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Background/aim: Enlarged polypoid gallbladder lesions should first be evaluated to rule out gallbladder cancer. Gallbladder lymphoma rarely develops, and gallbladder follicular lymphoma is seldom observed., Case Report: The case of a 70-year-old man with an enlarged polypoid gallbladder lesion and stable-sized multiple enlarged mesenteric lymph nodes is reported. No specific symptoms and obvious abnormalities were observed in laboratory data, such as tumor markers or soluble interleukin-2 receptor levels. The polypoid gallbladder lesion had enlarged from 10 mm to 15 mm in 1 year, had a slightly irregular surface, and showed moderate early enhancement with delayed washout on multiphase contrast-enhanced computed tomography (CT). The apparent diffusion coefficient on diffusion-weighted magnetic resonance imaging was 0.95×10 -3 mm 2 /s, indicating the high cell density and high water diffusion restriction. Positron-emission tomography/computed tomography revealed no increased fluorodeoxyglucose activity in the gallbladder lesion. Laparoscopic total cholecystectomy and excisional biopsy of the mesenteric lymph nodes were performed. Numerous polypoid lesions were detected in intraoperative contrast-enhanced ultrasonography with a high contrast effect. Gross specimens contained numerous polypoid lesions of various sizes. Immunohistochemical staining identified tumor lymphocytes positive for CD10, CD20, and BCL2 apoptosis regulator (BCL2), and CD23-positive fibroblastic reticulocytes forming a reticular network within the nodules. The gallbladder and mesenteric lymph nodes were finally diagnosed as grade 1 follicular lymphoma. The patient is being closely monitored every 6 months without medication., Conclusion: Gallbladder follicular lymphoma is difficult to diagnose preoperatively, however, extra-regional lymph node swelling and relatively low apparent diffusion coefficients on magnetic resonance imaging can help its diagnosis., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact., Methods: Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model., Results: In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare., Conclusions: F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Follow-up is recommended for an asymptomatic unilocular hepatic cystic lesion without wall-thickness and nodular components. A few liver cystic lesions represent biliary cystic neoplasms, which are difficult to differentiate from simple cysts with benign mural nodules on imaging alone., Case Presentation: An 84-year-old woman with a history of simple liver cyst diagnosed one year prior was admitted for evaluation of a developed mural nodule in the cystic lesion. She had no specific symptoms and no abnormalities in blood tests except for carcinoembryonic antigen (5.0 ng/mL) and carbohydrate antigen (43.5 U/mL) levels. Contrast-enhanced computed tomography revealed a well-defined, low-attenuation lesion without a septum that had enlarged from 41 to 47 mm. No dilation of the bile duct was observed. A gradually enhancing mural nodule, 14 mm in diameter, was confirmed. MRI revealed a uniform water-intense cystic lesion with a mural nodule. This was followed by T2-enhanced imaging showing peripheral hypointensity and central hyperintensity. Enhanced ultrasonography revealed an enhanced nodule with a distinct artery within it. A needle biopsy of the wall nodule or aspiration of intracystic fluid was not performed to avoid tumor cell spillage. The possibility of a neoplastic cystic tumor could not be ruled out, so a partial hepatectomy was performed with adequate margins. Pathologically, the cystic lesion contained a black 5 mm nodule consisting of a thin, whitish fibrous wall and dilated vessels lined by CD31 and CD34 positive endothelial cells. The final diagnosis was a rare cavernous hemangioma within a simple liver cyst., Conclusions: Cavernous hemangiomas mimicking well-enhanced mural nodules can arise from simple liver cysts. In less malignant cases, laparoscopic biopsy or percutaneous targeted biopsy of the mural nodules, together with needle ablation, may be recommended to avoid unnecessary surgery., (© 2024. The Author(s).)

Hepatic artery pseudoaneurysms have been reported to occur in approximately 1% of cases after metal stenting for malignant biliary obstruction. In contrast, only a few cases have been reported as complications after plastic stenting for benign biliary disease. We report a 61-year-old man with cholangitis who presented with a rare complication of hemobilia after implantation of 7 Fr double pigtail plastic biliary stents. No bleeding was observed approximately one month after biliary stent tube removal. Contrast-enhanced CT scan revealed a circularly enhanced lesion (5 mm in diameter) in the arterial phase at the tip of the previously inserted plastic bile duct stent. Color Doppler ultrasonography enhanced the lesion and detected arterial blood flow inside. He was diagnosed with a hepatic artery pseudoaneurysm. However, he had no risk factors such as prolonged catheterization, severe cholangitis, liver abscess, or long-term steroid use. Superselective transarterial embolization using two metal microcoils was successfully completed without damage to the surrounding liver parenchyma. If hemobilia is suspected after insertion of a plastic bile duct stent, immediate monitoring using contrast-enhanced computed tomography or Doppler ultrasonography is recommended., (© 2024. Japanese Society of Gastroenterology.)

It has been reported that patients with macroscopic vascular invasion accompanying hepatocellular carcinoma have a poor prognosis. Modern molecular therapy with multitargeted tyrosine kinase inhibitors and immune checkpoint inhibitors has shown promising results in patients with metastatic hepatocellular carcinoma; however, molecular therapy is limited to patients with Child-Pugh class A disease. This review summarizes the present status of surgical therapies, including conversion hepatectomy, for patients with MVI in the developing era of novel molecular therapy. Phase III studies showed patients with macroscopic vascular invasion had significant survival benefits from sorafenib [hazard ratio (HR)=0.68] and regorafenib (HR=0.67) versus placebo, and nivolumab (HR=0.74) versus sorafenib. Lenvatinib and atezolizumab plus bevacizumab showed marginal effects. It is currently widely assumed that molecular therapy alone will not cure the disease but that additional conversion hepatectomy will be required. A response other than progressive disease is essential but a pathological complete response is not always required. A significant randomized controlled trial has already started in China to assess the necessity for conversion hepatectomy after effective atezolizumab plus bevacizumab treatment, and the results are still awaited. According to Japanese national data, upfront hepatectomy can be recommended for patients with initially resectable disease and macroscopic vascular invasion other than for those with tumors in the main portal vein and the inferior vena cava. In addition, adequate adjuvant therapies with hepatic arterial chemotherapy and transarterial chemoembolization may be beneficial but an effective adjuvant molecular therapy is currently unavailable. In conclusion, novel molecular therapies with higher response rates customized to the oncologic characteristics of each hepatocellular carcinoma with macroscopic vascular invasion are needed to increase the likelihood of conversion surgery and improve long-term outcomes., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Multiple bilateral lung metastases secondary to hepatocellular carcinoma (HCC) are mainly treated with molecular therapy. Atezolizumab plus bevacizumab can provide excellent long-term survival for patients with a good response., Case Report: A 67-year-old woman underwent right hepatectomy for a primary solitary HCC, 11 cm in diameter, after portal embolization. After 2 years, she developed bilateral lung metastases with >100 nodules, <1 cm in size. She had no viral hepatitis or liver cirrhosis, and the Child-Pugh Grade was A (5 points). Lenvatinib (12 mg daily) was administered as a first-line treatment and continued for 18 months. The best response was stable disease (SD). Subsequently, intravenous atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) was administered once every three weeks. The best response was SD, which continued for 26 months. After that, cabozantinib treatment was initiated and discontinued after one cycle. Subsequently, dual immune checkpoint inhibitor treatment (durvalumab + tremelimumab) was administered. She has had multiple, but lung-only, metastases over four years. She has been well as an outpatient with the Child-Pugh Grade of A and a performance status of 0., Conclusion: Even if atezolizumab plus bevacizumab does not induce a good response, a durable SD could prolong survival in patients with metastatic HCC while maintaining liver function and a good quality-of-life., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Operable peritoneal dissemination from distal cholangiocarcinoma after pancreaticoduodenectomy is rare. Furthermore, peritoneal dissemination mimicking liver metastasis has scarcely been reported., Case Report: An 81-year-old woman received pancreaticoduodenectomy for distal cholangiocarcinoma. She was diagnosed with stage IIA (T3a N0 M0) and received curative resection. She did not receive adjuvant chemotherapy. As a result of the examination in our department, she showed two tumors, 20 mm and 8 mm in segments 7/8 and 7, respectively, in the subphrenic liver surface four and half years after the initial pancreaticoduo-denectomy. The larger tumor was slow-growing, and cystic degeneration was inside. Plain computed tomography imaging revealed an isodense tumor with a marginal high ring and weak early enhancement, and prolonged peripheral enhancement was recognized at the marginal portion. Magnetic resonance imaging showed a heterogeneous mass with peripheral hypointensity ring that may be caused by fibrous tissue. Although the smaller tumor was diagnosed only after admission, it presented similar imaging findings to the larger tumor. The preoperative diagnosis was suspected to be liver metastases from DCC or inflammatory pseudotumor. Laparoscopic partial liver resection with diaphragm dissection was performed for both tumors. Pathologically, the tumors were diagnosed as peritoneal dissemination from distal cholangiocarcinoma. In the disseminated cancer cells, the expression of Ki67 was decreased, which was suspected to be one of the reasons for the long recurrence-free interval. The patient is doing well without any recurrence three months after the second operation., Conclusion: Laparoscopic surgery can provide excellent results for diagnosing and treating unknown subphrenic tumors., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is highly malignant; therefore, continual, multidisciplinary treatments are essential., Case Report: In this study, two 78- and 81-year-old men were treated with the Vater papilla-preserving strategy. Case 1 had advanced HCC with BDTT expanding to the common bile duct (B4) and portal vein tumor thrombus (PVTT) of the umbilical portion. He showed triple-positive tumor markers. He underwent an extended left hepatectomy without bile duct resection following percutaneous transhepatic biliary drainage and transarterial chemoembolization (TACE). Later, TACE in combination with percutaneous microwave ablation was performed to treat four intrahepatic recurrent HCCs. Case 2 had diffuse-type HCCs accompanied by BDTT (B4) and PVTT to the right portal vein. He underwent liver partition associated with portal vein ligation for staged hepatectomy without bile duct resection. Six months later, he developed a solitary recurrent BDTT with obstructive jaundice. After percutaneous transhepatic biliary drainage, he was treated with two TACE from the various feeding arteries. Both patients achieved complete responses and are doing well without viable tumors approximately 2 years after the initial treatment., Conclusion: The Vater papilla-preserving strategy is essential for obtaining long-term survival and recurrent-free status for patients with HCC with highly extended BDTT., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In this real-world, retrospective cohort study of 9753 patients in Japan prescribed dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI), we investigated DAPT duration and determined factors associated with early DAPT discontinuation and with event rates in patients who discontinued DAPT. The study period was April 1, 2012-March 31, 2018; endpoints comprised composite efficacy [death, myocardial infarction (MI), and stroke] and bleeding (intracranial, gastrointestinal, and requiring transfusion) endpoints. Overall, 68.8% of patients were continuing DAPT at 3 months post-PCI. Patients without major efficacy or safety events within 3 months after index PCI were included in a landmark analysis set (LAS; n = 7056), and categorized as DAPT ≥ 3 months (continuation) versus < 3 months (discontinuation). In the two LAS analysis groups, there was no difference in the composite bleeding endpoint (P = 0.067), although the incidence of the composite efficacy endpoint was higher in the discontinuation group (P < 0.001). In multivariate regression analysis, age ≥ 75 years, minor bleeding after PCI, history of cerebral infarction, history of cerebral or gastrointestinal bleeding, atrial fibrillation, dialysis, and anticoagulant use after PCI were associated with early DAPT discontinuation. Acute coronary syndrome, history of MI, kidney disorder, and anticoagulant use after PCI were associated with the composite efficacy endpoint in the discontinuation group. In conclusion, early DAPT discontinuation is more likely in patients at high bleeding risk, but may influence the occurrence of ischemic events in these patients. Determination of DAPT duration should take into account potential ischemic risk, even in patients at high bleeding risk., (© 2022. The Author(s).)

Background/aim: Intrahepatic cholangiocarcinoma (ICC) is increasing in incidence and has a poor prognosis., Case Report: A 79-year-old woman with two liver tumors was referred to our institution. The tumors demonstrated irregular margins and continuous peripheral enhancement. She had a good liver function and an elevated CA19-9 level. Extended left hepatectomy, and partial hepatectomy was performed. The patient was diagnosed with poorly differentiated ICC. Two lung metastases, one liver metastasis, and localized intraperitoneal dissemination occurred 19, 24, and 32 months after the initial hepatectomy. The lung metastases were treated with computed tomography-guided radiofrequency ablation approximately after one year of observation. The liver metastasis was resected immediately. The peritoneal dissemination was removed entirely after effective 3-month chemotherapy using gemcitabine and S-1. The patient is alive with no tumor 44 months after the first surgery., Conclusion: Multidisciplinary treatment considering a metastatic site and tumor malignancy might be effective for patients with ICC who have multiple recurrences., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Fluorouracil plus leucovorin (5-FU/LV) is a less toxic but mild chemotherapy., Case Report: A 63-year-old male patient with rectal cancer and multiple colorectal liver metastases (CRLM, total volume of 1,826 ml) was hospitalized. He had several poor prognostic factors, including elevated levels of tumor markers, with carcinoembryonic antigen and carbohydrate antigen 19-9 levels of 17,119 ng/ml and 7,617 U/ml, respectively. Additionally, the patient had a low body mass index, poor performance status, and a history of apparent weight loss. After capecitabine and oxaliplatin for four cycles, 5-FU/LV has been lasting for nine months. Interestingly, tumor marker levels returned close to normal limits, and the total CRLM volume decreased to 154 ml without any enhancements. The patient's general condition clearly improved after a year of chemotherapy., Conclusion: Chemotherapy with 5-FU/LV and percutaneous microwave ablation is beneficial to achieve tumor control in patients with highly advanced liver-only CRLM and poor general condition., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)