Wen-Bin Zou

Risk factors for complications of pancreatic extracorporeal shock wave lithotripsy

BACKGROUND AND STUDY AIMS Extracorporeal shock wave lithotripsy is recommended as treatment for stones in chronic pancreatitis. The aim of this study was to investigate the risk factors for complications of pancreatic extracorporeal shock wave lithotripsy (P-ESWL). PATIENTS AND METHODS Patients with painful chronic pancreatitis and pancreatic stones (> 5 mm diameter) who were treated with P-ESWL between March 2011 and June 2013 were prospectively included. Adverse events after P-ESWL were classified as complications and transient adverse events, depending on severity. The major complications of P-ESWL included post-ESWL pancreatitis, bleeding, infection, steinstrasse, and perforation. Multivariate analyses based on univariate analysis were performed to detect risk factors of overall and moderate-to-severe complications. RESULTS A total of 634 patients underwent 1470 P-ESWL procedures. The overall complication rate was 6.7 % of all procedures. Complications occurred in 62 patients (9.8 %) after the first ESWL procedure. The risk factors for complications were pancreas divisum (odds ratio [OR] 1.28) and the interval between diagnosis of chronic pancreatitis and P-ESWL (OR 1.28). Protective factors were male sex (OR 0.50), diabetes (OR 0.45), and steatorrhea (OR 0.43). Male sex, the only identified predictor for moderate-to-severe complications, was a protective factor (OR 0.19). For the second P-ESWL procedure, complications occurred in 22/409 patients (5.4 %). Complication and asymptomatic hyperamylasemia after the first ESWL session were significantly associated with higher risk for complications after the second ESWL session (P < 0.05). CONCLUSIONS Patient-related factors were important in determining a high risk of P-ESWL complications when no procedure-related factors were identified. Patients suffering from complications after the first ESWL session were also likely to experience complications in subsequent P-ESWL sessions.

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 .

Extracorporeal Shock Wave Lithotripsy for Chinese Patients With Pancreatic Stones: A Prospective Study of 214 Cases.

Objectives This study aims to evaluate prospectively the safety and efficacy of extracorporeal shock wave lithotripsy (ESWL) in Chinese patients. Methods A total of 214 patients with painful chronic pancreatitis and pancreatic stones who underwent ESWL followed by endoscopic retrograde cholangiopancreatography from March 2011 to February 2012 in Changhai Hospital were enrolled. The main pancreatic duct clearance rate and complications were recorded prospectively. Symptoms, weight, quality of life, and pancreatic function were assessed before and after ESWL and endotherapy. Results A total of 473 ESWL procedures were performed in 214 patients. Stones were fragmented in all cases. Complete clearance of main pancreatic duct stones and successful endoscopic decompression were achieved in 155 (72.4%) and 188 (90.8%) of 214 patients, respectively. Complications were observed after 20 sessions (20 of 473, 4.23%). Follow-up (n = 195) after 18.5 ± 3.3 months showed that complete and partial pain relief were achieved in 71.3% and 24.0% of the patients, respectively. The scores for the quality of life (5.8 ± 1.7 vs 8.1 ± 1.2, P < 0.05) and mental health from the Medical Outcomes Study 36-Item Short-Form General Health Survey questionnaire (62.2 ± 21.5 vs 68.5 ± 16.4, P < 0.05) improved after ESWL. Conclusions Thus, ESWL is a safe and effective method to treat Chinese patients with pancreatic stones. This procedure can significantly improve the success rate of endotherapy.

Magnetic-controlled capsule endoscopy vs. gastroscopy for gastric diseases: a two-center self-controlled comparative trial.

BACKGROUND AND STUDY AIMS We developed a novel magnetic-controlled capsule endoscopy (MCE) system for use in the human stomach. The aim of the current study was to compare the diagnostic accuracy of MCE with that of standard gastroscopy for gastric diseases. PATIENTS AND METHODS A total of 68 patients were enrolled in this self-controlled trial. Patients were evaluated by both MCE and gastroscopy. Gastroscopy was performed 4 – 24 hours after completion of the MCE examination. RESULTS The positive percent agreement between MCE and gastroscopy was 96.0 %, and the negative percent agreement was 77.8 %. The overall agreement was 91.2 % with a kappa value of 0.765 (P < 0.001). A total of 68 pathological findings were detected, of which 53 were identified by both methods. The MCE and standard gastroscopy missed seven and eight findings, respectively. CONCLUSIONS MCE showed a diagnostic accuracy similar to that of standard gastroscopy. These results suggest that MCE is a promising alternative to gastroscopy for noninvasive screening of gastric diseases.Clinical trial registration number: NCT01903629.

Clarifying the clinical relevance of SPINK1 intronic variants in chronic pancreatitis

Recently, we reported the identification of a functional PRSS1 promoter variant in perfect linkage disequilibrium (LD) with the chronic pancreatitis (CP)-‘protective’ rs10273639.1 This, together with several other recent papers published in Gut ,2–4 underscored the importance of functional analysis for improving our understanding of the underlying pathophysiological mechanisms and also more fundamentally for establishing the clinical relevance or otherwise of CP-associated variants from the outset. In many diseases, in vitro functional analysis often represents the only practical means to determine the pathogenicity of patient-derived sequence variants, particularly when they are rare. Herein, we present a new and successful example in the context of CP. SPINK1 is one of the most extensively studied CP genes, with >100 variants being reported to date.5 Of 19 known intronic variants, the four in LD with the p.Asn34Ser variant have been functionally analysed in the context of both minigene6 and full-length genomic sequence7; none had any detectable effect on pre-mRNA splicing. In addition, the functional consequences of the c.194+2T>C splice donor site variant …

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.

Steinstrasse formation after extracorporeal shock wave lithotripsy for pancreatic stones.

To the Editor: Eosinophilic esophagitis (EoE) presents with symptoms of esophageal dysfunction and is characterized by large numbers of intraepithelial eosinophils in esophageal biopsies ( 1 ). Although it constitutes an increasingly reported cause for chronic dysphagia and food impaction, EoE remains unrecognized in many settings. In fact, some EoE patients have been diagnosed only aft er suff ering non-traumatic esophageal perforation or Boerhaave ’ s syndrome (2). A 46-year-old male who had presented an episode of meat impaction resolved by endoscopic removal 5 years before was admitted to the emergency room aft er suff ering a new food impaction episode. Th e endoscopy revealed a narrow, trachealized esophagus with a piece of meat in the lower third and a deep mucosal tear. Aft er presenting sudden retrosternal pain, crepitus was noted upon palpation of the cervicothoracic region. A transhiatal esophagectomy was performed, reconstructing the distal esophagus by means of tubular gastroplasty. Macroscopic study of the esophagetomy specimen showed thickened walls and stricture ( Figure 1a , hematoxilin and eosin × 20). A lineal ulcer was observed in the proximal esophagus ( Figure 1b , H & E × 2) at the site of impaction. Histological examination showed a dense neutrophilic infi ltration and necrosis beneath the ulcer. Numerous samples were taken around the site of the ulcer and from the esophageal segment between the upper and lower thirds. Histological fi ndings were compatible with EoE and consisted of diff use eosinophilic infi ltration of squamous mucosa ( Figure 1c , H & E × 10) with a density > 20 per HPF throughout the length of the esophagus, but predominantly in the medium and upper thirds. Th ere were several microabscesses on luminal portions of the mucosa with reactive acanthosis of the epithelium and basal layer hyperplasia. Eosinophilic infi ltration was observed throughout the esophageal wall, penetrating the submucosa (where lymph nodes were seen, Figure 1d , H & E × 10), dissecting muscle fi bers of inner muscularis propria ( Figure 1e , H & E × 4), and reaching parasympathetic ganglion cells of the myenteric plexus ( Figure 1f , H & E × 40) ( Figure 1 ). Trichrome stains revealed extensive fi brosis of the subepithelial layer and hypertrophy of muscularis mucosae, both responsible for the increased wall thickness ( Figure 1g , Masson trichrome × 4). Th is case represents the fi rst histopathological evaluation of the entire esophageal wall in a patient with EoE. Because endoscopic biopsy forceps usually sample above the lamina propria, the eosinophilic infi ltration and fi brous remodeling of deep esophageal layers was only a supposition based on murine samples and extrapolated from the pathophysiology of bronchial asthma ( 3 ). We observed that eosinophils permeate the submucosal and muscle layers and the neuronal plexus, promoting fi brous remodeling, intense collagen deposition, and smooth muscle hypertrophy, altering the mechanical properties of the esophageal wall and reducing esophageal distensibility in EoE patients. Cytotoxic proteins in the eosinophil granules can lead to tissue damage, increasing the risk of esophageal disruption. Th ese phenomena all have important clinical implications, as they determine dysphagia and explain not only strictures and dysmotility, but also the deep esophageal tears and perforation, resulting from vomiting to dislodge impacted food as frequently described in EoE patients.

No significant enrichment of rare functionally defective CPA1 variants in a large Chinese idiopathic chronic pancreatitis cohort

Rare functionally defective carboxypeptidase A1 (CPA1) variants have been reported to predispose to nonalcoholic chronic pancreatitis, mainly the idiopathic subtype. However, independent replication has so far been lacking, particularly in Asian cohorts where initial studies employed small sample sizes. Herein we performed targeted next‐generation sequencing of the CPA1 gene in 1,112 Han Chinese idiopathic chronic pancreatitis (ICP) patients—the largest ICP cohort so far analyzed in a single population—and 1,580 controls. Sanger sequencing was used to validate called variants, and the CPA1 activity and secretion of all newly found variants were measured. A total of 18 rare CPA1 variants were characterized, 11 of which have not been previously described. However, no significant association was noted with ICP irrespective of whether all rare variants [20 out of 1,112 (1.8%) in patients vs. 24 out of 1,580 (1.52%) in controls; P = 0.57] or functionally impaired variants [three out of 1,112 (0.27%) in patients vs. two out of 1,580 (0.13%) in controls; P = 0.68] were considered.

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.

Digging deeper into the intronic sequences of the SPINK1 gene

We read with great interest the recent paper by Beer and Sahin-Toth1 addressing the ‘missing heritability’ observed in approximately 60% of German cases of chronic pancreatitis.2 These authors opined that ‘discovery studies tend to focus on exons and exon–intron boundaries and may thus miss many intronic variants’.1 This premise seems eminently reasonable, given the generally much larger size of intronic sequences as compared with the coding sequences of protein-coding genes. However, there is a trade-off here. On the one hand, larger sequence size means larger target size for mutation, and hence the greater the number of mutations that could be missed if intronic sequences were not screened. On the other hand, to be of pathological significance, an intronic mutation must either create a new functional splicing donor or acceptor site or alternatively impact a functional sequence motif responsible for regulating splicing (eg, an intronic splicing enhancer), which depends upon many additional factors other than just sequence length. As yet, it is unclear what the ratio of pathological intronic:exonic variants will turn out to be, although intronic mutations are …