Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

BACKGROUND: The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. AIM: To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. DISCUSSION: Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

Liberal Application of Portal Vein Embolization for Right Hepatectomy Against Hepatocellular Carcinoma: Strategy to Achieve Zero Mortality for a Damaged Liver.

BACKGROUND/AIM: Right hepatectomy and extended right hepatectomy (Rt-Hr) are identified as risk factors for the development of post-hepatectomy liver failure (PHLF). Although portal vein embolization (PVE) has made it possible to safely perform extended hepatectomy, to ensure safety, in our department, PVE is performed prior to Rt-Hr for hepatocellular carcinoma (HCC) regardless of the resection rate. This study aimed to retrospectively investigate the clinical course of PVE prior to Rt-Hr for HCC cases resected in our department and the appropriateness of our policy by clarifying complications and deaths. PATIENTS AND METHODS: The target period was from 2005 to 2020. Among the HCC cases resected at our hospital, those in which PVE was performed prior to Rt-Hr were included in this study. For PHLF, the definition of the International Study Group of Liver Surgery was used. The Clavien-Dindo classification was used for postoperative complications. Perioperative mortality was defined as the overall mortality within 30 days following surgery and surgery-related deaths within 90 days following surgery. RESULTS: A total of 79 cases were included. Rt-Hr was possible in all cases after PVE and there were no cases in which serious complications occurred after PVE. PHLF was found in 14 cases (17.7%)/5 cases (6.4%)/0 cases (0%) of Grade A/B/C, respectively. Regarding postoperative complications, there were no Grade IV, and Grade IIIa/IIIb were found in 13 cases (16.5%). There were no perioperative deaths. CONCLUSION: Our department's policy of performing PVE prior to all Rt-Hr was considered to be a safe and reasonable treatment strategy.

A rare case of symptomatic grossly-visible biliary intraepithelial neoplasia mimicking cholangiocarcinoma.

BACKGROUND: Biliary intraepithelial neoplasia (BilIN) is often distinguished by what it is not: the precancerous lesions are not mass-forming, are not the cause of bile duct obstruction, and are small enough (less than 5 mm long) to evade detection by the naked eye. Here, we describe an atypical case of BilIN resembling cholangiocarcinoma (CC) that was large enough to be identified by diagnostic imaging and presented with obstructive jaundice caused by a hematoma in the common bile duct (CBD). CASE PRESENTATION: A 64-year-old man presented to our hospital with upper abdominal pain and anorexia. Initial laboratory examinations revealed increased total bilirubin and a computed tomography (CT) scan revealed a dilated CBD. Gastroenterologists performed an endoscopic sphincterotomy (EST), which revealed that the cause of obstructive jaundice was a hematoma in the CBD. Enhanced CT scan and magnetic resonance cholangiopancreatography (MRCP) performed after the hematoma was drained showed improved dilation of the CBD and an enhanced wall thickness of bile duct measuring 25 × 10 mm at the union of the cystic and common hepatic ducts. A cholangioscope detected an elevated tumor covered by sludge in the CBD, and we performed an extrahepatic bile duct resection and cholecystectomy. The postoperative course was uneventful and the pathological examination of the resected tumor revealed that although the ulcerated lesion had inflammatory granulation tissue, it did not contain the components of invasive carcinoma. Many consecutive intraepithelial micropapillary lesions spread around the ulcerated lesion, and the epithelial cells showed an increased nucleus-to-cytoplasm ratio, nuclear hyperchromasia, and architectural atypia. The pathological diagnosis was BilIN-1 to -2. Immunohistochemical staining showed that S100P was slightly expressed and MUC5AC was positive, while MUC1 was negative and p53 was not overexpressed. CONCLUSION: We experienced an atypical case of BilIN mimicking CC that presented with obstructive jaundice caused by a hematoma in the CBD. Our case suggested that the occurrence of BilIN can be triggered by factors other than inflammation, and can grow to a size large enough to be detected by image analyses.

Intrabiliary growth type of metastasis from colon cancer, 12 years after curative colectomy: a case report.

BACKGROUND: Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described. CASE PRESENTATION: An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9. He underwent right hemicolectomy for colon cancer 12 years prior. Enhanced computed tomography (CT) showed dilated bile ducts with periductal enhancement in S5; hence, cholangiocarcinoma was suspected. Upon anterior segmentectomy, we observed that the cut surface of the specimen exhibited a yellowish-white tumor within the bile ducts. Histologically, the tumor formed within the papillary process, extended along the lumen, and replaced the normal bile duct epithelium. Immunohistochemical studies showed that the liver tumor and primary colon cancer were negative for cytokeratin (CK) 7 and positive for CK20 and Caudal-type homeobox transcription factor 2 (CDX-2). In addition, both tumors showed a same KRAS mutation. We diagnosed the liver tumor as liver metastasis recurrence from colon cancer. CONCLUSION: Intrabiliary growth type of metastasis (IGM) is difficult to distinguish from cholangiocarcinoma, and sometimes develops long after surgery; thus, careful examination of a patient's history is needed in such cases.

[A Case of Recurrent Gallbladder Carcinoma Treated with Resection and Hepatic Arterial Infusion].

A 69-year-old woman underwent extended cholecystectomy for gallbladder cancer[T2N0M0, fStage Ⅱ(UICC 7th edition)]. She was then administered adjuvant S-1 and was treated for drug-induced neutropenia. One year later, recurrent lesions were detected in liver S4 and S5. We treated the patient with hepatectomy and hepatic arterial infusion adjuvant chemotherapy by cisplatin, along with the systemic administration of gemcitabine for 10 months. The patient is now doing well without any sign of recurrence 29 months after the initial operation and 16 months after the secondary liver resection.

Complete spontaneous necrosis of hepatocellular carcinoma accompanied by portal vein tumor thrombosis: A case report.

INTRODUCTION: We report a rare case of complete spontaneous necrosis of a hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT), as confirmed by resection. CASE PRESENTATION: A 64-year-old man was referred to our hospital for suspected HCC. Contrast-enhanced computed tomography (CECT) findings before admission revealed a 53-mm tumor in the posterior segment of the liver and were suspicious for PVTT in the right posterior PV. Both alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were elevated at 17,562 ng/mL and 153 mAU/mL, respectively. We diagnosed the findings as HCC with PVTT. Seven days after the first CECT scan, we performed CECT volumetry, which revealed that the tumor had regressed to 30 mm, along with regression of the PVTT. We performed portal vein ligation (PVL), and 10 days later, CECT revealed that the tumor had shrunk to 20 mm. AFP and PIVKA-II levels were 643 ng/mL and 14 mAU/mL, respectively. We suspected spontaneous regression of the patient's HCC, but performed a hepatectomy. Histopathology revealed a 22-mm tumor with a thin fibrous capsule and a tumor thrombus in the PV. Trabecular and pseudoglandular structures consisting of denucleated HCC epithelial cells made up both the tumor and thrombus, and the finding confirmed the spontaneous necrosis of HCC. CONCLUSIONS: We present an extremely rare case of complete spontaneous necrosis of HCC with PVTT. When spontaneous necrosis is suspected, surgery should be considered because of the potential risk of residual viable cancer cells.

Evaluation of Surgical Procedures for T2 Gallbladder Cancer in Terms of Recurrence and Prognosis.

T2 (tumor invades perimuscular connective tissue; no extension beyond serosa or into liver) gallbladder cancer has generally been treated by S4aS5 subsegmentectomy (S4aS5 HR). We investigated the therapeutic effect of full-thickness cholecystectomy (FC) and gallbladder bed resection (GBR), in terms of tumor location and resection margin (distance from the tumor). At our department we employ the following protocol to determine the extent of resection needed to achieve R0 status: (1) A tumor located in the gallbladder fundus (Gf) or body (Gb) and only on the free peritoneal side was classified as P-type, for which full-thickness cholecystectomy and regional lymph node dissection were performed. (2) A tumor located in Gf or Gb and in contact with the liver bed was classified as H-type, for which gallbladder bed resection and regional lymph node dissection were performed. (3) A tumor located in the gallbladder neck (Gn) was classified as N-type, for which gallbladder bed resection, bile duct resection, and regional lymph node dissection were performed. Twenty-two patients admitted to our department between January 2000 and December 2014 with pT2gallbladder cancers were included in our study. Surgical procedures performed were compared with those specified in our protocol, and patients in whom the extent of resection was greater than that specified in our strategy were evaluated clinicopathologically and in terms of recurrence and the prognosis. Six (27.2%), 7 (31.8%), and 9 (40.9%) patients underwent limited, standard, and extended surgery, respectively. Ten (66.7%) of 15 patients with tumors close to the liver bed underwent cholecystectomy or extended surgery, 7 (85.7%) of 8 patients with tumors close to the bile duct underwent bile duct resection, and 16 (72.7%) of 22 patients underwent regional lymph node dissection. Recurrence at the bile duct resection margin, para-aortic lymph node metastasis, and hepatic metastasis occurred in 2, 1, and 3 patients, respectively. The 3-year survival rates (for patients including those dying of noncancer causes) were 50, 100, and 75% after limited, standard, and extended surgery, respectively. There was a significant difference in the survival rate of patients who underwent standard or extended surgery (P=0.0273). Favorable results were obtained in T2 gallbladder cancer patients without performing S4aS5 subsegmentectomy. Depending on the tumor location, neither full-thickness cholecystectomy nor gallbladder bed resection appeared to pose problems regarding recurrence or prognosis. In conclusion, surgical treatment based on our protocol, which aims to achieve the condition of R0, may result in a sufficient therapeutic effect.

[A Case of Laparoscopic Resection of Peritoneal Hepatocellular Carcinoma Recurrence after Percutaneous Ethanol Injection Therapy].

Needle tract implantation after percutaneous ethanol injection therapy(PEIT)for hepatocellular carcinoma(HCC)is rare. Surgical treatment of such HCC implants is still controversial. We herein report the case of a patient who underwent laparoscopic resection for peritoneal dissemination after PEIT. An 81-year-old man underwent PEIT for primary HCC at another hospital. Thereafter, percutaneous radiofrequency ablation(RFA)was performed twice for intrahepatic recurrence. After the second RFA, a mass lesion was detected at the subhepatic space on computed tomography(CT). We reevaluated the CT and diagnosed the patient with peritoneal dissemination after PEIT. Laparoscopic resection was performed. However, the patient developed recurrences at the thoracic wall and peritoneum 12 months after laparoscopic surgery. Those 2 tumors were resected, and he remains alive, approximately 30 months after the laparoscopic resection. Laparoscopic extirpation of tract seeding may provide better clinical outcomes in select patients.