Publications by authors named "Hirochika Toyama"

120 Publications

Estimation of pancreatic fibrosis and prediction of postoperative pancreatic fistula using extracellular volume fraction in multiphasic contrast-enhanced CT.

Eur Radiol 2021 Oct 12. Epub 2021 Oct 12.

Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

Objective: To investigate the diagnostic performance of the extracellular volume (ECV) fraction in multiphasic contrast-enhanced computed tomography (CE-CT) for estimating histologic pancreatic fibrosis and predicting postoperative pancreatic fistula (POPF).

Methods: Eighty-five patients (49 men; mean age, 69 years) who underwent multiphasic CE-CT followed by pancreaticoduodenectomy with pancreaticojejunal anastomosis between January 2012 and December 2018 were retrospectively included. The ECV fraction was calculated from absolute enhancements of the pancreas and aorta between the precontrast and equilibrium-phase images, followed by comparisons among histologic pancreatic fibrosis grades (F0‒F3). The diagnostic performance of the ECV fraction in advanced fibrosis (F2‒F3) was evaluated using receiver operating characteristic curve analysis. Multivariate logistic regression analysis was used to evaluate the associations of the risk of POPF development with patient characteristics, histologic findings, and CT imaging parameters.

Results: The mean ECV fraction of the pancreas was 34.4% ± 9.5, with an excellent intrareader agreement of 0.811 and a moderate positive correlation with pancreatic fibrosis (r = 0.476; p < 0.001). The mean ECV fraction in advanced fibrosis was significantly higher than that in no/mild fibrosis (44.4% ± 10.8 vs. 31.7% ± 6.7; p < 0.001), and the area under the receiver operating characteristic curve for the diagnosis of advanced fibrosis was 0.837. Twenty-two patients (25.9%) developed clinically relevant POPF. Multivariate logistic regression analysis demonstrated that the ECV fraction was a significant predictor of POPF.

Conclusions: The ECV fraction can offer quantitative information for assessing pancreatic fibrosis and POPF after pancreaticojejunal anastomosis.

Key Points: • There was a moderate positive correlation of the extracellular volume (ECV) fraction of the pancreas in contrast-enhanced CT with the histologic grade of pancreatic fibrosis (r = 0.476; p < 0.001). • The ECV fraction was higher in advanced fibrosis (F2‒F3) than in no/mild fibrosis (F0‒F1) (p < 0.001), with an AUC of 0.837 for detecting advanced fibrosis. • The ECV fraction was an independent risk factor for predicting subclinical (odds ratio, 0.81) and clinical (odds ratio, 0.80) postoperative pancreatic fistula.
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http://dx.doi.org/10.1007/s00330-021-08255-4DOI Listing
October 2021

Salvage hepatectomy for local recurrence after particle therapy using proton and carbon ion beams for liver cancer.

Ann Gastroenterol Surg 2021 Sep 7;5(5):711-719. Epub 2021 May 7.

Division of Hepato-Biliary-Pancreatic Surgery Department of Surgery Kobe University Graduate School of Medicine Kobe Japan.

Aim: With the increased use of particle therapy for liver cancer, local recurrence after particle therapy increased. Salvage hepatectomy is an acceptable treatment option for local recurrence following particle therapy; however, its safety and effectiveness remain unclear. Therefore, this multi-center study aimed to verify the feasibility and efficacy of salvage hepatectomy and assess clinical issues associated with its application.

Methods: We retrospectively assessed the perioperative outcomes, prognosis, and pathological characteristics of 15 patients who underwent salvage hepatectomy for local recurrence after particle therapy between 2006 and 2019.

Results: Hepatocellular carcinoma and metastatic liver tumors were noted in eight and seven patients, respectively. The mean total dose and number of fractions were 66.5 Gy and 12, respectively, and the mean interval between particle therapy and surgery was 30.1 months. Major hepatectomy was performed in seven cases. Moreover, the mortality rate was 0%, and surgical complications of Clavien-Dindo grade IIIa or higher were observed in four cases (27%)-two bile leakages, one pleural effusion, and one refractory skin fistula. The median overall survival time and 5-year overall survival rate after salvage hepatectomy were 29.9 months and 43.1%, respectively. Histological examination of the irradiated liver tissue surrounding the tumor showed sinusoidal dilatation, loss of hepatocyte, and fibrosis in most cases.

Conclusion: Salvage hepatectomy after particle therapy is a feasible therapy; however, the risk of refractory complications associated with particle therapy is relatively high. Therefore, the first-line treatment for resectable liver cancer should be carefully determined considering second-line treatment after local recurrence.
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http://dx.doi.org/10.1002/ags3.12468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452475PMC
September 2021

ISOlation Procedure vs. conventional procedure during Distal Pancreatectomy (ISOP-DP trial): study protocol for a randomized controlled trial.

Trials 2021 Sep 16;22(1):633. Epub 2021 Sep 16.

Second Department of Surgery, School of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) is an isolation procedure in pancreatosplenectomy for pancreatic body/tail cancer. Connective tissues around the bifurcation of the celiac axis are dissected, followed by median-to-left retroperitoneal dissection. This procedure has the potential to isolate blood and lymphatic flow to the area of the pancreatic body/tail and the spleen to be excised. This is achieved by division of the inflow artery, transection of the pancreas, and then division of the outflow vein in the early phases of surgery. In cases of pancreatic ductal adenocarcinoma (PDAC), the procedure has been shown to decrease intraoperative blood loss and increase R0 resection rate by complete clearance of the lymph nodes. This trial investigates whether the isolation procedure can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo distal pancreatosplenectomy (DPS) compared with those that undergo the conventional approach.

Methods/design: Patients with PDAC scheduled to undergo DPS are randomized before surgery to undergo either a conventional procedure (arm A) or to undergo the isolation procedure (arm B). In arm A, the pancreatic body, tail, and spleen are mobilized, followed by removal of the regional lymph nodes. The splenic vein is transected at the end of the procedure. The timing of division of the splenic artery (SA) is not restricted. In arm B, regional lymph nodes are dissected, then we transect the root of the SA, the pancreas, then the splenic vein. At the end of the procedure, the pancreatic body/tail and spleen are mobilized and removed. In total, 100 patients from multiple Japanese high-volume centers will be randomized. The primary endpoint is 2-year recurrence-free survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 resection rate, and overall survival.

Discussion: If this trial shows that the isolation procedures can improve survival with a similar R0 rate and with a similar number of lymph node dissections to the conventional procedure, the isolation procedure is expected to become a standard procedure during DPS for PDAC. Conversely, if there were no significant differences in endpoints between the groups, it would demonstrate justification of either procedure from surgical and oncological points of view.

Trial Registration: UMIN Clinical Trials Registry UMIN000041381 . Registered on 10 August 2020. ClinicalTrials.gov NCT04600063 . Registered on 22 October 2020.
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http://dx.doi.org/10.1186/s13063-021-05523-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447574PMC
September 2021

Glucose Tolerance after Pancreatectomy: A Prospective Observational Follow-Up Study of Pancreaticoduodenectomy and Distal Pancreatectomy.

J Am Coll Surg 2021 Sep 13. Epub 2021 Sep 13.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Effects of pancreatectomy on glucose tolerance have not been clarified, and evidence regarding the difference in postoperative glucose tolerance between pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is lacking.

Study Design: This prospective, single-center observational study analyzed 40 patients undergoing PD and 29 patients undergoing DP (Clinical trial registry number UMIN000008122). Glucose tolerance, including insulin secretion (Δ C-peptide immunoreactivity, ΔCPR) and insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) were assessed before and 1 month after pancreatectomy using the oral glucose tolerance test (OGTT) and glucagon stimulation test. We assessed long-term hemoglobin A1c (HbA1c) levels in patients, with a follow-up time of 3 years.

Results: Percentages of patients diagnosed with abnormal OGTT decreased after PD (from 12 [30%] to 7 [17.5%] of 40 patients, p = 0.096); however, they increased after DP (from 4 [13.8%] to 8 [27.6%] of 29 patients, p = 0.103), although the changes were not statistically significant. ΔCPR decreased after both PD (from 3.2 to 1.0 ng/mL, p < 0.001) and DP (from 3.3 to 1.8 ng/mL, p < 0.001). HOMA-IR decreased after PD (from 1.10 to 0.68, p < 0.001), but did not change after DP (1.10 and 1.07, p = 0.42). Median HbA1c level was higher after DP than after PD for up to 3 years, but the differences were not statistically significant.

Conclusions: In comparisons of pre- and 1 month post-pancreatectomy data, glucose tolerance showed improvement after PD, whereas it worsened after DP. Insulin secretion decreased after both PD and DP. Insulin resistance improved after PD, but did not change after DP. Further studies are warranted to clarify mechanisms of improved insulin resistance after PD.
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http://dx.doi.org/10.1016/j.jamcollsurg.2021.08.688DOI Listing
September 2021

Lenvatinib Rechallenge After Ramucirumab Treatment Failure for Hepatocellular Carcinoma.

Anticancer Res 2021 Sep;41(9):4555-4562

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background/aim: While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored.

Patients And Methods: Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed.

Results: All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one.

Conclusion: Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.
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http://dx.doi.org/10.21873/anticanres.15268DOI Listing
September 2021

Indication of Surgical Hepatectomy for the Patients of Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombosis.

Kobe J Med Sci 2021 Jun 18;67(1):E10-E17. Epub 2021 Jun 18.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

The prognosis of hepatocellular carcinoma (HCC) presenting with inferior vena cava tumor thrombus (IVCTT) is extremely poor. The aim of this study was to reveal the postoperative course and to identify patients who have survived surgical hepatectomy among HCC patients with IVCTT. Between January 2006 and December 2018, 643 patients underwent surgical hepatectomy for HCC at Kobe University Hospital. Among them, 20 patients were categorized as Vv3 according to the Japanese staging system. We retrospectively collected detailed data on these patients. The statistical, clinical, and pathological data were recorded prospectively and analyzed retrospectively. The median survival time was 9.8 months. Among all patients, 11 (55%) achieved R0 resection, and only two survivors were from this group. The number of tumors (solitary vs. multiple; p=0.050) and pathological Vp (pVp0 vs. other; p=0.009) were identified as risk factors for overall survival in the univariate analysis. In the multivariate analysis, pathological Vp (pVp0 vs. other; p=0.037) was identified as a significant prognostic factor for survival. Pathological Vp affected overall survival among IVCTT patients; the median survival time was 53.7 months with pVp0, 10.2 months with pVp1, and 8.8 months with pVp2-4 (p=0.035). For patients with IVCTT, surgical hepatectomy should be indicated only for those who do not have portal vein invasion and could achieve R0 resection.
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June 2021

Indocyanine green (ICG) fluorography and digital subtraction angiography (DSA) of vessels supplying the remnant stomach that were performed during distal pancreatectomy in a patient with a history of distal gastrectomy: a case report.

Clin J Gastroenterol 2021 Aug 3. Epub 2021 Aug 3.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe University Hospital/International Clinical Cancer Research Center, 1-5-1 Minatojimaminamimachi, Chuo-ku, Kobe, 650-0047, Japan.

A 68-year-old man who had undergone distal gastrectomy for gastric cancer 3 years previously, presented to our hospital for examination of dilatation of the main pancreatic duct on follow-up computed tomography and magnetic resonance cholangiopancreatography. After examination, he was diagnosed with early-stage pancreatic cancer and distal pancreatectomy (DP) was planned. With informed consent, we performed indocyanine green (ICG) fluorography during DP and digital subtraction angiography (DSA) of vessels supplying the remnant stomach immediately before and after DP. On ICG fluorography, the remnant stomach gradually became fluoresced starting at the area of the lesser curvature, and the fluorescence eventually intensified over the entire area of the remnant stomach to the same brightness as that of the liver and duodenum. On DSA following DP, the terminal branches of the left inferior phrenic artery (LIPA) were distributed to more than half of the area of the remnant stomach, centering around the proximal area. It is useful to confirm blood flows to the remnant stomach by ICG fluorography using a near-infrared imaging camera during DP. We found that the LIPA played an important role in maintaining the blood supply to the remnant stomach in the absence of the left gastric artery and splenic artery.
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http://dx.doi.org/10.1007/s12328-021-01493-5DOI Listing
August 2021

Concordance of human equilibrative nucleoside transporter-1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial.

Cancer Rep (Hoboken) 2021 Jul 29:e1507. Epub 2021 Jul 29.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Nagaizumi, Japan.

Background: Expression of human equilibrative nucleoside transporter-1 (hENT1) is reported to predict survival of gemcitabine (GEM)-treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120.

Aim: We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis.

Methods: The subjects of this study were totally 332 whose formalin-fixed paraffin-embedded specimens and/or unstained sections were obtained. The individual H-scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively.

Results: The highest concordance rate (79.8%) was obtained when the cut-off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H-score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody.

Conclusion: The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut-off point and suggests that S-1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S-1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.
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http://dx.doi.org/10.1002/cnr2.1507DOI Listing
July 2021

The immunological impact of preoperative chemoradiotherapy on the tumor microenvironment of pancreatic cancer.

Cancer Sci 2021 Jul 19;112(7):2895-2904. Epub 2021 May 19.

Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, Japan.

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse-free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.
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http://dx.doi.org/10.1111/cas.14914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253289PMC
July 2021

Feasibility of Reductive Hepatectomy in Patients With BCLC B and C Hepatocellular Carcinoma.

Anticancer Res 2021 Apr;41(4):1975-1983

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background/aim: Few studies have established a definite conclusion regarding the limitation of surgical treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma (HCC).

Patients And Methods: A retrospective analysis was performed on 717 consecutive patients who underwent initial hepatectomy for HCC.

Results: Reductive hepatectomy was performed in 103 patients, with a median survival time (MST) of 18.0 months. Total bilirubin and albumin levels were identified as independent prognostic factors. The predictive score of these factors ranged from 0 to 2. Subsequent local treatment was performed in 91.0, 75.0, and 25.0% of patients who scored 0, 1, and 2, respectively. The MST for patients with a score of 0, 1, and 2 was 20.1, 14.8, and 2.7 months, respectively, with a significant difference.

Conclusion: Patients with BCLC stage B and C could be properly treated with reductive hepatectomy and subsequent local treatments.
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http://dx.doi.org/10.21873/anticanres.14965DOI Listing
April 2021

Portal vein tumor thrombosis after pancreaticoduodenectomy: An extremely rare case of recurrence of pancreatic neuroendocrine neoplasm.

J Hepatobiliary Pancreat Sci 2021 Aug 15;28(8):e36-e37. Epub 2021 Apr 15.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Highlight Venous tumor thrombus can occur in association with pancreatic neuroendocrine neoplasm. Ishida and colleagues report their experience with a patient in whom a solitary recurrent tumor developed in the portal vein after pancreaticoduodenectomy for pancreatic neuroendocrine neoplasm. They performed portal vein resection and reconstruction using a left external iliac vein graft.
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http://dx.doi.org/10.1002/jhbp.965DOI Listing
August 2021

Pancreatic metastasis of renal cell carcinoma filling into the duct of Santorini.

Clin J Gastroenterol 2021 Jun 6;14(3):905-909. Epub 2021 Mar 6.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.

A 78-year-old man who underwent right nephrectomy for renal cell carcinoma (RCC) 18 years ago visited our hospital complaining of abdominal pain. Imaging revealed that the pancreatic head tumor obstructed the Santorini duct. We suspected a pancreatic intraductal tumor, such as an intraductal tubulopapillary neoplasm or intraductal papillary mucinous neoplasm. Thus, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings confirmed the diagnosis of metastatic RCC. Herein, we report a case of pancreatic metastasis of an RCC that presented with a tumor in the pancreatic duct.
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http://dx.doi.org/10.1007/s12328-021-01369-8DOI Listing
June 2021

Surgical spacer placement for proton radiotherapy in locally advanced pancreatic body and tail cancers: initial clinical results.

Radiat Oncol 2021 Jan 6;16(1). Epub 2021 Jan 6.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Background: Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.

Methods: Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.

Results: Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy.

Conclusions: Surgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
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http://dx.doi.org/10.1186/s13014-020-01731-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788736PMC
January 2021

Acute pancreatitis in intraductal papillary mucinous neoplasms correlates with pancreatic volume and epithelial subtypes.

Pancreatology 2021 Jan 20;21(1):138-143. Epub 2020 Nov 20.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN.

Methods: This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated.

Results: AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes.

Conclusion: Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.
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http://dx.doi.org/10.1016/j.pan.2020.11.005DOI Listing
January 2021

Relationship between surgical R0 resectability and findings of peripancreatic vascular invasion on CT imaging after neoadjuvant S-1 and concurrent radiotherapy in patients with borderline resectable pancreatic cancer.

BMC Cancer 2020 Dec 2;20(1):1184. Epub 2020 Dec 2.

Department of Hepato-Biliary-Pancreatic Surgery, Chiba Cancer Center, Chiba, Japan.

Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC.

Methods: Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group.

Results: There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was - 10.0% [- 31.7-20.4%].

Conclusions: Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT.

Trial Registration: UMIN-CTR, UMIN000009172 . Registered 23 October 2012.
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http://dx.doi.org/10.1186/s12885-020-07698-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709301PMC
December 2020

Phase 1 study of Gemcitabine/Nab-paclitaxel/S-1 in patients with unresectable pancreatic cancer (GeNeS1S trial).

Cancer Chemother Pharmacol 2021 01 24;87(1):65-71. Epub 2020 Oct 24.

Department of Medical Oncology/Hematology, Kobe University Hospital and Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Purpose: We conducted a phase 1 study to determine the maximum tolerated dose and the recommended dose of gemcitabine/nab-paclitaxel/S-1 combination chemotherapy in patients with unresectable pancreatic cancer.

Methods: We enrolled patients aged 20 years or older with unresectable pancreatic cancer and who had not been treated with chemotherapy or radiation therapy. Gemcitabine and nab-paclitaxel were administered on days 1 and 8, and S-1 was administered orally twice daily for 2 weeks, repeated every 3 weeks. The starting dose was level 0 [gemcitabine 700 mg/m, nab-paclitaxel 90 mg/m, S-1 60/80/100 mg/day (< 1.25 m/1.25-1.50 m/ > 1.5 m)]. Dose-limiting toxicities were determined during the first course, and a classical 3 + 3 dose finding design was planned.

Results: From March 2018 to October 2019, 20 patients were enrolled. At dose level 0, three of six patients experienced dose-limiting toxicities; one grade 3 skin rash on day 8, and two grade 3 or 4 neutropenia on day 8. At dose level-1 (gemcitabine 600 mg/m, nab-paclitaxel 90 mg/m, and S-1 50/70/80 mg/day), two of twelve patients experienced dose-limiting toxicities, all of which were grade 3 neutropenia on day 8. The most frequently observed toxicity during eight courses was neutropenia. Other treatment-related adverse events were mild. Eleven out of 19 (58%) patients achieved partial response.

Conclusion: We defined the maximum tolerated dose and the recommended dose for combination therapy with gemcitabine/nab-paclitaxel/S-1 as dose level-1. Considering the observed response rate, further studies are warranted in order to determine the efficacy of this regimen (UMIN-CTR 000030007).
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http://dx.doi.org/10.1007/s00280-020-04174-1DOI Listing
January 2021

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-Label Multicenter Prospective Trial (JASPAC05).

Ann Surg 2020 Oct 15. Epub 2020 Oct 15.

Department of Hepato-biliary Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan.

Objective: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in borderline resectable pancreatic cancer (BRPC).

Summary Background Data: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established.

Methods: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a one-sided α = 0.05 and β = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively.

Results: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively.

Conclusions: S-1 and concurrent radiotherapy appear to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC.

Trial Registration: UMIN000009172.
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http://dx.doi.org/10.1097/SLA.0000000000004535DOI Listing
October 2020

A case of high-grade pancreatic intraepithelial neoplasia diagnosed based on focal pancreatic parenchymal atrophy after acute pancreatitis.

Clin J Gastroenterol 2020 Dec 17;13(6):1338-1342. Epub 2020 Aug 17.

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

A 60-year-old male visited a previous hospital with upper abdominal pain. He was diagnosed with localized mild acute pancreatitis. Three months later, abdominal contrast-enhanced computed tomography showed focal parenchymal atrophy of the pancreas with distal pancreatic duct dilation. No obvious solid mass could be found at the site of the pancreatic duct stenosis on imaging examinations. Endoscopic retrograde pancreatography showed focal mild stenosis with distal pancreatic duct dilation in the tail of the pancreas. Carcinoma in situ of the pancreas was strongly suspected, especially based on the presence of focal atrophy of the pancreas around the site of stenosis of the main pancreatic duct and the distal pancreatic duct dilation. Laparoscopic distal pancreatectomy was performed. Histologically, high-grade pancreatic intraepithelial neoplasia was found in the epithelium of the stenotic main pancreatic duct and its branches. This case suggests that localized acute pancreatitis and focal atrophy of the pancreas with distal dilation of the pancreatic duct could be important clinical manifestations of pancreatic carcinoma in situ.
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http://dx.doi.org/10.1007/s12328-020-01208-2DOI Listing
December 2020

Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.

Ann Surg 2020 Jul 8. Epub 2020 Jul 8.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Hyogo, Japan.

Objective: This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status.

Summary Of Background Data: The influence of the route of alimentary tract reconstruction on DGE after PD is controversial.

Methods: Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes.

Results: Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups.

Conclusions: This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.
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http://dx.doi.org/10.1097/SLA.0000000000004072DOI Listing
July 2020

Response to: "timing of administration of indocyanine green for fluorescence-guided surgery in pancreatic cancer: response to Shirakawa et al."

BMC Surg 2020 Jul 14;20(1):153. Epub 2020 Jul 14.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho Chuo-ku, Kobe Hyogo, Japan.

This is the response article to correspondence article received for our published article in BMC surgery titled "A prospective single-center protocol for using near-infrared fluorescence imaging with indocyanine green during staging laparoscopy to detect small metastasis from pancreatic cancer". Peter L. Labib, MBChB pointed out the necessity to administer indocyanine green intravenously in separate timing for detection of metastasis in liver and peritoneum. Preoperative injection is suitable to detect hepatic metastasis and intraoperative injection is reported to be well suited to detect peritoneal metastasis. However, we could not find the usefulness of intraoperative injection of indocyanine green for detecting peritoneal metastasis in cases with staging laparoscopy prior to this study. We employed this study protocol with only preoperative injection of indocyanine green to simplify the procedure with consideration of probably more frequent cases of hepatic metastasis that is difficult to detect with white-light imaging than those of peritoneal metastasis.
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http://dx.doi.org/10.1186/s12893-020-00815-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359577PMC
July 2020

Laparoscopic repeat hepatectomy is a more favorable treatment than open repeat hepatectomy for contralateral recurrent hepatocellular carcinoma cases.

Surg Endosc 2021 06 16;35(6):2896-2906. Epub 2020 Jun 16.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.

Background: We compared surgical outcomes, with a focus on tumor characteristics, of laparoscopic repeat hepatectomy (LRH) and open repeat hepatectomy (ORH) to identify recurrent hepatocellular carcinoma (HCC) cases where the LRH procedure would be more favorable than ORH.

Methods: Eighty-one HCC patients who underwent repeat hepatectomy in our hospital from 2008 to 2019 were retrospectively analyzed in this study. Of these patients, 30 and 51 patients underwent LRH and ORH, respectively. We analyzed surgical outcomes of LRH and ORH, focusing on tumor characteristics such as tumor size, location, distance from major vessels, and contralateral or ipsilateral tumor recurrence to determine what factors could affect surgical outcomes. Subsequently, using a propensity-matched cohort, we compared the impact of those factors on LRH and ORH outcomes.

Results: In the entire cohort, the LRH operation time was significantly shorter in contralateral recurrent HCC cases than in ipsilateral recurrent HCC cases (252 vs. 398 min, P = 0.008); however, such a difference was not observed in the ORH operation time. We subsequently compared the surgical outcomes, in terms of the location of tumor recurrence, between the LRH and ORH groups in a propensity-matched cohort. In total, 23 patients were included in each of these groups. We found that the LRH procedure had significantly shorter operative time than the ORH procedure in the contralateral recurrent HCC cases (253 vs. 391 min, P = 0.018); however, we did not observe such a difference in the ipsilateral recurrent HCC cases (372 vs. 333 min, P = 0.669). LRH had lower blood loss, similar postoperative complications and shorter hospital stay than ORH in both contralateral and ipsilateral recurrent HCC cases.

Conclusions: LRH is likely considered a more favorable approach than ORH in treating patients with contralateral recurrent HCC.
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http://dx.doi.org/10.1007/s00464-020-07728-9DOI Listing
June 2021

Clinical Significance of Hepatectomy for Hepatocellular Carcinoma Associated with Extrahepatic Metastases.

Dig Surg 2020 26;37(5):411-419. Epub 2020 May 26.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: This study evaluated the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases who can undergo hepatectomy.

Methods: A total of 32 patients who underwent hepatectomy for HCC with extrahepatic metastases, including lymph node and/or distant metastases were recruited for this study.

Results: Fourteen patients had lymph node metastasis only, 16 had distant metastasis only, and 2 had both metastasis types during preoperative diagnosis. The 3-year overall survival (OS) rate of all patients was 17.9%, and the median survival time (MST) was 11.8 months. Univariate analysis revealed that intrahepatic maximal tumor size, intrahepatic tumor number, and intrahepatic tumor control after hepatectomy were significant factors influencing OS (p < 0.05). Multivariate analysis revealed that independent risk factors for OS were intrahepatic maximal tumor size and intrahepatic tumor number (p < 0.05). The MST and 3-year OS rate of patients with maximal tumor size <100 mm and intrahepatic tumor number ≤2 were 39.0 months and 51.9%, respectively.

Conclusions: Hepatectomy is not recommended for HCC patients with extrahepatic metastasis with ≥3 intrahepatic tumors, even when all intrahepatic tumors can be eliminated via hepatectomy. Aggressive surgery may be justified for HCC patients with ≤2 intrahepatic tumors and maximal tumor size <100 mm, irrespective of vascular invasion.
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http://dx.doi.org/10.1159/000507436DOI Listing
August 2021

Two-in-one method: Novel pancreaticojejunostomy technique for the bifid pancreas.

Ann Gastroenterol Surg 2020 Mar 23;4(2):175-179. Epub 2019 Dec 23.

Division of Hepato-Biliary-Pancreatic Surgery Department of Surgery Kobe University Graduate School of Medicine Kobe Japan.

The bifid pancreas is a rare anatomical variation of the pancreatic duct in which double main pancreatic ducts in the body and tail of the pancreas join at the pancreas head and drain through the major papilla. When pancreaticoduodenectomies are carried out on bifid pancreases, close attention must be paid to the reconstruction because of the possibility that there may be two pancreatic ducts that need to be reconstructed. We present a case of pancreaticoduodenectomy for the bifid pancreas and a novel technique named the 'two-in-one' method for double pancreatic duct to jejunum anastomosis. Using the two-in-one method, we anastomosed one jejunal hole to a double pancreatic duct. Pancreatic texture was normal and postoperative volumes of pancreatic juice from the two external pancreatic duct stents were 250 mL and 100 mL/day, respectively. Postoperative recovery went well although the patient needed a slightly longer hospital stay as a result of surgical site infection. This novel anastomotic technique was as simple to carry out as a normal pancreaticojejunostomy and may be useful for reconstruction of the bifid pancreas.
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http://dx.doi.org/10.1002/ags3.12302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105849PMC
March 2020

Assessment of lenvatinib treatment for unresectable hepatocellular carcinoma with liver cirrhosis.

HPB (Oxford) 2020 10 29;22(10):1450-1456. Epub 2020 Mar 29.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.

Background: The present study aimed to assess the clinical features of patients who received lenvatinib treatment for unresectable hepatocellular carcinoma (HCC).

Methods: The clinical characteristics, adverse events, and radiological responses were evaluated for 51 consecutive patients.

Results: Of the study subjects, 37 patients had Child-Pugh class A (CPA) liver function, and 14 patients had Child-Pugh class B (CPB) liver function. The overall response rates in the CPA and CPB groups were 42.9% and 25.0%, respectively, and disease control rates were 82.9% and 83.3%, respectively, without significant difference (p = 0.2621 and 0.9697). There was no significant difference between CPA and CPB groups regarding the incidence of adverse events, except for hepatic coma. No significant difference was observed in the relative dose intensity between the CPA and CPB groups, for the first month, 1-2 months, or 2-3 months (p = 0.2368, 0.9368, and 0.9293).

Conclusion: The comparable outcomes between the CPA and CPB groups suggest the acceptability of lenvatinib treatment in patients with impaired liver function, at least in the acute phase. With careful follow-up, the dose can be relatively intensified, even in patients with impaired liver function and this may contribute to offering comparable treatment.
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http://dx.doi.org/10.1016/j.hpb.2020.03.002DOI Listing
October 2020

Space-making particle therapy for sarcomas derived from the abdominopelvic region.

Radiother Oncol 2020 05 25;146:194-199. Epub 2020 Mar 25.

Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Japan.

Background: The primary definitive treatment for abdominopelvic sarcomas (APSs) is resection, although incomplete resection has a negative prognostic impact. Although the effectiveness of particle therapy (PT) as a treatment for APS has already been demonstrated, its application for tumors adjacent to the gastrointestinal tract is frequently restricted, due to extremely low tolerance. Space-making PT, consisting of surgical spacer placement and subsequent PT, has been developed to overcome this limitation.

Materials And Methods: Between June 2006 and June 2018, a total of 75 patients with 12 types of APS underwent space-making PT.

Results: The 3-year local control rate of all patients was 90.3%. Fourteen surgery-related complications were observed in 12 patients (16%), and complications of Grade 3b or higher were observed in 3 patients. Ninety-five PT-related complications were seen in 66 patients (88.0%), and 13 patients (17.3%) had complications of Grade 3 or higher. The median V95% (volume irradiated with 95% of the treatment planning dose) of the gross tumor volume and clinical target volume were 99.9% and 99.5%, respectively. The median D95% (dose intensity covering 95% of the target volume) of the gross tumor volume/planned dose and clinical target volume/planned dose were 99.4%, and 99.1%, respectively.

Conclusion: The feasibility and effectiveness of space-making PT have been demonstrated via dosimetric evaluation, and our results indicate that this new strategy may potentially provide an effective and innovative treatment option for advanced APS.
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http://dx.doi.org/10.1016/j.radonc.2020.02.021DOI Listing
May 2020

Impact of Albumin-Bilirubin Score on Short- and Long-Term Survival After Living-Donor Liver Transplantation: A Retrospective Study.

Transplant Proc 2020 Apr 14;52(3):910-919. Epub 2020 Mar 14.

Department of Surgery, Division of Hepato-Biliary and Pancreatic Surgery, Graduate School of Medicine, Kobe University, Kobe City, Hyogo, Japan.

Background: The albumin-bilirubin (ALBI) grade, stratified from the ALBI score, may have prognostic value in patients with hepatocellular carcinoma. We aim to evaluate the prognostic abilities of the ALBI score/grade among living-donor liver transplantation patients.

Methods: We retrospectively collected data of 81 patients who underwent living-donor liver transplant at Kobe University Hospital between June 2000 and October 2018. The efficacy of the ALBI score/grade as a prognostic factor was assessed and compared with that of the well-established Model for End-Stage Liver Disease (MELD) score.

Main Findings: Multivariate analysis indicated that recipient age (P = .003), donor age (P = .003), ALBI score ≥ -1.28 (P = .002), and ALBI grade III (P = .004) were independently associated with post-transplant survival. A high MELD score was not associated with post-transplant survival in univariate or multivariate analyses. Although there was no significant difference in the overall survival rate relative to recipient and donor age, ALBI score/grade was significantly associated with the 1- and 5-year survival rates (P = .023, P = .005). ALBI scores specifically detected fatal complications of post-transplant graft dysfunction (P = .031) and infection (P = .020).

Conclusion: ALBI score/grade predicted patient survival more precisely than the MELD score did, suggesting that it is a more useful prognostic factor compared to the MELD score in living-donor liver transplantation cases.
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http://dx.doi.org/10.1016/j.transproceed.2020.01.020DOI Listing
April 2020

[Analysis of Surgical Resection for Elderly Patients with Biliary Tract Cancer].

Gan To Kagaku Ryoho 2019 Dec;46(13):2279-2281

Dept. of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine.

Although surgical resection is the first-line treatment for biliary tract cancer(BTC), elderly patients often have underlying diseases and decreased cardiopulmonary function that place them at a high risk of undergoing surgery. We examined the safety and efficacy of surgical resection in elderly BTC patients. Among the BTC cases that underwent surgical resection at Kobe University Hospital from 2009 to 2015, the safety and prognosis ofthose aged 75 years or older(Group 1)were compared to those younger than 75 years(Group 2)at the time ofsurgery. Fifty-two patients with perihilar cholangiocarcinoma( Bp), 29 patients with intrahepatic cholangiocarcinoma(ICC), and 40 patients with ampulla ofVater cancer(AV) were included. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲor above, while surgery-related death was more common in Bp and ICC ofGroup 1. The median survival ofGroup 1 following hepatectomy for Bp and ICC(22 months)was significantly shorter than that of Group 2(40 months)(p=0.023). There was no significant difference in overall survival of Group 1 and Group 2 patients with AV(p=0.094). Surgical resection for BP and ICC for elderly patients has a higher risk of hepatectomy; therefore, precise assessment of oncologic and patient risk factors should be performed. As we can expect to achieve similar prognoses between non-elderly and elderly patients with AV, aggressive treatments should be considered for elderly patients with AV.
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December 2019

Benefits and limitations of middle bile duct segmental resection for extrahepatic cholangiocarcinoma.

Hepatobiliary Pancreat Dis Int 2020 Apr 30;19(2):147-152. Epub 2020 Jan 30.

Department of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan.

Background: Pancreaticoduodenectomy (PD) is a standardized strategy for patients with middle and distal bile duct cancers. The aim of this study was to compare clinicopathological features of bile duct segmental resection (BDR) with PD in patients with extrahepatic cholangiocarcinoma.

Methods: Consecutive cases with extrahepatic cholangiocarcinoma who underwent BDR (n = 21) or PD (n = 84) with achievement of R0 or R1 resection in Kobe University Hospital between January 2000 and December 2016 were enrolled in the present study.

Results: Patients who underwent PD were significantly younger than those receiving BDR. The frequency of preoperative jaundice, biliary drainage and cholangitis was not significantly different between the two groups. The duration of surgery was longer and there was more intraoperative bleeding in the PD than in the BDR group (553 vs. 421 min, and 770 vs. 402 mL; both P<0.01). More major complications (>Clavien-Dindo IIIa) were observed in the PD group (46% vs. 10%, P<0.01). Postoperative hospital stay was also longer in that group (30 vs. 19 days, P = 0.02). Pathological assessment revealed that tumors were less advanced in the BDR group but the rate of lymph node metastasis was similar in both groups (33% in BDR and 48% in PD, P = 0.24). The rate of R0 resection was significantly higher in the PD group (80% vs. 38%, P<0.01). Adjuvant chemotherapy was more frequently administered to patients in the BDR group (62% vs. 38%, P = 0.04). Although 5-year overall survival rates were similar in both groups (44% for BDR and 51% for PD, P = 0.72), in patients with T1 and T2, the BDR group tended to have poorer prognosis (44% vs. 68% at 5-year, P = 0.09).

Conclusions: BDR was comparable in prognosis to PD in middle bile duct cancer. Less invasiveness and lower morbidity of BDR justified this technique for selected patients in a poor general condition.
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http://dx.doi.org/10.1016/j.hbpd.2020.01.002DOI Listing
April 2020

Human equilibrative nucleoside transporter-1 expression is a predictor in patients with resected pancreatic cancer treated with adjuvant S-1 chemotherapy.

Cancer Sci 2020 Feb 19;111(2):548-560. Epub 2019 Dec 19.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Nagaizumi, Japan.

The high expression of human equilibrative nucleoside transporter-1 (hENT1) and the low expression of dihydropyrimidine dehydrogenase (DPD) are reported to predict a favorable prognosis in patients treated with gemcitabine (GEM) and 5-fluorouracil (5FU) as the adjuvant setting, respectively. The expression of hENT1 and DPD were analyzed in patients registered in the JASPAC 01 trial, which showed a better survival of S-1 over GEM as adjuvant chemotherapy after resection for pancreatic cancer, and their possible roles for predicting treatment outcomes and selecting a chemotherapeutic agent were investigated. Intensity of hENT1 and DPD expression was categorized into no, weak, moderate or strong by immunohistochemistry staining, and the patients were classified into high (strong/moderate) and low (no/weak) groups. Specimens were available for 326 of 377 (86.5%) patients. High expression of hENT1 and DPD was detected in 100 (30.7%) and 63 (19.3%) of 326 patients, respectively. In the S-1 arm, the median overall survival (OS) with low hENT1, 58.0 months, was significantly better than that with high hENT1, 30.9 months (hazard ratio 1.75, P = 0.007). In contrast, there were no significant differences in OS between DPD low and high groups in the S-1 arm and neither the expression levels of hENT1 nor DPD revealed a relationship with treatment outcomes in the GEM arm. The present study did not show that the DPD and hENT1 are useful biomarkers for choosing S-1 or GEM as adjuvant chemotherapy. However, hENT1 expression is a significant prognostic factor for survival in the S-1 arm.
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http://dx.doi.org/10.1111/cas.14258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004513PMC
February 2020

Space-Making Particle Therapy with Surgical Spacer Placement in Patients with Sacral Chordoma.

J Am Coll Surg 2020 02 23;230(2):207-215. Epub 2019 Nov 23.

Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

Background: Sacral chordomas are rare malignant bone tumors and are often very large for complete resection. Particle therapy for these tumors, which are adjacent to the gastrointestinal tract, is restricted because the tolerance dose of the intestine is low. This study aimed to demonstrate the technical aspects and treatment results of space-making particle therapy with surgical spacer placement for sacral chordoma. We aimed to investigate the dosimetric change in the particle therapy before and after spacer placement and the safety, efficacy, and long-term outcomes of space-making particle therapy.

Study Design: Twenty-one patients with sacral chordomas who were excluded from typical particle therapy were enrolled between 2007 and 2015. Gore-Tex sheets (WL Gore & Assoc) were folded and placed between the sacral and rectum. Particle therapy with 70.4 Gy (relative biologic effectiveness) was then performed.

Results: The mean volume that allows 95% of the treatment plan dose of the gross tumor volume and clinical tumor volume after spacer placement was improved to 97.7% and 96.4% from preoperative values of 91.0% and 89.5%, respectively. The recurrence rate within the gross tumor volume was only 4.8%. The 4-year local progression-free survival rate was 68.4%. The 5-year overall survival rate was 100% and the adverse events were acceptable.

Conclusions: Considering improvements in the dose-volume histogram after spacer placement, low recurrence rates within the gross tumor volume, good survival rates, and low incidences of side effects, treatment of sacral chordoma with space-making particle therapy shows promise.
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.11.007DOI Listing
February 2020
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