Publications by authors named "Norifumi Harimoto"

223 Publications

Does intraoperative and postoperative analgesia cause bile leakage after hepatectomy?

Surg Today 2021 Sep 20. Epub 2021 Sep 20.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Purpose: To evaluate the effect of morphine or morphine equivalents on the risk of bile leakage (BL) after hepatectomy.

Methods: The subjects of this retrospective study were 379 patients who underwent hepatectomy without biliary reconstruction and biliary decompression tube insertion at Gunma University between 2016 and 2020. Clinical BL was defined as International Study Group of Liver Surgery post-hepatectomy bile leakage Grade B or C.

Results: Intra- and post-operative analgesia comprised intravenous patient-controlled analgesia (IV-PCA) with fentanyl (n = 58), epidural analgesia with fentanyl (n = 157), epidural analgesia with morphine (n = 151), and epidural analgesia with ropivacaine or levobupivacaine (n = 13). Clinical BL was diagnosed in 14 of the 379 (3.7%) patients. The significant risk factors for clinical BL were hepatocellular carcinoma (HCC), elevated serum total bilirubin, high indocyanine green retention at 15 min, elevated Mac-2-binding protein glycosylated isomer, prolonged duration of surgery, and a large volume of blood loss. There was no significant correlation of clinical BL with intra- and post-operative analgesia and total oral morphine equivalents.

Conclusion: Intra- and post-operative IV-PCA and epidural analgesia were not related to clinical BL after hepatectomy. Based on our data, fentanyl and morphine can be administered safely as epidural or intravenous analgesic agents.
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http://dx.doi.org/10.1007/s00595-021-02377-4DOI Listing
September 2021

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study.

Oncology 2021 10;99(10):641-651. Epub 2021 Aug 10.

Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

Aim: Atezolizumab plus bevacizumab (atezo + bev) shows a good overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients. However, the OS of patients with nonviral infection is quite worse than that in those with viral infection. The present study investigated the efficacy and safety of lenvatinib in patients with nonviral infection, who were unlikely to obtain benefit from atezo + bev.

Methods: We conducted a multicenter retrospective study that included 139 advanced HCC patients treated with lenvatinib between March 2018 and September 2020.

Results: The median age was 72 years, and 116 patients (83.5%) were male. Based on the etiology of liver disease, 84 (60.4%) and 55 patients (39.6%) were assigned to the viral infection and nonviral infection groups, respectively. The significant extents in patient characteristics were not observed in both groups. The objective response rate per mRECIST and progression-free survival (PFS) did not differ significantly between the viral infection and nonviral infection groups (36.0 vs. 33.0%, p = 0.85; and 7.6 vs. 7.5 months, p = 0.94, respectively). The 1-year survival rates were 68.7% (95% confidence interval [CI] 57.7-79.7%) in the viral infection group and 59.5% (95% CI 45.2-73.8%) in the nonviral infection group. The viral infection group was not a significant factor associated with the PFS or OS in a multivariate analysis.

Conclusions: Lenvatinib shows no significant difference in response between patients with and without viral infection. Treatment strategies based on the etiology of liver disease may lead to good clinical outcome.
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http://dx.doi.org/10.1159/000517494DOI Listing
September 2021

Direct Bilirubin in Drainage Fluid 3 days after Hepatectomy Is Useful for Detecting Severe Bile Leakage.

Eur Surg Res 2021 Aug 25:1-7. Epub 2021 Aug 25.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Introduction: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage.

Methods: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared.

Results: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3.

Conclusions: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.
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http://dx.doi.org/10.1159/000518267DOI Listing
August 2021

Skeletal Muscle Loss and Octogenarian Status Are Associated with S-1 Adjuvant Therapy Discontinuation and Poor Prognosis after Pancreatectomy.

Cancers (Basel) 2021 Aug 15;13(16). Epub 2021 Aug 15.

Division of Hepatobiliary and Pancreatic Surgery, Integrative Center of General Surgery, Gunma University Hospital, 3-39-15 Showa-Machi, Maebashi 371-8511, Japan.

The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy <6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy ( < 0.0001 and = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.
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http://dx.doi.org/10.3390/cancers13164105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391507PMC
August 2021

Gastrectomy history as a predictor of post-hepatectomy complications.

Surg Today 2021 Aug 24. Epub 2021 Aug 24.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.

Purpose: The effect of a history of gastrectomy on patients undergoing hepatectomy is unclear. We investigated the relationship between postoperative complications of Clavien-Dindo grade III or higher and a history of gastrectomy in patients undergoing hepatectomy.

Methods: The subjects of this retrospective analysis were 474 consecutive patients who underwent hepatectomy at our institute for hepatic malignancy, classified into groups of those with or without a history of gastrectomy and those with or without postoperative complications. We compared the clinicopathological factors between the groups.

Results: There were no hospital deaths. Gastrectomy history was identified in 22 patients (4.6%) and was significantly associated with advanced age, low body mass index, male sex, decreased serum albumin level, decreased hemoglobin level, low PNI, low CONUT score, high incidence of postoperative complications, and longer hospital stay. Multivariate analyses revealed that the independent risk factors for postoperative complications were gastrectomy history, an albumin-bilirubin score of 2/3, primary liver cancer, high serum creatinine level, advanced age, and prolonged operation time.

Conclusions: Gastrectomy history was an independent predictor of postoperative complications in patients undergoing hepatectomy for hepatic malignancies. Patients with a history of gastrectomy were likely to suffer postoperative bile leakage and pneumonia.
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http://dx.doi.org/10.1007/s00595-021-02366-7DOI Listing
August 2021

Prediction with functional liver volume assessment to achieve the resection limit after portal vein embolization in patients scheduled major hepatectomy.

HPB (Oxford) 2021 Jun 10. Epub 2021 Jun 10.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.

Background: Preoperative portal vein embolization (PVE) stimulates liver hypertrophy and improves the safety of major hepatectomy. It is essential to predict the future remnant liver volume (FRLV) and resection limit following PVE. Previously, we reported that evaluating functional FRLV (fFRLV) using EOB-MRI could predict post-hepatectomy liver failure. In this study, we investigated the usefulness of fFRLV in predicting the achieving of adequate resection limit for safe hepatectomy following PVE.

Methods: We included 55 patients who underwent PVE and were scheduled for major hepatectomy. We calculated the liver-to-muscle ratio in the remnant liver and fFRLV using EOB-MRI. We investigated the pre-PVE variables in determining the nonachievement of the resection limit.

Results: The median observation period between PVE and the first evaluation was 21 days, and the median growth rate of FRLV was 26.4%. In 54.5% of patients, the resection limit of fFRLV (615 mL/m) was achieved. In logistic regression and receiver-operating characteristic analyses, pre-PVE fFRLV (p < 0.001, area under the curve: 0.852) was the reliable predictor of achieving the resection limit; the cutoff value of pre-PVE fFRLV was 446 mL/m.

Conclusion: Pre-PVE fFRLV can be useful in predicting the achievement of adequate resection limit following PVE.
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http://dx.doi.org/10.1016/j.hpb.2021.05.013DOI Listing
June 2021

Systematic review of resectable intraductal tubulopapillary neoplasm with special reference to recurrence patterns.

Surg Today 2021 Jul 1. Epub 2021 Jul 1.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.

Purpose: Intraductal tubulopapillary neoplasm is a rare pancreatic tumor. The purpose of this study was to clarify the recurrence type and prognosis in recurrent cases after intraductal tubulopapillary neoplasm resection.

Methods: PubMed was searched for previous reports on surgical resection of intraductal tubulopapillary neoplasm of the pancreas that were published from 2009 to July 2020. The clinical features obtained from these reports were summarized and analyzed.

Results: The clinicopathological data of 35 intraductal tubulopapillary neoplasm cases were obtained. Of these, 21 were males, and 14 were females, with an average age of 57.9 years old. Invasive findings were observed in 21 of 35 patients (60%). Recurrence was observed in 11 of the 35 cases (31.4%), including remnant pancreatic recurrence in 6 cases (17.1%) and liver metastasis in 5 cases (14.3%). The tumor size was significantly larger in the liver metastasis group than in the remnant pancreas recurrence group (P = 0.04), and patients with liver metastases tended to have a poorer prognosis than those with remnant pancreas recurrence.

Conclusions: The recurrence type of intraductal tubulopapillary neoplasm resection was mainly remnant pancreatic recurrence and liver metastasis recurrence. Total pancreatectomy for remnant pancreatic recurrence may be suitable because of its good prognosis.
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http://dx.doi.org/10.1007/s00595-021-02324-3DOI Listing
July 2021

Impact of preoperative nutritional support and rehabilitation therapy in patients undergoing pancreaticoduodenectomy.

Int J Clin Oncol 2021 Sep 4;26(9):1698-1706. Epub 2021 Jun 4.

Division of Hepatobiliary and Pancreatic Surgery, Integrative Center of General Surgery, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi Gunma, 371-8511, Japan.

Background: Sarcopenia is closely associated with morbidity after pancreatic surgery. We investigated the impact of preoperative nutritional support and rehabilitation on patients undergoing pancreaticoduodenectomy.

Methods: This was a retrospective analysis of 101 patients who underwent pancreaticoduodenectomy. Skeletal muscle (SM) loss was defined using the SM index (cutoff level: 42 cm/m in men and 38 cm/m in women). A total of 33 and 30 patients received preoperative nutrition and prehabilitation, respectively. The neutrophil-to-lymphocyte ratio (NLR), Prognostic Nutritional Index (PNI), and modified Glasgow Prognostic Score (mGPS) values were calculated during the first visit and immediately before surgery.

Results: SM loss was present in 65 of 101 patients and was significantly correlated with female sex, older age, lower body mass index, and low PNI. Preoperative nutritional support and prehabilitation prevented the decrease in PNI values in patients with SM loss. The NLR significantly improved in patients with SM loss who received nutritional support and prehabilitation. In patients with SM loss, the lack of preoperative nutrition and prehabilitation was an independent risk factor for postoperative pancreatic fistula.

Conclusions: Preoperative nutritional support and prehabilitation may reduce the incidence of pancreatic fistula in patients with SM loss and improve the surgical outcomes of patients undergoing pancreaticoduodenectomy.
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http://dx.doi.org/10.1007/s10147-021-01958-0DOI Listing
September 2021

High membrane expression of CMTM6 in hepatocellular carcinoma is associated with tumor recurrence.

Cancer Sci 2021 Aug 29;112(8):3314-3323. Epub 2021 Jun 29.

Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan.

CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) maintains membrane PD-L1 expression by controlling its endosomal recycling. However, in patients with hepatocellular carcinoma (HCC), the correlation among CMTM6, B7 family ligands, and CD8-positive cytotoxic T lymphocytes (CTLs), and the molecular function of CMTM6 in HCC have not been established. We performed immunohistochemistry to evaluate the relationships among CMTM6 expression, clinicopathological factors, B7 family ligands expression, and CTL infiltration in HCC samples. Moreover, we established CMTM6-knockout human HCC cell lines to evaluate the function of human CMTM6 in immune regulation and tumor viability. CMTM6 expression was positively associated with membrane B7 family ligands expression and CTL infiltration in HCC samples. High CMTM6 expression in HCC tissues was associated with the expression of the proliferation marker Ki-67 and shorter recurrence-free survival. In vitro analysis showed the downregulation of membrane B7 family ligands and proliferation potency in the CMTM6-knockout human HCC cell line. High membrane CMTM6 expression was associated with tumor recurrence and proliferation via the regulation of membranous B7 family ligands expression. Thus, CMTM6 might be a biomarker to predict the risk of HCC recurrence and a therapeutic target to suppress tumor growth and increase CTL activity.
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http://dx.doi.org/10.1111/cas.15004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353897PMC
August 2021

FDG-PET for preoperative evaluation of tumor invasion in ampullary cancer: A retrospective analysis.

J Surg Oncol 2021 Sep 12;124(3):317-323. Epub 2021 May 12.

Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.

Background: Tumor invasion is the most significant prognostic factor in ampullary cancer and is thus a crucial factor in decision making for treatment. Endoscopic ultrasound can be performed to evaluate tumor invasion, but its diagnostic accuracy varies depending on the endoscopist. This study aimed to assess the usefulness of fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperatively predicting tumor invasion in ampullary cancer.

Methods: We retrospectively evaluated 44 patients with ampullary cancer (adenoma, n = 6; adenocarcinoma, n = 38) who underwent surgical resection. The SUVmax of the ampullary tumor site was assessed using FDG-PET, and the correlation among tumor invasion, lymph node metastasis, and other clinicopathological factors was evaluated.

Results: The SUVmax of the ampullary tumor site gradually increased depending on the extent of tumor invasion (p = 0.0075). Moreover, the SUVmax was significantly different between ≤T1a and ≥T1b, which is an indication for endoscopic papillectomy or surgical resection (p = 0.0015). The SUVmax of the ampullary section was significantly correlated with lymph node metastasis (p = 0.035).

Conclusion: The SUVmax of the ampullary tumor site is correlated with tumor invasion and lymph node metastasis in ampullary cancer. Thus, FDG-PET can be a useful modality for preoperative staging and treatment strategy.
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http://dx.doi.org/10.1002/jso.26513DOI Listing
September 2021

Hepatic stellate cell as a Mac-2-binding protein-producing cell in patients with liver fibrosis.

Hepatol Res 2021 Oct 29;51(10):1058-1063. Epub 2021 Apr 29.

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Background: Mac-2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum marker of liver fibrosis; M2BPGi is a glycosylated form of M2BP. Hepatocytes and hepatic stellate cells (HSCs) have been studied to determine the source of M2BP. This study proposes to identify the origin of M2BP in fibrotic liver.

Methods: Using liver fibrosis tissue specimens from 15 patients with liver cancer, M2BP mRNA and M2BP were detected by in situ hybridization and immunohistochemistry, respectively. The expression levels of M2BP mRNA were evaluated with scores of 3, 2, and 1. Fluorescent in situ hybridization was carried out to evaluate the distribution of M2BP mRNA and the activated-HSC marker αSMA mRNA; multicolor fluorescent immunohistochemistry was used for protein localization of M2BP, αSMA, and CD68. The Kruskal-Wallis test analyzed the relationship between M2BP mRNA expression and existing serum fibrosis markers.

Results: M2BP mRNA was expressed in spindle-shaped cells along the fibrous septa and in the perisinusoidal area of the fibrotic liver. The HSC markers αSMA mRNA and M2BP mRNA were colocalized in the spindle-shaped cells; on the protein level, M2BP was expressed in Kupffer cells. M2BP mRNA expression was positively correlated with serum M2BPGi levels. Aspartate transaminase-to-platelet ratio index, Fibrosis-4, hyaluronic acid, and the 15-minute indocyanine green retention rate were significantly correlated with M2BP mRNA expression.

Conclusions: M2BP mRNA transcription in fibrotic liver was primarily observed in HSCs but not at the M2BP level, which suggests that HSCs might produce and introduce M2BP to Kupffer cells and serum.
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http://dx.doi.org/10.1111/hepr.13648DOI Listing
October 2021

Conophylline Inhibits Hepatocellular Carcinoma by Inhibiting Activated Cancer-associated Fibroblasts Through Suppression of G Protein-coupled Receptor 68.

Mol Cancer Ther 2021 06 15;20(6):1019-1028. Epub 2021 Mar 15.

Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Gunma University, Graduate School of Medicine, Gunma, Japan.

Treatment of hepatocellular carcinoma (HCC) is currently challenging. Cancer-associated fibroblasts (CAFs) promote the malignancy of HCC cells via production of cytokines. Conophylline (CnP), a vinca alkaloid obtained from leaves, has been reported to suppress activation of hepatic stellate cells and liver fibrosis in rats. We examined the efficacy of CnP in suppressing tumor growth in HCC. Specifically, we investigated whether CnP could inhibit CAFs, which were derived from HCC tissues and Same as previous reports, CAFs promoted proliferative and invasive ability of HCC cells. CnP suppressed α-smooth muscle actin expression of CAFs, and inhibited their cancer-promoting effects. CnP significantly suppressed CAFs producting cytokines such as IL6, IL8, C-C motif chemokine ligand 2, angiogenin, and osteopontin (OPN). Combined therapy with sorafenib and CnP against HCC cells and CAFs showed to inhibit tumor growth the most compared with controls and single treatment with CnP or sorafenib. Transcriptome analysis revealed that GPR68 in CAFs was strongly suppressed by CnP. The cancer-promoting effects of cytokines were eliminated by knockdown of GPR68 in CAFs. CnP inhibited the HCC-promoting effects of CAFs by suppressing several HCC-promoting cytokines secreted by CAFs expressing GPR68. Combination therapy with CnP and existing anticancer agents may be a promising strategy for treating refractory HCC associated with activated CAFs.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0150DOI Listing
June 2021

Unclassified hepatocellular adenoma with beta-catenin mutation: a case report.

Surg Case Rep 2021 Feb 12;7(1):46. Epub 2021 Feb 12.

Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, 22 Showa-Machi, Maebashi, Gunma, 371-8511, Japan.

Background: Hepatocellular adenoma (HCA) subtypes are considered as risk factors for malignant transformation; thus, an accurate diagnosis is important. We report a case of resected HCA previously diagnosed as unclassified HCA using immunohistochemistry, subsequently discovered to harbor a mutation in exon 3 of the beta (β)-catenin gene using deoxyribonucleic acid (DNA) sequencing.

Case Presentation: The patient was a 26-year-old woman who was referred to our hospital because of a 150-mm tumor in the right lobe of the liver. Considering the possibility of malignancy, we performed right lobe hepatectomy. Based on the histopathological and immunohistochemical findings, the tumor was diagnosed as an unclassified HCA. Next, we performed sequencing of DNA isolated from the tumor and identified a mutation in exon 3 of β-catenin, suggesting that the tumor contained an activating mutation of the β-catenin gene.

Conclusion: β-Catenin mutations in HCA cannot be detected by immunohistochemistry alone, and molecular analysis is required to accurately diagnose and evaluate its prognosis.
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http://dx.doi.org/10.1186/s40792-021-01131-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881073PMC
February 2021

Imatinib and nutritional support can make successful treatment for a case of huge liver metastasis of duodenal gastrointestinal stromal tumor that initially showed jaundice and cachexia.

Clin J Gastroenterol 2021 Apr 28;14(2):570-576. Epub 2021 Jan 28.

Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.

It is very difficult to treat patients with liver metastasis presenting with jaundice or cachexia. We herein report a successfully treated case of huge liver metastasis of gastrointestinal stromal tumor (GIST) that initially showed jaundice and cachexia. The patient was a woman in her early 40 s. She had a history of duodenal GIST 4 years before this admission. She was admitted to our hospital for abdominal fullness and anorexia. Abdominal computed tomography revealed huge liver metastasis of GIST. She showed jaundice and cancer cachexia with a modified Glasgow Prognostic Score of 2. After applying nutritional support, 400 mg of imatinib was administered. Although leg edema transiently worsened, the withdrawal of imatinib and administration of diuretics improved it. Imatinib was re-administered, and nutritional support was continued. The total bilirubin level decreased, and the serum albumin level increased. The tumor gradually decreased in size. Finally, she received surgical resection after 16 months of treatment with imatinib. Although adjuvant imatinib administration was continued after surgery, and no recurrence was observed as of 18 months after surgery.
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http://dx.doi.org/10.1007/s12328-021-01340-7DOI Listing
April 2021

Long-term survival of two patients with pancreatic cancer after resection of liver and lung oligometastases: a case report.

Surg Case Rep 2020 Dec 7;6(1):309. Epub 2020 Dec 7.

Gunma University Graduate School of Medicine, Hepatobiliary and Pancreatic Surgery, 3-39-22 Showa-machi, Maebashi, Japan.

Background: The efficacy of resection of pancreatic cancer metastases has not been established. We here report two patients with long-term survival after resection of lung and liver metastases.

Case Presentation: The first patient underwent distal pancreatectomy for pancreatic cancer. One year later, she underwent partial hepatectomy for a single liver metastasis. She subsequently underwent pulmonary resections 7, 7.5, 9, and 10 years later for pulmonary metastases from pancreatic cancer. Thus, this patient underwent five surgeries for metastases, one for a liver metastasis and four for lung metastases. All of the tumors were pathologically diagnosed as metastatic pancreatic cancer. She is currently alive without new recurrence 10 years after the initial diagnosis. The second patient underwent pancreaticoduodenectomy for pancreatic cancer. Four years later, she underwent a thoracoscopic partial resection for lung metastasis. The tumor was similar to the pancreatic cancer on pathological examination. She is currently alive without new recurrences 6 years after the initial diagnosis.

Conclusion: Long-term survival can be achieved in some patients with pancreatic cancer by resection of metachronous liver or lung metastases.
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http://dx.doi.org/10.1186/s40792-020-01029-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721952PMC
December 2020

The Role of the Albumin-Bilirubin Score for Predicting the Outcomes in Japanese Patients with Advanced Hepatocellular Carcinoma Treated with Ramucirumab: A Real-World Study.

Oncology 2021 4;99(4):203-214. Epub 2020 Dec 4.

Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine​, Maebashi, Japan.

Aim: The aim of this retrospective study was to investigate the efficacy and safety of ramucirumab treatment under real-world conditions and to clarify the role of albumin-bilirubin (ALBI) score in predicting outcomes.

Methods: Between June 2019 and May 2020, a total of 16 patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab in Gunma Saiseikai Maebashi Hospital and its affiliated hospitals was included.

Results: The median age was 71 (interquartile range [IQR] 65-74) years old, and 12 patients (75.0%) were male. The modified ALBI (mALBI) grade was 1, 2a, and 2b at baseline in 4 (25.0%), 3 (18.8%), and 9 patients (56.3%), respectively. The Barcelona Clinic Liver Cancer stage was intermediate and advanced stage in 1 (6.3%) and 15 patients (93.8%), respectively. The serum α-fetoprotein at baseline was 4,911 (IQR 2,091-17,377) ng/mL. The disease control rate in patients with mALBI grade1 + 2a was significantly higher than in those with mALBI grade 2b (100 vs. 28.6%, p = 0.028). The patients with mALBI grade 1 + 2a had a significantly better overall survival (OS) and longer progression-free survival (PFS) than those with mALBI grade 2b (median OS 6.7 vs. 3.0 months; p = 0.036, median PFS 7.5 vs. 1.4 months; p = 0.002). The number of cycles of ramucirumab treatment was significantly correlated with the ALBI score (r = -0.452, p = 0.030). The patients with mALBI grade 1 + 2a showed a low incidence of adverse events (AEs) and discontinuation due to AEs.

Conclusions: Advanced HCC patients with mALBI grade 1 + 2a may be a good indication for ramucirumab treatment.
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http://dx.doi.org/10.1159/000511734DOI Listing
April 2021

The development of broncho-biliary fistula after treatment for hepatocellular carcinoma: a report of two cases.

Clin J Gastroenterol 2021 Feb 24;14(1):229-237. Epub 2020 Oct 24.

Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Broncho-biliary fistula (BBF) is a rare but severe disorder defined as abnormal communication between the biliary system and bronchial tree. Cases of BBF have occasionally been reported, but no standard treatment has been established. We report two cases of BBF that developed after the treatment of hepatocellular carcinoma (HCC) and reviewed the relevant literature. Case 1, a man in his early eighties was diagnosed with BBF 4 months after undergoing surgical resection for HCC (diameter, 7 cm; location, segments 4 and 5). Percutaneous drainage and endoscopic nasobiliary drainage (ENBD) improved BBF without recurrence for more than a year. Case 2, a woman in her late sixties was diagnosed with BBF after percutaneous radiofrequency ablation for HCC. Although the BBF was treated with ENBD, bronchial occlusion, and percutaneous transhepatic portal vein embolization, these treatments were unsuccessful and the patient died. Although non-invasive treatments have been developed, refractory BBF still exists. The prediction of BBF and the development of more effective treatments are necessary to improve outcomes.
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http://dx.doi.org/10.1007/s12328-020-01264-8DOI Listing
February 2021

Evaluation of overall and disease-free survival in patients with free flaps for oral cancer resection.

Microsurgery 2020 Nov 21;40(8):859-867. Epub 2020 Oct 21.

Department of Oral and Maxillofacial Surgery, and Plastic Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.

Purpose: Sarcopenia is characterized by depletion of skeletal muscle mass (SMM) and can cause increased postoperative complication in free flap procedure. One of the most important considerations while deciding the indication of the procedure is patients' survival. This study aimed to verify the relationship between low SMM and survival in patients who undergo oral cancer resection using free flap.

Methods: SMM was evaluated using the skeletal muscle index (SMI cm /m ), which was defined using cross-sectional areas of skeletal muscles on computed tomography at the level of the third lumbar vertebrae normalized for height. Overall, 111 patients who underwent primary oral cancer resection and free flaps were included. Multivariate Cox regression analyses were used to evaluate the prognostic factors for survival.

Results: A total of 25 patients (22.5%) were diagnosed with low SMM. The mean SMI was 42.2 cm /m . Multivariable analyses showed that increased age (hazard ratio [HR]; 4.98, p = .004), infiltrative growth pattern INF-c (HR; 3.83, p = .037), and low SMM (HR; 2.59, p = .034) were significant negative prognostic factors for overall survival. Increased age (HR; 3.18, p = .005), extra-nodal extension (HR; 3.30, p = .001), and low SMM (HR; 2.42, p = .017) were significant negative prognostic factors for disease-free survival.

Conclusions: Low SMM is a significant negative prognostic factor for overall and disease-free survival in oral cancer patients undergoing free flap. Future prospective studies are warranted to identify effective preoperative exercise and nutrition programs to improve low skeletal muscle and survival rate in patients undergoing free flap procedures.
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http://dx.doi.org/10.1002/micr.30668DOI Listing
November 2020

Liver Function Changes in Patients with Hepatocellular Carcinoma Treated with Lenvatinib: Predictive Factors of Progression to Child-Pugh Class B, the Formation of Ascites and the Candidates for the Post-Progression Treatment.

Cancers (Basel) 2020 Oct 10;12(10). Epub 2020 Oct 10.

Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-15 Showa, Maebashi, Gunma 371-8511, Japan.

The aim of this multicenter retrospective study was to assess the change in liver function in patients with hepatocellular carcinoma treated with lenvatinib. Among 139 consecutive patients receiving lenvatinib treatment between March 2018 and July 2019, 28 patients with Child-Pugh class B and one patient with inadequate patient information were excluded. Remaining 110 patients with Child-Pugh class A were analyzed. The median age of 110 patients was 73 years (IQR 66.7-80) and 88 patients (80.0%) were men. Child-Pugh score was 5 (CP5A) and 6 (CP6A) in 58 (52.7%) and 52 patients (47.3%), and ALBI grade was 1 and 2 in 38 (34.5%) and 72 patients (65.5%), respectively. The deterioration to Child-Pugh class B was found in 43 patients (39.1%) during the lenvatinib treatment. The favorable factors related to preserving liver function were significantly shown to be male, ALBI grade 1, CP5A and BCLC early or intermediate stage in the multivariate analysis. The formation of ascites was found in 32 patients (28.6%). The significant unfavorable factors associated with the formation of ascites were found to be low platelet count and CP6A. Among the 79 patients, there were 36 (45.6%) and 11 patients (13.9%) who fulfilled the criteria for candidate for the post-progression treatment and ramucirumab treatment, respectively. The predictive factors of the post-progression treatment were shown to be ALBI grade 1 and CP5A in multivariate analysis. In conclusion, male, ALBI grade 1, CP5A and BCLC early or intermediate stage were favorable factors related to sustaining liver function and the patients with ALBI grade 1 and CP5A were eligible for the post-progression treatment. Careful screening for ascites was needed in patients with low platelet count and CP6A.
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http://dx.doi.org/10.3390/cancers12102906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601832PMC
October 2020

Author response to: Comment on: Right hepatic venous system variation in living donors: a three-dimensional CT analysis.

Br J Surg 2020 12 29;107(13):e653. Epub 2020 Sep 29.

Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

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http://dx.doi.org/10.1002/bjs.11983DOI Listing
December 2020

Author response to: Comment on: Right hepatic venous system variation in living donors: a three-dimensional CT analysis.

Br J Surg 2020 11 16;107(12):e608. Epub 2020 Sep 16.

Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

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http://dx.doi.org/10.1002/bjs.11825DOI Listing
November 2020

Diffusion-Weighted MRI Predicts Lymph Node Metastasis and Tumor Aggressiveness in Resectable Pancreatic Neuroendocrine Tumors.

World J Surg 2020 Dec 14;44(12):4136-4141. Epub 2020 Aug 14.

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.

Objectives: The aim of this study was to identify whether diffusion-weighted magnetic resonance imaging (DW-MRI) can predict the malignant behavior of preoperative well-differentiated pancreatic neuroendocrine tumors (PanNETs).

Method: Forty patients with PanNETs who underwent pancreatectomy were enrolled in this study. The apparent diffusion coefficient (ADC) values were measured. Clinicopathological factors were compared in patients with high ADC and low ADC values and in patients with and without lymph node metastasis (LNM).

Result: The low ADC group was significantly associated with higher Ki-67 index, higher mitotic count, larger tumor size, higher rate of LNM, and venous invasion. In patients with low ADC values, the incidence of LNMs was 33.3%. In patients with high ADC values, there were no patients with LNM being 0%. A significant negative correlation was found between the mean ADC values and the Ki-67 index and between the mean ADC values and the mitotic count. In multivariate analysis, neural invasion and mean ADC values ≤ 1458 were independent predictors of LNM.

Conclusion: ADC values obtained using DW-MRI in the preoperative assessment of patients with PanNETs might be a useful predictor of malignant potential, especially LNM.
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http://dx.doi.org/10.1007/s00268-020-05736-3DOI Listing
December 2020

Multimodal approach to portal hypertension and gastric varices before hepatic resection for hepatocellular carcinoma: a case report.

Surg Case Rep 2020 Jul 31;6(1):190. Epub 2020 Jul 31.

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, 3-39-22, Showamachi, Maebashi, 371-8511, Japan.

Background: Liver cirrhosis occurs in approximately 80-90% of patients with hepatocellular carcinoma (HCC), and hepatic resection may be dangerous because of well-documented liver cirrhosis, which may be accompanied by portal hypertension (PH). Here we report a patient with advanced HCC with gastric varices and PH who experienced a good clinical course after undergoing balloon-occluded retrograde transvenous obliteration (BRTO), percutaneous transhepatic portal vein embolization (PTPE), hand-assisted laparoscopic (HALS) splenectomy, and right lobectomy of the liver.

Case Presentation: A 72-year-old man had two HCCs with gastric varices. CT revealed one tumor (4.5 cm) located in segment 7, involving the right hepatic vein, adjacent to the middle hepatic vein. Another tumor (2.7 cm) was located in segment 6. He first underwent BRTO for gastric varices and PTPE for planned right lobectomy of the liver. To reduce PH, HALS splenectomy was performed, and uncomplicated right lobectomy of the liver was performed 10 weeks after the first visit. He has remained free of recurrence for at least 1 year.

Conclusions: Our patient underwent uncomplicated BRTO, PTPE, HALS splenectomy, and right lobectomy of the liver for advanced HCC with PH. Controlling portal pressure is important when hepatic resection is required to treat HCC with PH.
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http://dx.doi.org/10.1186/s40792-020-00952-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394985PMC
July 2020

Association between intraoperative and postoperative epidural or intravenous patient-controlled analgesia and pancreatic fistula after distal pancreatectomy.

Surg Today 2021 Feb 30;51(2):276-284. Epub 2020 Jul 30.

Department of Hepatobiliary and Pancreatic Surgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Purpose: This study aimed to elucidate the association between postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) and clinicopathological factors and intraoperative and postoperative epidural or intravenous patient-controlled analgesia (IV-PCA).

Methods: We reviewed data of 116 patients who underwent distal pancreatectomy at Gunma University Hospital from October 2000 to October 2019. Clinical POPF was defined as the International Study Group of Pancreatic Fistula grade B or C.

Results: Intraoperative and postoperative analgesia included fentanyl-mediated IV-PCA (n = 37, 32%), fentanyl-mediated epidural analgesia (n = 39, 34%), and morphine-mediated epidural analgesia (n = 40, 34%). All patients had received analgesia. Clinical POPF occurred in 34 of the 116 (29%) DP cases. Male sex (P = 0.035) and the length of operation time (P = 0.0070) were significant risk factors of clinical POPF. Furthermore, a thick pancreas was more likely to cause clinical POPF than a thin one (P = 0.052). No statistically significant difference was found between other factors, including intraoperative and postoperative analgesia (P = 0.95), total median oral morphine equivalents (P = 0.23), and clinical POPF.

Conclusion: Intraoperative and postoperative epidural analgesia and IV-PCA are not associated with clinical POPF after DP. Our results suggest that morphine and fentanyl can be used as IV-PCA or epidural analgesia.
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http://dx.doi.org/10.1007/s00595-020-02087-3DOI Listing
February 2021

Predictors of Postoperative Ascites After Hepatic Resection in Patients With Hepatocellular Carcinoma.

Anticancer Res 2020 Aug;40(8):4343-4349

Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Background: We retrospectively investigated factors predictive for ascites after hepatic resection to treat hepatocellular carcinoma (HCC).

Patients And Methods: The data of 114 patients with HCC who underwent curative hepatic resection were reviewed. The patients were assigned to two groups according to the presence or not of postoperative ascites.

Results: Ascites occurred in 16 patients (14.0%), and refractory ascites in four (3.5%). A MAC2-binding protein glycosylation isomer (M2BPGi) cutoff index of 1.61 [sensitivity=75.0%, specificity 67.9%, area under the curve (AUC)=0.745] and virtual touch tissue quantification (VTQ) of 2.62 (sensitivity=68.8%, specificity=89.8%, AUC=0.827) were the best cut-off values. Patients with ascites had lower serum albumin levels, higher serum creatinine levels, higher albumin-bilirubin (ALBI) grade, higher M2BPGi, higher VTQ, and longer operative time. ALBI grade 2 and both M2BPGi>1.61 and VTQ>2.62 were independent predictors of postoperative ascites.

Conclusion: We demonstrated retrospectively that ALBI grade 2 and both high M2BPGi and VTQ were independent predictors of postoperative ascites in patients undergoing hepatic resection for HCC.
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http://dx.doi.org/10.21873/anticanres.14437DOI Listing
August 2020

Mac-2-binding protein glycan isomer enhances the aggressiveness of hepatocellular carcinoma by activating mTOR signaling.

Br J Cancer 2020 09 6;123(7):1145-1153. Epub 2020 Jul 6.

Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Graduate School of Medicine, 3-39-22 Showamachi, Maebashi, 371-8511, Gunma, Japan.

Background: Wisteria floribunda agglutinin (WFA) Mac-2-binding protein (M2BPGi) is a novel serum marker for liver fibrosis. Although an elevated serum level of M2BPGi can predict development of hepatocellular carcinoma (HCC), the effect of M2BPGi on HCC remains unclear. There are no reports about the association of M2BPGi with HCC aggressiveness. We aimed to clarify the significance of M2BPGi in HCC.

Methods: The protein expression of M2BPGi and galectin-3, a ligand of M2BP, and the mRNA expression of M2BP were evaluated in surgically resected human HCC samples. M2BPGi-regulating signals in HCC cells were investigated using transcriptome analysis. The effects of M2BPGi on HCC properties and galectin-3/mTOR signaling were evaluated.

Results: M2BPGi and galectin-3 proteins co-localised in HCC cells, while M2BP mRNA was detected in cirrhotic liver stromal cells. mTOR signaling was upregulated in M2BPGi-treated HCC cells. Moreover, M2BPGi treatment induced tumour-promoting effects on HCC in vitro by activated mTOR signaling. In addition, M2BPGi bound to galectin-3 to induce membranous galectin-3 expression in HCC cells. In vivo, M2BPGi enhanced the growth of xenografted HCC.

Conclusions: M2BPGi is produced in stromal cells of the cirrhotic liver. Furthermore, M2BPGi enhances the progression of HCC through the galectin-3/mTOR pathway.
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http://dx.doi.org/10.1038/s41416-020-0971-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525442PMC
September 2020

Efficiency of regional functional liver volume assessment using Gd-EOB-DTPA-enhanced magnetic resonance imaging for hepatocellular carcinoma with portal vein tumor thrombus.

Surg Today 2020 Nov 1;50(11):1496-1506. Epub 2020 Jul 1.

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Purpose: We investigated whether functional future remnant liver volume (fFRLV), assessed using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), could evaluate regional liver function in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and help establish the indication for hepatectomy.

Methods: The subjects of this study were 12 patients with PVTT [PVTT(+) group] and 58 patients without PVTT [PVTT(-) group], from among 191 patients who underwent hepatectomy of more than one segment for HCC. We calculated the liver-to-muscle ratio (LMR) in the remnant liver, using EOB-MRI and fFRLV. Preoperative factors and surgical outcome were compared between the groups. The LMR of the area occluded by PVTT was compared with that of the non-occluded area.

Results: The indocyanine green retention rate at 15 min (ICG-R15) and liver fibrosis indices were increased in the PVTT(+) group, but the surgical outcomes of patients in this group were acceptable, with no liver failure, no mortality, and no differences from those in the PVTT(-) group. The fFRLV in the PVTT(+) group was not significantly different from that in the PVTT(-) group (p = 0.663). The LMR was significantly lower in the occluded area than in the non-occluded area (p = 0.004), indicating decreased liver function.

Conclusion: Assessing fFRLV using EOB-MRI could be useful for evaluating regional liver function and establishing operative indications for HCC with PVTT.
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http://dx.doi.org/10.1007/s00595-020-02062-yDOI Listing
November 2020

Liver metastasis from papillary thyroid carcinoma treated by laparoscopic hepatectomy 43 years after resection of the primary tumor: a case report.

Surg Case Rep 2020 Jun 18;6(1):142. Epub 2020 Jun 18.

Division of Hepatobiliary and Pancreatic Surgery, Integrative Center of General Surgery, Gunma University Hospital, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.

Background: Papillary thyroid carcinoma (PTC) generally has a good prognosis, while liver metastasis from PTC is rare and difficult to diagnose.

Case Presentation: A 67-year-old woman was diagnosed with PTC and underwent a left hemithyroidectomy 43 years ago. Two years ago, thoracoscopic right middle lobectomy was performed for a lung tumor, and pathology reports confirmed a metastatic lung tumor of PTC. The patient was followed up regularly with computed tomography, and a liver tumor measuring 16 mm was found in the lateral segment of the liver. Fluorodeoxyglucose positron emission tomography (FDG-PET) was negative for liver tumor. However, FDG uptake was observed at the nodule outside the right lobe of the thyroid gland, suggesting metastasis to the right supraclavicular lymph node. Laparoscopic partial S2 hepatectomy was performed without complications. The final diagnosis was metastatic liver tumor from PTC, and the surgical margins were free of tumor. Postoperatively, the patient underwent complementary thyroidectomy and right supraclavicular lymph node dissection, followed by I-131 ablation. The final diagnosis was PTC of 7 mm and 4 mm and lymph node metastasis of 9 mm. The patient is currently doing well and has had no recurrence 1 year after surgery.

Conclusions: This case demonstrates that liver metastases from PTC may be found after long-term follow-up, and liver resection might be the most appropriate treatment.
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http://dx.doi.org/10.1186/s40792-020-00906-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7303250PMC
June 2020

Rare metastatic pancreatic tumors from lung cancer with cystic changes resembling intraductal papillary mucinous neoplasm: a case report.

Surg Case Rep 2020 May 28;6(1):117. Epub 2020 May 28.

Department of General Surgical Science, Division of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Gunma University, 3-39-15 Showamachi, Maebashi, Gunma, 371-8511, Japan.

Background: Metastatic pancreatic tumors from lung cancer (MPTLC) constitute 3% of all metastatic pancreatic tumors. We present an extremely rare case of cystic MPTLC that was difficult to distinguish from intraductal papillary mucinous neoplasm (IPMN).

Case Presentation: The patient was a 74-year-old woman who underwent lobectomy of lung cancer 2 years before presentation to our hospital. She was referred to our department for resection of cystic pancreatic tumors, which were diagnosed as IPMN with high-risk stigmata. Abdominal computed tomography (CT) showed a 37-mm-wide cystic tumor with a contrasted solid nodule in the pancreatic head and a 17-mm-wide cystic tumor in the pancreatic tail. We performed a total pancreatectomy for these lesions. According to histopathological and immunohistochemical findings, the tumors were diagnosed as metastatic pancreatic tumors from lung cancer.

Conclusion: In this case, the cystic morphology was formed by eosinophilic secretions from tumor cells, and it was difficult to distinguish from IPMN with high-risk stigmata. We consider this case, based on the variable clinical findings, an extremely rare variant of MPTLC.
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http://dx.doi.org/10.1186/s40792-020-00870-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256150PMC
May 2020

A Resected Case of Follicular Cholangitis That Was Positive on F-fluorodeoxyglucose-positron Emission Tomography.

Intern Med 2020 Sep 23;59(17):2123-2128. Epub 2020 May 23.

Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Japan.

We experienced a case of follicular cholangitis that was positive on fluorodeoxyglucose-positron emission tomography (F-FDG-PET). A 70-year-old man was admitted for jaundice. Endoscopic retrograde cholangiography showed stenosis of the middle to upper choledocus. F-FDG-PET depicted a localized hot spot at the stenotic lesion (maximum standardized uptake value = 8.2). Although no malignant findings were found in the cytology or on a bile duct biopsy, malignancy could not be excluded, so surgical treatment was performed. Follicular cholangitis is a new, rare disease that causes severe biliary stricture. Only 11 cases of follicular cholangitis have been reported, including the present case.
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http://dx.doi.org/10.2169/internalmedicine.4611-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516323PMC
September 2020
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