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Katsuhiko Uesaka

Publications and source records attributed to Katsuhiko Uesaka.

At least 19 recordsLinked to original sources

Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma.

INTRODUCTION: In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing. METHODS: Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with &#x2265; 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index. RESULTS: Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson-Steiner grading and greater retention of CTNNB1, TP53, ARID1A, and KEAP1 mutations. The number of shared variants (median: 115 vs. 0, and p&#xa0;<&#xa0;0.001) and the Jaccard index (median: 0.44 vs. 0.00 and p&#xa0;<&#xa0;0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation. CONCLUSION: Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.

clonal relapse↗

A genetic variant in the gene encoding the stress70 protein chaperone family member STCH is associated with gastric cancer in the Japanese population.

Association analysis, based on linkage disequilibrium between specific alleles in the candidate loci and nearby genetic markers, has been proposed to identify genes conferring susceptibility to multifactorial diseases. Using the affected sib-pair method, we previously mapped four candidate chromosomal regions, 1p32, 2q33-q35, 11p13-p14, and 21q21, for gastric cancer by linkage analysis. To identify genes involved in the disease, we performed a gene-based association analysis of 66 genes, located on 21p11-21q22, using 126 single nucleotide polymorphisms (SNPs) as genetic markers in 373 patients with 250 controls. We found a significant association of five SNPs in the stress70 protein chaperon family member STCH gene with gastric cancer, especially with the non-cardia localization subgroup (P=0.0005-0.02, odds ratio=1.44-1.72). Comparisons of haplotype frequency showed significant association between TTGGC haplotype and gastric cancer (P=0.0001, odds ratio=1.59). These results suggest that, in the Japanese population, STCH might be a new candidate for conferring susceptibility to this disease.

Alleles↗

Omental flap in pancreaticoduodenectomy for protection of splanchnic vessels.

Intraabdominal bleeding, the most life-threatening complication following pancreaticoduodenectomy (PD), most often is associated with failure of a pancreaticojejunostomy anastomosis or with intraabdominal infection. We investigated whether placement of an omental flap around the splanchnic vessels in PD could reduce the occurrence of intraabdominal bleeding and other postoperative complications. One hundred consecutive patients who underwent PD at the authors' institution between January 2000 and October 2004 were enrolled in this prospective study. After dissection of the hepatoduodenal ligament, the major splanchnic arteries and the portal vein were covered by the omental flap. Preoperative condition, incidence of pancreatic fistula, intra-abdominal bleeding, other complications, treatment mortality, and hospital stay were analyzed for interrelationships. The frequency of pancreatic fistula (20%) differed little from those in previous reports. However, intraabdominal bleeding was observed in only 1 (1.0%) patient, who was considered to have too thin a flap. No intraabdominal abscess was encountered. No mortality or complications occurred in relation to the omental flap. Thus, wrapping an omental flap around dissected splanchnic vessels in PD reduced postoperative intraabdominal bleeding and infection, but failed to prevent pancreatic fistulas.

Adult↗

Primary liver cancer with bidirectional differentiation into hepatocytes and biliary epithelium.

A 70-year old Japanese man with hepatitis B infection developed a 4.8-cm liver tumor in the right lobe. Computed tomographic findings suggested hepatocellular carcinoma or combined hepatocellular and cholangiocarcinoma. After right hepatectomy, the cut surface of the resected specimen showed a whitish tumor with indistinct borders. Microscopically, the tumor consisted of pleomorphic, eosinophilic cells forming thickened trabeculae, suggesting hepatocellular carcinoma, and also tumor cells forming glandular structures, suggesting adenocarcinoma. Cells comprising both the trabeculae and the glands were immunoreactive for cytokeratin (CK) 19. In some gland-forming cells, varying immunoreactivity for CK7 and carcinoembryonic antigen (CEA) was observed. In the cytoplasm of cells in the thickened trabeculae, hepatocyte paraffin (HepPar) 1 and alpha-fetoprotein (AFP) were focally reactive. Some of these tumor cells were also reactive for CK19. Accordingly, we concluded that this tumor was a combined hepatocellular and cholangiocarcinoma whose cells had undergone divergent differentiation into hepatocytes and biliary epithelium. Because the tumor expressed markers of both phenotypes, it may have originated from cells intermediate between hepatocytes and biliary epithelium. A few reported cases have shown similar histologic features.

Aged↗

Complete resection of hepatocellular carcinoma with direct invasion to the stomach remnant.

A 61-year-old man presented with anemia (hemoglobin, 5.9 mg/dl) and a history of alcoholic liver disease. The patient also had a past history of a distal gastrectomy and Billroth II reconstruction, due to a gastric ulcer, performed 20 years previously. Endoscopic gastroscopy revealed a hemorrhagic ulcerative tumor at the gastrojejunostomy site. Computed tomography and angiography demonstrated a 10-cm tumor and a 2-cm tumor in the left lateral segment of the liver, suggestive of hepatocellular carcinoma (HCC). The larger tumor showed extrahepatic growth, with invasion of the stomach remnant. Because transcatheter arterial embolization of the tumor failed to control the bleeding, we carried out an en-bloc resection of the left lateral segment of the liver and the stomach remnant. Direct invasion of HCC into the gastrointestinal tract is rarely encountered. Here we report a case of HCC that invaded the stomach remnant and present a review of the literature.

Carcinoma, Hepatocellular↗

Intestinal obstruction in the terminal ileum caused by an anomalous congenital vascular band between the mesoappendix and the mesentery: report of a case.

We report a case of intestinal obstruction caused by a congenital abnormal vascular band in a 17-year-old boy. The patient was admitted with acute colicky abdominal pain, and an emergency laparotomy revealed that the ileum was strangulated by a fibrous band with vessels about 2 mm in diameter and 7 cm in length, extending from the antemesenterium of the terminal ileum to the mesoappendix. The affected intestine was resected with the band and the appendix. Histologically, the fibrous band was composed of loose connective tissue containing arteries, veins, and nerve fibers, suggesting that it was congenital and originated from a remnant of the ventral mesentery in the embryonic period. There have been few reports of intestinal obstruction being caused by a congenital vascular band, especially in patients beyond the pediatric age group.

Abdominal Pain↗

Bile duct cancer developing 21 years after choledochoduodenostomy.

BACKGROUND: Cholangiocarcinoma in patients with choledochoenterostomy has been a rare condition with few cases reported in the literature written in English, and there have been few pathological descriptions of this disease. However, it has recently been documented as a late complication of choledochoenteric anastomosis, and has become a serious issue today since choledochoenterostomy and sphincteroplasty for benign biliary lesions were frequently resorted to in the 1970s and 1980s. The authors here present a case of a 67-year-old woman who developed a cholangiocarcinoma 21 years after choledochoduodenostomy. METHODS: The patient underwent a curative resection of the tumor with a hepatopancreatoduodenectomy after a detailed preoperative assessment, including cholangiography and cholangioscopy. RESULTS: Although this tumor has been reported to have a poor prognosis, a precise preoperative evaluation and aggressive surgery may contribute to better survival. Pathologically, the tumor originated in the bile duct mucosa of the choledochoduodenostomy, and was accompanied by intestinal and pyloric gland-like metaplasia. CONCLUSION: These epithelial changes presumably induced by chronic inflammation due to the reflux of intestinal contents and bile stasis may be responsible for the carcinogenesis.

Adenocarcinoma↗

Clinicoanatomical studies on the dorsal subsegmental bile duct of the right anterior superior segment of the human liver.

BACKGROUND: The dorsal subsegmental intrahepatic bile duct in the right anterior superior segment (B8c) sometimes joins the posterior sectorial duct. In such cases it can be misidentified as the right posterior superior segmental duct (B7). However, there are no published studies on the confluent pattern of B8c. MATERIALS AND METHODS: We studied B8c in the resected liver of 107 patients (65 with bile duct carcinoma and 42 with gallbladder carcinoma) who had undergone right hepatectomy or more extensive right-sided liver resection. RESULTS: B8c was identified in all cases. It joined the right posterior sectorial duct or B7 in 18 cases (16.8%). In 12 cases B8c joined independently the posterior sectorial duct or B7. In 6 cases B8c joined the posterior sectorial duct after making the common duct with the lateral subsegmental duct in the anterior superior or anterior inferior segment (B8b or B5c). CONCLUSIONS: B8c does not join the anterior sectorial bile duct in every sixth case.

Aged↗

Factors influencing postoperative hospital mortality and long-term survival after radical resection for stage IV gallbladder carcinoma.

Factors influencing postoperative hospital mortality and long-term survival after radical resection of stage IV gallbladder carcinoma remain unclear. The objective of this study was to identify characteristics of patients who are good candidates in terms of surgical risk and long-term survival for radical resection of stage IV gallbladder carcinoma. A retrospective study was made of attempted surgical cure in 72 patients with stage IV gallbladder carcinoma. There were 14 postoperative hospital deaths (19%). Eleven (19%) of the 58 patients discharged from hospital survived for more than 3 years. Multivariate analysis indicated male gender, extended right hepatic lobectomy in a cholestatic liver, and portal vein resection as independent risk factors that correlated with hospital death. Distant metastasis was the sole independent factor that related negatively with long-term survival by multivariate analysis. Subset analysis was performed with combinations of the four independent factors obtained by multivariate analyses. The hospital mortality rate and the 3-year survival rate in the 44 patients without portal vein involvement were 9% and 28%, respectively, and were 3% and 27%, for the 31 women in this group. The highest 3-year survival rate (39%) was observed in the 26 patients without distant metastasis and portal vein involvement, despite a hospital mortality rate of 12%. Better patient selection may improve the outcome of radical surgery for stage IV gallbladder carcinoma. These data may be useful in designing future trials of the surgical treatment of advanced gallbladder carcinoma.

Aged↗

Most informative projection for portography: quantitative analysis of 47 percutaneous transhepatic portograms.

The goal of this study was to determine which projection for percutaneous transhepatic portography best depicts the anatomy of the proximal portal vein. Portograms ( n = 47) obtained in the anteroposterior, right anterior oblique, and right anterior caudal oblique projections were analyzed retrospectively. Lengths of the right portal trunk, the transverse portion of the left portal vein, and the right anterior and posterior portal branches, as well as angles between the right portal trunk and the transverse portion of the left portal vein and between the right anterior and posterior portal branches were measured in the various projections. Differences were evaluated using analysis of variance with Scheffe's method. The transverse portion of the left portal vein and the right anterior and posterior portal branches appeared longer on the right anterior caudal oblique views than on the anteroposterior ( p < 0.0001, < 0.0001, < 0.0001) or right anterior oblique ( p < 0.0001, = 0.001, < 0.0001) views. The angle between the right portal trunk and the transverse portion of the left portal vein was wider on the right anterior oblique views than on the anteroposterior ( p < 0.0001) or right anterior caudal oblique ( p = 0.007) views. The angle between the right anterior and posterior portal branches was wider on the right anterior caudal oblique views than on the anteroposterior ( p < 0.0001) or right anterior oblique ( p = 0.030) views. The right anterior caudal oblique projection provides the best image of the proximal portal vein, and therefore should be obtained whenever possible in preoperative staging of hepatobiliary cancer.

Humans↗

Intrahepatic segmental bile duct patterns in hepatolithiasis: a comparative cholangiographic study between Taiwan and Japan.

BACKGROUND/PURPOSE: We analyzed confluence patterns of intrahepatic segmental bile ducts, seeking to relate hepato-lithiasis to anatomic variation. The comparative study was completed patients with hepatolithiasis in Taiwan and Japan. METHODS: Direct cholangiography was performed in 103 hepatolithiasis patients in Taiwan and 77 in Japan. Segmental ducts patterns were classified as type I, normal configuration; type II, "triad" confluence; type III, posterior segmental duct joining left hepatic duct; or type IV, distal confluence of the right posterior segmental duct. RESULTS: Taiwanese patients had only calcium bilirubinate or black stones, and were mostly female. As overall analysis, types I, II, III, and IV were found in 61, 26, 13, and 3 patients, respectively. In Japanese, types I, II, III, and IV were found in 52, 10, 13, and 2, respectively. There was no difference between the two institutes. Since no patients in Taiwan had cholesterol calculi, Japanese patients were reanalyzed including only 58 patients with calcium bilirubinate or black stones. Differences in those populations remained insignificant. CONCLUSION: Anatomic variations in segmental ducts apparently do not contribute to pathogenesis of hepatolithiasis.

Adolescent↗

Magnitude of serosal changes predicts peritoneal recurrence of gastric cancer.

BACKGROUND: Peritoneal dissemination is the most frequent mode of recurrence in patients with gastric cancer. We tried to identify factors that predict peritoneal recurrence with high sensitivity. STUDY DESIGN: Clinical and pathologic data from 587 consecutive patients with gastric cancer were reviewed retrospectively. The stepwise Cox proportional hazards regression model was used to assess the prognostic significance of the magnitude of serosal changes. Multiple stepwise logistic regression analysis was used to determine factors associated with peritoneal recurrence in 375 patients who underwent curative resection. RESULTS: The 5-year survival rate of patients with S2 disease (greatest dimension of macroscopic serosal changes >/= 2.5 cm) was 18%, which was worse than S0 (no serosal changes) and S1 disease (macroscopic serosal changes < 2.5 cm)(p < 0.001). Patients with S0 tumors who underwent curative resection had the best 5-year survival rate. Multivariate analyses indicated that the magnitude of serosal changes was an independent prognostic factor for survival both overall and after curative resection. Logistic regression analysis showed that peritoneal recurrence was more than four times as likely with S2 than with S0 or S1 tumors. The sensitivity for predicting peritoneal recurrence was 79%; the sensitivity of cytologic examination was 38%. CONCLUSIONS: Magnitude of serosal changes is easy to measure intraoperatively and predicts peritoneal recurrence of gastric cancer with greater sensitivity than conventional peritoneal lavage cytology.

Gastrectomy↗

Biliary bile acid concentration is a simple and reliable indicator for liver function after hepatobiliary resection for biliary cancer.

BACKGROUND: The functional recovery of the remnant liver after an extended hepatectomy is critical for the outcome of the patient. The aim of this prospective study was to examine whether biliary bile acids could be an indicator for postoperative liver function. METHODS: Externally drained bile samples were obtained from 51 patients with biliary or periampullary carcinomas before and after surgery. Patients were categorized into 3 groups: group A, 29 hepatectomized patients without liver failure; group B, 7 hepatectomized patients with liver failure (maximum serum bilirubin level, >10 mg/dL); and group C, 15 patients who underwent biliopancreatic resection without hepatectomy, with a good postoperative course. Bile samples were withdrawn 1 day before surgery and on postoperative days 1, 2, 3, 4, 6, and 7. Total bile acids were measured with a 3 alpha-hydroxysteroid dehydrogenase method. RESULTS: Before surgery, the concentration of bile acids was higher in groups A and C than in group B, and correlated significantly with the indocyamine green disappearance rate (KICG) values (R(2) = 0.557; P <.0001). After surgery, bile acid concentrations decreased in all 3 groups until postoperative day 2, which was followed by a gradual increase. The concentration recovered to the preoperative level in groups A and C but remained low in group B. Biliary bile acid concentrations on day 2 correlated significantly with remnant liver KICG values (R(2) = 0.257; P =.0019). Among several parameters studied, including KICG, remnant liver KICG, biliary bile acids, and biliary bilirubin, biliary bile acid concentration had the most predictive power for occurrence of postoperative liver failure. CONCLUSION: Biliary bile acid concentration could be a simple, real-time, reliable indicator of preoperative and postoperative liver function.

Aged↗

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with otherwise node-negative hilar cholangiocarcinoma.

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has prognostic significance in patients with histologically node-negative (pN0) hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, no reports have addressed this issue with regard to hilar cholangiocarcinoma. METHODS: A total of 954 lymph nodes from surgical specimens of 45 patients with histologically node-negative hilar cholangiocarcinoma who underwent macroscopically curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were examined for relationships with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 11 (24.4%) of the 45 patients, being found in 13 (1.4%) of 954 lymph nodes examined. Of the 13 nodal micrometastases, 11 (84.6%) were found in the N2 regional lymph node group rather than N1. Clinicopathologic features showed no associations with lymph node micrometastases. Survival curves were essentially similar between patients with and without micrometastasis. In addition, the grade of micrometastasis showed no effect on survival. The Cox proportional hazard model identified microscopic venous invasion, microscopic resection margin status, and histologic differentiation as significant prognostic factors in patients with pN0 disease. CONCLUSIONS: Lymph node micrometastasis has no survival impact in patients with otherwise node-negative hilar cholangiocarcinoma. The authors do not recommend extensive lymph node sectioning with keratin immunostaining for prognostic evaluation.

Adult↗

Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases.

OBJECTIVE: To better determine the role of portal vein resection and its effect on survival, as well as to appreciate the impact of portal vein invasion on prognosis in hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: Hepatectomy with portal vein resection is sometimes performed for locally advanced hilar cholangiocarcinoma. However, the significance of microscopic invasion of the portal vein has not been determined. METHODS: Medical records of 160 patients with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion of the portal vein was assessed histologically on the surgical specimen, and results were correlated with clinicopathologic features and survival. RESULTS: Surgical mortality, including all hospital deaths, was similar in patients who did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary tumor was more advanced in patients who underwent portal vein resection. Histologically, no invasion was found in 16 (30.8%) of resected portal veins. However, dense fibrosis adjacent to the portal vein was common, and the mean distance between the leading edge of cancer cells and the adventitia of the portal vein was 437 +/- 431 mum. The prognosis was worse in patients with than without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The presence or absence of microscopic invasion of the resected portal vein did not influence survival (16.6 months in patients with microscopic invasion vs. 19.4 months in those without; P = 0.1506). Multivariate analysis identified histologic differentiation, lymph node metastasis, and macroscopic portal vein invasion as independent prognostic factors. CONCLUSIONS: Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Adult↗