Local anesthetics often are used in rotator cuff tears as therapeutic tools, although some cases have reported that they have detrimental effects. Neurotropin (NTP) is used widely in Japan as a treatment for various chronic pain conditions and is shown to have protective effects on cartilage and nerve cells. In this study, we investigated the protective effect of NTP against lidocaine-induced cytotoxicity. Methods: Tenocytes from rotator cuff tendons were incubated with lidocaine, NTP, lidocaine with NTP, and a control medium. Cell viability was evaluated using the WST-8 assay. Cell apoptosis was detected via annexin V staining using flow cytometry. The expression of BCL-2 and cytochrome c, which are involved in the intrinsic mitochondrial pathway of apoptosis, was evaluated via Western blotting and immunohistochemical staining. Results: In the cell viability assay, lidocaine decreased cell viability in a dose-dependent manner, and NTP did not affect cell viability. Moreover, NTP significantly inhibited the cytotoxic effect of lidocaine. The flow cytometry analysis showed that lidocaine significantly induced apoptosis in tenocytes, and NTP considerably inhibited this lidocaine-induced apoptosis. Western blotting experiments showed that lidocaine decreased the protein expression of BCL-2, and that NTP conserved the expression of BCL-2, even when used with lidocaine. Immunohistochemical staining for cytochrome c showed that 0.1% lidocaine increased cytochrome c-positive cells, and NTP suppressed lidocaine-induced cytochrome c expression. Conclusions: NTP suppresses lidocaine-induced apoptosis of tenocytes by inhibiting the mitochondrial apoptotic pathway. Intra-articular/ bursal injection of NTP with lidocaine could protect tenocytes in rotator cuff tendons against lidocaine-induced apoptosis.

We report a case of intractable diarrhea successfully treated with daikenchuto. The patient was a 60-year-old female. She had suffered from diarrhea in spite of being prescribed Shimbuto, Kanzoshashinto, Shigyakuto and so on. After daikenchuto was administered her intractable diarrhea improved. However, she had not symptoms such as abdominal pain, coldness in the abdomen and abdominal movement disorder that often appear in daikenchuto-syo. We consider daikenchuto may be effective not only for diarrhea but also constipation in yin-syndrome and hypofunction when intestinal juice and gas are stagnated.

Although many guidelines for pancreatic cystic neoplasms focus on the management of intraductal papillary mucinous neoplasm of the pancreas (IPMN) at the highest oncological risk, there are many issues that surgeons need to consider at the time to plan the surgical procedures based on characteristics of IPMN subtypes, such as multiplicity of branch duct-IPMN (BDIPMN) and intraductal spreading of main duct-IPMN (MD-IPMN). For multifocal BD-IPMN, partial pancreatectomy would be selected to remove BD-IPMN with predictors of malignancy, while the other lesions without risk factors can be left, although total pancreatectomy might be considered if the patients have a strong family history of pancreatic cancer. Partial pancreatectomy would be also adequate procedure for MD-IPMN if negative surgical margin for highgrade dysplasia or invasive carcinoma were achieved. It has become to be well-known that patients with BD-IPMN are at increased risk for developing not only IPMN-associated pancreatic ductal adenocarcinoma (PDAC) but also PDAC independent from the IPMN. Hence, the detection of a concomitant PDAC is also an important focus for strategies after resection of BDIPMNs. Our recent analysis of patients after partial pancreatectomy for MD-IPMN with negative surgical margin identified an unexpected recurrence pattern, which we called “monoclonal skip” recurrence. MD-IPMN seems to be disseminated in the pancreatic ductal systems and MD-IPMN with identical genetic background was detected in the remnant pancreas even in a long time after index surgery. We proposed strategies of postoperative surveillance based on characteristics and natural history of each morphological subtype.

Although many guidelines for pancreatic cystic neoplasms focus on the management of intraductal papillary mucinous neoplasm of the pancreas (IPMN) at the highest oncological risk, there are many issues that surgeons need to consider at the time to plan the surgical procedures based on characteristics of IPMN subtypes, such as multiplicity of branch duct-IPMN (BDIPMN) and intraductal spreading of main duct-IPMN (MD-IPMN). For multifocal BD-IPMN, partial pancreatectomy would be selected to remove BD-IPMN with predictors of malignancy, while the other lesions without risk factors can be left, although total pancreatectomy might be considered if the patients have a strong family history of pancreatic cancer. Partial pancreatectomy would be also adequate procedure for MD-IPMN if negative surgical margin for highgrade dysplasia or invasive carcinoma were achieved. It has become to be well-known that patients with BD-IPMN are at increased risk for developing not only IPMN-associated pancreatic ductal adenocarcinoma (PDAC) but also PDAC independent from the IPMN. Hence, the detection of a concomitant PDAC is also an important focus for strategies after resection of BDIPMNs. Our recent analysis of patients after partial pancreatectomy for MD-IPMN with negative surgical margin identified an unexpected recurrence pattern, which we called “monoclonal skip” recurrence. MD-IPMN seems to be disseminated in the pancreatic ductal systems and MD-IPMN with identical genetic background was detected in the remnant pancreas even in a long time after index surgery. We proposed strategies of postoperative surveillance based on characteristics and natural history of each morphological subtype.

Purpose: Preoperative sarcopenia worsens postoperative outcomes in various cancer types including colorectal cancer. However, we often experienced postoperative anastomotic leakage in muscular male patients such as Judo players, especially in rectal cancer surgery with lower anastomosis. It is controversial whether the whole skeletal muscle mass impacts the potential for anastomotic failure in male rectal cancer patients. Thus, the purpose of this study was to clarify whether skeletal muscle mass impacts anastomotic leakage in rectal cancer in men. Methods: We reviewed the medical charts of male patients suffering from rectal cancer who underwent colo-procto anastomosis below the peritoneal reflection without a protective diverting stoma. We measured the psoas muscle area and calculated the psoas muscle index. Results: One hundred ninety-seven male rectal cancer patients were enrolled in this study. The psoas muscle index was significantly higher in patients with anastomotic leakage (P<0.001). Receiver operating characteristic curve determined the optimal cut-off value of the psoas muscle index for predicting anastomotic leakage as 812.67 cm2/m2 (sensitivity of 60% and specificity of 74.3%). Multivariate analysis revealed that high psoas muscle index (risk ratio [RR], 3.933; P<0.001; 95% confidence interval [CI], 1.917–8.070) and super low anastomosis (RR, 2.792; P=0.015; 95% CI, 1.221–6.384) were independent predictive factors of anastomotic leakage. Conclusion This study showed that male rectal cancer patients with a large psoas muscle mass who underwent lower anastomosis had a higher rate of postoperative anastomotic leakage.

Objective: The aim of this study was to establish the proper definitions of venous thromboembolism (VTE) and bleeding events for a healthcare database in Japan.
Study Design: Validation study.
Methods: The study comprised patients with VTE or who had undergone orthopedic surgery of the lower extremities and whose outpatient or inpatient medical information from April 1, 2008 to September 30, 2013 was available.  The source population of the database was derived from 100 acute-care hospitals.  The endpoints were VTE events (deep venous thrombosis [DVT], pulmonary thromboembolism [PE]) and bleeding events (bleeding requiring blood transfusion, intracranial hemorrhage, intraocular hemorrhage, upper gastrointestinal [GI] bleeding, and lower GI bleeding).  The frequent events with laboratory data were randomly extracted and evaluated, while all the infrequent events with laboratory data were extracted and evaluated.  Positive predictive value (PPV) was defined as the proportion of events judged to be clinical by medical experts of all the extracted events.  First, we conducted a test with a small number of cases and then revised the definitions of events.  Second, we extracted and evaluated data in 50 patients for VTE and bleeding events patients, based on which we defined the target PPV level between 60 and 70%.
Results: Of the 5,044,743 patients in the database, 36,947 patients underwent orthopedic surgeries of the lower extremities and 3,578 patients experienced a VTE event.  The PPV at the first evaluation was 80.0% (8/10) for DVT, 57.1% (4/7) for PE, and 27.3% (6/22) for bleeding events.  At the second evaluation using the revised definitions, the PPV were 75.0% (42/56) for VTE and 73.3% (33/45) for bleeding events.  Overall, the PPVs for VTE and bleeding events were over 70%.  The PPV of the VTE events were 76.9% (30/39) for DVT and 70.6% (12/17) for PE.  The PPVs of each type of bleeding event were over 70% except for intracranial hemorrhage (44.4%, 4/9).
Conclusion: The PPV was high for VTE events (75.0%) and bleeding events (73.3%).  The definitions used in this study are rational for the identification of VTE, DVT, PE, and bleeding events in the healthcare database in Japan.  The definition for each type of bleeding event should be investigated in further studies.

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

Cardiac Imaging Techniques ; Cohort Studies ; Cytidine Triphosphate ; Humans ; Image Enhancement ; Multidetector Computed Tomography ; Myocardial Perfusion Imaging ; Myocardium ; Perfusion Imaging ; Radiation Dosage ; Radiation Exposure ; Retrospective Studies

Endoscopic management is presently the recommended first-line of treatment for biliary strictures. However, surgery still has an important role especially for biliary obstruction (BO) with duodenal obstruction. Even though endoscopic treatment for concurrent BO and gastric-outlet obstruction has been proposed, it is still not widespread. Duodenal obstruction is often associated with malignant BO which makes endoscopic treatment more challenging. Biliary and gastrointestinal double bypass with Roux-en-Y hepaticojejunostomy and gastrojejunostomy is the most common surgical intervention for malignant biliary and gastric-outlet obstruction. A variety of procedures of biliary bypass and gastrointestinal bypass have been reported. According to several studies, mortality rates range from 0% to 7%, while morbidity rates range from 3% to 50%. Higher morbidity was observed in symptomatic patients caused by the disease. Most common morbidity after double bypass was delayed gastric emptying. Recurrence of BO and gastric-outlet obstruction was less frequently seen after surgical bypass compared to after endoscopic treatment. Minimally invasive approach has been applied to double bypass. Studies showed that laparoscopic double bypass has a shorter hospital stay and reduced postoperative pain; however, due to its technical demand, it is still presently an uncommon procedure. Robotic bypass surgery may resolve this issue in the future. Further analyses of outcomes of both surgical and endoscopic treatments are necessary to establish better and suitable palliation options for concurrent biliary and duodenal obstruction caused by unresectable malignant tumors.
Cholestasis ; Constriction, Pathologic ; Duodenal Obstruction ; Gastric Bypass ; Gastric Emptying ; Humans ; Length of Stay ; Mortality ; Pain, Postoperative ; Recurrence ; Surgical Procedures, Operative

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.
B-Lymphocytes ; Clone Cells ; Dacryocystitis ; Diagnosis ; Fibrosis ; Humans ; Immunoglobulins ; Molecular Biology ; Plasma Cells ; Sequence Analysis, RNA ; Sialadenitis ; T-Lymphocytes