Jin-Huan Lin

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2011 Patients

AbstractDiabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%–50.0%) and 90.0% (95% CI, 75.4%–97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08–2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43–2.79), steatorrhea (HR, 1.46; 95% CI, 1.01–2.11), biliary stricture (HR, 2.25; 95% CI, 1.43–3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80–6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy .

Risk Factors for Steatorrhea in Chronic Pancreatitis: A Cohort of 2,153 Patients.

This study aimed to investigate the occurrence of and determine the risk factors for steatorrhea in chronic pancreatitis (CP). It was based on analysis of both retrospectively and prospectively acquired database for CP patients admitted to our center from January 2000 to December 2013. Demographic data, course of disease, medical history, and follow-up evaluations of patients were documented in detail. Cumulative rate of steatorrhea was calculated by using the Kaplan–Meier method. For risk factor analysis, multivariate analysis by Cox proportional hazards regression model was performed. A total of 2,153 CP patients were included with a mean follow-up duration of 9.3 years. Approximately 14% (291/2,153) of CP patients presented with steatorrhea at diagnosis of CP. Cumulative rates of steatorrhea at 1, 5, 10, and 20 years after diagnosis of CP were 4.27% (95% CI: 3.42%–5.34%), 12.53% (95% CI: 10.74%–14.59%), 20.44% (95% CI: 17.37%–23.98%) and 30.82% (95% CI: 20.20%–45.21%), respectively. Male gender (HR = 1.771, p = 0.004), diabetes (HR = 1.923, p < 0.001), alcohol abuse (HR = 1.503, p = 0.025) and pancreaticoduodenectomy (HR = 2.901, p < 0.001) were independent risk factors for steatorrhea while CP in adolescents (HR = 0.433, p = 0.009) was a protective factor. In conclusion, male gender, adult, diabetes, alcohol abuse and pancreaticoduodenectomy lead to increased risk of steatorrhea in CP patients.

Incidence of and risk factors for pancreatic cancer in chronic pancreatitis: A cohort of 1656 patients

BACKGROUND Risk of pancreatic cancer may increase in chronic pancreatitis patients. AIMS This study aimed to identify the incidence of and risk factors for pancreatic cancer in chronic pancreatitis patients. METHODS Chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic cancer and survival rates were calculated. The standardized incidence ratio was calculated based on the pancreatic cancer incidence in general population of China. Risk factors for pancreatic cancer were identified. RESULTS In a total of 1656 patients, the median follow-up duration was 8.0 years. Pancreatic cancer was detected in 21 patients (1.3%). The expected number of cases of pancreatic cancer was 1.039, yielding a standardized incidence ratio of 20.22. The standardized incidence ratios for patients with a >60 pack-year smoking history were much higher (145.82). Two risk factors for pancreatic cancer were identified: age at the onset of chronic pancreatitis (hazard ratio, 1.05) and a >60 pack-year smoking history (hazard ratio, 11.83). CONCLUSION The risk of pancreatic cancer is markedly increased in chronic pancreatitis patients compared with the general population, especially in patients with an older age at onset and a >60 pack-year smoking history. The high-risk populations were suggested to be followed up closely.

Novel blood-based microRNA biomarker panel for early diagnosis of chronic pancreatitis

Chronic pancreatitis (CP) is an inflammatory disease characterized by progressive fibrosis of pancreas. Early diagnosis will improve the prognosis of patients. This study aimed to obtain serum miRNA biomarkers for early diagnosis of CP. In the current study, we analyzed the differentially expressed miRNAs (DEmiRs) of CP patients from Gene Expression Omnibus (GEO), and the DEmiRs in plasma of early CP patients (n = 10) from clinic by miRNA microarrays. Expression levels of DEmiRs were further tested in clinical samples including early CP patients (n = 20), late CP patients (n = 20) and healthy controls (n = 18). The primary endpoints were area under curve (AUC) and expression levels of DEmiRs. Four DEmiRs (hsa-miR-320a-d) were obtained from GEO CP, meanwhile two (hsa-miR-221 and hsa-miR-130a) were identified as distinct biomarkers of early CP by miRNA microarrays. When applied on clinical serum samples, hsa-miR-320a-d were accurate in predicting late CP, while hsa-miR-221 and hsa-miR-130a were accurate in predicting early CP with AUC of 100.0% and 87.5%. Our study indicates that miRNA expression profile is different in early and late CP. Hsa-miR-221 and hsa-miR-130a are biomarkers of early CP, and the panel of the above 6 serum miRNAs has the potential to be applied clinically for early diagnosis of CP.

Risk Factors and Nomogram for Pancreatic Pseudocysts in Chronic Pancreatitis: A Cohort of 1,998 Patients

Pancreatic pseudocyst is a common complication of chronic pancreatitis. The identification of risk factors and development of a nomogram for pancreatic pseudocysts in chronic pancreatitis patients may contribute to the early diagnosis and intervention of pancreatic pseudocysts.

Extracorporeal shock wave lithotripsy is safe and effective for pediatric patients with chronic pancreatitis

Background and aims Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is recommended as the first-line treatment for pancreatic stones. However, how well P-ESWL performs in pediatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for pediatric patients with chronic pancreatitis. Methods This prospective observational study was conducted in patients with painful chronic pancreatitis who underwent P-ESWL. Patients aged under 18 years were included in the pediatric group; patients aged over 18 years who underwent P-ESWL in the same period were assigned to the control group. For investigation of long-term follow-up, the pediatric group were matched with patients from the control group in a 1:1 ratio. The primary outcomes were P-ESWL complications and pain relief. The secondary outcomes included: stone clearance, physical and mental health, quality of life score, and growth and developmental state. Results From March 2011 to March 2015, P-ESWL was performed in 1135 patients (72 in the pediatric group, 1063 in the control group). No significant differences were observed in the occurrence of P-ESWL complications between the two groups (11.1 % vs. 12.8 %; P = 0.68). Among the 67 pediatric patients (93.1 %) who underwent follow-up for 3.0 years (range 1.3 - 5.2), complete pain relief was achieved in 52 patients (52 /67; 77.6 %); this value was not significantly different from that of the matched controls (55 /69; 79.7 %; P = 0.94). Conclusions P-ESWL is safe and effective for pediatric patients with chronic pancreatitis. It can promote significant pain relief and stone clearance, and can benefit growth and development.

Diagnosis of Chronic Pancreatitis

It is difficult to some extent to make the definitive diagnosis of chronic pancreatitis, especially if the disease is not recognized by the physicians treating the patients. Basing on the presence of several different diagnostic characters of the CP, the Zurich workshop on alcoholic chronic pancreatitis proposed a classification in which CP was divided into ‘probable’ and ‘definite’ (Ammann 1997). There is a similar grading recommended by the Japan Pancreas Society (Homma et al. 1997). In 2007, Schneider and his colleagues established a new MANNHEIM classification system referring to the understandings of the Zurich workshop, but they decided to include smaller amounts of alcohol intake as risk factors for the development of CP than before, as well as a subgroup of ‘borderline’ CP into the classification system. The M-ANNHEIM diagnostic criteriaof CP are listed in Table 7.1 (Schneider et al. 2007).

The different course of alcoholic and idiopathic chronic pancreatitis: A long-term study of 2,037 patients

Background Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis (ICP). Methods CP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated. Results A total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients. Conclusion The long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.

Identifying miRNA-mRNA regulation network of chronic pancreatitis based on the significant functional expression

Background: The aim of this study was to explore the underlying molecular mechanism and potential molecular biomarkers of chronic pancreatitis (CP) and construct a miRNA-mRNA regulation network. Methods: To explore the involvement of miRNAs in CP, we downloaded the miRNA and mRNA expression profiles of CP patients and healthy controls and identified the differentially expressed miRNAs and genes. Functional analysis was conducted and significant pathways were utilized. Finally, the miRNA-mRNA regulation network of CP was constructed. Results: A total of 44 miRNA risk gene pathway relationships were identified, and a complex regulation network was constructed with 3 genes (ABL1, MYC, and ANAPC13) having the highest degree in affecting the network of CP. Importantly, 4 risk genes (NOTCH3, COX5A, THBS1, and KARS) and 1 risk miRNA (hsa-miR-324-5p) were identified with high prediction accuracy. Conclusions: In conclusion, we analyzed miRNAs and mRNAs expression profiles in CP, 1 risk miRNA, and 4 risk genes were identified with high prediction accuracy as biomarkers of CP. Although further evaluation in clinical study is needed, our findings provide new insights into the pathogenesis of CP and may improve the diagnosis and therapy by identifying novel targets.