High-risk Patients With Colorectal Liver Metastases Assessed by the Beppu Score Can Have Excellent Survival Through Multidisciplinary Treatment Including Local Ablation.

BACKGROUND/AIM: The Beppu score assessed by the Japanese Society of Hepato-Biliary-Pancreatic Surgery nomogram helps predict postoperative disease-free survival for patients with resectable colorectal liver metastases (CRLM). Using the Beppu score, patients with resectable CRLM were divided into three groups according to recurrence risk: low (≤6 points), moderate (7-10 points), and high-risk (≥11 points). Hepatectomy following preoperative chemotherapy is recommended for high-risk patients. The surgical outcome, local recurrence rates, and long-term survival were assessed, focusing on local ablation. PATIENTS AND METHODS: Twenty high-risk and unresectable CRLM patients were enrolled between April 2016 and April 2022. Hepatectomy with or without local ablation was performed after induction chemotherapy. Local ablation was permissive for patients with effective chemotherapy (partial response and stable disease) with CRLM ≤2 cm and ≥5 mm distant from major vessels. RESULTS: The median diameters and numbers of CRLM were 26 (10-150) mm and 9 (1-46). All 18 patients who received preoperative chemotherapy were disease controls. Local ablation was performed simultaneously on hepatectomy in 14 patients. The median diameters and numbers of the ablated nodules were 12 (5-17) mm and 3 (1-21). Local recurrence was 8.5% per 82 ablative nodules. Three-year disease-free and five-year overall survival was 57.4% and 56.2%, respectively. There was no significant difference in patients with or without local ablation. CONCLUSION: Our treatment strategy for high-risk CRLM patients is feasible and can provide an excellent long-term prognosis regardless of adding local ablation to hepatectomy.

Surgery for Hepatocellular Carcinoma With Macroscopic Vascular Invasion in the Era of Modern Molecular Therapy.

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.

Durable Stable Disease by Atezolizumab/Bevacizumab Can Provide Long-term Survival of Patients With Hepatocellular Carcinoma Lung Metastases.

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.

A Laparoscopically Treated Case of Peritoneal Dissemination Mimicking Liver Metastases from Distal Cholangiocarcinoma Four Years After the Initial Pancreaticoduodenectomy.

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.

Vater Papilla-preserving Strategy for Advanced Hepatocellular Carcinoma With Excessive Bile Duct Tumor Thrombus.

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.

Antiviral therapy and long-term outcome for hepatitis B virus-related hepatocellular carcinoma after curative liver resection in a Japanese cohort.

AIM: The aim of this study was to determine whether antiviral therapy with nucleotide/nucleoside analog (NA) is beneficial for Japanese patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) who underwent initial curative liver resection. PATIENTS AND METHODS: In 162 patients with positive hepatitis B surface antigen and negative anti-hepatitis C virus antibody, sixty-two patients received antiviral therapy with NA (NA group) and the remaining 100 patients did not (non-NA group). Prognostic factors for disease-free survival (DFS) and overall survival (OS) were evaluated. Moreover, to equalize the background covariates, a one-to-one propensity case-matched analysis was used. RESULTS: NA administered were lamivudine (LAM) solely for 21 patients, LAM plus adefovir dipivoxil (ADV) for 6, LAM switched to entecavir (ETV) for 5 and ETV solely for 31. DFS did not significantly differ between the NA group and non-NA group (p=0.19). However, OS was significantly different (p=0.0063); 1-,3- and 5-year OS were 100% and 85.9%, 88.3% and 61.9% and 65.1% and 58.0%, respectively. In multivariate analysis, no antiviral therapy with NA was an independent poor prognostic factor (hazard ratio (HR)=2.72; p=0.0229). However, after propensity case-matched analysis, disease-free and overall survival were not significantly different between the two groups. CONCLUSION: In a Japanese cohort, antiviral therapy with NAs might provide longer survival for postoperative HBV-related HCC patients compared to patients without antiviral therapy. However, deterministic evaluation was impossible by this study alone.

Spontaneous rupture of adrenocortical carcinoma.

Massive hemorrhage from an adrenocortical carcinoma seldom occurs in the retroperitoneal or abdominal cavity. We report a case of spontaneous rupture of primary adrenocortical carcinoma occurring in an adolescent. A right adrenalectomy with complete removal of the tumor was performed successfully.

[Hand-assisted laparoscopic adrenalectomy to a solitary adrenal metastasis from lung cancer].

A 75-year-old man with right chest pain was diagnosed with primary lung cancer in the right apical portion, and was treated with chemoradiotherapy because of a synchronous left adrenal tumor of 1.6 cm. Since the adrenal tumor did not increase in size for three months and there were no other relapses, the right upper lobectomy of the lung with the excision of the chest wall was performed. Afterward, an enlargement of the left adrenal tumor was encountered; he was admitted to our hospital for an operation. For the metastatic adrenal tumor from lung cancer, we performed a hand-assisted laparoscopic adrenalectomy. He recovered rapidly and returned to the previous hospital in two weeks after the operation. After the first report in 1992, the laparoscopic adrenalectomy has been established as the curative operation to adrenal benign tumor. The indication is being expanded to the malignancy because of the improvement of operation techniques and advancement of the operation equipments. We conclude that the laparoscopic adrenalectomy for malignant tumor is a safe, curative, and clinically useful surgical technique.

[A promising new procedure: laparoscopic devascularization for hepatocellular carcinoma with extra-hepatic feeding arteries].

We have developed a new therapeutic modality: laparoscopic devascularization (LDEV) for hepatocellular carcinoma (HCC). Thirteen patients with HCC were treated with LDEV from March 1998 to March 2002. All LDEV procedures were performed under laparoscopic surgery using laparoscopic coagulating shears (LCS), endo-clip and endo-GIA. To prevent recanalization of extra-hepatic feeding arteries, we always add local ablation therapy (LAT) intraoperatively. The results are as follows. 1. The right gastroepiploic artery in 11 patients, right gastric artery in 1 and right inferior phrenic artery in 2 were devascularized. 2. The amount of intraoperative bleeding ranged 5-150 g and the operating time for devasculalization ranged 5-50 min, with an average of 30 min. 3. LAT was also performed in all cases. 4. No complications occurred. 5. A recurrent feeding artery developed in only one case (8%). 6. Nine patients are living (6-52, average 27 months) and 4 have died (5-28, average 16 months).