Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer.

OBJECTIVE: To examine whether long-term surveillance of intraductal papillary mucinous neoplasms (IPMNs) leads to early diagnosis and better clinical outcomes of pancreatic ductal adenocarcinomas (PDACs) developing concomitantly with IPMNs. SUMMARY BACKGROUND DATA: Long-term image-based surveillance is recommended for patients with low-risk IPMNs. However, it is unknown whether the surveillance can improve surgical and survival outcomes of patients with concomitant PDACs. METHODS: Using a prospective single-institutional cohort of 4,620 patients with pancreatic cysts including 3,638 IPMN patients, we identified 63 patients who developed concomitant PDAC during long-term surveillance. We compared overall survival (OS) of 46 cases with concomitant PDAC to that of 460 matched cases diagnosed with non-IPMN-associated PDAC at the same institution. Multivariable hazard ratios and 95% confidence intervals (CIs) for overall mortality were computed using the Cox regression model with adjustment for potential confounders. RESULTS: Concomitant PDACs were identified at an earlier cancer stage compared to non-IPMN-associated PDACs with 67% and 38% cases identified at stage 2 or earlier, respectively (P<0.001) and 57% and 21% cases with R0 resection, respectively (P<0.001). Compared to non-IPMN-associated PDACs, concomitant PDACs were associated with longer OS (P=0.034) with a multivariable hazard ratio of 0.61 (95% CI, 0.39-0.96). The 5-year survival rate of patients with concomitant PDAC was higher compared to patients with non-IPMN-associated PDAC (34% vs. 18%, respectively; P=0.018). CONCLUSIONS: The surveillance for patients with IPMNs was associated with early identification of concomitant PDACs and longer survival of patients diagnosed with this malignancy.

ABO Blood Group and Risk of Pancreatic Carcinogenesis in Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: ABO blood group has been associated with risks of various malignancies, including pancreatic cancer. No study has evaluated the association of ABO blood group with incidence of pancreatic carcinogenesis during follow-up of patients with intraductal papillary mucinous neoplasms (IPMN). METHODS: Among 3,164 patients diagnosed with pancreatic cysts at the University of Tokyo (Tokyo, Japan) from 1994 through 2019, we identified 1,815 patients with IPMN with available data on ABO blood group. We studied the association of ABO blood group with incidence of pancreatic carcinoma, overall and by carcinoma types [IPMN-derived carcinoma or concomitant pancreatic ductal adenocarcinoma (PDAC)]. Utilizing competing-risks proportional hazards models, we estimated subdistribution hazard ratios (SHR) for incidence of pancreatic carcinoma with adjustment for potential confounders, including cyst characteristics. RESULTS: During 11,518 person-years of follow-up, we identified 97 patients diagnosed with pancreatic carcinoma (53 with IPMN-derived carcinoma and 44 with concomitant PDAC). Compared with patients with blood group O, patients with blood groups A, B, and AB had multivariable SHRs (95% confidence intervals) for pancreatic carcinoma of 2.25 (1.25-4.07; P = 0.007), 2.09 (1.08-4.05; P = 0.028), and 1.17 (0.43-3.19; P = 0.76), respectively. We observed no differential association of ABO blood group with pancreatic carcinoma incidence by carcinoma types. CONCLUSIONS: In this large long-term study, patients with IPMN with blood group A or B appeared to be at higher risk of pancreatic carcinoma compared with those with blood group O. IMPACT: ABO blood group can be a biomarker for pancreatic cancer risk among patients with IPMNs.

Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers.

BACKGROUND: Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. METHODS: In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. RESULTS: Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44-8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08-16.2), and heart disease (OR 3.05; 95% CI 1.11-8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36-28.7). CONCLUSION: In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

Long-term survival after palliative argon plasma coagulation for intraductal papillary mucinous neoplasm of the bile duct.

Intraductal papillary mucinous neoplasm of the bile duct (IPNB) is an epithelial tumor that can cause obstructive jaundice and cholangitis due to mucin production. Although the effectiveness of argon plasma coagulation in IPNB treatment has been demonstrated, the long-term effect of the therapy is largely unknown. Here, we have presented a patient with IPNB who underwent argon plasma coagulation with a follow-up period of more than 2 years. A 74-year-old woman was referred to our department for treatment of obstructive jaundice. Endoscopic retrograde cholangiopancreatography revealed marked dilation of intrahepatic and extrahepatic bile ducts and thick mucin drainage from the ampulla of Vater. IPNB was diagnosed pathologically from biopsy specimens. Surgery was not recommended because of the extensive intrahepatic spread of the lesion. Endoscopic sphincterotomy, endoscopic papillary large balloon dilation, and insertion of a metallic stent could not resolve the obstructive jaundice. Finally, argon plasma coagulation with percutaneous cholangioscopy was performed 3 times over 1 month. After treatment, obstructive jaundice was resolved and the patient's clinical condition has been stable for more than 2 years, except for a single episode of transient cholangitis. In conclusion, argon plasma coagulation may be an alternative to surgery for the palliation of jaundice with IPNB.

Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report.

BACKGROUND: Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion. CASE PRESENTATION: A 74-year-old Japanese man who had hepatitis C virus-related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy. CONCLUSIONS: Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.

Long-term Risk of Malignancy in Branch-Duct Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS: Long-term outcomes of patients with branch-duct intraductal papillary mucinous neoplasms (IPMNs), particularly those after 5 years of surveillance, have not been fully evaluated in large studies. We analyzed incidences of IPMN-derived carcinoma and concomitant ductal adenocarcinoma (pancreatic ductal adenocarcinoma [PDAC]) over 20 years in a large population of patients. METHODS: We identified 1404 consecutive patients (52% women; mean age, 67.5 years) with a diagnosis of branch-duct IPMN, from 1994 through 2017, at the University of Tokyo in Japan. Using a competing risk analysis, we estimated cumulative incidence of pancreatic carcinoma, overall and by carcinoma type. We used competing risks proportional hazards models to estimate subdistribution hazard ratios (SHRs) for incidences of carcinomas. To differentiate IPMN-derived and concomitant carcinomas, we collected genomic DNA from available paired samples of IPMNs and carcinomas and detected mutations in GNAS and KRAS by polymerase chain reaction and pyrosequencing. RESULTS: During 9231 person-years of follow-up, we identified 68 patients with pancreatic carcinomas (38 patients with IPMN-derived carcinomas and 30 patients with concomitant PDACs); the overall incidence rates were 3.3%, 6.6%, and 15.0% at 5, 10, and 15 years, respectively. Among 804 patients followed more than 5 years, overall cumulative incidence rates of pancreatic carcinoma were 3.5% at 10 years and 12.0% at 15 years from the initial diagnosis. The size of the IPMN and the diameter of the main pancreatic duct associated with incidence of IPMN-derived carcinoma (SHR 1.85; 95% confidence interval 1.38-2.48 for a 10-mm increase in the IPMN size and SHR 1.56; 95% confidence interval 1.33-1.83 for a 1-mm increase in the main pancreatic duct diameter) but not with incidence of concomitant PDAC. CONCLUSIONS: In a large long-term study of patients with branch-duct IPMNs, we found the 5-year incidence rate of pancreatic malignancy to be 3.3%, reaching 15.0% at 15 years after IPMN diagnosis. We observed heterogeneous risk factor profiles between IPMN-derived and concomitant carcinomas.

Paraneoplastic dermatomyositis appearing after nivolumab therapy for gastric cancer: a case report.

BACKGROUND: While dermatomyositis is often associated with malignancy, several autoimmune diseases like myositis can be caused by immune checkpoint inhibitors. Differentially diagnosing malignancy-associated dermatomyositis or myositis caused by immune checkpoint inhibitors is sometimes difficult, particularly when a patient with malignancy shows the symptoms of myositis after checkpoint inhibitor administration. We experienced such a case in which we had difficulties in diagnosing paraneoplastic dermatomyositis or drug-associated myositis. In this case, all of our team initially assumed that the diagnosis was myositis caused by immune checkpoint inhibitors. However, it turned out finally that the diagnosis was paraneoplastic dermatomyositis. Because the diagnosis was unexpected, we report here. CASE PRESENTATION: We report the case of a 71-year-old Japanese man who developed clinical symptoms of myositis, such as muscle aches and weakness, after initiation of nivolumab therapy for his gastric cancer. He was initially diagnosed with nivolumab-induced myositis, because the myositis symptoms appeared after nivolumab administration, and nivolumab is known to trigger various drug-associated autoimmune diseases. However, according to his characteristic skin lesions, the type of muscle weakness, his serum marker profiles, electromyography of his deltoid muscle, and magnetic resonance imaging, he was finally diagnosed as having paraneoplastic dermatomyositis. Accordingly, treatment with intravenously administered corticosteroid pulse treatment, immunoglobulin injection, and tacrolimus was applied; his symptoms subsequently improved. However, to our regret, at day 142 after administration, he died due to rapid worsening of his gastric cancer. CONCLUSION: Differentially diagnosing paraneoplastic dermatomyositis or drug-associated myositis caused by immune checkpoint inhibitors is difficult in some cases. The differential diagnosis is crucial because it influences the decision regarding the appropriateness of the use of immunosuppressive treatment against the autoimmune diseases as well as the decision regarding the appropriateness of the continuous use of immune checkpoint inhibitors against the primary cancers. Because subclinical autoimmune disease may become overt after administering immune checkpoint inhibitors, non-apparent autoimmune diseases, which have already existed, should also be considered to avoid the delay of appropriate treatment, when symptoms of autoimmune diseases are recognized.

A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer.

OBJECTIVE: Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients. METHODS: Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival. RESULTS: A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070). CONCLUSIONS: In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study.

OBJECTIVES: Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy. METHODS: This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups. RESULTS: A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P < 0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131). CONCLUSIONS: The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

Procalcitonin is a useful biomarker to predict severe acute cholangitis: a single-center prospective study.

BACKGROUND: Procalcitonin is being increasingly used to diagnose and grade acute systemic bacterial infection at an early stage of disease onset. The aim of this prospective study was to evaluate the usefulness of procalcitonin for severity grading of acute cholangitis on patient admission. METHODS: Patients with acute cholangitis were prospectively enrolled. The severity of acute cholangitis was graded on the basis of the 2013 Tokyo guidelines (Japanese Society of Hepato-Biliary-Pancreatic Surgery, 2013). We compared the ability of procalcitonin level on admission to predict moderate/severe (vs mild) or severe (vs mild/moderate) acute cholangitis with the abilities of white blood cell (WBC) count and C-reactive protein (CRP) level. RESULTS: Two hundred thirteen patients were analyzed, and the severity of acute cholangitis was graded as mild, moderate, and severe in 108, 76, and 29 patients respectively. Procalcitonin level, WBC count, and CRP level all increased significantly according to the severity. In the receiver operating characteristic analyses, the area under the curve for procalcitonin for severe acute cholangitis was 0.90 [95% confidence interval (CI) 0.85-0.96] and was significantly greater than that for WBC (0.62; 95% CI 0.48-0.76) and that for CRP (0.70; 95% CI 0.60-0.80). The optimal cutoff value for procalcitonin for prediction of severe acute cholangitis was 2.2 ng/mL (sensitivity 0.97; specificity 0.73; accuracy 0.77). The areas under the curve for procalcitonin, WBC, and CRP for moderate/severe acute cholangitis were not significantly different. CONCLUSIONS: Procalcitonin predicted severe acute cholangitis better than conventional biomarkers. Severe cases for which urgent biliary drainage is indicated might be identified on admission on the basis of the cutoff values for procalcitonin suggested in this study.

Indications for endoscopic ultrasonography (EUS)-guided biliary intervention: Does EUS always come after failed endoscopic retrograde cholangiopancreatography?

BACKGROUND AND AIM: Endoscopic ultrasonography-guided biliary drainage (EUS-BD), first reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) after failed endoscopic retrograde cholangiopancreatography (ERCP), is increasingly reported as a primary procedure without failed ERCP. The present study aims to evaluate the outcomes of therapeutic biliary ERCP and to compare the safety and effectiveness of primary EUS-BD with those of ERCP, rescue EUS-BD and PTBD. METHODS: We retrospectively studied therapeutic biliary ERCP as well as subsequent rescue PTBD and EUS-BD. Additionally, indications, safety and technical success of primary EUS-BD were evaluated. RESULTS: Between August 2013 and September 2015, a total of 520 therapeutic biliary ERCP with a native papilla were analyzed. We encountered 23 cases with inaccessible papilla and 22 cases with failed cannulation, which were rescued by 21 PTBD, 16 EUS-BD and two repeat ERCP. Additionally, 40 primary EUS-BD were carried out during the same period as a result of 10 recurrent cholangitis cases after transpapillary drainage, five outside failed cannulation, four altered anatomy, two history of ERCP-related adverse events (AE), two technical difficulties in stenting under enteroscopy-assisted ERCP and 17 on study protocol. Technical success and AE rates were 95.6% and 14.5% in ERCP, 90.5% and 33.3% in rescue PTBD, 93.8% and 18.8% in rescue EUS-BD, and 95.0% and 22.5% in primary EUS-BD, respectively. CONCLUSIONS: Rescue EUS-BD was used in 3.1% among all ERCP. Given the comparable technical success and AE rates of both primary and rescue EUS-BD, primary EUS-BD without failed ERCP can be a treatment option if it provides advantages over ERCP.

No Survival Benefit from the Inhibition of Renin-Angiotensin System in Biliary Tract Cancer.

AIM: The renin-angiotensin system (RAS) was investigated as a target for cancer treatment. PATIENTS AND METHODS: A total of 287 patients with biliary tract cancer (BTC) receiving chemotherapy were retrospectively studied to evaluate the role of inhibition of RAS by angiotensin system inhibitors (ASIs). Progression-free survival (PFS) and overall survival (OS) were compared between 74 patients with hypertension, on ASIs (ASI group), 50 patients with hypertension not on ASIs (non-ASI with HT group) and 163 patients without hypertension (non-HT group). Interactions between the use of ASIs and various subgroups were explored. RESULTS: The median PFS was 3.6, 3.9 and 4.6 months (p=0.495) and the median OS was 11.6, 10.9 and 13.1 months (p=0.668), respectively. The use of ASIs was not associated with OS (hazard ratio 1.00, p=0.975) and no subgroups with better survival were identified. CONCLUSION: No survival benefit from ASIs was observed in BTC.

Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience.

The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions.

Outcome of Long-term Maintenance Steroid Therapy Cessation in Patients With Autoimmune Pancreatitis: A Prospective Study.

OBJECTIVE: To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis. PATIENTS AND METHODS: The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G<1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of >1600 mg/dL. RESULTS: During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038). CONCLUSIONS: ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period >3 years to prevent relapse.

Placement of multiple metal stents for malignant intrahepatic biliary obstruction via an endoscopic ultrasound-guided choledochoduodenostomy fistula.

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a fully-covered self-expandable metal stent (SEMS) is increasingly used as an alternative to failed endoscopic retrograde cholangiopancreatography. An EUS-CDS fistula can provide endoscopists with a new approach route for intrahepatic bile ducts. Here, we present successful placement of multiple SEMS for intrahepatic biliary obstruction via an EUS-CDS fistula.

Smoking, family history of cancer, and diabetes mellitus are associated with the age of onset of pancreatic cancer in Japanese patients.

OBJECTIVES: The aim of this study was to examine the association of risk factors including diabetes mellitus (DM) with the age of onset in Japanese pancreatic cancer (PC) patients. METHODS: We retrospectively reviewed 688 PC patients diagnosed at our institute. We analyzed the association between the age of onset of PC and the following variables: sex, smoking, alcohol, DM, and a family history of cancer especially PC. RESULTS: The mean age of PC diagnosis was 67.6 years. The onset of PC occurred earlier in current smokers (63.6 years old, P < 0.001) compared with past smokers (69.5 years old) and never smokers (68.6 years old). Patients with long-standing DM (>2 years) were older (70.5 years, P < 0.001) when diagnosed with PC than patients with new-onset DM (within 2 years) (66.9 years old) and patients without DM (66.7 years old). In the multivariate analysis, current smokers and a family history of cancer other than PC were associated with earlier onset. Conversely, long-standing DM was associated with later onset. CONCLUSIONS: In Japanese PC patients, current smokers and a family history of cancer other than PC were associated with a younger age of onset. Conversely, long-standing DM was associated with a later onset.

Incidence of malignancies in patients with IgG4-related disease.

OBJECTIVE: It has been discussed whether IgG4-related disease (IgG4-RD), including autoimmune pancreatitis (AIP), is associated with malignancy; however, the issue has not been clarified. METHODS: We analyzed 113 patients with IgG4-RD in whom malignancy was not diagnosed at the time of IgG4-RD onset and the follow-up period was longer than six months. A total of 95 patients had AIP. The mean follow-up period was 73 months. The incidence of the observed malignancies was compared with the expected incidence in an age- and sex-matched general Japanese population based on the Vital Statistics of Japan. RESULTS: There were 15 malignancies (lung cancer in five patients, pancreatic cancer in two patients, gastric cancer in two patients, bile duct cancer in one patient, renal cancer in one patient, breast cancer in one patient, tongue cancer in one patient, malignant melanoma in one patient and acute myeloid leukemia in one patient) in 14 patients during the follow-up period. The calculated standardized incidence rate of the total malignancies was not significant, that is, 1.04 (95% CI 0.57-1.75). CONCLUSION: The incidence of total malignancies in IgG4-RD patients is similar to that observed in the general population. At present, it is reasonable to conclude that IgG4-RD is not associated with an increased incidence of total malignancies.