). Results:A total of seven studies were included, including three randomized controlled trials and four retrospective studies with 708 patients. There were 513 males and 195 females. Endoscopic interventions were performed in 364 patients and 344 patients underwent surgery. The results of meta-analysis showed that the total pain relief rate ( OR=0.38, 95% CI: 0.24-0.59) and the complete pain relief rate ( OR=0.47, 95% CI: 0.29-0.77), short-term (1-1.5 years) pain relief rate ( OR=0.42, 95% CI: 0.24-0.74), clinical relief rate ( OR=0.23, 95% CI: 0.10-0.55) were better than the endoscopic group, and could significantly reduce the number of reoperation ( WMD=1.64, 95% CI: 0.89-2.40), and the difference was statistically significant (all P<0.05). There were no significant differences in complications, new-onset endocrine insufficiency, new-onset exocrine insufficiency and length of hospital stay between the endoscopy group and the surgical group (all P>0.05). Conclusion:Surgical intervention is superior to endoscopic treatment in controlling pain associated with chronic pancreatitis and in clinical relief after the first treatment, and can effectively reduce the number of reoperations.
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Objective:To evaluate the prevalence and related risk factors of new onset diabetes after chronic pancreatitis by meta-analysis.Methods:Chronic pancreatitis, diabetes, post pancreatitis diabetes, type 2 diabetes, type 3c diabetes, endocrine dysfunction, chronic pancreatitis, diabetes mellitus, post pancreatitis diabetes mellitus, endocrine efficiency, risk factors were used as keywords, and the network database such as the CNKI database, Wanfang, Weipu, Chinese Medical Journal Full Text, PubMed, Embase, Cochrane Library, Web of Science, and so on from the database establishment to January 2023 were searched. The prospective and retrospective cohort studies on new diabetes after chronic pancreatitis published were searched and retrieved, and the papers were screened and the quality were evaluated according to preset inclusion and exclusion criteria; and the important data were extracted. Review Manager 5.4 was used for meta-analysis.Results:22 papers were finally included, including 13 785 patients with chronic pancreatitis, of which 4 233 were patients with new onset diabetes. Meta-analysis showed that the incidence of new diabetes after chronic pancreatitis was 29% ( RD=0.29, 95% CI 26%-32%, P<0.0001), which increased and tended to be stable along with the disease course. Alcohol drinking, smoking, alcoholic chronic pancreatitis, pancreatic calcification, biliary stricture, male, conservative treatment, pancreatic cyst and older onset age were considered as risk factors for new diabetes after chronic pancreatitis, and endoscopic treatment was considered as protective factors. Conclusions:The incidence of new diabetes after the diagnosis of chronic pancreatitis is relatively high. Clinically, we can identify high-risk groups exposed to risk factors, and early intervention can reduce the incidence rate of new diabetes after chronic pancreatitis and improve the prognosis of patients.
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Objective:To evaluate the quality of life (QoL) of Chinese chronic pancreatitis (CP) patients based on the Chinese version of the pancreatitis quality of life Instrument (PANQOLI) and explore its impact factors.Methods:404 patients with CP admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between September 2021 and January 2022 were enrolled. The Chinese version of PANQOLI was used for questionnaire survey on QoL of CP patients. Univariate analysis and multiple linear regression analysis were used to explore the impact factors for QoL of CP patients.Results:The total score of QoL of 404 Chinese CP patients was 28-94(72.47±13.61), which declined by 29.64% compared to the highest total score (103) in the Chinese version of PANQOLI. Score of physical function, role function, emotional function, and self-worth domain was 25.63±4.84, 13.86±2.78, 16.98±6.21 and 16.00±4.65, respectively. Compared to the highest scores (30, 25, 24 and 24), the scores of aforementioned four domains declined by 14.57%, 44.56%, 29.25% and 33.33%, respectively. Univariate analysis showed that sex, age, employment status, smoking, alcohol consumption, and frequency of pancreatitis recurrence were significantly associated with QoL of CP patients. Multiple linear regression analysis indicated that older age (coefficient=-0.127), unemployment status (coefficient=-0.106), smoking (coefficient=-0.176), and high frequency of pancreatitis recurrence (coefficient=-0.123) were independent factors for QoL of CP patients (all P value <0.05). Conclusions:The Chinese version of PANQOLI could be effectively applied to Chinese CP patients. Older age, unemployment, smoking, and pancreatitis attacks were risk factors for QoL of CP patients, indicating that the formulation of personalized intervention measures may help to improve QoL of CP patients.
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Objective:To investigate the value of evaluating pancreatic exocrine insufficiency with fecal pancreatic elastase-1 in the clinical staging of chronic pancreatitis and prognosis evaluation.Methods:A total of 100 patients with pancreatic exocrine insufficiency (patient group) who received treatment in Wenzhou Central Hospital from January 2021 to June 2022 and 100 subjects without pancreatic exocrine insufficiency (control group) were included in this study. Fecal pancreatic elastase-1 content was measured by an enzyme linked immunosorbent assay. The receiver operating characteristic (ROC) curve was plotted to evaluate the value of fecal pancreatic elastase-1 content in the diagnosis of pancreatic exocrine insufficiency. Fecal pancreatic elastase-1 content was compared among patients with different clinical stages of chronic pancreatitis. The factors that affect the prognosis of patients with chronic pancreatitis were analyzed using logistic regression analysis.Results:Pancreatic elastase-1 content in the patient group was (63.28 ± 13.24) μg/g, which was significantly lower than (768.29 ± 102.59) μg/g in the control group ( t = 68.16, P < 0.05). The sensitivity, specificity, Youden index, and 95% CI of using pancreatic elastase-1 content to diagnose pancreatic exocrine insufficiency were 74.7%, 63.5%, 0.724, and 0.740-0.870, respectively. Among the 200 included subjects, 103 had chronic pancreatitis. With the increase in M-ANNHEIM clinical stage, fecal pancreatic elastase-1 content in patients with chronic pancreatitis gradually decreased ( F = 182.66, P < 0.05). Pancreatic elastase-1 content < 200 μg/g was used as a standard to evaluate pancreatic exocrine function. Results showed that 35 patients had stage I chronic pancreatitis, 40 patients had stage II chronic pancreatitis, and 28 patients had stage III chronic pancreatitis. There was no significant difference in the number of patients with different stages of chronic pancreatitis between the two clinical stage classification methods ( χ2 = 12.46, P = 0.002). Six-month follow-up results showed that among 103 patients with chronic pancreatitis, 31 had a poor prognosis (30.1%). Univariate analysis revealed that there were significant differences in age at onset, body mass index, triglyceride level, alcohol consumption, and pancreatic elastase-1 content among patients with different prognoses ( χ2 = 24.07, 4.27, 5.43, 8.38, 4.93, P < 0.05). Multivariate logistic regression analysis showed that age at onset, body mass index, triglyceride level, alcohol consumption, and pancreatic elastase-1 content were the independent influential factors of prognosis in patients with chronic pancreatitis [ OR (95% CI) = 4.207 (2.741-11.609), 1.870 (1.241-2.972), 1.984 (1.437-3.113), 2.769 (1.827-5.125), 1.951 (1.469-3.387), all P < 0.05]. Conclusion:Pancreatic elastase-1 content is of great value in assessing pancreatic exocrine insufficiency, and is closely related to the clinical staging and prognosis of patients with chronic pancreatitis. Therefore, fecal pancreatic elastase-1 content is expected to be a reliable reference for assessing the progress of chronic pancreatitis and predicting its prognosis.
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Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.
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Objective:To investigate the safety and long-term outcomes of fully covered self-expanding metal stent (FCSEMS) placement in patients with benign refractory pancreatic stenosis.Methods:Data of 18 patients with benign refractory pancreatic stenosis who underwent endoscopic treatment with FCSEMS in Nanjing Drum Tower Hospital between March 2013 and July 2020 were collected. The technical success, clinical success, adverse events and long-term outcomes were analyzed.Results:FCSEMS placement was successful in all 18 patients, with technical success rate of 100.0% (18/18). After stenting, the visual analogue scale (VAS) significantly decreased [2.00 (1.75, 3.00) VS 6.00 (5.00, 7.00), Z=-3.572, P<0.001]. The VAS decreased by more than 50% in 15 cases, and the clinical success rate was 83.3% (15/18). Stent-related adverse events included intolerable pain in 3 patients, stented-induced de novo stricture in 2 patients, and distal migration of stent in 2 patients. The stents were successfully removed in all patients after 137.5 (59.0, 417.0) days. There was significant reduction in terms of decreased upstream ductal dilatation after stent removal [9.1 (6.7, 14.1) mm VS 11.0 (7.6, 16.2) mm, Z=10.508, P<0.001]. After stent removal, 10 of the 14 patients maintained the response to pancreatic stenting and 4 recurred during the follow-up of 37-1 246 days. Conclusion:FCSEMS placement appears to be safe and effective in the treatment of benign refractory pancreatic stenosis and can provide persistent improvement in the stricture.
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Objective:To study the characteristics and management of peripancreatic effusion in chronic pancreatitis.Methods:Data of 32 patients with chronic pancreatitis and 141 acute pancreatitis admitted to the First Affiliated Hospital of Guangxi Medical University from January 2018 to December 2019 were collected. According to the Atlanta classification, the peripancreatic effusion was divided into four categories: acute peripancreatic fluid collection (APFC), acute necrotic collection(ANC), pancreatic pseudocyst (PPC) and walled-off necrosis (WON). The general information, clinical manifestations, medical history, laboratory examination indicators and treatment of the four types of patients were recorded and analyzed.Results:Among the 32 patients with chronic pancreatitis complicated with peripancreatic effusion, 27 patients (84.4%) were diagnosed as having PPC, 3 patients (9.4%) WON and 2 (6.2%) APFC. No chronic pancreatitis with ANC was found. The incidence of PPC was higher in patients with chronic pancreatitis than those with acute pancreatitis [84.4% (27/32) VS 31.2% (44/141), P<0.01], and the APFC was lower [6.2% (2/32) VS 24.8% (35/141), P=0.021]. The incidence of ANC was also lower [0.0% (0/32) VS 36.9% (52/141), P<0.01], and there was no significant difference in the incidence of WON [9.4% (3/32) VS 7.1% (10/141), P=0.944]. Compared with patients with peripancreatic effusion of chronic pancreatitis, acute pancreatitis showed a higher proportion of clinical manifestations: fever [19.1% (27/141) VS 3.1% (1/32)], nausea [59.6% (84/141) VS 21.9% (7/32)], vomit [56.7% (80/141) VS 21.9% (7/32)], tenderness [79.4% (112/141) VS 34.4% (11/32)], rebounding pain [42.6% (60/141) VS 0.0% (0/32)], increase of C reactive protein [95.7% (135/141) VS 40.6% (13/32)] ( P< 0.05), and the mean hospital stay was longer (13 days VS 11 days, P=0.048). Imaging examination showed that the proportion of lesions >5 cm in diameter in PPC patients with acute pancreatitis was higher than those with chronic pancreatitis [70.5% (31/44) VS 29.6% (8/27), P=0.001]. WON in chronic pancreatitis patients was limited to the pancreas [3/3 VS 1/10, P =0.014]. In terms of treatment strategies, 25 patients (78.1%) received conservative treatment in 32 chronic pancreatitis. There was no significant difference in treatment strategy between patients with acute pancreatitis and those with chronic pancreatitis. Conclusion:In the peripancreatic effusion of chronic pancreatitis, PPC is the most common. Peripancreatic effusion is mainly treated conservatively. There is no difference in treatment among different types of peripancreatic effusion in chronic pancreatitis. However, compared with chronic pancreatitis, peripancreatic effusion in acute pancreatitis may need more active intervention.
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Objective:To study the effects of naringenin on pancreatic fibrosis in the mouse model of chronic pancreatitis (CP) and its effects on the activation, proliferation and apoptosis of pancreatic stellate cells (PSCs).Methods:Eighteen C57BL/6 mice were randomly divided into control group, CP group and naringenin group, with 6 mice in each group. The CP mouse model was established by intraperitoneal injections of caerulein. Naringenin group was given naringenin (200 mg/kg/day) by gavage once a day from the first day of the fourth week of modeling process to the day before the killing; the control group and CP group were treated by gavage with an equivalent amount of drug solvent containing 0.5% sodium carboxymethyl cellulose (CMC-Na). Mice were killed 5 days after the last caerulein injection, and their pancreatic tissues were collected for hematoxylin-eosin staining and Sirius Red staining, pathological scoring and collagen sedimentation detection. Naringenin with different concentrations (0, 5, 10, 20, 50, 100, 150, 200 μmol/L) were used to intervene HPSC for 24 hours, and CCK-8 method was used to detect the cell activity. TGF-β1 recombinant protein (2 ng/ml) was used to induce PSCs for 1 hour (TGF-β1 stimulation group), and naringenin with low (50 μmol/L), middle (100 μmol/L) and high (150 μmol/L) concentration was used to intervene for 36 hours after TGF-β1 stimulation, respectively. Western Blotting was used to detect the expression of PSC activation related proteins FN and COL1A1, cell proliferation marker p21, anti-apoptotic protein Bcl-xL, pro-apoptotic protein Bax and Bid.Results:The pathological scores of pancreatic tissue [(7.33±1.15), (4.67±1.15)] and the percentage of collagen positive areas [(46±4), (28±2)%] in CP group and naringenin group were higher than those in the control group [0, (4±2)%]. However, these indexes in the naringenin group were lower than those in CP group, and the differences were all statistically significant (all P value <0.05). The relative expression of FN in control group, TGF-β1 stimulation group and low, medium and high naringenin group was 0.02, 0.76, 0.67, 0.34 and 0.07, respectively; the expression of COL1A1 in these groups was 0.51, 1.71, 1.34, 0.84 and 0.11. The expression of FN and COL1A1 in TGF-β1 stimulation group was significantly higher than that in control group, and the expression of FN and COL1A1 in low, medium and high naringenin group was significantly lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). The expression of p21 in the above five groups was 0.87, 1.18, 1.27, 1.22 and 1.00. The expression of p21 in TGF-β1 stimulation group was higher than that in control group, and the expression of p21 in high naringenin group was obviously lower than that in TGF-β1 stimulation group, and the differences were all statistically significant (all P value <0.05). In addition, the expression of Bcl-xL in these groups was 2.09, 2.21, 2.38, 2.50 and 2.12; the expression of Bax was 0.98, 0.88, 0.98, 1.00 and 0.88; the expression of Bid was 1.15, 1.09, 1.14, 1.18 and 1.18. There was no statistically significant difference among these groups (all P value >0.05). Conclusions:Naringenin could significantly alleviate the inflammation, atrophy and fibrosis in the CP mouse model, and inhibit the activation and proliferation of PSCs. However, naringenin had no significant effect on the apoptosis of PSCs, indicating that naringenin may be potentially used to treat pancreatic fibrosis in CP.
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Objective:To summarize the experience of treatment for chronic pancreatitis by analyzing the clinical information of 10 533 patients with chronic pancreatitis admitted to First Affiliated Hospital of Naval Medical University (Changhai Hospital) in the past 28 years.Methods:Clinical data including the age, sex, place of birth, admission time, admission age, admission department, discharge time, hospitalization times and treatment methods of chronic pancreatitis patients admitted to Changhai Hospital from January 1995 to February 2022 were analyzed retrospectively. The changes of chronic pancreatitis patients′ admission, demographic characteristics and treatment mode were summarized.Results:A total of 10 533 patients were analyzed, including 7 443 males (70.66%) and 3 090 females (29.34%), and male to female ratio was 2.41∶1. The average age of admission was (45.7±15.0) years. In terms of geographical distribution, East China was the largest, followed by North China and Northwest China. 10 533 patients were admitted for 19 920 times, and there were 18 156 times (91.14%) in gastroenterology department and 1 452 times (7.29%) in general surgery department. Patients in gastroenterology department were admitted for (1.88±1.45) times and the average length of hospitalization was (10.33±5.63) days. A total of 14 134 endoscopic retrograde cholangiopancreatography [(1.45±1.41) times per patient] were performed among 8 022 patients, and 13 882 pancreatic extracorporeal shock wave lithotripsy [(2.22±0.36) times per patient] were performed among 6 629 patients. In general surgery department, patients were admitted for (1.03±0.16) times and the average length of hospitalization was (14.90±9.00) days. 1 242 patients underwent surgical treatment. The ratio of endoscopic therapy to surgery increased from 0.12∶1 in 1995 to 15.72∶1 in 2021.Conclusions:The study shows that chronic pancreatitis was more common in middle-aged males in China, and the treatment modes of chronic pancreatitis in Changhai Hospital had changed from surgery to endoscopic therapy.
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Objective:To explore the safety and efficacy of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating painful chronic pancreatitis patients with pancreatic stones.Methods:The painful chronic pancreatitis patients receiving P-ESWL alone or P-ESWL combined with ERCP at Shanghai Pudong New Area Gongli Hospital from August 2019 to December 2021 were retrospectively analyzed. The success rate of stone fragmentation following P-ESWL, occurrence of postoperative complications, stone clearance rate of the main pancreatic duct and degree of pain relief in the follow-up were evaluated.Results:Among 113 patients, 7 patients were treated with P-ESWL alone and 106 patients were treated by P-ESWL combined with ERCP. The success rate of stone fragmentation was 98.2%. The occurrence of P-ESWL complications was 6.2%. Complete clearance of the main pancreatic duct stones was achieved in 75.2% of patients. With the mean follow-up of 17.5(3-31) months, complete pain relief was achieved in 84.1% of patients. The pain frequency and VAS score of patients treated with P-ESWL alone and P-ESWL combined with ERCP were obviously lower than those before treatment, and the body weight and body mass index were significantly higher than those before treatment, all with statistically significant differences (all P value <0.01). Conclusions:P-ESWL is safe and effective for the management of painful chronic pancreatitis patients with main pancreatic duct stones.
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Objective:To screen the serum exosomal microRNAs differentially expressed in early pancreatic cancer patients and evaluate the diagnostic value of exosomal hsa-let-7f-5p.Methods:From January 2019 to January 2020, 19 patients with early pancreatic cancer (early pancreatic cancer group) and 16 patients with chronic mass-forming pancreatitis (pancreatitis group) were selected from Affiliated Hospital of Nanjing University of Chinese Medicine who underwent surgery and were confirmed by pathology. Serum samples of the two groups of patients were collected. At the same time, serum samples of 19 healthy volunteers were selected as the normal control group. The exoEasy Maxi Kit was used to isolate serum exosomes. The structural characteristics of exosomes were observed by transmission electron microscopy (TEM). The particle size of exosomes was observd by nanoparticle tracking analysis. CD 63 and CD 81, the specific protein marker on the surface of exosomes, were identified by western blotting. The total RNA of exosomes was extracted by the miRNeasy Serum/Plasma Kit, and a small RNA library was constructed after quality inspection. With reference to the small RNA database, the differentially expressed exosomal microRNAs in early pancreatic cancer group, pancreatitis group and normal control group were filtered out. The miRNA candidates were validated by quantitative polymerase chain reaction (qPCR) and different expressions of them were analyzed. The role of target genes and metabolic pathways of candidate miRNAs in the occurrence and development of early pancreatic cancer were analyzed by gene ontology (GO) and Kyoto Encyclopeda of Genes and Genomes(KEGG) enrichment pathway. Results:The isolated serum exosomes can be seen to have cup-like vesicle with the double lipid layer by TEM. The main peak of the particle size of target exosomes was about 150 nm. The expression of exosome specific protein markers CD 63 and CD 81 was positive. Comparing the expression of miRNAs among early pancreatic cancer group, pancreatitis group and normal control group, the specific tumor marker exosomal hsa-let-7f-5p was screened out in this study, and its expression in early pancreatic cancer group was significantly higher than that in pancreatitis group and normal control group (both P values <0.05). Receiver operating characteristic curve analysis (ROC) showed that the area under curve (AUC) of exosomal hsa-let-7f-5p to distinguish pancreatic cancer from pancreatitis was 0.843 (95% CI 0.640-1.000). The sensitivity and specificity were 100% and 81.82% respectively. The AUC for distinguishing pancreatic cancer from normal controls was 1.000 (95% CI 1.000-1.000), and both sensitivity and specificity were 100%. The diagnostic efficiency of exosomal hsa-let-7f-5p was equivalent to that of CA19-9 ( P>0.05). The GO analysis results showed that target genes of exosomal hsa-let-7f-5p were mainly involved in complement activation lectin pathway in biological processes, and the proteins expressed by target genes were mainly distributed in cilium, and molecules mostly functioned by combining with nitric-oxide synthase. The KEGG pathway enrichment analysis showed that the target genes were closely related to MAPK signaling pathway. Conclusions:Serum exosomal hsa-let-7f-5p has the potential to be a diagnostic biomarker for early pancreatic cancer.
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RESUMEN La diabetes mellitus secundaria a enfermedades pancreáticas está clasificada como diabetes pancreatogénica o tipo 3c (DM3c), y es clínica y metabólicamente distinta de las otras formas de diabetes. Se presenta el caso de una paciente de 35 años de edad con historia de dolor abdominal superior episódico crónico, que consume alcohol desde los 17 años y ha sido diagnosticada de diabetes mellitus tipo 2. Consulta por una infección urinaria complicada y por dolor agudo en el abdomen superior. Durante la hospitalización presentó episodios de hiperglicemia seguidos de hipoglicemias, con insulinoterapia administrada bajo supervisión. Este caso nos motiva para estudiar a los pacientes diabéticos con historia de dolor abdominal mal referido o signos de malabsorción y mejorar la intervención sanitaria para prevenir o tratar la desnutrición, controlar la esteatorrea y minimizar la hiperglucemia inducida por las comidas o estilos de vida.
ABSTRACT Diabetes mellitus secondary to pancreatic diseases is classified as pancreatogenic diabetes or type 3c diabetes mellitus (T3cDM), which is clinically and metabolically different from the other types of diabetes. We present the case of a 35-year-old female patient with a history of chronic episodic upper abdominal pain, alcohol consumption since she was 17, and type 2 diabetes mellitus. She sought medical attention because of a complicated urinary tract infection in addition to acute upper abdominal pain. During hospitalization, she presented episodes of hyperglycemia followed by hypoglycemia with insulin therapy administered under supervision. This case encourages us to delve into the study of diabetic patients with a history of poorly referred abdominal pain or malabsorption signs, thus improving health intervention to prevent or treat malnutrition, control steatorrhea, and reduce hyperglycemia induced by meals or lifestyles.
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Objective:To develop a visualized nomogram with a predictive value to differentiate mass-forming chronic pancreatitis (MFCP) from pancreatic ductal adenocarcinoma (PDAC) patients with chronic pancreatitis (CP) history.Methods:The clinical and radiological data of 5 433 CP patients acoording to the Asia-Pacific Diagnostic Criteria between February 2011 and February 2021 in the First Affiliated Hospital of Naval Medical University were retrospectively analyzed, and 71 PDAC patients with CP history and 67 MFCP who underwent surgery or biopsy and pathologically confirmed were eventually enrolled. The training set included 44 patients with MFCP and 59 patients with PDAC who were diagnosed between February 2011 and April 2018. The validation set consisted of 23 patients with MFCP and 12 patients with PDAC who were diagnosed between May 2018 and February 2021. Univariate and multivariate logistic regression analyses were performed to develop a prediction model for PDAC and MFCP, and the model was visualized as a nomogram. ROC was used to evaluate the predictive efficacy of the nomogram, and the clinical usefulness was judged by decision curve analysis.Results:The univariate analysis showed that a significant association with pancreatic cancer were observed for the duct-to-parenchyma ratio ≥0.34, pancreatic duct cut-off, pancreatic portal hypertension, arterial CT attenuation, portal venous CT attenuation, delayed CT attenuation, and vascular invasion in both the training and validation cohorts, but the duct-penetrating sign in the training cohort only. The multivariable logistic regression analysis showed that statistically significant differences (all P value <0.05) existed in cystic degeneration, a duct-to-parenchyma ratio ≥0.34, the duct-penetrating sign, pancreatic portal hypertension and arterial CT attenuation between the two cohorts. The above parameters were selected for the logistic regression model. The predicted model=3.65-2.59×cystic degeneration+ 1.26×duct-to-parenchyma ratio≥0.34-1.40×duct-penetrating sign+ 1.36×pancreatic portal hypertension-0.05×arterial CT attenuation. Area under the curve, sensitivity, specificity and accuracy of the model-based nomogram were 0.87 (95 CI 0.80-0.94), 89.0%, 75.0% and 83.5% in the training cohort, and 0.94 (95 CI 0.82-0.99), 91.7%, 100% and 97.1% in the validation cohort, respectively. Decision curve analysis showed that when the nomogram differentiated MFCP from PDAC patients with CP history at a rate of 0.05-0.85, the application of the nomogram could benefit the patients. Conclusions:The nomogram based on CT radiological features accurately differentiated MFCP from PDAC patients with CP history and provide reference for guiding the treatment and judging the prognosis.
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Chronic pancreatitis is a progressive chronic inflammatory disease of caused by gene and other environmental factors, and clinical manifestation includes recurrent abdominal pain and dysfunction of exocrine and endocrine. For the chronic pancreatitis therapy, surgical treatment mainly aims at the intractable pain which is unresponsive to medical and endoscopic treatment, as well as complications of chronic pancreatitis. Total pancreatectomy with islet autotransplantation (TPIAT) gradually becomes a major therapeutic option for chronic pancreatitis surgical treatment, because it relieves the abdominal pain, reduces the opioid dependent, improves the quality of life, and increases the opportunity of insulin independent. In the past few years, a range of researches have been focusing on islet isolation, surgical approach, curative effect and postoperative complication, improvement of islet function after operation. The purpose of this article is to summarize the progression of TPIAT related research in the recent years.
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Chronic pancreatitis (CP) is characterized by progressive pancreatic fibrosis, which can lead to irreversible pancreatic endocrine and exocrine dysfunction. Previous reported studies suggested that in patients with CP, there are varying degrees of intestinal bacteria imbalance. In addition, intestinal bacteria have been found to associate with a variety of fibrosis-related diseases. The purpose of this study is to analyze the possible mechanisms of intestinal bacteria in progression of pancreatic fibrosis in CP, by investigating regulation of intestinal barrier, regulation of immunity, and synthesis and release of metabolites, to provide further references in exploring the clinical value of intestinal bacteria in diagnosis and treatment of CP.