A genome-wide association study identified PTPN2 as a population-specific susceptibility gene locus for primary biliary cholangitis.

BACKGROUND AIMS: Previous genome-wide association studies (GWAS) have indicated the involvement of shared (population-non-specific) and non-shared (population-specific) susceptibility genes in the pathogenesis of primary biliary cholangitis (PBC) among European and East-Asian populations. Although a meta-analysis of these distinct populations has recently identified more than 20 novel PBC susceptibility loci, analyses of population-specific genetic architecture are still needed for a more comprehensive search for genetic factors in PBC. APPROACH RESULTS: Protein tyrosine phosphatase non-receptor type 2 (PTPN2) was identified as a novel PBC susceptibility gene locus through a GWAS and subsequent genome-wide meta-analysis involving 2,181 cases and 2,699 controls from the Japanese population (GWAS-lead variant: rs8098858, p=2.6×10-8). In-silico and in-vitro functional analyses indicated that the risk allele of rs2292758, which is a primary functional variant, decreases PTPN2 expression by disrupting Sp1 binding to the PTPN2 promoter in T follicular helper cells (Tfh) and plasmacytoid dendritic cells (pDCs). Infiltration of PTPN2-positive T-cells and pDCs were confirmed in the portal area of the PBC-liver by immunohistochemistry. Furthermore, transcriptomic analysis of PBC-liver samples indicated the presence of a compromised negative feedback loop in-vivo between PTPN2 and IFNG in patients carrying the risk allele of rs2292758. CONCLUSIONS: PTPN2, a novel susceptibility gene for PBC in the Japanese population, may be involved in the pathogenesis of PBC via an insufficient negative feedback loop caused by the PTPN2 risk allele of rs2292758 in IFN signaling. This suggests that PTPN2 could be a potential molecular target for PBC treatment.

The CpxRA two-component system of adherent and invasive Escherichia coli contributes to epithelial cell invasion and early-stage intestinal fitness in a dysbiotic mouse model mediated by type 1 fimbriae expression.

Adherent and invasive Escherichia coli (AIEC) is a pathobiont that is involved in the onset and exacerbation of Crohn's disease. Although the inducible expression of virulence traits is a critical step for AIEC colonization in the host, the mechanism underlying AIEC colonization remains largely unclear. We here showed that the two-component signal transduction system CpxRA contributes to AIEC gut competitive colonization by activating type 1 fimbriae expression. CpxRA from AIEC strain LF82 functioned as a transcriptional regulator, as evidenced by our finding that an isogenic cpxRA mutant exhibits reduced expression of cpxP, a known regulon gene. Transcription levels of cpxP in LF82 increased in response to envelope stress, such as exposure to antimicrobials compromising the bacterial membrane, whereas the cpxRA mutant did not exhibit this response. Furthermore, we found that the cpxRA mutant exhibits less invasiveness into host cells than LF82, primarily due to reduced expression of the type 1 fimbriae. Finally, we found that the cpxRA mutant is impaired in gut competitive colonization in a mouse model. The colonization defects were reversed by the introduction of a plasmid encoding the cpxRA gene or expressing the type 1 fimbriae. Our findings indicate that modulating CpxRA activity could be a promising approach to regulating AIEC-involved Crohn's disease.

Possible link between colonization of the gastrointestinal tract by Citrobacter rodentium in C57BL/6 mice and microbiota composition.

Colonization resistance, conferred by the host's microbiota through both direct and indirect protective actions, serves to protect the host from enteric infections. Here, we identified the specific members of the gut microbiota that impact gastrointestinal colonization by Citrobacter rodentium, a murine pathogen causing colonic crypt hyperplasia. The gut colonization levels of C. rodentium in C57BL/6 mice varied among breeding facilities, probably due to differences in microbiota composition. A comprehensive analysis of the microbiota revealed that specific members of the microbiota may influence gut colonization by C. rodentium, thus providing a potential link between the two.

Prevalence and diagnostic significance of non-invasive follicular thyroid neoplasm with papillary-like nuclear features in Japan-A multi-institutional study.

This multi-institutional study investigated non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) frequency and its diagnostic significance in Japan. We reviewed 4008 thyroid nodules resected in six institutions before NIFTP was proposed. Overall, 26 cases diagnosed as non-invasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) and 145 cases of follicular thyroid adenoma (FTA) were included. Of these nodules, 80.8% and 31.0%, respectively, were NIFTPs. In five institutions, NIFTPs were more commonly found in FTA than in PTC nodules. When NIFTP was included with PTC, the overall prevalence was 2.3%, with rates in five institutions below 5.0% (0.8%-4.4%). One NIFTP case with nuclear score 3 revealed nodal metastasis 2.5 years post-resection, and the carcinoma cells were immunohistochemically positive for BRAF. FTAs or NIFTPs with nuclear score 2 did not metastasize. NIFTP was more common among FTA than among PTC nodules, possibly due to underdiagnosis of PTC on nuclear findings. Considering the clinical findings, molecular pathogenesis, and therapeutic strategy in Japan, NIFTP with nuclear score 2 is not different from FTA, and use of this entity terminology is not meaningful. In contrast, NIFTP with nuclear score 3 has potential for metastasis and BRAFV600E mutation. Therefore, in NIFTP cases, nuclear scores 2 and 3 should be separately reported.

Novel quinazolin-4(3H)-one based Cyclin K degraders regulate alternative polyadenylation activity.

Phenotypic screening is gaining attention as a powerful method for identifying compounds that regulate cellular phenotypes of interest through novel mechanisms of action. Recently, a new modality of compounds, called molecular glues, which can induce the degradation of target proteins by forming ternary complexes of E3 ligases, has emerged from phenotypic screening. In this study, using global proteomic analysis, we identified a novel Cyclin K degrader, T4, which was previously discovered through phenotypic screening for alternative polyadenylation regulation. Our detailed mechanistic analysis revealed that T4 induced Cyclin K degradation, leading to the regulation of alternative polyadenylation. Additionally, we generated a more potent Cyclin K degrader, TR-213, through a structure-activity relationship study of T4. T4 and TR-213 are structurally distinct from other Cyclin K degraders and can be used as novel chemical tools to further analyze the degradation of Cyclin K and the regulation of alternative polyadenylation.

The PAF1 complex cell autonomously promotes oogenesis in Caenorhabditis elegans.

The RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in RNA polymerase II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects oogenesis. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutant and leo-1(RNAi), pafo-1(RNAi), and cdc-73(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesis-defective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.

Identification of genes essential for bile acid resistance in the probiotic Lacticaseibacillus paracasei strain Shirota.

Bile acid resistance is crucial to allow probiotic strains to survive in the gastrointestinal tract and exert health-promoting effects on their hosts. Our aim here was to determine the mechanism of this resistance via a genetic approach by identifying the genes essential for bile acid resistance in Lacticaseibacillus paracasei strain Shirota (LcS). We generated 4649 transposon-inserted lines of L. paracasei YIT 0291, which has the same genome sequence as LcS but lacks the pLY101 plasmid, and we screened them for bile-acid-sensitive mutants. The growth of 14 mutated strains was strongly inhibited by bile acid, and we identified 10 genes that could be involved in bile acid resistance. Expression of these genes was not markedly induced by bile acid, suggesting that their homeostatic expression is important for exerting bile acid resistance. Two mutants in which the transposon was independently inserted into cardiolipin synthase (cls) genes, showed strong growth inhibition. Disruption of the cls genes in LcS caused decreased cardiolipin (CL) production and the accumulation of the precursor phosphatidylglycerol in bacterial cells. These data suggest that LcS possesses several mechanisms for exerting bile acid resistance, and that homeostatic CL production is among the factors most essential for this resistance.

[A Case of Locally Advanced, Unresectable Pancreatic Cancer with Superior Mesenteric Artery Invasion Treated with FOLFIRINOX plus Radiation Therapy, followed by Conversion Surgery].

We report a case of a woman in her 70s who underwent conversion surgery after FOLFIRINOX, followed by radiation therapy for initially locally advanced unresectable pancreatic cancer. She visited her local doctor with a chief complaint of upper abdominal pain. Contrast-enhanced CT scan of the abdomen revealed an irregular mass invading the superior mesenteric artery, and the first and second jejunal arteries(>180°)in the pancreatic uncinate region. Based on imaging, she was diagnosed as UR-LA(sm), cT4N0M0, cStage Ⅲ pancreatic cancer, and underwent 5 courses of modified FOLFIRINOX. Radiation therapy of 50.4 Gy was added for local control, and CA19-9 decreased from 394.1 U/mL to 10.5 U/mL. The treatment effect was judged as RECIST: partial response. The tumor was considered to be potentially curative, and a subtotal stomach preserving pancreaticoduodenectomy was performed 8 months after the initial treatment. The tumor was found to be 3× 2 mm in size, pStage ⅠA, R0, and the response to preoperative chemotherapy: Evans Grade Ⅲ. The patient is alive at 5 months postoperatively without recurrence.

[A Case of Local Recurrent Liver Metastasis from Sigmoid Colon Cancer after Complete Histological Remission, Treated with Rehepatectomy].

We report a case of a patient with sigmoid colon cancer and multiple liver metastases who underwent hepatectomy after chemotherapy and pathological results showed complete remission. However, after chemotherapy was discontinued, the patient developed a local recurrence of the liver metastasis and underwent rehepatectomy. The patient came to our hospital with lower abdominal pain. Colonoscopy revealed a circumferential type Ⅱ, well-differentiated adenocarcinoma. Laparoscopic sigmoidectomy with lymph node dissection was performed. Postoperative CT scan showed multiple liver metastases at S5, S7, and S8. 11 cycles of bevacizumab plus modified FOLFOX(mFOLFOX)were subsequently performed. The liver metastases shrank at all sites, and the patient underwent right hepatectomy. The resected specimen was considered to be in complete remission, with no evidence of viable malignant cells. Postoperatively, bevacizumab plus mFOLFOX was resumed for 6 cycles and the patient remained in remission. However, 3 months after stopping chemotherapy and 1 year and 6 months after hepatectomy, a follow-up CT scan showed local recurrence of the liver edge, and a diagnosis of local recurrence of liver metastasis was made, and a partial hepatectomy was performed. The patient is recurrence-free and resuming modified FOLFOX 9 months after surgery.

uvrY Deletion and Acetate Reduce Gut Colonization of Crohn's Disease-Associated Adherent-Invasive Escherichia coli by Decreasing Expression of Type 1 Fimbriae.

Adherent-invasive Escherichia coli (AIEC) is involved in onset and/or exacerbation of Crohn's disease (CD). AIEC adapts to the gut environment by altering gene expression programs, leading to successful gut-lumen colonization. However, the underlying mechanism of gut colonization is still far from clarified. Here, we show the role of UvrY, a response regulator of bacterial two-component signal transduction systems, in AIEC gut colonization. An AIEC mutant lacking the uvrY gene exhibited impairment of competitive colonization in the murine intestinal tract. UvrY contributes to functional expression of type 1 fimbriae by activating expression of small RNA CsrB, which confers adherence and invasion into epithelial cells on AIEC. In contrast, acetate suppresses the UvrY-dependent expression of type 1 fimbriae, resulting in less efficient cell invasion and attenuated gut colonization. Our findings might lead to therapeutic interventions for CD, in which inhibitions of UvrY activation and acetate supplementation reduce the colonization levels of AIEC by decreasing type 1 fimbria expression.

Fatty Acid Homeostasis Tunes Flagellar Motility by Activating Phase 2 Flagellin Expression, Contributing to Salmonella Gut Colonization.

Long-chain-fatty-acid (LCFA) metabolism is a fundamental cellular process in bacteria that is involved in lipid homeostasis, energy production, and infection. However, the role of LCFA metabolism in Salmonella enterica serovar Typhimurium (S. Tm) gut infection remains unclear. Here, using a murine gastroenteritis infection model, we demonstrate involvement of LCFA metabolism in S. Tm gut colonization. The LCFA metabolism-associated transcriptional regulator FadR contributes to S. Tm gut colonization. fadR deletion alters the gene expression profile and leads to aberrant flagellar motility of S. Tm. Colonization defects in the fadR mutant are attributable to altered swimming behavior characterized by less frequently smooth swimming, resulting from reduced expression of the phase 2 flagellin FljB. Notably, changes in lipid LCFA composition by fadR deletion lead to reduced expression of fljB, which is restored by exogenous LCFA. Therefore, LCFA homeostasis may maintain proper flagellar motility by activating fljB expression, contributing to S. Tm gut colonization. Our findings improve the understanding of the effect of luminal LCFA on the virulence of enteric pathogens.

rs9459874 and rs1012656 in CCR6/FGFR1OP confer susceptibility to primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune liver disease that appears to be strongly influenced by genetic factors. Recently, an international meta-analysis of genome-wide association studies (GWAS) identified CC-Motif Chemokine Receptor-6 (CCR6) and FGFR1 Oncogene-Partner (FGFR1OP) as PBC-susceptibility genes. However, the lead single nucleotide polymorphisms (SNPs) of CCR6/FGFR1OP showed low linkage disequilibrium with each other in East Asian and European populations. Additionally, the primary functional variants and the molecular mechanisms responsible for PBC-susceptibility remain unclear. Here, among the PBC-susceptibility SNPs identified by high-density association mapping in our previous meta-GWAS (Patients: n = 10,516; healthy controls: n = 20,772) within the CCR6/FGFR1OP locus, rs9459874 and rs1012656 were identified as primary functional variants. These functional variants accounted for the effects of GWAS-identified lead SNPs in CCR6/FGFR1OP. Additionally, the roles of rs9459874 and rs1012656 in regulating FGFR1OP transcription and CCR6 translation, respectively, were supported by expression quantitative trait loci (eQTL) analysis and gene editing technology using the CRISPR/Cas9 system. Immunohistochemistry showed higher expression of CCR6 protein in the livers of patients with PBC than in those of a non-diseased control. In conclusion, we identified primary functional variants in CCR6/FGFR1OP and revealed the molecular mechanisms by which these variants confer PBC-susceptibility in an eQTL-dependent or -independent manner. The approach in this study is applicable for the elucidation of the pathogenesis of other autoimmune disorders in which CCR6/FGFR1OP is known as a susceptibility locus, as well as PBC.

Natural history of intracholecystic papillary neoplasm (ICPN): a rare case of ICPN whose natural history was closely followed by ultrasound.

The natural history of intracholecystic papillary neoplasm (ICPN), especially the speed of growth from small benign to a carcinomatous lesion, is quite unrevealed. Here, we report an extremely rare case of ICPN, in which the papillary lesion was observed transforming from small and benign to malignant using abdominal ultrasound (AUS) over 2 years during routine health checks. A 44-year-old man underwent a routine health check-up. The initial AUS showed a small sessile polyp in the gallbladder, which enlarged slightly at the next AUS, a year later. In the third year, the polypoid lesion enlarged markedly, with a maximum diameter of 10 × 9 × 7 mm. Therefore, a laparoscopic cholecystectomy was performed. Microscopically, the 10 mm tumor had intracytoplasmic mucus, and a clear cytoplasm compatible with gastric-type features. Immunohistochemical analysis showed positive staining of atypical cells for MUC6 and PAS. These findings led to the diagnosis of ICPN with high-grade intraepithelial neoplasia of the gastric type. In conclusion, sessile polyps with rapid growth might be a crucial finding in the early stage of ICPN.

Implementation strategies for the patient safety reporting system using Consolidated Framework for Implementation Research: a retrospective mixed-method analysis.

BACKGROUND: Healthcare-related adverse events occur because of complex healthcare systems. The patient safety reporting system is a core component of patient safety initiatives in hospitals. However, hospital management often encounters a cultural barrier with its implementation and struggles to overcome the same. Implementation science would be useful for analysing implementation strategies. This study determines the effects of the implemented strategy on an increase in the number of patient safety reports and the determinants of successful implementation, using the implementation framework. METHODS: Mixed method analysis was performed in Fujita Health University Hospital (FHUH), a large volume hospital in Japan. We identified strategies to implement the patient safety reporting system by scrutinising internal documents using the Consolidated Framework for Implementation Research (CFIR). The electronic reporting systems developed in 2004 in the FHUH and the number of reports were analysed using the staff data and hospital volumes. RESULTS: Reports (n = 110,058) issued between April 2004 and March 2020 were analysed. The number of reports increased from 2004 to 2008 and from 2013 to 2019, reaching 14,037 reports per year. Between 2009 and 2012, the FHUH experienced a stagnation period where the number of reports were not increasing. From the qualitative materials, we identified 74 strategies which contributed to the implementation of the patient safety reporting system. Among these, the domain of 'intervention characteristics' in the CFIR contained 12 strategies, 'outer settings' contained 20, 'inner settings' contained 21, 'characteristics of individuals' contained 8, and 'process' contained 13. There were two concentrated periods of the implemented strategies, the number was 17 in 2007 and 10 in 2016. These concentrated periods preceded a remarkable increase in the number of patient safety reports. CONCLUSIONS: A safety culture had been fostered in FHUH in the study period. A relationship between number of strategies and development of a reporting culture was observed. The intensity of adequate strategies was needed for implementation of patient safety reporting system. Therefore, the implementation framework is useful for analysing patient safety initiatives for safety culture.

A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib.

In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.

A preserved pancreatic exocrine function after pancreatectomy may be a crucial cause of pancreatic fistula: paradoxical results of the 13C-trioctanoin breath test in the perioperative period.

PURPOSE: The aim of this study was to elucidate the association between pancreatic fistula (PF) and the sequential changes in the perioperative exocrine function after pancreatectomy. METHODS: The subjects were 96 patients who underwent a 13C-trioctanoin breath test before and 1 month after pancreatectomy, between 2006 and 2018. We retrospectively compared the pre- and postoperative fat absorption levels between patients with PF (PF group; n = 17) and without PF (non-PF group; n = 79) using the breath test. RESULTS: The preoperative level of 13C-trioctanoin absorption (%dose/h) was comparable between the non-PF and PF groups (36.5 vs. 36.9). In the non-PF group, 13C-trioctanoin absorption was significantly decreased after surgery in comparison to the preoperative setting (post-operative 28.5; pre-operative 36.5; p < 0.0001), whereas these values were comparable (post-operative 36.9; pre-operative 34.5; p = 0.129) in the PF group. Moreover, postoperative absorption in the PF group was significantly better than that in the non-PF group (34.5 vs. 28.5%, p = 0.0003). The maximum drain amylase level was significantly higher in patients with a 13C-trioctanoin absorption level (%dose/h) of ≥ 30 in comparison to patients with levels of < 30 (2502 vs. 398 U/L, p = 0.001). CONCLUSION: PF did not exacerbate the pancreatic exocrine function in the early postoperative period, and the acceleration or preservation of the exocrine function after surgery may be an important cause of PF.

Right hepatectomy with preservation of the entire caudate lobe in patients with metastatic liver tumors: a case of a new hepatectomy technique and treatment strategy for patients with marginal liver function.

BACKGROUND: Performing major hepatectomy for patients with marginal hepatic function is challenging. In some cases, the procedure is contraindicated owing to the threat of postoperative liver failure. In this case report, we present the first case of marginal liver function (indocyanine green clearance retention rate at 15 min [ICGR15]: 28%) successfully treated with right hepatectomy, resulting in total caudate lobe preservation. CASE PRESENTATION: A 71-year-old man was diagnosed with sigmoid colon cancer with three liver metastases (S5, S7, and S8). All of metastatic lesions shrunk after chemotherapy, but his ICGR15 and indocyanine green clearance rate (ICGK) were 21% and 0.12, respectively. Moreover, the remnant liver volume was only 39%. Therefore, portal venous embolism (PVE) of the right portal vein was suggested. Portography showed divergence of the considerably preserved right caudate lobe branch (PV1R) from the root of the right portal vein. The liver function was reevaluated 18 days after PVE was suggested. During this time, the ICGR15 (21-28%) and ICGK rate (0.12-0.10) deteriorated. The right caudate lobe was significantly enlarged; thus, a total caudate lobe-preserving hepatectomy (TCPRx) was performed. Patients eligible for TCPRx included those with (1) hepatocellular carcinoma or metastatic liver cancer, (2) no tumor in the caudate lobe, (3) marginal liver function (ICG Krem greater than 0.05 if TCPRx was adapted; otherwise, less than 0.05) and Child-Pugh classification category A, and (4) preserved PV1R and right caudate bile duct branch. The procedure was performed through (A) precise estimation of the remnant liver volume preoperatively, (B) repeated intraoperative cholangiography to confirm the biliary branch of the right caudate lobe (B1R) conservation, and (C) stapler division of posterior and anterior Glisson's pedicles laterally to avoid injuries to the PV1R and B1R. CONCLUSIONS: Right hepatectomy with total caudate lobe preservation, following PVE, was a safe and viable surgical technique for patients with marginal liver function.

The usefulness of preoperative exocrine function evaluated by the 13C-trioctanoin breath test as a significant physiological predictor of pancreatic fistula after pancreaticoduodenectomy.

BACKGROUND: The association between pancreatic fistula (PF) after pancreaticoduodenectomy (PD) and preoperative exocrine function is yet to be elucidated. This study aimed to evaluate the association between the preoperative results of the 13C-trioctanoin breath test and the occurrence of PF, showing the clinical relevance of the breath test in predicting PF. METHOD: A total of 80 patients who underwent 13C-trioctanoin breath tests prior to PD from 2006 to 2018 were included in this study. Univariate and multivariate analyses were conducted to reveal the preoperative predictors of PF, showing the association between 13C-trioctanoin absorption and PF incidence. RESULTS: Among 80 patients (age, 68.0 ± 11.9 years, 46 males and 34 females; 30 pancreatic ductal adenocarcinoma [PDAC]/50 non-PDAC patients), the incidence of PF was 12.5% (10/80). Logistic regression analysis results revealed that the frequency of PF increased significantly as the 13C-trioctanoin breath test value (Aa% dose/h) increased (odd's ratio: 1.082, 95% confidence interval: 1.007-1.162, p = 0.032). Moreover, the optimal cutoff value of the preoperative fat absorption level to predict PF was 38.0 (sensitivity, 90%; specificity, 74%; area under the curve, 0.78; p = 0.005). Indeed, the incidence of PF was extremely higher in patients whose breath test value was greater than 38.0 (33%, 9/27) compared with that in patients with values less than 38.0 (1.8%, 1/53). CONCLUSIONS: Favorable preoperative fat absorption evaluated using the 13C-trioctanoin breath test is a feasible and objective predictor of PF after PD.

[A Case of Resection of Pancreatic Body Cancer Successfully Treated with GEM plus Nab-PTX].

The case was a 72-year-old man who had been on medication due to chronic pancreatitis since 2009 and was referred to our hospital because dilation of the main pancreatic duct was shown by abdominal ultrasonography. The contrast CT scan of the abdomen showed a 30 mm in size, poorly enhanced tumor at the body of the pancreas, which was suspected to invasion the celiac artery, common hepatic artery, and splenic artery. EUS showed a hypoechoic tumor with a diameter of 29× 24 mm. ERCP showed disruption of the pancreatic duct in the body of the pancreas, and cytological examination of the pancreatic juice showed a suspicious positive result. We diagnosed unresectable locally advanced pancreatic cancer in the body of the pancreas and underwent chemotherapy(gemcitabine plus nab-paclitaxel: GnP). Contrast-enhanced CT after 6 courses of GnP showed tumor shrinkage. FDG-PET/CT revealed a slightly in fluorine-18-deoxyglucose(FDG)accumulation in the tumor, but no accumulation around the blood vessels. Based on the above, it was judged that the tumor was possible radical resection, and surgery was performed. Intraoperative frozen section examination revealed no malignant findings in the tissues surrounding the main artery near the pancreatic body cancer, and distal pancreatectomy was performed. Histopathologically, the tumor showed findings of tubular adenocarcinoma, and the histological response to neoadjuvant therapy was Grade 2. We report a case in which conversion surgery was possible by chemotherapy.

[Efficacy of Hepatic Artery Resection without Reconstruction in Pancreaticoduodenectomy, Paying Attention to the Anomaly of the Artery].

In performing PD, it is very important to understand the running and anatomy of the hepatic artery and the positional relation with the tumor before surgery, leading to planning a proper surgical procedure. In this case series, we report 2 cases in which radical resection was achieved by pancreaticoduodenectomy(PD)with combined hepatic artery resection(without reconstruction)while paying attention to the positional relationship between the bifurcated hepatic artery and the tumor in the head of the pancreas. Case 1: A 73-year-old man. He visited the hospital with jaundice and was diagnosed with distal bile duct cancer. Preoperative contrast-enhanced CT showed that the replaced right hepatic artery(RRHA)was involved by the tumor. Intraoperatively, it was confirmed by ultrasonography that the arterial blood flow in the right lobe of the liver was flowing from the left hepatic artery through the hepatic hilar plate after clamping the right hepatic artery. Thus, PD with combined RRHA resection(without reconstruction)was performed. After the operation, there was no problem with hepatic artery blood flow, and R0 resection was achieved. Case 2: A 65-year-old man. He visited the hospital with jaundice as the chief complaint and was diagnosed with pancreatic head cancer with encasement in the proper hepatic artery(PHA). In this case, the right hepatic artery branches from the SMA and the left hepatic artery branches from the left gastric artery. Intraoperative findings showed no problem with hepatic artery blood flow even after test-clamping the common hepatic artery, and the common hepatic artery was not reconstructed. There is no postoperative complication, and R0 resection was achieved pathologically. Conclusion: For pancreatic head tumors with hepatic artery infiltration, it is important to understand the anatomy of hepatic artery preoperatively and to confirm the intraoperative blood flow. In such cases, pancreaticoduodenectomy with hepatic artery resection may contribute to achieving R0.