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1.
Ann Gastroenterol Surg ; 8(5): 845-859, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39229554

ABSTRACT

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

2.
Int Cancer Conf J ; 13(3): 263-267, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38962036

ABSTRACT

Duodenopancreatic neuroendocrine neoplasia (DP-NEN) is in approximately 10% of cases of multiple endocrine neoplasia type 1 (MEN1). We encountered a case in which the onset of NEN led to suspicion and diagnosis of MEN1. Although genetic testing showed MEN1 variant of uncertain significance (VUS), we considered it pathological from the clinical course, promoting the provision of genetic counseling and screening for relatives. MEN1 has a variety of clinical manifestations, and DP-NENs are the second-most common manifestation after primary hyperparathyroidism (pHPT). It is important to assume that MEN1 is an underlying cause of NEN.

3.
Eur J Surg Oncol ; 50(10): 108538, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39053042

ABSTRACT

OBJECTIVE: To investigate whether robotic surgery (RS) decreases the risk of circumferential resection margin (CRM) positivity compared with conventional laparoscopic surgery (LS) in patients with rectal cancer (RC) undergoing mesorectal excision (ME). BACKGROUND: Although it is well known that CRM positivity affects postoperative outcomes in patients with RC undergoing ME, few studies have investigated whether RS is superior to conventional LS for the risk of CRM positivity. METHODS: We performed a comprehensive electronic search of the literature up to December 2022 to identify studies that compared the risk of CRM positivity between patients with RC undergoing robotic and conventional laparoscopic surgery. A meta-analysis was performed using random-effects models to calculate risk ratios (RRs) and 95 % confidence intervals (CIs), and heterogeneity was analyzed using I2 statistics. RESULTS: Eighteen studies, consisting of 4 randomized controlled trials (RCTs) and 14 propensity score matching (PSM) studies, involved a total of 9203 patients with RC who underwent ME were included in this meta-analysis. The results demonstrated that RS decreased the overall risk of CRM positivity (RR, 0.82; 95 % CI, 0.73-0.92; P = 0.001; I2 = 0 %) compared with conventional LS. Results of a meta-analysis of the 4 selected RCTs also showed that RS decreased the risk of CRM positivity (RR, 0.62; 95 % CI, 0.43-0.91; P = 0.01; I2 = 0 %) compared with conventional LS. CONCLUSIONS: This meta-analysis revealed that RS is associated with a decreased risk of CRM positivity compared with conventional LS in patients with RC undergoing ME.


Subject(s)
Laparoscopy , Margins of Excision , Rectal Neoplasms , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Laparoscopy/methods , Proctectomy/methods
4.
Int J Surg ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869986

ABSTRACT

INTRODUCTION: Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. METHODS: We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004). CONCLUSION: In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

5.
Eur J Surg Oncol ; 50(6): 108356, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38685177

ABSTRACT

BACKGROUND: Because repeat hepatectomy for recurrent hepatocellular carcinoma is a potentially invasive procedure, it is necessary to identify patients who truly benefit from repeat hepatectomy. Albumin-bilirubin grading has been reported to predict survival in patients with hepatocellular carcinoma. However, as prognosis also depends on tumor factors, a staging system that adds tumor factors to albumin-bilirubin grading may lead to a more accurate prognostication in patients with recurrent hepatocellular carcinoma. METHODS: Albumin-bilirubin grading and serum alpha-fetoprotein levels were combined and the albumin-bilirubin-alpha-fetoprotein score was created ([albumin-bilirubin grading = 1; 1 point, 2 or 3; 2 points] + [alpha-fetoprotein<75 ng/mL, 0 points; ≥5, 1 point]). Patients were classified into three groups, and their characteristics and survival were evaluated. The predictive ability of the albumin-bilirubin-alpha-fetoprotein score was compared with that of the Cancer of the Liver Italian Program and the Japan Integrated Stage scores. RESULTS: Albumin-bilirubin-alpha-fetoprotein score significantly stratified postoperative survival (albumin-bilirubin-alpha-fetoprotein score = 1/2/3: 5-year recurrence-free survival [%]: 22.4/20.7/0.0, p < 0.001) and showed the highest predictive value for survival among the integrated systems (albumin-bilirubin-alpha-fetoprotein score/Japan Integrated Stage/Cancer of the Liver Italian Program: 0.785/0.708/0.750). CONCLUSIONS: Albumin-bilirubin-alpha-fetoprotein score is useful for predicting the survival of patients with recurrent hepatocellular carcinoma undergoing repeat hepatectomy.


Subject(s)
Bilirubin , Carcinoma, Hepatocellular , Hepatectomy , Liver Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Serum Albumin , alpha-Fetoproteins , Adult , Aged , Female , Humans , Male , Middle Aged , alpha-Fetoproteins/metabolism , Bilirubin/blood , Biomarkers, Tumor/blood , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/surgery , Liver Neoplasms/blood , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/blood , Predictive Value of Tests , Prognosis , Retrospective Studies , Serum Albumin/metabolism , Aged, 80 and over
6.
Clin Gastroenterol Hepatol ; 22(7): 1416-1426.e5, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38615727

ABSTRACT

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.


Subject(s)
Pancreatectomy , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/mortality , Male , Female , Retrospective Studies , Middle Aged , Aged , Japan/epidemiology , Adult , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/diagnosis , Aged, 80 and over , Lymphatic Metastasis , Neoplasm Grading , Tumor Burden
7.
Jpn J Clin Oncol ; 54(8): 880-886, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-38677983

ABSTRACT

BACKGROUND: Somatostatin analogs, molecular-targeted agents and cytotoxic anticancer agents are available as therapeutic agents for the systemic treatment of pancreatic neuroendocrine tumors, and we have developed a first-line treatment selection MAP to enable selection of the optimal treatment strategy for pancreatic neuroendocrine tumors. The purpose of this study was to validate the usefulness of the treatment selection MAP. METHODS: Patients who had received systemic therapy for a pancreatic neuroendocrine tumor between January 2017 and December 2020 were compared according to whether they had been treated as recommended by the MAP (matched patients) or not (unmatched patients) to determine whether better outcomes were achieved by the matched patients. The primary endpoint was progression-free survival of the matched group and unmatched groups in the somatostatin analog, molecular-targeted agent and cytotoxic anticancer agents areas of the MAP. RESULTS: There were 41 (55%) MAP-matched patients in all areas among the 74 patients registered at seven hospitals. The MAP-matched rates were 100, 77 and 38% in the somatostatin analog area, molecular-targeted agent area and cytotoxic anticancer agents area, respectively. All of the unmatched patients had been selected for less intensive treatment. The median progression-free survival in the matched group and unmatched group in the molecular-targeted agent area of the MAP were 46.6 and 15.4 months, respectively, and a multivariate analysis identified MAP-matched (hazard ratio 0.18 [95% confidence interval: 0.04-0.87], P = 0.032) as the only significant independent favorable predictive factor. CONCLUSION: The usefulness of the MAP for treatment selection was validated in the molecular-targeted agent area of the MAP.


Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Female , Male , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Middle Aged , Aged , Adult , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Patient Selection , Antineoplastic Agents/therapeutic use , Molecular Targeted Therapy/methods , Aged, 80 and over , Progression-Free Survival , Retrospective Studies
8.
J Gastrointest Surg ; 28(4): 548-558, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38583909

ABSTRACT

BACKGROUND: Although several recent meta-analyses have investigated the clinical influence of the addition of lateral lymph node dissection (LLND) on oncologic outcomes in patients with mid-low rectal cancer (RC) undergoing mesorectal excision (ME), most studies included in such meta-analyses were retrospectively designed. Therefore, this study aimed to explore the clinical influence of prophylactic LLND on oncologic outcomes in patients with mid-low RC undergoing ME. METHODS: A comprehensive electronic search of the literature up to July 2022 was performed to identify studies that compared oncologic outcomes between patients with mid-low RC undergoing ME who underwent LLND and patients with mid-low RC undergoing ME who did not undergo LLND. A meta-analysis was performed using fixed-effects models and the generic inverse variance method to calculate hazard ratios (HRs) and 95% CIs, and heterogeneity was analyzed using I2 statistics. RESULTS: A total of 6 studies, consisting of 3 randomized and 3 propensity score matching studies, were included in this meta-analysis. The results of the meta-analysis of 2 randomized studies demonstrated no significant effect of prophylactic LLND on improving oncologic outcomes concerning overall survival (OS) (HR, 1.22; 95% CI, 0.89-1.69; I2 = 0%; P = .22) and relapse-free survival (RFS) (HR, 1.03; 95% CI, 0.81-1.31; I2 = 28%; P = .83). CONCLUSION: The results of this meta-analysis revealed no significant influence of prophylactic LLND on oncologic outcomes-OS and RFS-in patients with mid-low RC who underwent ME.


Subject(s)
Lymph Node Excision , Neoplasm Recurrence, Local , Rectal Neoplasms , Humans , Lymph Node Excision/methods , Lymph Nodes/surgery , Lymph Nodes/pathology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Rectal Neoplasms/pathology , Treatment Outcome
9.
World J Surg ; 48(5): 1219-1230, 2024 05.
Article in English | MEDLINE | ID: mdl-38468392

ABSTRACT

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.


Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/virology , Non-alcoholic Fatty Liver Disease/surgery , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/mortality , Male , Female , Retrospective Studies , Middle Aged , Aged , Treatment Outcome , Hepatitis, Viral, Human/complications , Hepatitis, Viral, Human/surgery , Postoperative Complications/epidemiology , Adult
10.
Cancers (Basel) ; 16(5)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38473272

ABSTRACT

In addition to established evidence of the efficacy of adjuvant chemotherapy (AC) for pancreatic ductal adenocarcinoma (PDAC), evidence of the effects of neoadjuvant treatments (NATs), including chemotherapy and chemoradiotherapy, has also been accumulating. Recent results from prospective studies and meta-analyses suggest that NATs may be beneficial not only for borderline resectable PDAC, but also for resectable PDAC, by increasing the likelihood of successful R0 resection, decreasing the likelihood of the development of lymph node metastasis, and improving recurrence-free and overall survival. In addition, response to NAT may be informative for predicting the clinical course after preoperative NAT followed by surgery; in this way, the postoperative treatment strategy can be revised based on the effect of NAT and the post-neoadjuvant therapy/surgery histopathological findings. On the other hand, the response to NAT and AC is also influenced by the tumor biology and the patient's immune/nutritional status; therefore, planning of the treatment strategy and meticulous management of NAT, surgery, and AC is required on a patient-by-patient basis. Our experience of using gemcitabine plus S-1 showed that this NAT regimen achieved tumor shrinkage and decreased the levels of tumor markers but failed to provide a survival benefit. Our results also suggested that response/adverse events to NAT may be predictive of the efficacy of AC, as well as survival outcomes.

11.
Clin J Gastroenterol ; 17(3): 537-542, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38396137

ABSTRACT

A 72-year-old male patient presented to our department complaining of with upper abdominal pain and jaundice. He had a history of a side-to-side pancreaticojejunostomy performed 40 years previously for chronic pancreatitis. A diagnostic workup revealed a tumor 3 cm in size in the pancreatic head as the etiology of the jaundice. Subsequently, the patient was diagnosed with resectable pancreatic cancer. Following two cycles of neoadjuvant chemotherapy, an extended pancreatoduodenectomy was performed because of tumor invasion at the previous pancreaticojejunostomy site. Concurrent portal vein resection and reconstruction were performed. Pathological examination confirmed invasive ductal carcinoma (T2N1M0, Stage IIB). This case highlights the clinical challenges in pancreatic head carcinoma following a side-to-side pancreaticojejunostomy. Although pancreaticojejunostomy is believed to reduce the risk of pancreatic cancer in patients with chronic pancreatitis, clinicians should be aware that, even after this surgery, there is still a chance of developing pancreatic cancer during long-term follow-up.


Subject(s)
Pancreatic Neoplasms , Pancreaticojejunostomy , Pancreatitis, Chronic , Humans , Male , Aged , Pancreatic Neoplasms/surgery , Pancreatitis, Chronic/surgery , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/etiology , Pancreaticoduodenectomy/adverse effects , Carcinoma, Pancreatic Ductal/surgery , Postoperative Complications/etiology , Tomography, X-Ray Computed
12.
Clin J Gastroenterol ; 17(2): 292-299, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38071671

ABSTRACT

The combination regimen of atezolizumab plus bevacizumab (Atezo/Bev) is currently used as first-line treatment in patients with unresectable hepatocellular carcinoma. Herein, we report a rare case of curative hepatic resection performed as conversion surgery in a patient with intermediate-stage hepatocellular carcinoma following preoperative Atezo/Bev therapy. After five treatment cycles of Atezo/Bev therapy, followed by four cycles of atezolizumab monotherapy, the tumor marker levels decreased to baseline levels and 22 small daughter nodules disappeared, leaving only the primary tumor. Therefore, we performed resection of the primary tumor as conversion surgery, and postoperative histopathology confirmed complete tumor necrosis. No cancer recurrence has been observed until the 5-month postoperative follow-up, and the patient remains drug free. Consistent with the findings in this case, a review of previously reported cases revealed that in cases of successful conversion surgery, neoadjuvant Atezo/Bev therapy was associated with intra-tumoral bleeding, immune-related adverse events, and normalization of the tumor marker levels.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/surgery , Hepatectomy , Bevacizumab/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Pathologic Complete Response , Biomarkers, Tumor
14.
Invest New Drugs ; 41(6): 777-786, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37856005

ABSTRACT

There are several options for systemic therapy of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), including somatostatin analogues (SSA), molecular-targeted agents, cytotoxic agents, and peptide receptor radionuclide therapy. However, the effectiveness of each agent varies according to the primary site. Although SSA and everolimus are key drugs used for systemic therapy of neuroendocrine tumors arising from the gastrointestinal tract (GI-NET), the optimal strategy for selecting among these modalities remains unexplored. Japanese experts on GI-NET discussed and determined optimal first-line treatment strategies based on the results of previously reported pivotal trials. The consensus was reached that tumor aggressiveness and prognosis can be predicted using hepatic tumor load and Ki-67 labeling index, which are thought to be clinically important factors when selecting systemic therapy for unresectable GI-NET. SSA therapy is considered appropriate for patients with a low hepatic tumor load and low Ki-67 value and everolimus for those with contraindications to SSA therapy. There was also agreement that the treatment strategy should be determined according to whether the origin is in the midgut, considering the biological differences. Based on this strategy, the experts have tentatively created treatment maps and applied them in representative cases of unresectable GI-NET. Japanese experts proposed tentative maps for optimal first-line treatment in patients with unresectable GI-NET. Further investigation is warranted to validate the usefulness of these maps.


Subject(s)
Gastrointestinal Neoplasms , Liver Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Octreotide , Everolimus/therapeutic use , Ki-67 Antigen , East Asian People , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Somatostatin/therapeutic use , Liver Neoplasms/drug therapy , Pancreatic Neoplasms/drug therapy
15.
Oncol Rep ; 50(5)2023 Nov.
Article in English | MEDLINE | ID: mdl-37732519

ABSTRACT

Extracellular vesicles (EVs) produced by various cells, including tumor cells, carry biomolecules to neighboring cells. In hepatocellular carcinoma (HCC), adenosine to inosine RNA editing of antizyme inhibitor 1 (AZIN1), specifically regulated by adenosine deaminase acting on RNA­1 (ADAR1), promotes carcinogenesis. The present study examined if EVs and ADAR1 in the EVs released from HCC cells are transferred to neighboring cells in co­culture systems and reporter assay. Distribution of the ADAR1 expression in human tissues were examined by immunohistochemistry. EVs released from HCC cells containing ADAR1 were delivered to neighboring HCC cells and non­cancerous hepatocytes. The increased ADAR1 protein levels resulted in serine to glycine substitution at residue 367 of AZIN1, which augmented transformation potential and increased aggressive behavior of cancer cells. In clinically resected samples, ADAR1 distribution was highly heterogeneous within the tumor specimen and denser in non­cancerous tissue surrounding the HCC tissue. These observations suggested that ADAR1 protein may be delivered from HCC cells to neighboring cells via EVs and that EV­mediated RNA editing may serve a pivotal role in determining HCC heterogeneity and spread.


Subject(s)
Carcinoma, Hepatocellular , Extracellular Vesicles , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , RNA Editing/genetics , Liver Neoplasms/genetics , Extracellular Vesicles/genetics , Hepatocytes
16.
Surgery ; 174(5): 1145-1152, 2023 11.
Article in English | MEDLINE | ID: mdl-37599194

ABSTRACT

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.


Subject(s)
Bile Duct Neoplasms , Biliary Tract Neoplasms , Cholangiocarcinoma , Gallbladder Neoplasms , Klatskin Tumor , Humans , Prognosis , Klatskin Tumor/pathology , Retrospective Studies , Biliary Tract Neoplasms/surgery , Biliary Tract Neoplasms/complications , Cholangiocarcinoma/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/pathology , Bile Ducts, Intrahepatic/pathology
17.
Surg Case Rep ; 9(1): 67, 2023 Apr 30.
Article in English | MEDLINE | ID: mdl-37121923

ABSTRACT

BACKGROUND: Microhepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult. CASE PRESENTATION: A 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located. CONCLUSIONS: Based on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery.

18.
Anticancer Res ; 43(5): 2219-2225, 2023 May.
Article in English | MEDLINE | ID: mdl-37097679

ABSTRACT

BACKGROUND/AIM: Fluoropyrimidine therapy or oxaliplatin combination therapy is recommended for patients with stage III colorectal cancer as adjuvant chemotherapy (AC). However, the criterion for selecting these regimens is still unclear in patients with stage III rectal cancer (RC). In order to select an appropriate regimen of AC for such patients, it is needed to identify characteristics associated with tumor recurrence. PATIENTS AND METHODS: The records of 45 patients with stage III RC undergoing AC using tegafur-uracil/leucovorin (UFT/LV) were retrospectively reviewed. The cut-off value of characteristics was determined using a receiver operating characteristic curve for recurrence. Univariate analyses using Cox-Hazard model for predicting recurrence were performed with clinical characteristics. Survival analysis was performed using Kaplan-Meier method and log-rank test. RESULTS: Thirty patients (66.7%) completed AC using UFT/LV. Fifteen patients (33.3%) did not complete AC because of adverse events, tumor recurrence and others. Sixteen patients (35.6%) had recurrence. Univariate analyses revealed that lymph node metastasis (N2/N1) (p=0.002) was associated with tumor recurrence. Survival analysis showed that lymph node metastasis (N2/N1) could stratify recurrence-free survival (p<0.001). CONCLUSION: N2 lymph node metastasis can predict tumor recurrence in patients with stage III RC undergoing AC using UFT/LV.


Subject(s)
Antimetabolites, Antineoplastic , Leucovorin , Lymph Nodes , Neoplasm Recurrence, Local , Rectal Neoplasms , Tegafur , Aged , Female , Humans , Male , Middle Aged , Antimetabolites, Antineoplastic/therapeutic use , Chemotherapy, Adjuvant , Leucovorin/therapeutic use , Lymph Nodes/pathology , Lymphatic Metastasis , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Tegafur/therapeutic use , Retrospective Studies
19.
Diagn Cytopathol ; 51(8): 467-474, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37078538

ABSTRACT

BACKGROUND: The purpose of this study was to clarify the role of cytology when using endoscopic ultrasound-guided fine needle aspiration or biopsy (EUS-FNA/FNB) for pancreatic lesions by comparison with histology, and also to examine differences in diagnostic accuracy depending on the puncture route and sample acquisition method. METHODS: We studied 146 cases in which cytology and histology were performed when undertaking pancreatic EUS-FNA/FNB and the final histological diagnosis was obtained from surgically resected samples. Cytological, histological, and combined diagnoses with cytology and histology (combined diagnosis) detected malignant including suspected malignancy, indeterminate, and benign lesions. RESULTS: The accuracy of both cytology and histology in pancreatic EUS-FNA/FNB was 80.1%, with the combined diagnosis having an improved accuracy of 88.4%. The accuracy obtained with cytology was 80.0% for trans-duodenal puncture samples and 80.3% for trans-gastric puncture samples, with no difference between them. By contrast, the accuracy obtained with histology was 76.5% for trans-duodenal samples and 85.2% for trans-gastric samples, and they differed depending on the puncture route. The cytology accuracy was 80.9% for FNA and 79.8% for FNB, while the histology accuracy was 72.3% for FNA and 83.8% for FNB. CONCLUSIONS: Combining cytological diagnosis with histological diagnosis improved the diagnostic accuracy of EUS-FNA/FNB. Compared with histological diagnosis, cytological diagnosis showed stable diagnostic accuracy without being affected by differences in the puncture route or sample acquisition method.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Pancreatic Neoplasms , Humans , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Pancreas/pathology , Stomach/pathology , Punctures
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