Publications by authors named "Yukiyasu Okamura"

133 Publications

Pathological characterization of intracholecystic papillary neoplasm: A recently proposed preinvasive neoplasm of gallbladder.

Ann Diagn Pathol 2021 Mar 3;52:151723. Epub 2021 Mar 3.

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

Intracholecystic papillary neoplasm (ICPN) is a recently proposed gallbladder neoplasm. Its prevalence and pathologies remain to be clarified. A total of 38 ICPN cases (28 ICPNs identified among 1904 cholecystectomies (1.5%) and in 100 surgically resected primary gallbladder neoplasms (28%) in Fukui Prefecture Saiseikai Hospital, Japan, and other 10 ICPNs) were examined pathologically and immunohistochemically. They were composed of 21 males and 17 females with a mean age of 75 years old, and presented intraluminal growth of papillary lesions with fine fibrovascular stalks. ICPNs were relatively frequent in the fundus (n = 11) and body (n = 9). Grossly, the conglomerated sessile type (n = 30) was more frequent than the isolated polypoid type (n = 8). All cases were classified as high-grade dysplasia, and they were further divided into 22 cases presenting irregular structures and 16 cases presenting regular structures. The former showed frequent complicated lesions and stromal invasion (54.5%) compared to the latter (12.5%). Twenty-four cases showed predominantly either of four subtypes (11 gastric, 7 intestinal, 4 biliary and 2 oncocytic subtype), while the remaining14 cases showed mixture of more than two subtypes. In conclusion, ICPN presented unique preinvasive neoplasm with characteristic histopathologies. Irregular histologies and complicated lesions of ICPN were related to stromal invasion.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151723DOI Listing
March 2021

Anatomical resection is useful for the treatment of primary solitary hepatocellular carcinoma with predicted microscopic vessel invasion and/or intrahepatic metastasis.

Surg Today 2021 Feb 9. Epub 2021 Feb 9.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Purpose: The aim of this study was to evaluate anatomical resection (AR) versus non-AR for primary solitary hepatocellular carcinoma (HCC) with predicted microscopic vessel invasion (MVI) and/or microscopic intrahepatic metastasis (MIM).

Methods: This retrospective study included 358 patients who underwent hepatectomy and had no evidence of MVI and/or MIM on preoperative imaging. The predictors of MVI and/or MIM were identified. The AR group (n = 222) and the non-AR group (n = 136) were classified by number of risk factor, and the survival rates were compared.

Results: Microscopic vessel invasion and/or MIM were identified in 81 (22.6%) patients. A multivariate analysis showed that high des-gamma-carboxy prothrombin concentration [odds ratio (OR) 3.35], large tumor size (OR 3.16), and high aspartate aminotransferase concentration (OR 2.13) were significant predictors. The 5-year overall survival (OS) in the patients with zero, one, two, and three risk factors were 97.4%, 73.5%, 71.5%, and 65.5%, respectively. The OS of AR is superior to that of non-AR only in patients with one or two risk factors.

Conclusion: The present findings suggest that AR should be performed for patients with one or two risk factors, and that AR may prevent recurrence, as these patients are at risk of having MVI and/or MIM.
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http://dx.doi.org/10.1007/s00595-021-02237-1DOI Listing
February 2021

Reappraisal of pathological features of intraductal papillary neoplasm of bile duct with respect to the type 1 and 2 subclassifications.

Hum Pathol 2021 Jan 27;111:21-35. Epub 2021 Jan 27.

Department of Diagnostic Pathology, Yonsei Medical Center, Seoul, 03722, South Korea.

The pathological spectrum of intraductal papillary neoplasm of bile duct (IPNB) remains to be clarified. A total of 186 IPNBs were pathologically examined using the type 1 and 2 subclassifications proposed by Japanese and Korean biliary pathologists incorporating a two-tiered grading system (low-grade and high-grade dysplasia), with reference to four subtypes (intestinal [i], gastric [g], pancreatobiliary [pb], and concocytic [o] subtype). IPNBs were classifiable into type 1 composed of low-grade dysplasia and 'high-grade dysplasia with regular structures' (69 IPNBs), and type 2 of 'high grade dysplasia with irregular structures and complicated lesions' (117 IPNBs). Type 1 was more common in the intrahepatic bile duct (78%), whereas type 2 was frequently located in the extrahepatic bile duct (58%). Mucin hypersecretion was more common in type 1 (61%) than in type 2 (37%). IPNBs were classifiable into the four subtypes: 86 iPNBs, 40 gIPNBs, 31 pbIPNBs, and 29 oIPNBs. The four subtypes were histologically evaluable with reference to the type 1 and 2 subclassifications. iIPNB and pbIPNBs were frequently classified as type 2, whereas types 1 and 2 were observed at similar rates in gIPNB and oIPNB. Stromal invasion was almost absent in type 1, irrespective of subtype, but was found in 66 of 117 type 2 IPNBs (P < .01), and postoperative outcome was favorable in IPNBs without invasion compared with IPNBs with invasion (P < .05). The type 1 and 2 subclassifications with reference to the four subtypes may provide useful information for understanding IPNB.
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http://dx.doi.org/10.1016/j.humpath.2021.01.002DOI Listing
January 2021

Clinical Significance of Preoperative Albumin-Bilirubin Grade in Pancreatic Cancer.

Ann Surg Oncol 2021 Jan 23. Epub 2021 Jan 23.

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

Background: No study has clarified the clinical significance of albumin-bilirubin (ALBI) grade in a large cohort of pancreatic cancer patients.

Methods: A total of 1006 consecutive patients diagnosed with pancreatic cancer and deemed eligible for surgical resection were analyzed. The ALBI score was calculated as: ALBI score = (log bilirubin [µmol/L] × 0.66) + (albumin [g/L]  × - 0.0852). ALBI grade was assigned as grade 1, 2a, 2b, and 3. ALBI grade 1 was assigned to the ALBI low group (N = 566), and grades 2a, 2b, and 3 to the ALBI high group (N = 440).

Results: The primary lesion could not be resected in 129 patients. Among all patients, overall survival (OS) was significantly worse in the ALBI high group than in the ALBI low group (P = 0.024). Overall, 877 patients underwent pancreatectomy. In these patients, the ALBI high group was associated with high CA19-9 level (P < 0.001), lower morbidity rate (P < 0.001), and pancreatic head tumor (P = 0.001). Patients' OS after resection was significantly worse in the ALBI high group than in the ALBI low group (P < 0.001). Cox proportional hazard analysis revealed ALBI grade as an independent predictor for prognosis (hazard ratio, 1.33; P = 0.015). Even in the CA19-9 negative patients, OS was significantly worse in the ALBI high group than in the ALBI low group (P = 0.046).

Conclusions: The ALBI grade is a clinically useful predictor for prognosis in pancreatic cancer patients.
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http://dx.doi.org/10.1245/s10434-021-09593-9DOI Listing
January 2021

Clinical Implication of Node-negative Resectable Pancreatic Cancer.

Ann Surg Oncol 2021 Apr 15;28(4):2257-2264. Epub 2021 Jan 15.

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

Background: Lymph node metastasis is one of the strongest prognostic factors of pancreatic cancer. However, the clinical implication of pathologically node-negative pancreatic cancer (pN0-PC) has not been fully investigated.

Methods: Patients who underwent surgical resection for radiologically resectable pancreatic cancer between 2002 and 2018 were included in this study. A clinicopathological examination focusing on pN0-PC was performed.

Results: Of all 533 patients, 155 (29.1%) were diagnosed with pN0-PC and 378 (70.9%) were diagnosed with node-positive pancreatic cancer (pN1/2-PC). The 5-year survival rates of patients with pN0-PC and pN1/2-PC were 57.1% and 25.0%, respectively (p < 0.001). A multivariate analysis revealed six prognostic factors in pN0-PC: age ≥ 70 years, nonadministration of adjuvant chemotherapy, anterior serosal invasion, nerve plexus invasion, and microscopic lymphatic and venous invasions. The 5-year survival rates of patients who had pN0-PC with 0-1 risk factor, with 2-3 risk factors, and with 4-6 risk factors were 87.6%, 47.9%, and 16.4%, respectively. Survival of patients who had pN0-PC with 4-6 risk factors was comparable to that of pN1/2 patients. The diagnostic capability of metastasis-negative lymph node was unsatisfactory, with a predictive value of < 43%.

Conclusions: Although the prognosis of patients with pN0-PC was better than that of patients with pN1/2-PC, it is not satisfactory. Survival of patients who had pN0-PC with 0-1 risk factors was extremely favorable; however, survival of patients who had pN0-PC with 4-6 risk factors was similar to those with pN1/2-PC.
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http://dx.doi.org/10.1245/s10434-020-09543-xDOI Listing
April 2021

The prognostic roles of the prognostic nutritional index in patients with intraductal papillary mucinous neoplasm.

Sci Rep 2021 Jan 12;11(1):568. Epub 2021 Jan 12.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88-138.5, P = 0.011) and a carbohydrate antigen (CA) 19-9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73-25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.
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http://dx.doi.org/10.1038/s41598-020-79583-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803756PMC
January 2021

The evaluation of the 8th and 7th edition of the American joint committee on cancer tumor classification for distal cholangiocarcinoma: the proposal of a modified new tumor classification.

HPB (Oxford) 2020 Dec 19. Epub 2020 Dec 19.

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

Background: The 7th and 8th editions of the American Joint Committee on Cancer (AJCC) tumor (T) classification of distal cholangiocarcinoma (DCC), which are based on either layer or depth, may not accurately stratify patient survival.

Methods: A total of 121 patients who underwent resection for DCC between 2002 and 2016 were analyzed. The impact of the AJCC staging system on survival was examined and a new T classification was established based on independent prognostic factors.

Results: Regarding overall survival, the optimal depth of invasion (DOI) cut-off value (8 mm) was the only independent prognostic factor. Regarding the relapse-free survival (RFS), a DOI >8 mm, portal vein (PV) invasion, and duodenal or pancreatic invasion were independent prognostic factors. A new T classification was developed as follows: T1, no invasion of adjacent organs; T2, invasion of the duodenum or pancreas; T3, invasion >8 mm into the bile duct wall; and T4, invasion of the PV or arteries. There were no significant differences in RFS according to the 8th edition of the AJCC. However, significant differences were observed in the RFS between T1 and T2 and between T2 and T3.

Conclusion: A new T classification based on the layer and depth may be more feasible.
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http://dx.doi.org/10.1016/j.hpb.2020.12.001DOI Listing
December 2020

The prognostic impact of skeletal muscle status and bone mineral density for resected distal cholangiocarcinoma.

Clin Nutr 2020 Dec 15. Epub 2020 Dec 15.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan.

Background & Aims: The preoperative body composition and bone mineral density (BMD) have been reported as prognostic factors for several cancers. However, the prognostic impact of the preoperative body composition and BMD for resected distal cholangiocarcinoma (DCC) remains unclear.

Methods: A total of 111 patients who underwent pancreatoduodenectomy for DCC between 2002 and 2017 were analyzed. The skeletal muscle index (SMI) and BMD were measured by preoperative computed tomography. The optimal cut-off value of the body composition and BMD were selected based on the minimum P-value obtained by the log-rank test. The prognostic significance of the preoperative body composition and BMD was investigated using multivariate analysis.

Results: The median values of the SMI (45.7 vs. 36.7 cm/m, P < 0.001) and BMD (128.5 vs. 101.0 Hounsfield units [HU], P = 0.005) in male and female were significantly different. The optimal cut-off values for the SMI were 55 cm/m in male and 36 cm/m in female, and those for the BMD were 75 HU in male and 74 HU in female. A multivariate analysis identified low SMI (hazard ratio [HR], 4.340; P = 0.044), low BMD (HR, 5.333; P < 0.001) and microscopic venous invasion (HR, 2.019; P = 0.026) as independent prognostic factors for the survival.

Conclusions: A preoperative low SMI and low BMD were independent prognostic factors for resected DCC.
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http://dx.doi.org/10.1016/j.clnu.2020.12.011DOI Listing
December 2020

Description of the Vascular Anatomy of Livers with Absence of the Portal Bifurcation.

World J Surg 2021 Mar 9;45(3):833-840. Epub 2020 Nov 9.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Background: The absence of the portal bifurcation (APB) is a rare anatomic variation, in which the horizontal part of the left portal vein (PV) is missing. The aim of this study was to identify the vascular architecture in livers with APB.

Methods: Computed tomography data for 17,651 patients were reviewed; five patients (0.03%) were found to present with APB. The liver volume and anatomy of APB patients were compared with those of 30 patients with normal livers.

Results: All the APB patients exhibited an independent posterior branch of the PV. The intrahepatic left PV (LPV) ran through either the ventral (n = 2, 40%) or dorsal side (n = 3, 60%) of the middle hepatic vein. The frequency of medial branches diverging from the LPV was higher in patients with APB than in normal patients (p < 0.001). The left hepatic duct (LHD) ran through the inside of the left lobe along the left PV in 40% of the patients with APB, whereas in the remaining 60% of the patients with APB, the LHD ran on the outside of the liver separately from the left PV and joined the right hepatic duct. The liver volume of the left lateral section was significantly smaller (p = 0.014), and the posterior section was significantly larger (p = 0.014) in patients with APB than in patients with normal livers.

Conclusion: The unique anatomical characteristics and the positional relation of the vessels should be considered preoperatively in patients with APB.
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http://dx.doi.org/10.1007/s00268-020-05848-wDOI Listing
March 2021

Analysis of right-sided ligamentum teres: The novel anatomical findings and classification.

J Hepatobiliary Pancreat Sci 2021 Feb 17;28(2):221-230. Epub 2020 Nov 17.

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

Background: The true anatomy of right-sided ligamentum teres (RSLT) has not been fully explained for a century. This study aimed to clarify the exact anatomy of RSLT.

Methods: The computed tomography data of 17 651 surgical patients were observed and 76 patients with RSLT, were classified into the bilateral ligamentum teres (LT) group (type A) and three RSLT groups, (B) bifurcation type, (C) trifurcation type, and (D) independent posterior branch type.

Results: Type A had double LT that connected to both the right and left sides of the umbilical portion (UP). Types B-D had a P3 + 4 rather than a left UP. Type D was anatomically different from types A-C. Upon comparing types A-C and type D, type D had a significantly smaller volume of segments 3 + 4 (P < .001), and the UP was more often on the left side. The position of the gallbladder fundus in type D was more commonly observed on the right side of the LT compared with that observed in the other types (P = .007).

Conclusions: The change in the volume of segments 3 + 4 and the extent of the RSLT shift create a false perception that the gallbladder changes the position.
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http://dx.doi.org/10.1002/jhbp.856DOI Listing
February 2021

The influence of familial pancreatic cancer on postoperative outcome in pancreatic cancer: relevance to adjuvant chemotherapy.

J Gastroenterol 2021 Jan 22;56(1):101-113. Epub 2020 Oct 22.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Background: Familial pancreatic cancer (FPC) is defined as a family in which at least two first-degree relatives have pancreatic cancer (PC). The prognostic significance of PC in an FPC family after surgery is not fully understood.

Methods: This was a retrospective study of 427 patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma between January 2008 and December 2016. PC patients who also had at least one first-degree relative with PC were defined as FPC patients. The associations between recurrence and clinicopathological characteristics were analyzed for both FPC and non-FPC patients.

Results: FPC patients accounted for 31 of the 427 (7.3%) patients. Recurrence occurred in 72.1% of the total cohort and in 87.1% of the 31 FPC patients. Multivariate analysis showed that being an FPC patient was an independent predictor for relapse-free survival (RFS) (hazard ratio [HR] 1.52, P = 0.038). Although univariate analysis revealed that being an FPC patient was significantly associated with poorer overall survival (OS) (P < 0.001), multivariate analysis showed that being an FPC patient was not an independent predictor for OS (P = 0.164). Dichotomization of the 427 patients into those who received (n = 317: 17 FPC and 300 non-FPC patients) and did not receive (n = 110: 14 FPC and 96 non-FPC patients) adjuvant chemotherapy revealed that being an FPC patient was an independent predictor for RFS (HR 2.50, P < 0.001) and OS (HR 2.30, P = 0.003) only for patients who received adjuvant chemotherapy.

Conclusions: This study has shown that being an FPC patient is a significant prognostic indicator for PC patients who undergo resection and receive adjuvant chemotherapy.
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http://dx.doi.org/10.1007/s00535-020-01730-7DOI Listing
January 2021

Prognostic Impact of Paraaortic Lymph Node Metastasis in Extrahepatic Cholangiocarcinoma.

World J Surg 2021 Feb 20;45(2):581-589. Epub 2020 Oct 20.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007, Shimo-Nagakubo, Sunto- Nagaizumi, Shizuoka, 4118777, Japan.

Background: Surgical resection in patients with extrahepatic cholangiocarcinoma (EHCC) with paraaortic lymph node metastasis (PALNM) remains controversial. The objective of this study was to investigate the prognostic impact of PALNM in resected EHCC.

Methods: The present retrospective study included 410 patients, including 16 patients with PALNM, who underwent surgical resection of EHCC between September 2002 and December 2018. These were compared to 9 patients in whom EHCC was not resected due to PALNM. The clinicopathological features and survival outcomes were investigated to identify the prognostic factors in resected EHCC.

Results: The overall survival in the resected patients with PALNM was significantly better than that in unresected patients (median survival time [MST] 33.7 vs. 16.7 months, p=0.009) and was not significantly worse than that of patients with regional lymph node metastasis (LNM) (MST 33.7 vs 36.0 months, p=0.278). The multivariate analysis identified age > 70 years, male sex, tumor location (perihilar), residual tumor status, histological grade, microscopic venous invasion, and regional LNM as independent prognostic factors.

Conclusions: There was no significant difference in survival between the resected patients with PALNM and patients with regional LNM, and PALNM was not a significant prognostic factor in the multivariate analysis. Surgical resection may be considered an acceptable approach for EHCC with PALNM in selected patients.
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http://dx.doi.org/10.1007/s00268-020-05834-2DOI Listing
February 2021

Middle segment-preserving pancreatectomy for multifocal pancreatic ductal adenocarcinoma located in the head and tail of the pancreas: a case report.

J Surg Case Rep 2020 Oct 7;2020(10):rjaa383. Epub 2020 Oct 7.

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

A 77-year-old woman with a solitary existence was referred to our hospital for the treatment of pancreatic tumors. Computed tomography revealed an 18-mm mass in the pancreatic head that had invaded the right side of the superior mesenteric vein (SMV) and a 32-mm mass in the pancreatic tail. We performed middle segment-preserving pancreatectomy (MSPP) with SMV resection and reconstruction. The TNM classifications were T2, N1, M0, stage IIB in the pancreatic head, and T2, N0, M0, stage IB in the pancreatic tail, respectively. Postoperatively, the blood glucose was well controlled using only hypoglycemic drug, and insulin preparation was not necessary. No fatty diarrhea was found using a pancreatic enzyme supplement. After 9 months of follow-up, no recurrence was found. MSPP for pancreatic head and tail carcinomas seemed acceptable for both preserving the postoperative quality of life and ensuring curative resection especially in elderly patient with a solitary existence.
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http://dx.doi.org/10.1093/jscr/rjaa383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540631PMC
October 2020

Laparoscopic repeat liver resection for hepatic epithelioid hemangioendothelioma.

Surg Case Rep 2020 Oct 1;6(1):254. Epub 2020 Oct 1.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Background: Optimal treatment for patients with hepatic epithelioid hemangioendothelioma (HEHE) remains unclear. Laparoscopic repeat liver resection (LR) is a minimally invasive and potentially effective surgical option for multiple HEHEs.

Case Presentation: A 42-year-old woman with no relevant history was admitted for multiple liver tumors. Six tumors were observed on T2-weighted magnetic resonance imaging (MRI) including one in S2, two in S3, two in S7, and one in S8. Pathological evaluation of percutaneous tumor biopsy tissue suggested a diagnosis of HEHE and laparoscopic LR was planned. The procedure began with partial resection of S7 and partial resection of S8 and left lateral sectionectomy were performed. Another tumor was found intraoperatively on the surface of S6, necessitating removal by partial resection. Pathological evaluation of the resected tumor tissue from all seven tumors concurred with that of the preoperative biopsy. The patient was discharged on postoperative day 6 without any complications. A follow-up MRI 15 months after the primary surgery revealed one tumor each in S4, S6, and S8. Laparoscopic repeat LR was performed. The patient was discharged on postoperative day 5 without any complications. All three recurrent tumors were pathologically confirmed as HEHEs.

Conclusions: We successfully treated primary and recurrent HEHEs with laparoscopic LR, which is a reasonable minimally invasive procedure considering the possibility of multiple courses of liver surgery in patients with HEHE.
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http://dx.doi.org/10.1186/s40792-020-01036-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530154PMC
October 2020

The Prognostic Relevance of the Number and Location of Positive Lymph Nodes for Ampulla of Vater Carcinoma.

World J Surg 2021 Jan 9;45(1):270-278. Epub 2020 Sep 9.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan.

Background: Lymph node metastasis (LNM) has been regarded as one of the prognostic factors in patients with ampulla of Vater carcinoma (AC). However, the consensus about an optimal cutoff value of the number of LNMs and the definition of the regional lymph nodes (RLNs) has not been achieved.

Methods: This study included 114 consecutive patients who underwent pancreatoduodenectomy for AC between January 2002 and March 2019.

Results: The minimum p value approach for the greatest difference in the overall survival classified the number of LNM into none (N0, n = 66), from 1 to 2 (N1, n = 32), and ≥3 LNM (N2, n = 11) (p = 0.004). Distant LNM was defined as M1 (n = 5). Significant differences in relapse-free survival (RFS) were found between N0 and N1 (p < 0.001), N1 and N2 (p = 0.047), and N1 and M1 (p = 0.044) but not between N2 and M1 (p = 0.683). Moreover, the patients with regional LNM were classified into two groups: Np group (n = 35, LNM only in pancreatic head region) and Nd group (n = 8, LNM in other regional location). Significant differences in the RFS were found between N0 and Np (p < 0.001), Np and Nd (p = 0.004), and Np and M1 (p = 0.033) but not between Nd and M1 (p = 0.883). A Cox proportional hazards analysis for RFS revealed that ≥ 3 LNMs (hazards ratio [HR], 3.22) and LNM except for pancreatic head region (HR, 4.27) were individually independent worse prognostic factors.

Conclusions: ≥3 LNMs and regional LNM except for pancreatic head region were associated with poor prognosis comparable to that of the patients with M1.
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http://dx.doi.org/10.1007/s00268-020-05770-1DOI Listing
January 2021

Reconsidering the Optimal Regional Lymph Node Station According to Tumor Location for Pancreatic Cancer.

Ann Surg Oncol 2021 Mar 29;28(3):1602-1611. Epub 2020 Aug 29.

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

Background: A consensus regarding the optimal extent of lymph node dissection for pancreatic cancer has not yet been achieved. The purpose of this study was to evaluate the efficacy of lymph node dissection according to the location for pancreatic cancer.

Methods: A total of 495 patients diagnosed with invasive ductal carcinoma of the pancreas who had undergone a pancreatectomy between October 2002 and December 2015 were analyzed. The efficacy index (EI) was calculated for each lymph node station via multiplication of the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to that station.

Results: For pancreatic head (Ph) tumors, mesocolon lymph nodes had a high EI, although not regional. For pancreatic body (Pb) tumors, peri-Ph lymph nodes had a high EI, although not regional. For pancreatic tail (Pt) tumors, lymph nodes along the celiac axis and common hepatic artery had a zero EI, although regional. When the Ph was segmented into the pancreatic neck (Ph-neck), uncinate process (Ph-up), and periampullary regions, hepatoduodenal ligament lymph nodes had a zero EI for Ph-up, although regional; the mesojejunum lymph node also had a zero EI, even for Ph-up, regardless of a high incidence of metastasis. Regarding lymph node recurrence after surgery, recurrence was most frequently found at the peri-Ph lymph node (12%) in patients with Pb tumors who had undergone a distal pancreatectomy.

Conclusions: The optimal extent of lymph node dissection should be estimated in regard to the tumor location.
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http://dx.doi.org/10.1245/s10434-020-09066-5DOI Listing
March 2021

The clinical impact and risk factors of latent pancreatic fistula after pancreatoduodenectomy.

J Hepatobiliary Pancreat Sci 2020 Dec 18;27(12):1002-1010. Epub 2020 Sep 18.

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

Background: Latent pancreatic fistula (LPF) is difficult to diagnose during the early postoperative phase because of initially normal drain fluid amylase (DFA) levels. The present study investigated the clinical significance and risk factors of LPF after pancreatoduodenectomy.

Methods: A total of 662 patients who underwent pancreatoduodenectomy between 2010 and 2018 were retrospectively analyzed. LPF was defined as pancreatic fistula that developed later regardless of initially low DFA levels.

Results: Among the 372 patients with DFA ≤375 U/L (three times the upper limit for serum) on postoperative day (POD) 3, LPF occurred in 37 (10%). The rates of postoperative hemorrhaging (11% vs 1.5%), intraabdominal abscess (57% vs 7.2%) and reintervention (46% vs 2.7%) were significantly higher in the patients with LPF than in those without LPF. A multivariate analysis revealed that a body mass index ≥25 kg/m , a non-combined portal vein resection, a DFA on POD 1 ≥650 U/L and a C-reactive protein level on POD 3 ≥11 mg/dL were independent risk factors for LPF.

Conclusions: Latent pancreatic fistula was significantly associated with severe complications and worse outcomes after pancreatoduodenectomy. Early drain removal may be unfavorable for patients with some of these risk factors.
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http://dx.doi.org/10.1002/jhbp.820DOI Listing
December 2020

Prognostic impact of abutment to the branches of the superior mesenteric artery in borderline resectable pancreatic cancer.

Langenbecks Arch Surg 2020 Nov 27;405(7):939-947. Epub 2020 Aug 27.

Divisions of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Sunto-Nagaizumi, Shizuoka, 4118777, Japan.

Purpose: The clinical impact of abutment to an artery and its branch on resectability and prognosis in patients with borderline resectable pancreatic cancer is unclear.

Methods: Patients diagnosed with borderline resectable pancreatic cancer due to artery abutment between April 2012 and December 2018 were enrolled. Contact between arteries and the tumour was assessed by computed tomography (CT).

Results: A primary lesion was resected in 63 patients (R group) and unresected in 19 patients (UR group). Overall survival (OS) was worse in the UR group than in the R group (P < 0.001). Multivariate analysis showed that abutment to the superior mesenteric artery (SMA) branches (P = 0.001) was an independent predictor of poor OS after surgery. Regarding the initial recurrence pattern, abutment to the SMA branches was significantly associated with high incidence of distant metastasis (P < 0.001). According to the most distal SMA branch attached on CT, significant differences in RFS were found between absent-J1A (P = 0.017), J2A-J3A (P = 0.0313) and J3A-middle colic artery (MCA, P = 0.0476) but not between J1A-J2A (P = 0.8207). Significant prognostic differences in OS after initiation of the treatment were found between absent-J1A/J2A (P = 0.006) and J1A/J2A-J3A/MCA (P = 0.033) but not between J3A/MCA-UR (P = 0.494).

Conclusion: Abutment to the SMA branches was associated with high incidence of distant metastasis after resection and a poor survival. Especially, abutment to the J3A or MCA was associated with poor prognosis comparable with that of the UR group.
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http://dx.doi.org/10.1007/s00423-020-01970-4DOI Listing
November 2020

Intraductal tubulopapillary neoplasms with rupture of the distal main pancreatic duct: a case report.

Surg Case Rep 2020 Aug 14;6(1):210. Epub 2020 Aug 14.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Background: Intraductal tubulopapillary neoplasm (ITPN) is a rare and newly described entity defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. Because of its rarity, the clinical and molecular aspects of ITPN have not been fully investigated.

Case Presentation: A 73-year-old woman presented to a local hospital with epigastric discomfort and pain. Abdominal multidetector-row computed tomography (MDCT) revealed a 2.5-cm hypovascular tumor in the pancreatic body with distal pancreatic duct dilatation and a slightly low-density area spreading over the ventral side of the pancreatic body. Endoscopic ultrasonography and fine-needle biopsy of the tumor revealed adenocarcinoma of the pancreas. She was referred to our hospital 2 months later. MDCT performed at our hospital showed no significant change in the tumor size or pancreatic duct dilatation. However, the low-density area at the ventral side of the pancreas had shrunk; therefore, this finding was considered to have been an inflammatory change. Under a preoperative diagnosis of resectable pancreatic ductal adenocarcinoma, distal pancreatectomy was performed. The final diagnosis was ITPN with associated invasive carcinoma. Macroscopically and microscopically, the main pancreatic duct (MPD) had ruptured at the distal side of the tumor, and the fistula connected the MPD and extrapancreatic scar tissue.

Conclusions: ITPN with rupture of the pancreatic duct is extremely rare. In the present case, a sudden increase in the pancreatic duct internal pressure or acute inflammation likely caused the rupture of the MPD.
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http://dx.doi.org/10.1186/s40792-020-00972-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427828PMC
August 2020

Use of preoperative controlling nutritional status (CONUT) score as a better prognostic marker for distal cholangiocarcinoma after pancreatoduodenectomy.

Surg Today 2021 Mar 6;51(3):358-365. Epub 2020 Aug 6.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Shizuoka, Sunto-gun, 411-8777, Japan.

Purpose: The controlling nutritional status (CONUT) score can be easily calculated from the serum albumin concentration, total cholesterol concentration, and total lymphocyte count. The study aim was to assess the preoperative prognostic factors for the overall survival (OS) of distal cholangiocarcinoma (DCC) following pancreatoduodenectomy (PD) and to demonstrate the utility of the CONUT score.

Methods: A total of 149 consecutive patients who underwent PD for DCC between September 2002 and December 2016 were divided into a low-CONUT (LC) group (CONUT scores ≤ 2) and a high-CONUT (HC) group (CONUT scores ≥ 3). The clinicopathological characteristics and OS of the patients were evaluated retrospectively. Prognostic factors of DCC were identified by multivariate analyses.

Results: The LC and HC groups included 113 and 36 patients, respectively. The OS was better in the LC group than in the HC group (median survival time and 5 year survival rate: 82 months and 56.8% vs. 38 months and 27.6%, P = 0.005). Multivariate analyses for the OS in all patients showed that the tumor differentiation, perineural invasion, residual tumor status, portal vein resection, blood transfusion, and preoperative CONUT score ≥ 3 were independently associated with a poor survival.

Conclusion: The CONUT score may be a useful preoperative factor for predicting the long-term survival in patients with DCC.
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http://dx.doi.org/10.1007/s00595-020-02098-0DOI Listing
March 2021

Adjuvant chemoradiotherapy for positive hepatic ductal margin on cholangiocarcinoma.

Ann Gastroenterol Surg 2020 Jul 15;4(4):455-463. Epub 2020 May 15.

Division of Gastrointestinal Oncology Shizuoka Cancer Center Shizuoka Japan.

Aim: This study evaluated the effects of postoperative adjuvant chemoradiotherapy (A-CRT) for positive hepatic ductal margin (HM+) in extrahepatic cholangiocarcinoma (EHCC).

Methods: Patients with EHCC who underwent surgical resection between 2002 and 2014 were included in this retrospective study. For patients with HM+, A-CRT was conducted. The clinical effect of A-CRT for HM+ on the survival and recurrence and prognostic factors of EHCC was reviewed.

Results: Among 340 patients, the hepatic ductal margin was negative in 296 and positive in 44. Of the 44 patients with HM+, 22 received postoperative A-CRT, and 22 did not. Hepatic stump recurrence occurred in 19 patients. The incidence was significantly higher in patients with HM+ (20%, 9/44) than in those with negative hepatic ductal margin (HM-) (3%, 10/296) ( < .001). Among the patients with HM+, the incidence was almost identical between the patients with and without A-CRT: 23% (5/22) in HM+/CRT- and 18% (4/22) in HM+/CRT+ patients ( = .999). The median survival time was 49 months in HM-, 43 months in HM+/CRT-, and 49 months in HM+/CRT+ patients. The differences were not significant among the groups. A multivariate analysis revealed CA 19-9 ≥ 300 U/mL, combined vascular resection, histologic grade G2/G3, and lymph node metastasis to be significant prognostic factors. However, the performance of postoperative A-CRT did not contribute to prolonging survival.

Conclusion: A-CRT for HM+ in patients with EHCC did not affect the survival or stump recurrence.
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http://dx.doi.org/10.1002/ags3.12345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382438PMC
July 2020

ASO Author Reflections: Pancreatic Invasion is a Crucial Independent Prognostic Factor in Duodenal Carcinoma.

Ann Surg Oncol 2020 Oct 27;27(11):4561. Epub 2020 May 27.

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

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http://dx.doi.org/10.1245/s10434-020-08526-2DOI Listing
October 2020

The preoperative controlling nutritional status (CONUT) score is an independent prognostic marker for pancreatic ductal adenocarcinoma.

Updates Surg 2021 Feb 15;73(1):251-259. Epub 2020 May 15.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

The controlling nutritional status (CONUT) score was developed as a nutritional score that can be calculated from the serum albumin level, total cholesterol concentration, and total lymphocyte count. The aim of this study was to assess the prognostic factors for the overall survival (OS) of pancreatic cancer patients following a curative resection and to compare the CONUT score with other prognostic factors to demonstrate its utility. Between January 2007 and December 2015, 307 consecutive patients who underwent surgery for pancreatic ductal adenocarcinoma (PDAC) were divided into a low CONUT group (LC; CONUT score ≤ 3) and a high CONUT group (HC; CONUT score ≥ 4) according to the results of their preoperative blood examination. The clinicopathological characteristics and prognosis of the patients were evaluated retrospectively. The prognostic factors of PDAC were detected using multivariate analyses. The LC and HC groups included 279 and 28 patients, respectively. The overall survival of the LC group was better than that of the HC group (LC, median survival time [MST] 27.9 months, 5-year survival rate 33.4%, respectively; HC, 13.9 months, 6.7%, p < 0.001). The multivariate analyses showed that age ≥ 70 years, lymph node metastasis, absence of postoperative adjuvant chemotherapy, CA19-9 ≥ 200 U/ml, and a preoperative CONUT score ≥ 4 were independently associated with poor survival. However, the Glasgow prognostic score, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and prognostic nutritional index were not significant factors. The CONUT score may be useful for predicting the long-term survival of patients with PDAC.
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http://dx.doi.org/10.1007/s13304-020-00792-9DOI Listing
February 2021

Prognostic Impact of Pancreatic Invasion in Duodenal Carcinoma: A Single-Center Experience.

Ann Surg Oncol 2020 Oct 4;27(11):4553-4560. Epub 2020 May 4.

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

Background: The prognostic factors for duodenal carcinoma (DC) remain unclear because of its rarity. This study aimed to investigate the prognostic impact of pancreatic invasion (PI) on postoperative survival for patients with DC.

Methods: This study retrospectively analyzed 86 patients with DC, including 18 patients with PI, who underwent surgical resection between October 2002 and March 2018. The clinicopathologic features and survival outcomes of these patients were investigated to identify the prognostic factors in DC. The long-term survival for the DC patients with PI was compared with that for the patients who underwent resection for resectable pancreatic head carcinoma (RPHC) during the same period.

Results: The median survival time (MST) for the DC patients with PI was 25.7 months, which was significantly worse than for the patients with T2 or deeper DC without PI (p = 0.010). The multivariate analysis showed that the independent prognostic factors were PI (hazard ratio [HR] 7.59; p = 0.019) and lymph node metastasis (LNM) (HR 5.01; p = 0.026). The MST for the DC patients with PI did not differ significantly from that for the RPHC patients treated without adjuvant chemotherapy (p = 0.135). Comparable rates of microscopic venous invasion and hematogenous metastasis were observed for the DC patients with PI and the RPHC patients.

Conclusions: Pancreatic invasion was an independent prognostic factor in DC. The survival outcomes for the DC patients with PI did not differ from those for the patients with RPHC, which was associated with a high rate of hematogenous recurrence.
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http://dx.doi.org/10.1245/s10434-020-08512-8DOI Listing
October 2020

Oncological benefit of metformin in patients with pancreatic ductal adenocarcinoma and comorbid diabetes mellitus.

Langenbecks Arch Surg 2020 May 4;405(3):313-324. Epub 2020 May 4.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.

Purpose: Some clinical studies have suggested that metformin improved prognoses in several cancers. This study aimed to identify prognostic factors for pancreatic ductal adenocarcinoma (PDAC) and determine the utility of metformin administration.

Methods: Between January 2007 and December 2015, 373 consecutive patients underwent curative surgery for PDAC. Among the patients, 121 were diagnosed as having diabetes mellitus (DM) before surgery. The characteristics and overall survival (OS) between patients with and without DM were compared retrospectively. Based on their metformin intake, patients with DM were divided into two groups. OS rates between patients with and without metformin intake were compared. Univariate and multivariate analyses were performed to identify prognostic factors for OS among all patients and those with PDAC and DM.

Results: No significant differences in the 5-year survival rates between patients with and without DM were observed. Among the 121 patients with DM, 18 received metformin and 103 did not (other medications group). The 5-year survival rate was significantly better in the metformin group than in the other medications group (66.7% and 24.4%, respectively; p = 0.034). Multivariate analysis identified pN1 (p = 0.002), metformin administration (p = 0.022), and microvascular invasion (p = 0.023) as independent prognostic factors for OS in the patients with DM. Matched-pair analysis showed that OS tended to be better in the metformin group than in the other medications group (p = 0.067).

Conclusions: History of metformin intake may contribute to favorable prognosis in patients with PDAC and pre-existing DM.
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http://dx.doi.org/10.1007/s00423-020-01874-3DOI Listing
May 2020

Surgical Indication for Advanced Gallbladder Cancer Considering the Optimal Preoperative Carbohydrate Antigen 19-9 Cutoff Value.

Dig Surg 2020 9;37(5):390-400. Epub 2020 Apr 9.

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

Background: Selecting patients who will benefit from resection among those with advanced gallbladder cancer (GBCa) having poor prognostic factors is difficult.

Methods: One hundred twenty-one patients who underwent resection for stage II-IV GBCa and 19 unresected patients (unresectable group) were enrolled. The clinical impact of carbohydrate antigen 19-9 (CA19-9) and advanced surgical procedures for GBCa was evaluated.

Results: The optimal CA19-9 cutoff value (based on the greatest difference in overall survival) was 250 U/mL. CA19-9 ≥250 U/mL was found to be an independent prognostic factor. Patients with CA19-9 <250 U/mL who developed jaundice (median survival time [MST], 49.1 months) or who required major hepatectomy (MST, 21.5 months) or pancreatoduodenectomy (PD; MST, 50.3 months) had a better prognosis than those with CA19-9 ≥250 U/mL who developed jaundice (MST, 16.1 months; p = 0.061) or who required major hepatectomy (MST, 9.2 months; p = 0.066) or PD (MST, 8.6 months; p = 0.025); their prognosis was comparable to that of the unresectable group (jaundice: p = 0.145, major hepatectomy: p = 0.292, PD: p = 0.756).

Conclusions: Even if GBCa patients develop jaundice or require major hepatectomy, or combined PD, resection can be considered for those with CA19-9 <250 U/mL. However, surgical indication should be carefully determined in patients with CA19-9 ≥250 U/mL.
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http://dx.doi.org/10.1159/000506628DOI Listing
April 2020

Reply to comment on "Is surgical resection superior to proton beam therapy for operable hepatocellular carcinoma?"

Surg Today 2020 12 26;50(12):1716. Epub 2020 Mar 26.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

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http://dx.doi.org/10.1007/s00595-020-01994-9DOI Listing
December 2020

A case of perihilar cholangiocarcinoma with bilateral ligamentum teres hepatis treated with hepatopancreatoduodenectomy.

Surg Case Rep 2020 Jan 30;6(1):32. Epub 2020 Jan 30.

Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.

Background: Bilateral ligamentum teres (BLT) hepatis is a very rare anomaly defined as the connection of the bilateral fetal umbilical veins to both sides of the paramedian trunk, and it has never been reported in the English literature.

Case Presentation: A 72-year-old man who presented with obstructive jaundice was referred to our hospital. Contrast-enhanced computed tomography revealed that the patient had right-sided ligamentum teres (RSLT) and left-sided ligamentum teres (LSLT). The umbilical portion of the left portal vein, which the LSLT connected, became relatively atrophic in this patient. The RSLT attached to the tip of the right anterior pedicle and formed the umbilical portion of the right portal vein. The patient was diagnosed with perihilar cholangiocarcinoma which had invaded the root of the posterior branch of the bile duct, LHD, and intrapancreatic bile duct. The central bisectionectomy, in which the liver parenchyma was resected along the RHV on the right side and the LSLT on the left side, and caudate lobectomy combined with pancreatoduodenectomy were performed. The presence of the patient with BLT is important for ascertaining the mechanism of the development of RSLT. Two umbilical veins are present initially during the embryonic stage. In general, the right-sided vein disappears, and the atrophic left-sided vein remains connected to the left portal vein originating from the vitelline vein. Several papers on the mechanism of the development of RSLT have been published. Some authors have mentioned that a residue of the right umbilical vein and the disappearance of the left umbilical vein are the causes of RSLT. On the other hand, some authors have asserted that RSLT is the result of atrophy of the medial liver area. The presence of BLT in patients indicates that the mechanism of the development of RSLT is characterized by a residue of the right umbilical vein and the disappearance of the left umbilical vein.

Conclusions: The mechanism and origin of RSLT can be understood through cases of BLT, and surgeons must pay attention to anomalies of the portal and hepatic veins in patients with abnormal ligamentum teres.
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http://dx.doi.org/10.1186/s40792-020-0793-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992831PMC
January 2020