Early Tumor Shrinkage and Depth of Response as Predictors of Survival for Advanced Biliary Tract Cancer: An Exploratory Analysis of JCOG1113.

BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.

Effect of systemic inflammatory response on induction chemotherapy followed by chemoradiotherapy for locally advanced pancreatic cancer: an exploratory subgroup analysis on systemic inflammatory response in JCOG1106.

OBJECTIVE: JCOG1106, a randomized phase II trial conducted to compare chemoradiotherapy (S-1 concurrent radiotherapy) with (Arm B) or without (Arm A) induction chemotherapy using gemcitabine in patients with locally advanced pancreatic cancer, showed a more favorable long-term survival in Arm A. This study was aimed at exploring whether some subgroups classified by the systemic inflammatory response might derive greater benefit from either treatment. METHODS: All subjects eligible for JCOG1106 were included in this analysis (n = 51/49 in Arm A/B). This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of the systemic inflammatory response, as assessed based on the serum C-reactive protein, serum albumin (albumin), Glasgow Prognostic Score and derived neutrophil-lymphocyte ratio, at the baseline on overall survival. P values <0.1 for the interaction were regarded as denoting significant association. RESULTS: Glasgow prognostic score showed significant treatment interactions for overall survival. Hazard ratios of Arm B to Arm A were 1.35 (95% confidence interval, 0.82-2.23) in the Glasgow Prognostic Score 0 (C-reactive protein ≤10 mg/L and albumin ≥35 g/L) (n = 44/34 in Arm A/B) and 0.59 (95% confidence interval, 0.24-1.50) in the Glasgow Prognostic Score 1/2 (C-reactive protein >10 mg/L and/or albumin <35 g/L) (n = 7/15) (P-interaction = 0.06). C-reactive protein alone and albumin alone also showed significant treatment interactions for overall survival. CONCLUSIONS: Survival benefits of induction chemotherapy in chemoradiotherapy for locally advanced pancreatic cancer were observed in patients with elevated Glasgow Prognostic Score, high C-reactive protein and low albumin. These results suggest that systemic inflammatory response might be considered to apply induction chemotherapy preceding chemoradiotherapy.

Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer.

The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

Clinicopathological investigation of steatohepatitic hepatocellular carcinoma: A multicenter study using immunohistochemical analysis of adenoma-related markers.

AIMS: Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). METHODS: This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. RESULTS: The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45 mm/20 mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P < 0.01 and 42%/16%, respectively; P = 0.01). CONCLUSIONS: We confirmed that SH-HCC was strongly associated with MS and NAFLD, and found that classification markers of inflammatory HCA were significantly higher in SH-HCC. Further studies are needed to elucidate the relationship between SH-CCC and HCA for understanding the carcinogenic pathways in these diseases.

A multicenter Phase II study of sorafenib in Japanese patients with advanced hepatocellular carcinoma and Child Pugh A and B class.

OBJECTIVE: To evaluate prospectively the efficacy and safety of sorafenib, which has been the first-line treatment for advanced hepatocellular carcinoma (HCC), in Japanese HCC patients (pts) with not only Child-Pugh (C-P) A class but also C-P B class. METHODS: Sorafenib was administered orally at the dose of 400 mg twice daily for pts with HCC and liver function of C-P score of 5-8. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint was time to progression (TTP), and toxicity and the secondary endpoints included objective response, overall survival (OS). RESULTS: Forty C-P A pts and 12 C-P B pts were enrolled. The median TTP in the C-P A pts and C-P B pts was 3.3 months and 3.2 months, respectively. Among the pts with C-P A, complete response, partial response, and stable disease were achieved for 2.5%, 7.5% and 47.5%. Among the pts with C-P B, there were no treatment responses, 66.7% of pts had stable disease. The median OS in the C-P A pts and C-P B pts was 13.4 months and 7.4 months, respectively. With regard to toxicities, fewer C-P A pts experienced Grade 3/4 toxicities than C-P B pts (77.5% vs. 91.6%). There were no treatment-related deaths in either group of patients. CONCLUSIONS: This study shows sorafenib has similar effectiveness in the recent post-approval studies and is well-tolerated in Japanese pts with HCC and Child Pugh A class. Sorafenib should be used with great care for Child Pugh class B pts.

Farnesoid X Receptor Activation Enhances Transforming Growth Factor ß-Induced Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma Cells.

Farnesoid X receptor (FXR) is a receptor for bile acids and plays an important role in the regulation of bile acid metabolism in the liver. Although FXR has been shown to affect hepatocarcinogenesis through both direct and indirect mechanisms, potential roles of FXR in epithelial­mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) remain unclear. We examined the effect of several FXR ligands on EMT-related morphological changes in HCC cell lines, such as HuH-7 and Hep3B cells. FXR agonists (chenodeoxycholic acid, GW4064, and obeticholic acid)­but not an antagonist (guggulsterone)—induced actin polymerization and expression of N-cadherin and phosphorylated focal adhesion kinase, although they were less effective than transforming growth factor ß (TGF-ß). FXR agonist treatment enhanced TGF-ß-induced EMT morphologic changes and FXR antagonist inhibited the effect of TGF-ß. Thus, FXR activation enhances EMT in HCC and FXR antagonists may be EMT-suppressing drug candidates.

Gadoxetic acid disodium-enhanced MR imaging of cholangiolocellular carcinoma of the liver: imaging characteristics and histopathological correlations.

OBJECTIVES: To review the gadoxetic acid disodium (EOB)-enhanced magnetic resonance (MR) imaging features of cholangiolocellular carcinoma (CoCC) of the liver and compare them with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: EOB-enhanced MR images of 19 patients with CoCC, 23 with ICC, and 51 with HCC were retrospectively evaluated qualitatively and quantitatively. Univariate and multivariate analyses were performed to determine the characteristic MR features of CoCC with histopathological-imaging correlation. RESULTS: Multivariate logistic regression analysis showed that dot-/band-shaped internal enhancement during the arterial and portal phases (P < 0.001), and larger arterial ring enhancement ratio (CoCC, 0.13 ± 0.04; ICC, 0.074 ± 0.04; P = 0.013) were significantly independently associated with CoCC in contrast to ICC, whereas several MR features including progressive enhancement during the portal and late phases (P < 0.001), target appearance in the hepatocyte phase (P = 0.004), and vessel penetration (P = 0.013) were significantly more frequently associated with CoCC than HCC. The dot-/band-like internal enhancement (78.9% of CoCCs) histopathologically corresponded to the tumour cell nest with vascular proliferations and retained Glisson's sheath structure. CONCLUSIONS: EOB-enhanced MR features of CoCC largely differ from those of HCC but are similar to those of ICC. However, the finding of thicker arterial ring enhancement with dot-/band-like internal enhancement could help differentiate CoCC from ICC. KEY POINTS: • Gadoxetic acid-enhanced MR features of cholangiolocellular carcinoma (CoCC) resembled those of intrahepatic cholangiocarcinoma (ICC). • Gadoxetic acid-enhanced MR features of CoCC largely differed from those of hepatocellular carcinoma. • Dot-/band-like internal enhancement of CoCC may be helpful for differentiating from ICC. • Arterial ring enhancement of CoCC was larger than that of ICC.

Clinical and pathological significance of myeloid differentiation factor 88 expression in human hepatocellular carcinoma tissues.

The innate immune system, which includes toll-like receptor (TLR) signaling, plays an important role in inflammation and oncogenesis. Although TLR common adaptor myeloid differentiation factor 88 (MyD88) is known to have multiple effects on carcinogenesis, the role of MyD88 in hepatocarcinogenesis remains unknown. In this study, MyD88 expression was examined in 105 samples of human hepatocellular carcinoma (HCC) tissue by immunohistochemistry, Western blot, and quantitative reverse-transcriptase polymerase chain reaction methods. The relationships between MyD88 expression and clinical and pathological parameters were analyzed. The results showed that attenuated expression of MyD88 in HCC tissue tumor cells was significantly related to hepatitis B virus infection, large tumor size, positive vascular invasion, and intrahepatic metastasis (P < 0.05). Western blot analysis of MyD88 protein in nine normal livers and 28 HCCs showed gender disparity (P < 0.01, P < 0.05), and attenuated expression in cirrhotic livers (P < 0.05). Low expression of MyD88 mRNA was evident in HCCs with vascular invasion (P < 0.01). In contrast to previous reports, these results suggest that attenuated expression of MyD88 in HCC is associated with tumor progression.

Diffusion-weighted MR imaging of pancreatic cancer and inflammation: Prognostic significance of pancreatic inflammation in pancreatic cancer patients.

BACKGROUND: Pancreatic cancer often accompanies chronic obstructive pancreatitis (COP) due to obstruction of the main pancreatic duct, and the inflammatory environment may enhance cancer progression. The purpose of this study is to evaluate COP using the apparent diffusion coefficient (ADC) value measured by diffusion-weighted MR imaging (DWI), and to assess its prognostic significance in pancreatic cancer. METHODS: Twenty-eight patients (16 men, 12 women; mean age 67.1 years) with pancreatic cancers who underwent DWI followed by curative surgery were evaluated. The ADC value of pancreatic parenchyma upstream to the tumor (upstream pancreas) was measured and compared with the upstream pancreatic duct dilatation to assess whether DWI could reflect COP. The ADC values of tumor and upstream portion were compared with overall survival (OS) using Cox regression and Kaplan-Meier analysis. RESULTS: The ADC value of upstream pancreas was significantly lower in patients with greater dilated pancreatic duct than those with less (P = 0.03). In univariate Cox regression analysis, the ADC value of upstream pancreas showed a significant association with OS (P = 0.01), but that of tumor did not (P = 0.06). In Kaplan-Meier analysis, patients with lower ADC value of upstream pancreas (<1.36 × 10(-3) mm(2)/s) were significantly associated with poor OS (P = 0.0006). In multivariate analysis, the ADC value of upstream pancreas was identified as an independent prognostic factor (P = 0.01; hazards ratio, 0.05; 95% CI, 0.004-0.59). CONCLUSIONS: The ADC value of upstream pancreas was an independent prognostic factor for OS in pancreatic cancer patients. Inflammatory environment may play an important role in pancreatic cancer progression.

Proteomic analysis of mouse choroid plexus cell line ECPC-4 treated with lipid A.

OBJECTIVES: Choroid plexus (CP) epithelial cells have multiple functions in the cerebral ventricles, including cerebrospinal fluid (CSF) production and forming part of the blood-CSF barrier. They are also responsible for producing inflammatory mediators involved in meningitis. The present study aimed to elucidate the functions of the CP epithelial cells during CNS inflammation. MATERIALS AND METHODS: We analyzed the proteome and phosphoproteome in lipid A-treated ECPC-4 mouse CP cells by gel electrophoresis and mass spectrometry. RESULTS: Levels of 10 proteins and seven phosphoproteins were significantly altered by lipid A in time-dependent manners, including V-type proton ATPase subunit B (ATP6V), protein 40 kD, elongation factor-1δ, coatomer subunit ε (COPE), vimentin (isoform CRA a), purine nucleoside phosphorylase, eukaryotic initiation factor-4F splicing variant, put. ß-actin, peroxiredoxin-6 isoform 1, and immunoglobulin heavy chain variable region. These proteins could be classified as having cytoskeleton/intermediate filament, protein-folding, signal-transduction, cell-growth, metabolism, and redox-regulation functions. The identified phosphoproteins were HSP 84, γ-actin, HSP 70 cognate, vimentin, tubulin ß-4B chain, protein disulfide-isomerase A6 precursor, and heterogenous nuclear ribonucleoprotein, which could be classified as having cytoskeleton/intermediate filament, protein-folding, and metabolism functions. CONCLUSIONS: These results indicate that lipid A can change the levels of proteins and phosphoproteins in ECPC-4 cells, suggesting that the identified proteins and phosphoproteins may play important roles in inflammation of the CP.

The protective role of protein L-isoaspartyl (D-aspartate) O-methyltransferase for maintenance of mitochondrial morphology in A549 cell.

PURPOSE: The increasing amounts of evidence with abnormal aging process have been involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Mice with deficient protein L-isoaspartate (D-aspartate) O-methyl transferase 1 (PCMT1) expression reveal acceleration of aging and result in the increased proportion of D-aspartate (D-Asp) residues and dysfunction in proteins. Furthermore, mitochondrial morphology and functions are associated with COPD and IPF pathogenesis. The purpose of the current study was to investigate the role of PCMT1 on mitochondrial morphology using A549 cells. MATERIALS AND METHODS: We investigated PCMT1, prohibitin1 (PHB1), mitochondrial membrane proteins expression, mitochondrial morphology, and the proportion of D-Asp residues in PHB1 in A549 cells with (PCMT1-KD) and without the context of decreased PCMT1 expression (PCMT1-Cont) using electron microscopy, fluorescence staining, Western blot analysis, and the ATP content per cells. To investigate the effects of the PCMT1-KD cells, we developed double-transfected cell lines containing either the cytosolic or the endoplasmic isoform of PCMT1. RESULTS: We found a significantly higher proportion of D-Asp residues in PHB1 in PCMT1-KD cells than that in PCMT1-Cont cells. The PCMT1-KD cells without cigarette smoke extract exposure were characterized by a significantly increased proportion of the D-Asp residues in PHB1, damaged mitochondrial ultrastructure, and a tendency toward the fission direction of the mitochondrial dynamics followed by a significant decrease in the cellular ATP content. CONCLUSIONS: The increased proportion of the D-Asp residues may contribute to COPD pathogenesis, via irreversible protein conformational changes, followed by mitochondrial dysfunction.

Is it possible to define early distal cholangiocarcinoma?

PURPOSE: The feasibility of defining early cholangiocarcinoma has not been adequately evaluated. The surgical outcomes of patients who had undergone pancreatoduodenectomy (PD) for pathological T1 (pT1) distal cholangiocarcinoma (DCC) were evaluated to determine whether it is possible to define early DCC. METHODS: The clinicopathological data of 18 patients with pT1 DCC who had undergone PD were reviewed retrospectively. Depth of fibromuscular (fm) layer invasion was divided into two categories: fm1 and fm2 (without adventitia fascia invasion and with adventitia fascia invasion). Comparative analyses were performed according to the depth of invasion. RESULTS: Disease-specific survival rates of patients with five mucosal tumors and 13 fm-invasive tumors were 80 and 61.9 % at 5 years and 80 and 41.2 % at 10 years, respectively. There was no significant difference in disease-specific survival rates between the two groups (P = 0.244). Disease-specific survival rates of patients with 7 fm1-invasive tumors and 6 fm2-invasive tumors were 85.7 and 40 % at 5 years and 85.7 and 0 % at 10 years. A significant difference in disease-specific survival rates was observed between mucosal tumors and fm2-invasive tumors (P = 0.043), and disease-specific survival rates of mucosal tumors and fm1-invasive tumors were similar (P = 0.968). CONCLUSIONS: Defining early DCC as carcinoma confined to the fm of the bile duct might be inappropriate; early DCC should be limited to the mucosal carcinoma.

Preserved or enhanced OATP1B3 expression in hepatocellular adenoma subtypes with nuclear accumulation of ß-catenin.

AIM: Recent studies have indicated that hepatocellular adenoma (HCA) is a heterogenous group of benign tumors with various genetic and clinicopathological characteristics. We delineated the clinicopathological characteristics of HCA subtypes and evaluated the expression of transporter protein OATP1B3 in HCA. METHODS: HCA in 34 Japanese patients were investigated immunohistochemically and classified into four subtypes (HNF1α-inactivated type, H-HCA; ß-catenin-activated type, b-HCA; inflammatory type, I-HCA; unclassified type, u-HCA). Immunostaining of OATP1B3 protein in HCA tissue sections was performed to determine the association between OATP1B3 expression and HCA subtypes. RESULTS: HCA was categorized into the following four subtypes and two combined subtypes: 10 H-HCA (29%), 10 I-HCA (29%), seven b-HCA (21%), two b-HCA/H-HCA (6%), two b-HCA/I-HCA (6%) and three u-HCA (9%). The male-to-female ratio was 18:16. Oral contraceptive use was rare but seven HCA were found in patients with glycogen storage disease, congenital absence of the portal vein and idiopathic portal hypertension. OATP1B3 expression was decreased in 24 HCA but was preserved or increased in 10 HCA. All nine HCA with nuclear staining for ß-catenin showed preserved or enhanced OATP1B3 expression, indicating a significant association between nuclear ß-catenin accumulation and OATP1B3 expression in HCA. CONCLUSION: HCA subtype classification was validated in 91% of our Japanese subjects although their clinical backgrounds including rare contraceptive use were different from European subjects. A close association between preserved or enhanced OATP1B3 expression and b-HCA subtype indicated important modalities for clinical decisions in the treatment and follow up of patients with HCA.

A case of ß-catenin-positive hepatocellular adenoma with MR imaging sign of diffuse intratumoral fat deposition.

Hepatocellular adenoma (HCA) is a rare primary benign tumor of the liver, which occurs predominantly in young and middle-aged women. Recently, the subclassification of HCA was proposed by the Bordeaux group. Subsequently, characteristic radiological and clinical features have been revealed in each HCA subtype. According to the previous literature, diffuse intratumoral fat deposition is a very common finding in hepatocyte nuclear factor 1α-negative HCA, but this finding has been reported in ß-catenin-positive HCA in the literature for only one case. In this case report, we report the second case of ß-catenin-positive HCA with MR imaging sign of diffuse intratumoral fat deposition, confirmed immunohistologically on the basis of a surgical specimen. In addition, our case showed hypovascularity and isointensity on the hepatobiliary phase which have been reported as characteristic findings in ß-catenin-positive HCA. Diffuse intratumoral fat deposition can be observed in ß-catenin-positive HCA, which has a greater probability of malignant transformation than other types of HCA.

A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

Long-term surgical outcomes of patients with type 1 autoimmune pancreatitis.

BACKGROUND: Although pancreatectomy has sometimes been performed for patients with autoimmune pancreatitis (AIP) presenting atypical radiologic findings under the diagnosis of pancreatobiliary malignancy, the long-term surgical outcome of these patients had not yet been fully elucidated. METHODS: The long-term surgical outcomes of 13 patients with pathologically diagnosed type 1 AIP with immunohistochemical staining for immunoglobulin G4 (IgG4) were retrospectively compared with those of 34 patients with conventional chronic pancreatitis to evaluate the residual pancreatic function. RESULTS: A definite relapse of AIP in terms of the clinical manifestations and diagnostic imaging was not found in any of the patients, although one patient experienced an attack of acute pancreatitis caused by pancreatic stones, and stricture of the hepaticojejunostomy occurred in one patient. The overall body weight decreased significantly more in patients with AIP than in patients with conventional chronic pancreatitis (p < 0.05); however, there was no difference in the preoperative nondiabetic patients. Refractory diarrhea occurred in only one patient with AIP. The cumulative new-onset rates of diabetes mellitus of the ten patients with AIP and 24 patients with conventional chronic pancreatitis at 5 years after the surgery were 32.5 and 26.1 %, respectively (p = 0.70). CONCLUSIONS: Careful long-term follow-up is needed for patients undergoing pancreatectomy for type 1 AIP because remnant pancreatic function can deteriorate as severely as that of patients who undergo pancreatectomy for conventional chronic pancreatitis. In the present series, however, there were few definite manifestations indicating relapse or the persistent existence of AIP.

Is Low Volume Drainage of Ascites Associated With Improved Survival in Digestive System Cancer Patients With Malignant Ascites?-A Retrospective Cohort Study.

Objectives: To determine whether the volume of paracentesis for malignant ascites in acute care hospital wards is associated with survival and symptom relief. Methods: Patients with malignant ascites caused by digestive system cancer who underwent paracentesis between January 2010 and April 2022 were retrospectively analyzed from medical records. Collected data included the drainage volume per paracentesis procedure, survival time from the first paracentesis procedure, symptoms, and adverse events. According to the volume per paracentesis procedure, we divided the patients into the "small-drainage" (≤1500 mL) and "standard-drainage" (>1500 mL) groups. Results: The median age of the 144 patients was 69 years, 33% were female, and 64% had gastrointestinal cancer. The median survival from the first paracentesis procedure was 36 days. Eighty-nine (61.8%) and 55 (38.2%) patients were allocated to the small-drainage and standard-drainage groups, respectively. The median number of paracentesis procedures in the small-drainage and standard-drainage groups was 12 and 7, respectively (P=.001). The median survival in the small-drainage and standard-drainage groups was 50 and 44 days, respectively (P=.76). The multivariate analysis showed that the amount of drainage per session was not significantly associated with survival. Symptoms improved similarly in the 2 groups. No serious adverse events were observed. Conclusions: Paracentesis was demonstrated to be effective and safe, irrespective of the amount of fluid drained, for patients with malignant ascites in an acute care hospital. Thus, a strategy of limiting the amount of drainage is not associated with longer survival.

A nationwide certification system to increase the safety of highly advanced hepatobiliary-pancreatic surgery.

BACKGROUND: To ensure that highly advanced hepatobiliary-pancreatic surgery (HBPS) is performed safely, the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) board certification system for expert surgeons established a safety committee to monitor surgical safety. METHODS: We investigated postoperative mortality rates based on summary reports of numbers and outcomes of highly advanced HBPS submitted annually by the board-certified training institutions from 2012 to 2019. We also analyzed summary reports on mortality cases submitted by institutions with high 90-day post-HBPS mortality rates and recommended site visits and surveys as necessary. RESULTS: Highly advanced HBPS was performed in 121 518 patients during the 8-year period. Thirty-day mortality rates from 2012 to 2019 were 0.92%, 0.8%, 0.61%, 0.63%, 0.70%, 0.59%, 0.48%, and 0.52%, respectively (P < .001). Ninety-day mortality rates were 2.1%, 1.82%, 1.62%, 1.28%, 1.46%, 1.22%, 1.19%, and 0.98%, respectively (P < .001). Summary reports were submitted by 20 hospitals between 2015 and 2019. Mortality rates before and after the start of report submission and audit were 5.72% and 2.79%, respectively (odds ratio 0.690, 95% confidence interval 0.487-0.977; P = .037). CONCLUSIONS: Development of a system for designation of board-certified expert surgeons and safety management improved the mortality rate associated with highly advanced HBPS.

Single-incision laparoscopic enucleation for pancreatic insulinoma with preoperative nasopancreatic stent placement: A case report.

INTRODUCTION AND IMPORTANCE: Most insulinomas are benign and solitary, with a tumor diameter less than 2 cm; therefore, laparoscopic enucleation, which is a minimally invasive procedure that can preserve the pancreatic parenchyma, is considered an optimal procedure. The key to enucleation is to avoid injury to the main pancreatic duct (MPD). Herein, we present a case in which single-incision laparoscopic enucleation (SILE) was performed for insulinomas, with preoperative nasopancreatic stent (NPS) placement. CASE PRESENTATION: A male patient in his fifties underwent SILE for insulinomas. To prevent injury to the MPD, an NPS was preoperatively placed. All surgical procedures were performed through a single mini-laparotomy site in the umbilicus. NPS placement facilitated identification of the MPD under laparoscopic ultrasonography. Enucleation was successfully completed without any injury to the MPD, and the NPS was removed immediately after confirming that there was no injury to the MPD by the NPS via pancreatography. The postoperative course was uneventful. CLINICAL DISCUSSION: This report serves to highlight the maximum safety and minimal invasiveness of SILE with the preoperative NPS placement. Preoperative NPS placement is useful for avoiding injury to the MPD during enucleation and has the merit of helping to recognize whether leakage occurs by intraoperative pancreatography via the NPS. CONCLUSION: Preoperative NPS placement helps to ensure the safe enucleation of pancreatic insulinomas even in single-incision laparoscopic surgery, with minimal invasiveness and better cosmetic outcomes.