研究者詳細 - 北郷　実

論文 - 北郷　実

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膵体尾部脂肪置換により残膵非再建とした膵頭十二指腸切除を施行した2例

阿部紘大, 北郷実, 眞杉洋平, 篠田昌宏, 八木洋, 阿部雄太, 大島剛, 堀周太郎, 益田悠貴, 林航輝, 北川雄光

日本消化器外科学会雑誌（(一社)日本消化器外科学会） 54 （ 7 ） 480 - 489 2021年07月

ISSN 0386-9768

症例1は47歳の女性で,膵癌を疑う膵腫瘍に対し亜全胃温存膵頭十二指腸切除を施行した.膵尾部は脂肪置換され残膵断端の主膵管は同定できなかったため,膵管空腸吻合をせず膵断端を縫合し挙上空腸と膵実質を密着縫合した.術後に膵液漏は認めたが内分泌機能は良好で術後第33病日に退院した.術後2年5ヵ月無再発で耐糖能良好である.症例2は46歳の男性で,慢性膵炎の既往がある膵神経内分泌腫瘍に対して亜全胃温存膵頭十二指腸切除を施行した.膵実質は脂肪置換され主膵管を同定できなかった.断端迅速組織診断にてランゲルハンス氏島細胞のみを認め主膵管は退縮していたため,膵断端を縫合閉鎖して残膵空置とした.術後Cペプチドの軽度低下を認め,ヒューマログ2-2-2で経過観察中である.膵体尾部脂肪置換に対する膵頭十二指腸切除は,残膵空置して可能なかぎりランゲルハンス氏島を残すことで膵全摘よりも良好な耐糖能を維持できると考えられた.(著者抄録)

Indication for resection and possibility of observation for intraductal papillary mucinous neoplasm with high-risk stigmata

Abe K., Kitago M., Masugi Y., Iwasaki E., Yagi H., Abe Y., Hasegawa Y., Fukuhara S., Hori S., Tanaka M., Nakano Y., Yokose T., Shimane G., Sakamoto M., Kitagawa Y.

Pancreatology （Pancreatology） 21 （ 4 ） 755 - 762 2021年06月

ISSN 14243903

Background/Objectives: According to the revised international intraductal papillary mucinous neoplasm (IPMN) guidelines (2017), the indication for surgery is based on risk classification. However, some IPMNs with high-risk stigmata (HRS) can be observed for long periods without resection. Hence, we need to reconsider the risk stratification, and this study aimed to propose a novel risk stratification for HRS-IPMNs. Methods: We enrolled 328 patients diagnosed with IPMN using endoscopic ultrasound between 2012 and 2019. We compared clinicopathological features between HRS and worrisome features (WF) and evaluated outcomes of HRS-IPMN. Results: Fifty-three patients (HRS 38, WF 15) underwent resection at initial diagnosis and 275 patients were observed. Following observation for 30 months, 22 patients (17 HRS, 5 WF) underwent resection. Analysis of resected IPMNs (n = 75) revealed that HRS had dominantly pancreatobiliary mucin subtype. Pancreatobiliary-type IPMN had larger nodule sizes and lymphatic invasion and high recurrence with poor prognosis. Seventy-four patients were diagnosed with HRS, 55 underwent resection, and 19 continue to be observed. The resected group had larger nodule sizes (median 8 mm vs. 5 mm; P = 0.060), whereas the observed group had more main pancreatic duct (MPD) dilation (median 10 mm vs. 5 mm; P = 0.005). In the resected HRS group, only patients with MPD dilation ≥10 mm (n = 10) had no recurrence but had a favorable prognosis compared with those nodule size ≥5 mm (n = 45). Conclusions: Large nodule size may be associated with pancreatobiliary subtype and poor prognosis; however, patients with MPD dilation ≥10 mm with nodule size <5 mm did not require resection.

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Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Endo Y., Fujimoto M., Ito N., Takahashi Y., Kitago M., Gotoh M., Hiraoka N., Yoshida T., Kitagawa Y., Kanai Y., Arai E.

Journal of Cancer Research and Clinical Oncology （Journal of Cancer Research and Clinical Oncology） 147 （ 5 ） 1341 - 1354 2021年05月

ISSN 01715216

Purpose: The present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC). Methods: Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort. Results: The DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in the CDK14 gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively. Conclusion: These findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients.

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Estimating copy number using next-generation sequencing to determine ERBB2 amplification status

Nakamura K., Aimono E., Oba J., Hayashi H., Tanishima S., Hayashida T., Chiyoda T., Kosaka T., Hishida T., Kawakubo H., Kitago M., Okabayashi K., Funakoshi T., Okita H., Ikeda S., Takaishi H., Nishihara H.

Medical Oncology （Medical Oncology） 38 （ 4 ） 36 2021年04月

ISSN 13570560

Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.

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Does laparoscopic resection for colorectal cancer liver metastasis have a long-term oncologic advantage?

Hasegawa Y, Kitago M, Abe Y, Kitagawa Y

Hepatobiliary surgery and nutrition 10 （ 2 ） 246 - 248 2021年04月

ISSN 2304-3881

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Long-term outcomes of living donor liver transplantation after locoregional treatment for hepatocellular carcinoma: an experience from a single institute

Inomata K., Yagi H., Hibi T., Shinoda M., Matsubara K., Abe Y., Kitago M., Obara H., Itano O., Kawachi S., Tanabe M., Wakabayashi G., Shimazu M., Kitagawa Y.

Surgery Today （Surgery Today） 51 （ 3 ） 350 - 357 2021年03月

ISSN 09411291

Purpose: The precise role of downstaging or bridge therapy for cirrhotic patients with hepatocellular carcinoma (HCC) beyond or within the Milan criteria (MC) before living donor liver transplantation (LDLT) remains undefined. Methods: We conducted a single-center, retrospective cohort study of 40 cirrhotic patients with HCC who underwent LDLT from 2000 to 2018. Dynamic computed tomography images at the initial presentation and immediately before LDLT as well as the final histopathological findings were reviewed to determine whether they met or exceeded MC. Results: Overall, 29 patients underwent various pre-transplant HCC treatments, including ablation and embolization (bridge therapy, n = 20; downstaging, n = 9). Of the 9 patients who were initially beyond the MC, 4 (44.4%) were successfully downstaged to within the MC. Five patients beyond the MC immediately before LDLT demonstrated a significantly worse 5-year overall survival rate than patients within the MC (16.7% vs. 82.2%, P = 0.004), regardless of the radiological HCC stage at presentation or the final pathological tumor status. All 3 recurrent patients had HCC beyond the MC immediately before transplant and died of their disease at 13, 24, and 50 months after transplantation. Conclusions: Successful downstaging for HCC cases beyond the MC provides similar outcomes to those within the MC at presentation, regardless of the histopathological findings.

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Development of human hepatocellular carcinoma in X-linked severe combined immunodeficient pigs: An orthotopic xenograft model

Mishima K., Itano O., Matsuda S., Suzuki S., Onishi A., Tamura M., Inoue M., Abe Y., Yagi H., Hibi T., Kitago M., Shinoda M., Kitagawa Y.

PLoS ONE （PLoS ONE） 16 （ 3 March ） e0248352 2021年03月

ISSN 1932-6203

Hepatocellular carcinoma (HCC) is the fifth most common primary tumor and the third leading cause of cancer-related deaths worldwide. Rodent models of HCC have contributed to the advancement of studies investigating liver carcinogenesis, tumor-host interactions, and drug screening. However, their small size renders them unsuitable for surgical or clinical imaging studies, necessitating the development of larger-size HCC models. Here, we developed a xenograft model of human HCC in X-linked interleukin-2 receptor gamma chain gene (Il2rg)-targeted severe combined immunodeficient (SCID) pigs. HepG2 cell suspension in serum-free medium containing 50% membrane matrix was directly injected into the liver parenchyma of eight X-linked Il2rg-targeted SCID pigs (6.6-15.6 kg) via ultrasonography- guided percutaneous puncture. Tumor engraftment was evaluated weekly using ultrasonography, and cone-beam computed tomography was performed during arterial portography (CTAP) and hepatic arteriography (CTHA) to evaluate the hemodynamics of engrafted tumors. The engrafted tumors were histologically analyzed following necropsy and assessed for pathological similarities to human HCCs. Macroscopic tumor formation was observed in seven of the eight pigs (simple nodular tumors in three and multinodular tumors in four). Engrafted tumors were identified as low-echoic upon ultrasonography and as perfusion-defect nodules on the CTAP images. Meanwhile, CTHA showed that the tumors were hyperattenuating. Further, histopathological findings of the engrafted tumors were consistent with those of human HCC. In conclusion, the porcine model of human HCC, successfully generated herein, might help develop more effective therapeutic strategies for HCC.

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Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model

Mihara K., Matsuda S., Nakamura Y., Aiura K., Kuwahata A., Chikaki S., Sekino M., Kusakabe M., Suzuki S., Fuchimoto D., Onishi A., Kuramoto J., Kameyama K., Itano O., Yagi H., Abe Y., Kitago M., Shinoda M., Kitagawa Y.

PLoS ONE （PLoS ONE） 16 （ 3 March ） e0248531 2021年03月

ISSN 1932-6203

Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5–15.9 μT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 μT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.

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Prospective evaluation and refinement of an S-1 dosage formula based on renal function for clinical application

Takeuchi M., Imamura C.K., Booka E., Takeuchi H., Mizukami T., Kawakami T., Funakoshi T., Wakuda K., Aoki Y., Hamamoto Y., Kitago M., Kawakubo H., Boku N., Tanigawara Y., Kitagawa Y.

Cancer Science （Cancer Science） 112 （ 2 ） 751 - 759 2021年02月

ISSN 13479032

In patients with impaired renal function, S-1–related toxicities increase due to higher exposure of 5-fluorouracil (5-FU). Our previous pharmacokinetic study in 16 cancer patients with various renal functions developed an S-1 dosage formula based on individual creatinine clearance (CLcr) and body surface area (BSA). To evaluate and refine the formula, this prospective study was conducted. Thirty-three patients with various renal functions received S-1 for 4 weeks at doses determined by the nomogram derived from the previously developed formula. A series of blood samples were collected after the first dose to calculate the area under the concentration-time curve (AUC) of 5-FU. Thirty patients with BSA of 1.14-1.84 m2 and CLcr of 23.8-96.4 mL/min were assessable for pharmacokinetics. The observed daily AUC ranged from 712.6 to 2868.7 ng·h/mL, and 18 patients achieved the target AUC (1447.8 ± 545.4 ng·h/mL). Three patients experienced S-1–related grade 3 adverse events during the first course. In the population pharmacokinetic analysis from the combined data of 46 patients in this study and the previous study, sex was identified as a statistically significant covariate for 5-FU clearance. Hence, the refined formula includes sex as an additional factor: Recommended daily dose = target AUC × (14.5 + 8.23 × SEX [0 for female and 1 for male] + 0.301 × CLcr) × BSA. Revised nomograms for recommended daily doses derived from the refined formula can be used in clinical practice to achieve the target AUC ensuring efficacy and safety of S-1.

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Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration: A case report and literature review

Kojima H., Kitago M., Iwasaki E., Masugi Y., Matsusaka Y., Yagi H., Abe Y., Hasegawa Y., Hori S., Tanaka M., Nakano Y., Takemura Y., Fukuhara S., Ohara Y., Sakamoto M., Okuda S., Kitagawa Y.

World Journal of Gastroenterology （World Journal of Gastroenterology） 27 （ 3 ） 294 - 304 2021年01月

ISSN 10079327

BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lymphadenectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS-FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.

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Three distinct stroma types in human pancreatic cancer identified by image analysis of fibroblast subpopulations and collagen

Ogawa Y., Masugi Y., Abe T., Yamazaki K., Ueno A., Fujii-Nishimura Y., Hori S., Yagi H., Abe Y., Kitago M., Sakamoto M.

Clinical Cancer Research （Clinical Cancer Research） 27 （ 1 ） 107 - 119 2021年01月

ISSN 10780432

Purpose: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. Experimental Design: A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-nave PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein a (FAP)dominant fibroblast-rich stroma, and a smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8þ cell density. Results: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06–2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8þ cell infiltrates and intense neutrophil infiltration. Conclusions: This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.

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The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure

Mizota T., Hishiki T., Shinoda M., Naito Y., Hirukawa K., Masugi Y., Itano O., Obara H., Kitago M., Yagi H., Abe Y., Matsubara K., Suematsu M., Kitagawa Y.

Journal of Clinical Biochemistry and Nutrition （Journal of Clinical Biochemistry and Nutrition） 70 （ 1 ） 54 - 63 2021年

ISSN 09120009

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-L-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH3 levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.

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Pancreaticoduodenectomy with Non-Reconstruction of the Remnant Pancreas in Patients with Fat Replacement of the Pancreatic Tail: A Report of Two Cases

Abe K., Kitago M., Masugi Y., Shinoda M., Yagi H., Abe Y., Oshima G., Hori S., Masuda Y., Hayashi K., Kitagawa Y.

Japanese Journal of Gastroenterological Surgery （Japanese Journal of Gastroenterological Surgery） 54 （ 7 ） 480 - 489 2021年

ISSN 03869768

Case 1: The patient was a 47-year-old woman who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) for suspected pancreatic cancer. The pancreatic tail was replaced by fat and the main pancreatic duct was not identified in the remnant pancreatic segment; therefore, the pancreatic segment was sutured without pancreaticojejunal anastomosis, and the upper intestine and pancreatic parenchyma were closely sutured. The patient was discharged on postoperative day 33 without evidence of endocrine dysfunction, although postoperative pancreatic juice leakage was observed. She has had no recurrence for 2 years and 5 months postoperatively, with good glucose tolerance. Case 2: The patient was a 46-year-old man with a history of chronic pancreatitis who underwent SSPPD for a pancreatic neuroendocrine tumor. The pancreatic parenchyma was replaced by fat and the main pancreatic duct could not be identified. Histopathological examination of an intraoperative frozen section revealed only islets of Langerhans in the specimen with main pancreatic duct regression; therefore, the pancreatic parenchyma was sutured closed and the remnant pancreas was left intact. Postoperatively, only a mild decrease in serum C-peptide was observed and the patient was administered Humalog 2-2-2 with regular follow-up. In patients who undergo pancreaticoduodenectomy for fat replacement of the pancreatic tail, pancreatectomy with pancreatic remnant preservation may achieve better glucose tolerance than total pancreatectomy. This is because the former procedure ensures that the islets of Langerhans remain intact as far as possible.

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Diagnostic utility of presepsin in infections after liver transplantation: A preliminary study

Yokose T., Takeuchi M., Obara H., Shinoda M., Kawakubo H., Kitago M., Yagi H., Abe Y., Yamada Y., Matsubara K., Oshima G., Hori S., Fujimura T., Takemura R., Ishii R., Kuroda T., Kitagawa Y.

Annals of Transplantation （Annals of Transplantation） 26 e933774 2021年

ISSN 14259524

Background: Infectious complications after solid organ transplantation can be fatal, and early diagnosis and intervention are important. To the best of our knowledge, no study has examined the diagnostic utility of presepsin, a known accurate biomarker, for infectious complications after liver transplantation. This study aimed to evaluate the utility of presepsin for detecting infection and perioperative kinetics of presepsin after liver transplantation. Material/Methods: This single-institutional prospective, observational study included 13 patients who underwent living-donor or de-ceased-donor liver transplantation. Perioperative serum presepsin level was measured 6 times within a week to evaluate its association with infectious complications and compare it with procalcitonin and C-reactive protein levels and leukocyte count. Postoperatively, patients were followed up for 15 days for infectious complications. Results: Five of the 13 patients developed infectious complications after liver transplantation. The median time for infection diagnosis was 9 postoperative days (25th-75th percentile, 7-10). Presepsin levels on 5 and 7 postoperative days were significantly higher in patients with infection than in those without (P=0.019 and P=0.011, re-spectively). In receiver operating characteristic analysis, area under the curve values of presepsin on 5 and 7 postoperative days (0.881 and 0.905, respectively) were higher than those of other biomarkers. The optimal cut-off value of presepsin was 1361 pg/mL on postoperative day 5 and 1375 pg/mL on postoperative day 7. Conclusions: Although this study included a small number of patients, presepsin levels on postoperative days 5 and 7 may be useful indicators for infectious complications after liver transplantation.

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Independent predictors of secondary invasive pancreatic remnant tumors after initial resection of an intraductal papillary mucinous neoplasm: a nationwide large-scale survey in Japan

Takigawa Y., Kitago M., Matsui J.

Surgery Today （Surgery Today） 50 （ 12 ） 1672 - 1680 2020年12月

ISSN 09411291

Purpose: There is no standardized surveillance protocol after intraductal papillary mucinous neoplasm (IPMN) resection. We report the findings of a large-scale survey in Japan, investigating the independent predictors of secondary invasive tumors by analyzing the epidemiology of secondary tumors of the remnant pancreas after initial IPMN resection. Methods: An institutional questionnaire about the remnant pancreas after pancreas resection was distributed at the 41st Annual Meeting of the Japanese Society of Pancreatic Surgery in Tokyo. We retrospectively analyzed the patient data including pathological diagnosis, postoperative outcomes, and evaluation methods. Results: Redo pancreatectomy was performed for secondary disease in 213 (1.4%) of a total 15,777 patients. Eighty-eight of these 213 patients had undergone initial resection of IPMN. The types of secondary tumors after IPMN resection significantly depended on those of the primary tumors. Through short-interval and long-term follow-up, most of the secondary tumors were detected within 1–4 years. Logistic regression analysis revealed that the initial pathological diagnosis of invasive IPMN was an independent predictor of secondary invasive tumors in the remnant pancreas. Conclusion: Primary invasive IPMN proved to be a significant predictor of secondary invasive IPMN. Both short-interval and long-term follow-up may help to determine the prognosis of patients after IPMN resection.

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High risk pathogens and risk factors for postoperative pancreatic fistula after pancreatectomy; a retrospective case-controlled study

Abe K., Kitago M., Shinoda M., Yagi H., Abe Y., Oshima G., Hori S., Yokose T., Endo Y., Kitagawa Y.

International Journal of Surgery （International Journal of Surgery） 82 136 - 142 2020年10月

ISSN 17439191

Background: Although the rates of surgical site infection are decreasing, surgical site infection after pancreatectomy remains frequent because of postoperative pancreatic fistula. Recent studies suggested a relationship between postoperative pancreatic fistula and pathogens cultured from drainage fluids after pancreatectomy. This study aimed to assess and evaluate high-risk pathogens cultured from postoperative drainage fluids for postoperative pancreatic fistulas or severe postoperative complications after pancreatectomy. Materials and methods: We retrospectively enrolled patients who underwent pancreaticoduodenectomy or distal pancreatectomy between 2012 and 2019. We assessed clinical characteristics and microbiological results of drainage cultures of pancreaticoduodenectomy or distal pancreatectomy patients, and we investigated the risk factors for clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status using univariate and multivariate analyses. Finally, we detected high-risk pathogens from drainage cultures and analyzed the correlation between these pathogens and the severity of clinically relevant postoperative pancreatic fistula or Clavien-Dindo status. Results: Four hundred and twenty-nine patients were enrolled: 257 underwent pancreaticoduodenectomy and 172 underwent distal pancreatectomy. Clinically relevant postoperative pancreatic fistulas and Clavien-Dindo status ≥ III were more frequently seen in pancreaticoduodenectomy patients than in distal pancreatectomy patients, namely grade C postoperative pancreatic fistula, which was observed in 19 pancreaticoduodenectomy patients. The most common pathogen found from drainage cultures was Enterococcus species, followed by Enterobacter species and Candida species. All pathogens were associated with clinically relevant postoperative pancreatic fistulas; however, Candida species was a dominant microorganism of clinically relevant postoperative pancreatic fistulas grade C, Clavien-Dindo status ≥ IV, and hemorrhage due to pseudoaneurysm. Conclusion: The presence of Candida species in the drainage fluid culture after pancreaticoduodenectomy can be a predictive factor of severe infectious complications, including postoperative pancreatic fistulas; thus, we should regularly collect cultures from drainage fluids and monitor for Candida infection.

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Acute Phase Response and Postprocedural Evaluation of Open and Laparoscopic Cryoablation Procedures in Porcine Pancreases

Imai S., Kitago M., Matsuda S., Nakamura Y., Shinoda M., Yagi H., Abe Y., Fujita Y., Nakano Y., Iwata K., Nakatsuka S., Kitagawa Y.

Pancreas （Pancreas） 49 （ 9 ） 1255 - 1262 2020年10月

ISSN 08853177

Objectives Cryoablation is a potentially less invasive locoregional ablation modality. Although cryoablation has been used to treat malignancy in various organs, a limited application of this modality in the pancreas has been reported. Methods Acute phase response assessments and postprocedural course evaluations of 2 experimental locoregional ablation methods were conducted. In one method, open and laparoscopic cryoablation of a porcine pancreas using an argon-helium gas-based cryoablation system and monitoring of tissue temperature during the procedure were performed. In the other method, open cryoablation of a porcine pancreas using liquid nitrogen was performed. The animals were evaluated postoperatively. Results The size of the cryolesion was larger in the second treatment than in the first. Laparoscopic cryoablation was associated with the formation of an iceball, which possibly affected the surrounding structures. The ablated region was adequately cooled with 10 minutes of freeze/repeat cycles. The area cooled to a temperature of less than -40°C was approximately half the size of the cryolesion in diameter. The swine used for the evaluation of the postprocedural course survived 3 weeks after the procedure with a temporal elevation of the serum lipase level. Conclusions Cryoablation of the pancreas was experimentally practicable without severe complications under direct or laparoscopic vision.

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O-glycan-altered extracellular vesicles: A specific serum marker elevated in pancreatic cancer

Yokose T., Kabe Y., Matsuda A., Kitago M., Matsuda S., Hirai M., Nakagawa T., Masugi Y., Hishiki T., Nakamura Y., Shinoda M., Yagi H., Abe Y., Oshima G., Hori S., Nakano Y., Honda K., Kashiro A., Morizane C., Nara S., Kikuchi S., Shibahara T., Itonaga M., Ono M., Minegishi N., Koshiba S., Yamamoto M., Kuno A., Handa H., Sakamoto M., Suematsu M., Kitagawa Y.

Cancers （Cancers） 12 （ 9 ） 1 - 17 2020年09月

ISSN 2072-6694

Pancreatic cancer (PC) is among the most lethal malignancies due to an often delayed and difficult initial diagnosis. Therefore, the development of a novel, early stage, diagnostic PC marker in liquid biopsies is of great significance. In this study, we analyzed the differential glycomic profiling of extracellular vesicles (EVs) derived from serum (two cohorts including 117 PC patients and 98 normal controls) using lectin microarray. The glyco-candidates of PC-specific EVs were quantified using a high-sensitive exosome-counting system, ExoCounter. An absolute quantification system for altered glycan-containing EVs elevated in PC serum was established. EVs recognized by O-glycan-binding lectins ABA or ACA were identified as candidate markers by lectin microarray. Quantitative analyses using ExoCounter revealed that the ABA-or ACA-positive EVs were significantly increased in the culture of PC cell lines or in the serum of PC patients including carbohydrate antigen 19-9 negative patients with high area under curve values. The elevated numbers of EVs in PC serum returned to normal levels after pancreatectomy. Histological examination confirmed that the tumors stained with ABA/ACA. These specific EVs with O-glycans recognized by ABA/ACA are elevated in PC sera and can act as potential biomarkers in a liquid biopsy for PC patients screening.

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腹腔鏡下脾部分切除が有用であった血球貪食症候群の1例

大島剛, 北郷実, 篠田昌宏, 八木洋, 阿部雄太, 北川雄光

手術（金原出版(株)） 74 （ 10 ） 1513 - 1517 2020年09月

ISSN 0037-4423

症例は31歳女性で、不明熱と血小板減少を契機に精査が行われた。腹部CTでは腹部大動脈周囲のリンパ節腫大と、軽度脾腫および脾内に低吸収域が認められ、悪性リンパ腫を含むリンパ増殖性疾患が疑われた。診断目的で骨髄穿刺、CTガイド下腹部大動脈周囲リンパ節生検および肝生検が施行され、血球貪食の所見が認められた。病理学的検索に十分量の脾組織を採取する目的と膵体尾部切除を回避するために、腹腔鏡下脾部分切除を施行した。膵尾部から脾門部は白苔様の組織を認め、浮腫と硬化性変化を認めた。腫瘍の浸潤あるいは組織の炎症による影響が疑われ、術前評価通り脾門の脈管処理は困難と考えられた。脾組織をIO電極ソフト凝固モードや超音波切開装置等を用いて約3×3cm角程度で切除した。術後経過は良好で合併症は認めなかった。第1病日から離床し食事が開始された。採取された脾組織で腫瘍細胞は認められず、特発性血球貪食症候群の診断となり、第4病日から速やかなステロイド治療を開始することが可能であった。

Incidentally detected microcystic serous cystadenoma of the pancreas with splenic invasion: a case report and literature review.

Yagi F, Akita H, Ueno A, Takano K, Masugi Y, Sakamoto M, Kitago M, Shinoda M, Kitagawa Y, Toyama K, Matsusaka Y, Yashiro H, Okuda S, Jinzaki M

BJR case reports 6 （ 2 ） 20190109 - 20190109 2020年09月

Serous cystic neoplasms are relatively uncommon and rarely possess malignant potential. We report a rare case of pancreatic serous cystadenoma with splenic invasion in a female in her 60s. Dynamic contrast-enhanced CT revealed a 3 cm mass in the tail of the pancreas. The lesion showed marked enhancement in the arterial phase on dynamic CT, which extended into the spleen. No cystic components were detected in the pancreatic mass on either magnetic resonance cholangiopancreatography or T 2 weighted imaging. No metastasis or lymph node swelling was detected. Based on the hypervascularity of the tumour, the pre-operative diagnosis was pancreatic neuroendocrine tumour with splenic invasion. The patient underwent laparoscopic distal pancreatectomy with splenectomy. The pathological diagnosis was microcystic serous cystadenoma with locally aggressive features (infiltration into spleen, lymph nodes, and splenic vein). A few cases of pancreatic serous cystadenomas with splenic invasion have been reported; all were symptomatic, with diameters greater than approximately 9 cm. This is the first known case of incidentally detected serous cystadenoma with splenic invasion, reported with detailed imaging findings of dynamic CT and MRI.

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