Publications by authors named "Asahi Sato"

26 Publications

  • Page 1 of 1

Diffuse large B-cell lymphoma in the liver accompanied by primary biliary cholangitis: A rare and difficult-to-diagnose tumor with portal venous thrombosis.

Int J Surg Case Rep 2021 May 30;82:105936. Epub 2021 Apr 30.

Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga 524-8524, Japan. Electronic address:

Introduction And Importance: The most common liver malignancies are hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic tumors. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma may invade the portal vein (PV). An association between diffuse large B-cell lymphoma (DLBCL) and primary biliary cholangitis (PBC) remains unclear. We herein report a thought-provoking case of a difficult-to-diagnose liver tumor with PV thrombosis in a PBC patient.

Presentation Of Case: A 66-year-old woman had PBC, systemic sclerosis, diabetes, and osteoporosis. A solitary liver tumor accompanied by macrovascular thrombosis in the PV was detected incidentally. Based on dynamic imaging findings, we considered the tumor to be intrahepatic cholangiocarcinoma, and right lobectomy with lymphadenectomy was performed. Unexpectedly, pathological assessment made a definitive diagnosis of DLBCL that did not invade the vessels and bile duct. In fluorine-18-fluorodeoxyglucose positron emission tomography, abnormal accumulations were clearly observed in the breast tissue and peritracheal, parasternal, mediastinal, and pericardial lymph nodes. The patient achieved complete remission after systemic chemotherapy, and there has been no recurrence 3 years after surgery.

Clinical Discussion: Primary lymphoma in the liver is rare, and we did not consider our patient's tumor as primary liver lymphoma. Our case actually showed no tumor thrombosis in the PV. Although autoimmune disorders may increase the risk of non-Hodgkin's lymphoma, an association between DLBCL and PBC is still unclear, and we must remember that DLBCL may develop rarely in a PBC patient.

Conclusion: Our case report provides a timely reminder for clinicians and surgeons in the fields of hepatology and hematology.
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http://dx.doi.org/10.1016/j.ijscr.2021.105936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114119PMC
May 2021

Fatal arterial hemorrhage after pancreaticoduodenectomy: How do we simultaneously accomplish complete hemostasis and hepatic arterial flow?

World J Hepatol 2021 Apr;13(4):483-503

Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan.

Background: Although arterial hemorrhage after pancreaticoduodenectomy (PD) is not frequent, it is fatal. Arterial hemorrhage is caused by pseudoaneurysm rupture, and the gastroduodenal artery stump and hepatic artery (HA) are frequent culprit vessels. Diagnostic procedures and imaging modalities are associated with certain difficulties. Simultaneous accomplishment of complete hemostasis and HA flow preservation is difficult after PD. Although complete hemostasis may be obtained by endovascular treatment (EVT) or surgery, liver infarction caused by hepatic ischemia and/or liver abscesses caused by biliary ischemia may occur. We herein discuss therapeutic options for fatal arterial hemorrhage after PD.

Aim: To present our data here along with a discussion of therapeutic strategies for fatal arterial hemorrhage after PD.

Methods: We retrospectively investigated 16 patients who developed arterial hemorrhage after PD. The patients' clinical characteristics, diagnostic procedures, actual treatments [transcatheter arterial embolization (TAE), stent-graft placement, or surgery], clinical courses, and outcomes were evaluated.

Results: The frequency of arterial hemorrhage after PD was 5.5%. Pancreatic leakage was observed in 12 patients. The onset of hemorrhage occurred at a median of 18 d after PD. Sentinel bleeding was observed in five patients. The initial EVT procedures were stent-graft placement in seven patients, TAE in six patients, and combined therapy in two patients. The rate of technical success of the initial EVT was 75.0%, and additional EVTs were performed in four patients. Surgical approaches including arterioportal shunting were performed in eight patients. Liver infarction was observed in two patients after TAE. Two patients showed a poor outcome even after successful EVT. These four patients with poor clinical courses and outcomes had a poor clinical condition before EVT. Fourteen patients were successfully treated.

Conclusion: Transcatheter placement of a covered stent may be useful for simultaneous accomplishment of complete hemostasis and HA flow preservation.
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http://dx.doi.org/10.4254/wjh.v13.i4.483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080554PMC
April 2021

Aggressive Resection of Malignant Paraaortic and Pelvic Tumors Accompanied by Arterial Reconstruction with Synthetic Arterial Graft.

Am J Case Rep 2021 May 1;22:e931569. Epub 2021 May 1.

Department of Surgery, Shiga General Hospital, Moriyama, Shiga, Japan.

BACKGROUND Advanced malignancies in the lower abdomen easily invade the retroperitoneal and pelvic space and often metastasize to the paraaortic and pelvic lymph nodes (LNs), resulting in paraaortic and/or pelvic tumor (PPT). CASE REPORT A total of 7 cases of aggressive malignant PPT resection and orthotopic replacement of the abdominal aorta and/or iliac arteries with synthetic arterial graft (SAG) were experienced during 16 years. We present our experience with aggressive resection of malignant PPTs accompanied by arterial reconstruction with SAG in detail. The primary diseases included 2 cases endometrial cancer and 2 cases of rectal cancer, and 1 case each of ovarian carcinosarcoma, vaginal malignant melanoma, and sigmoid cancer. Surgical procedures are described in detail. Briefly, the abdominal aorta and iliac arteries were anastomosed to the SAG by continuous running suture using unabsorbent polypropylene. Five Y-shaped and 2 I-shaped SAGs were used. This en bloc resection actually provided safe surgical margins, and tumor exposures were not pathologically observed in the cut surfaces. Graphical and surgical curability were obtained in all cases in which aggressive malignant PPT resections were performed. The short-term postoperative course of our patients was uneventful. From a vascular perspective, the SAGs remained patent over the long term after surgery, and long-term oncologic outcomes were satisfactory. CONCLUSIONS To our knowledge, this case series is the first report of aggressive malignant PPT resection accompanied by arterial reconstruction with SAG. This procedure is safe and feasible, shows curative potential, and may play a role in multidisciplinary management of malignant PPTs.
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http://dx.doi.org/10.12659/AJCR.931569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097745PMC
May 2021

Mucinous Cystic Adenoma of the Liver: A Thought-Provoking Case of an Uncommon Hepatic Neoplasm.

Am J Case Rep 2021 Apr 3;22:e931368. Epub 2021 Apr 3.

Department of Surgery, Shiga General Hospital, Moriyama, Shiga, Japan.

BACKGROUND Mucinous cystic neoplasm (MCN) of the liver is a rare hepatic neoplasm: a cystic, mucus-producing tumor. Histopathologic examination reveals ovarian-like stroma. The origin of MCN of the liver is still unknown, although ectopic ovarian-like stroma in the liver has been suggested as a possibility. We document a thought-provoking case of MCN of the liver, and intratumoral fatty tissue may support the opinion that ectopic ovarian-like stroma in the liver is a possible origin for both MCN and ovarian teratoma. CASE REPORT An expansive 10.5-cm cystic tumor was incidentally detected in a 71-year-old woman. Imaging studies revealed that the tumor was multiloculated, with cyst contents comprising mucus, muddy-looking fluid (inspissated bile), and hematoma. Imaging studies revealed fatty tissue and calcifications in the cyst walls. The diagnosis of MCN of the liver was made, although MCNs have never been reported to include fatty tissue. Extended left lobectomy was performed, and the tumor was curatively removed without any rupture. A multilocular cyst, mucus, calcifications, and fatty tissue were clearly observed on gross inspection. Histopathological examination revealed ovarian-like stroma. Evidence of malignancy was not detected. Her postoperative course was uneventful. To the best of our knowledge, our patient is the first case of MCN of the liver with intratumoral fatty tissue. This case may support the hypothesis that MCN originates from ectopic ovarian-like stroma in the liver. CONCLUSIONS We documented a thought-provoking case of MCN of the liver in detail, and this MCN accompanied with fatty tissue might originate from ectopic ovarian-like stroma.
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http://dx.doi.org/10.12659/AJCR.931368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8029594PMC
April 2021

Adrenocorticotropic hormone-dependent hypercortisolism caused by pancreatic neuroendocrine carcinoma: A thought-provoking but remorseful case of delayed diagnosis.

Int J Surg Case Rep 2021 Apr 5;81:105729. Epub 2021 Mar 5.

Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan. Electronic address:

Introduction And Importance: Definitive diagnosis of functioning neuroendocrine neoplasms (NENs) in the pancreas is challenging. Adrenocorticotropic hormone (ACTH) regulates adrenal cortisol production. Ectopic ACTH secretion by functioning NENs may cause hypercortisolism.

Presentation Of Case: A 62-year-old woman who was receiving medications for hypertension and hyperlipidemia was referred to our hospital because of abnormal blood tests. Diabetes mellitus was initially diagnosed. Dynamic computed tomography and endoscopic ultrasound revealed a 35-mm diameter hypovascular tumor in the distal pancreas and multiple liver metastases. Endoscopic ultrasound-guided fine-needle aspiration resulted in a diagnosis of neuroendocrine carcinoma. The patient developed pancreatic leakage progressing to peritonitis, abscess formation, pleural effusion, and ascites after the fine-needle aspiration biopsy. Her clinical condition deteriorated to a septic state, necessitating emergency surgery comprising distal pancreatectomy, intraperitoneal lavage, and drainage. Wound healing was protracted and accompanied by ongoing high white blood cell counts and neutrophilia. She also developed a gastric ulcer postoperatively. Systematic endocrine investigations were performed because hypercortisolism caused by a functioning NEN was suspected. Eventually, a definitive diagnosis of an ACTH-producing NEN in the pancreas was made. Systemic chemotherapy was proposed; however, the patient and her family opted for palliative treatment only. She died 42 days after the initial diagnosis.

Clinical Discussion: We here present a patient with ACTH-dependent hypercortisolism attributable to a pancreatic NEN who died of progressive cancer after a delay in definitive diagnosis.

Conclusion: Detailed investigation, including systematic endocrine examination and functional imaging studies, are important for precise diagnosis of, and appropriate treatment for, NENs.
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http://dx.doi.org/10.1016/j.ijscr.2021.105729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957145PMC
April 2021

Ectopic endometriosis, menstruation, and acute appendicitis: A thought-provoking case.

Int J Surg Case Rep 2021 Mar 1;80:105605. Epub 2021 Feb 1.

Department of Surgery, Shiga General Hospital, Moriyama, 5-4-30 Moriyama, Moriyama, Shiga 524-8524, Japan. Electronic address:

Introduction And Importance: Ectopic endometrium in the appendix is rare. The relationships between ectopic endometrium in the alimentary tract and digestive symptoms and between digestive symptoms due to ectopic endometriosis and periodic menstruation are controversial. We herein describe the successful treatment of acute appendicitis that we suspect was caused by ectopic endometriosis and periodic menstruation.

Presentation Of Case: A 38.9-year-old multipara with uterine didelphys developed lower abdominal pain during menstruation, and she was clinically diagnosed with acute appendicitis. She received conservative management with cephem antibiotics, and her pain disappeared uneventfully. However, the lower abdominal pain during menstruation later recurred, and she again received conservative treatment. Laparoscopic appendectomy was subsequently performed because for 4 months, her appendicitis-induced digestive symptoms had recurred in association with periodic menstruation. Ectopic endometrial gland proliferations were histopathologically observed in the proper muscular layer of the appendiceal tip. She developed no further episodes of digestive symptoms postoperatively.

Clinical Discussion: Ectopic endometriosis of the alimentary tract may be accompanied by digestive symptoms; moreover, these symptoms may be related to periodic menstruation. However, the sensitivity of ectopic endometrium to hormones shows considerable variation among patients. We speculate that the acute appendicitis might have been triggered by ectopic endometriosis in our case because the patient developed repeated digestive symptoms in association with periodic menstruation. Ectopic endometrium may be incidentally observed in histopathological assessments of resected specimens. The therapeutic strategy should be carefully decided on a case-by-case basis.

Conclusion: We hope this thought-provoking case provides a timely reminder for gastrointestinal clinicians and general surgeons.
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http://dx.doi.org/10.1016/j.ijscr.2021.01.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893425PMC
March 2021

Acute intestinal infarction caused by initially unexplained splanchnic venous thromboses in a patient with protein C deficiency: A thought-provoking emergency case.

Int J Surg Case Rep 2021 Feb 22;79:390-393. Epub 2021 Jan 22.

Department of Surgery, Shiga General Hospital, 5-4-30 Moriyama, Moriyama, Shiga, 524-8524, Japan. Electronic address:

Introduction And Importance: Splanchnic venous thrombosis (SVT) originating in the superior mesenteric vein (SMV) is rare and may cause acute intestinal infarction (AII). Protein C deficiency (PCD) results in thrombophilia.

Presentation Of Case: Acute unexplained SVT originating in the SMV and portal vein was detected in 68-year-old man. Pan-peritonitis and AII were diagnosed and emergency surgery performed. Part of the small intestine was necrotic and partial resection without anastomotic reconstruction was performed. Heparin was administered intravenously continuously from postoperative day (POD) 1. Hereditary, heterozygous, type 1 PCD was diagnosed postoperatively. The anastomosis was reconstructed on POD 16. Warfarin was substituted for heparin on POD 22. No recurrent thrombosis occurred during 2 years of follow-up.

Clinical Discussion: Patients with the rare condition of SVT require prompt diagnosis and treatment and may have underlying disease. PCD can cause SVT even in intact veins and anticoagulation therapy should be administered immediately postoperatively. Misdiagnosis and/or delayed treatment of SVT can result in AII, a life-threatening condition with a high mortality rate. Insufficient clinician awareness can result in serious mismanagement of patients with PCD and SVT; emergency patients with AII caused by unexplained SVT should therefore be further investigated for prothrombotic states and assessment of coagulation-fibrinolysis profiles to clarify the underlying mechanism.

Conclusion: We here present a thought-provoking emergency case of AII associated with acute SVT caused by underlying PCD that was successfully treated by two-stage surgery and anticoagulation therapy. This case provides a timely reminder for emergency clinicians and gastrointestinal surgeons.
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http://dx.doi.org/10.1016/j.ijscr.2021.01.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848722PMC
February 2021

Impact of vascular abnormality on contrast-enhanced CT and high C-reactive protein levels on postoperative pancreatic hemorrhage after pancreaticoduodenectomy: A multi-institutional, retrospective analysis of 590 consecutive cases.

Pancreatology 2021 Jan 1;21(1):263-268. Epub 2020 Dec 1.

Department of Surgery, Division of Hepato-biliary-pancreatic Surgery and Transplantation, Kyoto University, Japan.

Background: /Objectives: This study aimed to elucidate the efficacy of CT findings and perioperative characteristics to predict post-pancreatectomy hemorrhage (PPH): a critical complication after pancreaticoduodenectomy.

Methods: The records of 590 consecutive patients who underwent pancreaticoduodenectomy at three institutes between 2012 and 2018 were included. The presence of a vascular wall abnormality or ascites with high density (vascular abnormality) on postoperative day (POD) 5-10 contrast-enhanced CT (early CT), perioperative characteristics, and any PPH or pseudoaneurysm formation (PPH events) were analyzed through a multivariate analysis.

Results: PPH events occurred in 48 out of 590 patients (8%). The vascular abnormality on early CT and the C-reactive protein (CRP) value on POD 3 were independent risk factors for PPH events after POD5 (vascular abnormality: odds ratio 6.42, p = 0.001; CRP on POD 3: odds ratio 1.17, p = 0.016). The sensitivity of vascular abnormality for PPH events was 24% (7/29), and the positive predictive value was 30% (7/23). The combination of vascular abnormality and a high CRP value (≥15.5 mg/dL) on postoperative day 3 had a higher positive predictive value of 64% (7/11) than the vascular abnormality alone. None of the seven PPH events that occurred more than one month after surgery were foreseen via early CT.

Conclusion: The combination of vascular abnormality and high CRP value was associated with increasing risk of PPH events after pancreaticoduodenectomy, but the low sensitivity of early CT must be noted as an important shortcoming. The normal findings on early CT could not eliminate the risk of late PPH.
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http://dx.doi.org/10.1016/j.pan.2020.11.007DOI Listing
January 2021

Time-frequency analysis of serum with proton nuclear magnetic resonance for diagnosis of pancreatic cancer.

Sci Rep 2020 12 14;10(1):21941. Epub 2020 Dec 14.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Postgraduate School of Medicine, Kyoto University, 54 Shogoin-kawaharacho, Sakyo-ku, Kyoto, Japan.

Although serum markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) have been widely used in screening for pancreatic cancer (PC), their sensitivity and specificity are unsatisfactory. Recently, a novel tool of analyzing serum using the short-time Fourier transform (STFT) of free induction decays (FIDs) obtained by H-NMR has been introduced. We for the first time evaluated the utility of this technology as a diagnostic tool for PC. Serum was obtained from PC patients before starting any treatments. Samples taken from individuals with benign diseases or donors for liver transplantation were obtained as controls. Serum samples from both groups underwent H-NMR and STFT of FIDs. STFT data were analyzed by partial least squares discriminant analysis (PLS-DA) to clarify whether differences were apparent between groups. As a result, PLS-DA score plots indicated that STFT of FIDs enabled effective classification of groups with and without PC. Additionally, in a subgroup of PC, long-term survivors (≥ 2 years) could be discriminated from short-term survivors (< 2 years), regardless of pathologic stage or CEA or CA19-9 levels. In conclusion, STFT of FIDs obtained from H-NMR have a potential to be a diagnostic and prognostic tool of PC.
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http://dx.doi.org/10.1038/s41598-020-79087-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736857PMC
December 2020

Do liver metastases from gastric cancer contraindicate aggressive surgical resection? A 14-year single-center experience.

World J Gastrointest Pharmacol Ther 2020 Nov;11(5):110-122

Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan.

Background: Advanced gastric cancer (GC) with liver metastasis is often characterized by multiple and bilobular metastases and may also be associated with extrahepatic metastatic lesions. Hence, many physicians consider that radical surgeries are contraindicated for liver metastases from GC (LMGC). According to the 2017 Japanese treatment guideline for GC, a smaller number of liver metastases without unresectable factors may be an indication for liver resection (LR) with curability. The actual 5-year overall survival (OS) rate ranges from 0 to 0.37.

Aim: To present the institutional indications for LR for LMGC and identify important factors for prognostic outcomes.

Methods: In total, 30 patients underwent LR for LMGC during a 14-year period, and we evaluated the clinical, surgical, and oncological findings. In all patients, radical surgery with intentional lymphadenectomy was performed for the primary GC. The median follow-up duration after the initial LR was 33.7 mo, and three patients with no recurrence died of causes unrelated to the LMGC. The OS and recurrence-free survival rates after the initial LR were assessed.

Results: Seventeen patients had metachronous LMGC. The initial LR achieved curability in 29 patients. Perioperative chemotherapy was introduced in 23 patients. The median greatest LMGC dimension was 30 mm, and the median number of LMGC was two. Twenty-two patients had unilobular LMGC. The 5-year OS and recurrence-free survival rates were 0.48 and 0.28, respectively. The median survival duration and recurrence-free duration after the initial LR were 16.8 and 8.6 mo, respectively. Twenty-one patients developed recurrence after the initial LR. Additional surgeries for recurrence were performed in nine patients, and these surgeries clearly prolonged the patients' survival. Pathological serosal invasion was an independent predictor of a poor prognostic outcome after the initial LR. Aggressive LR may be indicated for carefully selected patients with LMGC.

Conclusion: Our results of LR for LMGC seem acceptable. Additional surgeries for recurrence after the initial LR might prolong OS. Pathological serosal invasion is important for poor prognostic outcomes.
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http://dx.doi.org/10.4292/wjgpt.v11.i5.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667407PMC
November 2020

Surgical treatment of gallbladder cancer: An eight-year experience in a single center.

World J Hepatol 2020 Sep;12(9):641-660

Department of Surgery, Shiga General Hospital, Moriyama 524-8524, Shiga, Japan.

Background: Gallbladder cancer (GBC) is the most common biliary malignancy and has the worst prognosis, but aggressive surgeries [., resection of the extrahepatic bile duct (EHBD), major hepatectomy and lymph node (LN) dissection] may improve long-term survival. GBC may be suspected preoperatively, identified intraoperatively, or discovered incidentally on histopathology.

Aim: To present our data together with a discussion of the therapeutic strategies for GBC.

Methods: We retrospectively investigated nineteen GBC patients who underwent surgical treatment.

Results: Nearly all symptomatic patients had poor outcomes, while suspicious or incidental GBCs at early stages showed excellent outcomes without the need for two-stage surgery. Lymph nodes around the cystic duct were reliable sentinel nodes in suspicious/incidental GBCs. Intentional LN dissection and EHBD resection prevented metastases or recurrence in early-stage GBCs but not in advanced GBCs with metastatic LNs or invasion of the nerve plexus. All patients with positive surgical margins (., the biliary cut surface) showed poor outcomes. Hepatectomies were performed in sixteen patients, nearly all of which were minor hepatectomies. Metastases were observed in the left-sided liver but not in the caudate lobe. We may need to reconsider the indications for major hepatectomy, minimizing its use except when it is required to accomplish negative bile duct margins. Only a few patients received neoadjuvant or adjuvant chemoradiation. There were significant differences in overall and disease-free survival between patients with stages ≤ IIB and ≥ IIIA disease. The median overall survival and disease-free survival were 1.66 and 0.79 years, respectively.

Conclusion: Outcomes for GBC patients remain unacceptable, and improved therapeutic strategies, including neoadjuvant chemotherapy, optimal surgery and adjuvant chemotherapy, should be considered for patients with advanced GBCs.
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http://dx.doi.org/10.4254/wjh.v12.i9.641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522563PMC
September 2020

Chloroquine induces apoptosis in pancreatic neuroendocrine neoplasms via endoplasmic reticulum stress.

Endocr Relat Cancer 2020 07;27(7):431-439

Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Although pancreatic neuroendocrine neoplasms (PanNENs) are generally indolent, patients with distant metastasis have a dismal prognosis. Recently, the autophagy inhibitor chloroquine (CQ) has been shown to suppress the tumour growth of PanNENs, but the detailed mechanisms have not been elucidated. Furthermore, these results were obtained from poorly differentiated cell lines rather than well-differentiated cell lines, which is the most prevalent type in this tumour. To explore the mechanism and efficacy of CQ on PanNENs, we applied CQ to cell lines and evaluated the resulting apoptosis and endoplasmic reticulum (ER) stress. CQ treatment induced ER stress, and an unfolded protein response was activated through the PERK-eIF2α-ATF4 pathway, resulting in the expression of the pro-apoptotic protein C/EBP homologous protein (CHOP), which reflects ER-stress-mediated apoptotic cell death. Furthermore, hydroxychloroquine (HCQ) was effective in Men1 heterozygous-deficient (Men1+/ΔN3-8) mice, a mouse PanNEN model that is considered to correspond to human low-grade PanNEN. HCQ administration decreased tumour size in Men1+/ΔN3-8 mice. In the HCQ group, histological analyses revealed that proliferative activity was unchanged, but apoptosis was accelerated, accompanied by CHOP expression. These results suggest that autophagy inhibition by CQ/HCQ could be used for the treatment of PanNEN, including the well-differentiated type.
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http://dx.doi.org/10.1530/ERC-20-0028DOI Listing
July 2020

Risk factors for short recurrence-free survival after resection of pancreatic neuroendocrine tumor (PanNET) liver metastases: which patients should undergo resection?

Scand J Gastroenterol 2020 Apr 30;55(4):479-484. Epub 2020 Mar 30.

Department of Surgery, Kyoto University, Kyoto, Japan.

In the treatment of metastatic pancreatic neuroendocrine tumors (PanNETs), surgical resection is the first choice if curative resection is expected. However, most patients develop recurrence after resection of liver metastasis. Because one of the benefits of resection is to gain a tumor-free period for the patients, it is important to identify which patients achieve longer recurrence-free survival (RFS) by resection. In this study, the clinicopathological factors associated with RFS after resection of metastatic PanNETs in the liver were evaluated to identify the patient group that is suitable for resection. Consecutively diagnosed patients with PanNET liver metastasis with resection at our hospital from January 2000 to July 2019 were evaluated. A total of 26 metastatic PanNET patients with primary liver resections were evaluated. The median follow-up time was 48.3 months. There were 18 NET recurrences of the total 26 resections, with a median RFS of 17.9 months. Independent risk factors for short RFS were a high Ki67 index ( = .009) and the number of resected tumors ( = .045). When the cut-off value for the Ki67 index was 5.0% and that for the number of resected tumors was 6, Ki67 > 5.0% tumors had shorter RFS (4.9 months vs. 38.2 months  = .006), and patients with tumors > = 7 tumors had shorter RFS (4.7 months vs. 27.5 months  = .001). These findings indicate that good candidates for resection of metastatic tumors of PanNETs could be patients with low Ki67 tumors and a small number of metastatic tumors.
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http://dx.doi.org/10.1080/00365521.2020.1743352DOI Listing
April 2020

Usefulness of F-FDG-PET/CT in the diagnosis and prediction of recurrence of pancreatic neuroendocrine neoplasms.

J Hepatobiliary Pancreat Sci 2020 Jul 14;27(7):414-420. Epub 2020 May 14.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan.

Background: Although F-FDG-PET/CT is a widely used diagnostic tool for several malignancies, its efficacy in diagnosing pancreatic neuroendocrine tumors is reported to be controversial because of the short-term follow-up.

Methods: We retrospectively compared demographics and pathological features between F-FDG-positive and -negative diseases. Additionally, we evaluated whether the avidity of F-FDG-PET/CT affected earlier recurrence after curative treatment of non-functioning tumors. The median duration of observation was 65.6 months.

Results: Seventy-two patients were enrolled. F-FDG-positive diseases were pathologically advanced and significantly associated with metastatic behavior. In a multivariate analysis, metastatic behavior and WHO tumor grade was independently associated with F-FDG accumulation. Only 25% of functional tumors (4/16) and 8% of insulinomas (1/12) were F-FDG-positive. In a Kaplan-Meier analysis in patients with non-functioning tumors (n = 56), F-FDG-positivity was significantly correlated with poorer recurrence-free survival (RFS) but had no correlation with overall survival. In univariate analysis of factors associated with shorter RFS, male gender, prevalence of nodal metastasis, WHO tumor grade ≥G2, or F-FDG-positive disease were significantly higher in patients with shorter RFS, whereas only F-FDG-positivity was associated with shorter RFS in multivariate analyses.

Conclusions: The avidity of F-FDG-PET/CT was associated with metastatic behavior of pancreatic neuroendocrine tumors and recurrence after treatment of non-functioning tumors.
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http://dx.doi.org/10.1002/jhbp.734DOI Listing
July 2020

Predictive value of the Ki67 index for lymph node metastasis of small non-functioning pancreatic neuroendocrine neoplasms.

Surg Today 2019 Jul 5;49(7):593-600. Epub 2019 Mar 5.

Department of Surgery, Kyoto University, 54 Shogoin, Kawaracho, Sakyo, Kyoto, 606-8507, Japan.

Background: We evaluated the clinicopathological factors associated with lymph node metastasis in patients with non-functioning pancreatic neuroendocrine neoplasms (PanNENs), focusing on the risk factors and range of lymph node metastasis for tumors ≤ 2 cm in diameter.

Methods: The subjects of this study were patients with PanNENs consecutively diagnosed at our hospital between January, 2000 and June, 2018. We analyzed 69 patients who underwent R0 resection of a non-functioning sporadic PanNEN with no distant metastasis, as well as 43 patients with tumors ≤ 20 mm in radiological diameter.

Results: Nineteen patients (27.5%), including 7 (16.3%) with a small PanNEN, had lymph node metastasis. A large radiological diameter, a high Ki67 index, and cyst formation correlated significantly with positive lymph node metastasis. In patients with tumors ≤ 20 mm in diameter, a high Ki67 index correlated significantly with lymph node metastasis. When we set the cut-off Ki67 index as 3.3%, 2 of 43 patients had lymph node metastasis. Tumors in the uncinate process readily metastasized to the region around the superior mesenteric artery.

Conclusions: These findings suggest that a high Ki67 index indicates a risk of lymph node metastasis for tumors ≤ 20 mm in diameter and that lymphadenectomy should be performed in the region spatially adjacent to the primary tumor.
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http://dx.doi.org/10.1007/s00595-019-01779-9DOI Listing
July 2019

Nutritional support and therapy in pancreatic surgery: A position paper of the International Study Group on Pancreatic Surgery (ISGPS).

Surgery 2018 Nov 17;164(5):1035-1048. Epub 2018 Jul 17.

Clinic for Digestive Surgery, Clinical Center of Serbia and School of Medicine, University of Belgrade, Belgrade, Serbia.

Background: The optimal nutritional therapy in the field of pancreatic surgery is still debated.

Methods: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group.

Results: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement.

Conclusion: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes.
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http://dx.doi.org/10.1016/j.surg.2018.05.040DOI Listing
November 2018

Computer tomographic assessment of postoperative peripancreatic collections after distal pancreatectomy.

Langenbecks Arch Surg 2018 May 27;403(3):349-357. Epub 2018 Mar 27.

Division of Hepatobiliary Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Syogoinkawaharacho 54, Sakyo-ku, Kyoto, Japan.

Background: Peripancreatic collections occur frequently after distal pancreatectomy. However, the sequelae of peripancreatic collections vary from case to case, and their clinical impact is uncertain. In this study, the correlations between CT findings of peripancreatic collections and complications after distal pancreatectomy were investigated.

Methods: Ninety-six consecutive patients who had undergone distal pancreatectomy between 2010 and 2015 were retrospectively investigated. The extent and heterogeneity of peripancreatic collections and background clinicopathological characteristics were analyzed. The extent of peripancreatic collections was calculated based on three-dimensional computed tomography images, and the degree of heterogeneity of peripancreatic collections was assessed based on the standard deviation of their density on computed tomography.

Results: Of 85 patients who underwent postoperative computed tomography imaging, a peripancreatic collection was detected in 77 (91%). Patients with either a large extent or a high degree of heterogeneity of peripancreatic collection had a significantly higher rate of clinically relevant pancreatic fistula than those without (odds ratio 5.95, 95% confidence interval 2.12-19.72, p = 0.001; odds ratio 8.0, 95% confidence interval 2.87-24.19, p = 0.0001, respectively).

Conclusions: A large and heterogeneous peripancreatic collection was significantly associated with postoperative complications, especially clinically relevant postoperative pancreatic fistula. A small and homogenous peripancreatic collection could be safely observed.
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http://dx.doi.org/10.1007/s00423-018-1668-zDOI Listing
May 2018

A Prospective Study of Intensity-modified Radiation Therapy in Comparison with Conventional 3D-RT for BR Pancreatic Cancer Patients with Arterial Involvement.

Anticancer Res 2017 12;37(12):7023-7030

Department of Surgery, Kyoto University, Kyoto, Japan.

Background/aim: Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that allows accurate irradiation with reduced damage to surrounding tissues. Here, we analyzed borderline-resectable pancreatic cancer (BRPC) with arterial abutment (BR-A) patients with IMRT as neoadjuvant therapy and performed comparisons with patients with conventional RT to clarify the advantages of IMRT as a neoadjuvant therapy.

Patients And Methods: Thirty BR-A patients treated at our hospital between January 2012 and December 2015 were divided into two groups: 12 patients underwent conventional 3D-RT before resection (RT group); and 18 patients underwent IMRT before resection (IMRT group). We analyzed safety, tumor resection rate, histological classification of the tumor and overall survival.

Results: The R0 rate was 84% for the IMRT group and 83% for the RT group. Local therapeutic effects as assessed by Evans classification showed a higher local control rate in the IMRT group (Grade: 1, 0%; 2a, 25%; 2b, 41.6%; 3, 17%; 4, 8%) than in the RT group (Grade: 1, 17%; 2a, 50%; 2b, 17%; 3, 17%; 4, 0%). The cumulative dose of S1 treatment as adjuvant therapy was much smaller in the RT group (18.3%) compared to that in the IMRT group (57.1%, p=0.047), and with better subsequent overall survival rate (MST 32 months vs. 13.8 months, p=0.0273).

Conclusion: The IMRT group showed a better control rate than the RT group. The neoadjuvant IMRT has advantages of higher completion rate of adjuvant chemotherapy with better nutritional status and better subsequent overall survival rate (OS).
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http://dx.doi.org/10.21873/anticanres.12172DOI Listing
December 2017

Comparison of Recurrence Between Pancreatic and Duodenal Neuroendocrine Neoplasms After Curative Resection: A Single-Institution Analysis.

Ann Surg Oncol 2018 Feb 21;25(2):528-534. Epub 2017 Nov 21.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Kyoto University, Kyoto, Japan.

Background: The primary site of a neuroendocrine neoplasms (NEN) around the head of the pancreas is sometimes difficult to assess before resection, and the characteristics of the primary site around this region have not been elucidated for recurrence after curative resection. In this study, the clinicopathologic characteristics of pancreatic NEN (PanNEN) and duodenal NEN (DuNEN) were evaluated, and the risk factors as well as the recurrence types after resection were investigated.

Methods: Consecutively diagnosed NEN patients at the authors' hospital from January 2000 to July 2016 were evaluated in this study. For 117 PanNEN patients and 31 non-ampullary DuNEN patients, R0 resection was achieved. The median follow-up period was 8.1 years.

Results: In this study, 27 PanNEN patients (23.1%) had recurrences, with a median disease-free survival (DFS) of 133 months, whereas 11 DuNEN patients (35.5%) had recurrences, with a median DFS of 156 months. The PanNEN patients tended to have primary recurrence in the liver (85.2%), followed by lymph nodes (11.1%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.001) and microvascular invasion (p = 0.048). In contrast, the DuNEN patients were likely to have lymph node metastasis (81.8%). The independent risk factors for short DFS were lymph node metastasis at resection (p = 0.003) and large diameter (p = 0.013).

Conclusions: Most initial recurrences of PanNEN occurred in the liver, whereas those of DuNEN appeared in lymph nodes, suggesting that proper diagnosis of the primary site and appropriate imaging methods for surveillance after resection are necessary.
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http://dx.doi.org/10.1245/s10434-017-6260-1DOI Listing
February 2018

A case of successful conversion from everolimus to surgical resection of a giant pancreatic neuroendocrine tumor.

Surg Case Rep 2017 Dec 20;3(1):82. Epub 2017 Jul 20.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin. Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Although pancreatic neuroendocrine tumors generally have a far better prognosis relative to pancreatic cancer, the varied manifestations lead to treatment-related challenges. Everolimus therapy is generally recommended for patients with advanced pancreatic neuroendocrine tumors; however, its efficacy in a neoadjuvant setting remains unclear. Here we present a case of a giant pancreatic neuroendocrine tumor with a portal tumor thrombus that became resectable after everolimus therapy.

Case Presentation: A 62-year-old woman was admitted to our hospital for surgical resection of a giant pancreatic neuroendocrine tumor in the left upper abdomen. Unfortunately, she was ineligible for surgery because the tumor had extended near the hepatic hilus in the portal vein, and she was administered everolimus (10 mg/day). After 2 years of this therapy, the extent of portal vein involvement had decreased, despite the lack of significant changes in the tumor size, and the hepatic hilus became free of disease. She was subsequently referred to us for resection via distal pancreatectomy with portal vein reconstruction because the tumor had begun to grow slowly. Pathological review identified a grade 2 neuroendocrine tumor with no lymph node metastasis. The patient's postoperative course was uneventful, and she has remained recurrence-free for 27 months, despite a lack of additional treatment.

Conclusions: Our experience suggests that everolimus could be useful for neoadjuvant therapy in cases of locally advanced pancreatic neuroendocrine tumor.
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http://dx.doi.org/10.1186/s40792-017-0361-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519517PMC
December 2017

Abdominal contamination with Candida albicans after pancreaticoduodenectomy is related to hemorrhage associated with pancreatic fistulas.

Pancreatology 2017 May - Jun;17(3):484-489. Epub 2017 Mar 18.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Japan.

Background/objectives: Pancreatic fistulas are one of the most frequent morbidities after pancreaticoduodenectomy. Several reports have suggested a relationship between bacterial infections and postoperative pancreatic fistulas, although details of the mechanisms involved in hemorrhage in association with the fistulas have not been elucidated. This study retrospectively examined the relationship between positive drainage culture and hemorrhage associated with pancreatic fistulas after pancreaticoduodenectomy.

Methods: From January 2012 to December 2015, 142 consecutive patients underwent pancreaticoduodenectomy at our institution. We retrospectively reviewed the patients' demographic data, perioperative laboratory data, and drainage culture results.

Results: Twenty-four (17%) patients had clinically relevant postoperative pancreatic fistulas, whereas thirty-four (24%) patients experienced positive drainage culture. Multivariable analysis revealed that positive drainage culture was independently associated with clinically relevant postoperative pancreatic fistulas (odds ratio, 18.1; 95% confidence interval, 5.5-72.2; P < 0.001). Additionally, the prevalence of Candida albicans in the lavage of eight patients significantly correlated with hemorrhage associated with pancreatic fistulas (odds ratio, 43.5; 95% confidence interval, 6.2-513.3; P < 0.001). Seventy-five percent (6/8) of these patients suffered potentially lethal hemorrhagic complications and needed intervention.

Conclusions: A positive abdominal drainage culture is associated with the development of pancreatic fistulas. Moreover, the presence of Candida albicans in drainage fluid may be a risk factor for hemorrhagic complications.
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http://dx.doi.org/10.1016/j.pan.2017.03.007DOI Listing
March 2018

Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors.

Surg Today 2016 Nov 9;46(11):1282-9. Epub 2016 Feb 9.

Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo, Kyoto, 606-8507, Japan.

Purposes: In the surgical treatment of pancreatic cancer, margin-negative status is one of the most important determinants of survival. We conducted this study to explore surgical margin status as well as other factors affecting the survival of borderline-resectable pancreatic cancer (BRPC) patients who received neoadjuvant chemotherapy with gemcitabine and S-1.

Methods: Eighteen BRPC patients were prospectively treated with concurrent gemcitabine and S-1 neoadjuvant chemotherapy (NAC+) and 15 of these patients underwent resection. We evaluated the safety and efficacy of this treatment regimen by comparing the outcomes of these patients with those of 19 BRPC patients who did not receive neoadjuvant chemotherapy (NAC-) during the same period.

Results: Fifteen (83 %) of the NAC+ patients underwent pancreatectomy. The remaining three patients (17 %) had regional tumor progression or liver metastasis. Of the 15 NAC+ patients who underwent resection, 3 (20 %) had margin-positive status, whereas 9 of the 19 (43 %) NAC- patients had margin-positive status (p = 0.002). However, disease-free survival and overall survival were similar in the two groups (MST 21.7 vs. 21.1 months). NAC+ patients with tumors smaller than 30 mm had favorable overall survival (MST 43.9 vs. 23.1 months, p = 0.0321). Most recurrences developed at distant sites rather than locally in both groups.

Conclusions: In the neoadjuvant setting, gemcitabine and S-1 improved the negative surgical margin rate in BRPC patients, but it did not improve survival. Thus, neoadjuvant chemotherapy should be given to BRPC patients at an earlier stage.
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http://dx.doi.org/10.1007/s00595-016-1310-zDOI Listing
November 2016

Bundled strategies against infection after liver transplantation: Lessons from multidrug-resistant Pseudomonas aeruginosa.

Liver Transpl 2016 Apr;22(4):436-45

Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto, Japan.

Infection is a life-threatening complication after liver transplantation (LT). A recent outbreak of multidrug-resistant Pseudomonas aeruginosa triggered changes in our infection control measures. This study investigated the usefulness of our bundled interventions against postoperative infection after LT. This before-and-after analysis enrolled 130 patients who underwent living donor or deceased donor LT between January 2011 and October 2014. We initiated 3 measures after January 2013: (1) we required LT candidates to be able to walk independently; (2) we increased the hand hygiene compliance rate and contact precautions; and (3) we introduced procalcitonin (PCT) measurement for a more precise determination of empirical antimicrobial treatment. We compared factors affecting the emergence of drug-resistant microorganisms, such as the duration of antimicrobial and carbapenem therapy and hospital stay, and outcomes such as bacteremia and death from infection between before (n = 77) and after (n = 53) the LT suspension period. The utility of PCT measurement was also evaluated. Patients' backgrounds were not significantly different before and after the protocol revision. Incidence of bacteremia (44% versus 25%; P = 0.02), detection rate of multiple bacteria (18% versus 4%; P = 0.01), and deaths from infections (12% versus 2%; P =  0.04) significantly decreased after the protocol revision. Duration of antibiotic (42.3 versus 25.1 days; P =  0.002) and carbapenem administration (15.1 versus 5.2 days; P < 0.001) and the length of postoperative hospital stay (85.4 versus 63.5 days; P =  0.048) also decreased after the protocol revision. PCT mean values were significantly higher in the bacteremia group (10.10 ng/mL), compared with the uneventful group (0.65 ng/mL; P =  0.002) and rejection group (2.30 ng/mL; P =  0.02). One-year overall survival after LT significantly increased in the latter period (71% versus 94%; P =  0.001). In conclusion, the bundled interventions were useful in preventing infections and lengthening overall survival after LT.
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http://dx.doi.org/10.1002/lt.24407DOI Listing
April 2016

Rhabdomyosarcoma of the duodenum: report of a case.

Surg Today 2014 Feb 27;44(2):378-82. Epub 2012 Nov 27.

Department of Digestive Surgery, Toranomon Hospital, 2-2-2, Minato-ku, Tokyo, Japan,

This report presents a case of primary pleomorphic rhabdomyosarcoma arising in the duodenum. A 63-year-old male with persistent melena was referred for a solid tumor in his right upper abdomen detected using ultrasonography. Gastrofiberscopy revealed a protrusion in the upper part of the duodenum, with a large ulcer on the top of it. Enhanced computed tomography showed that the tumor extended to the pancreas. Pancreaticoduodenectomy was performed, despite the absence of malignant cells in the biopsy specimen, with a preoperative diagnosis of duodenal cancer. The tumor consisted of multiple cell types, and immunohistochemical staining was positive for desmin, HHF-35 and alpha smooth muscle actin. Electron microscopy revealed primitive Z-band structures in the tumor. The final diagnosis was pleomorphic rhabdomyosarcoma of the duodenum. This is the first report of primary rhabdomyosarcoma occurring in the duodenum, confirmed by immunohistochemical staining and electron microscopy.
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http://dx.doi.org/10.1007/s00595-012-0421-4DOI Listing
February 2014

[Quadricuspid aortic valve associated with rapidly progressive aortic stenosis during chronic hemodialysis; report of a case].

Kyobu Geka 2012 Jul;65(7):575-8

Department of Cardiovascular Surgery, Toranomon Hospital, Tokyo, Japan.

A 70-year-old man was referred to our department for surgical treatment for aortic valve stenosis. He was diagnosed with aortic regurgitation 30 years ago, but he was asymptomatic at that time. Ten years ago, chronic hemodialysis was instituted for diabetic nephropathy. In recent years, he became aware of nocturnal dyspnea and echocardiography revealed moderate aortic stenosis. After that, the symptom was getting worse and surgical treatment was indicated. We performed aortic valve replacement. Intraoperatively, we noticed his aortic valve was quadricuspid. The postoperative course was uneventful and he was discharged without complications. Quadricuspid aortic valve is rare congenital anomaly and patients are often operated on for aortic regurgitation. Our case is indicated for valve replacement because of aortic stenosis. In addition, there are a few reports of quadricuspid aortic valve associated with hemodialysis. We consider hemodialysis is one of the cause of rapid progression of aortic stenosis in this patient.
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July 2012

Elevation of pancreatic enzymes in gallbladder bile associated with heterotopic pancreas. A case report and review of the literature.

JOP 2012 Mar 10;13(2):235-8. Epub 2012 Mar 10.

Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan.

Context: This is the first report associating heterotopic pancreas in the gallbladder and elevated pancreatic enzymes in bile.

Case Report: A 60-year-old woman underwent abdominal ultrasonography at a medical check-up, revealing a nodular protrusion at the neck of the gallbladder. It seemed likely to be a lymph node, but we could not exclude the possibility of gallbladder cancer. In order to make a correct diagnosis, laparoscopic cholecystectomy was successfully performed. Pathological examination revealed heterotopic pancreatic tissue in the gallbladder wall. In addition, we detected elevated levels of amylase and lipase in gallbladder bile.

Conclusions: Preoperative diagnosis of heterotopic pancreas in the gallbladder is difficult. However, an increase of pancreatic enzymes in gallbladder bile may potentially play an important role in the occurrence of acalculous cholecystitis and biliary cancer. We need more accumulation of cases to know the true significance of this anomaly.
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March 2012