Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma.

Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.

Sigmoid Colon Cancer Masked by Refractory Diverticulitis With Abscess.

Colorectal cancer (CRC) can occasionally coexist with diverticulitis, thereby complicating diagnosis and treatment. In cases of refractory diverticulitis, it is important to consider the possibility of malignancy and determine appropriate treatment strategies. An 85-year-old male presented with lower left abdominal pain; he was admitted for further examination and the treatment of suspected sigmoid diverticulitis. On examination, a firm mass was palpated in the lower left quadrant. Imaging revealed sigmoid diverticulitis, partial abscess formation, and the involvement of the small bowel and abdominal wall. Although malignancy was suspected, a definitive diagnosis was not made. Because of the refractory nature of the disease, early surgical intervention, sigmoid colectomy, partial small bowel resection, abdominal wall resection, and lymph node dissection, was performed in accordance with the malignancy protocol. Pathologic diagnosis revealed adenocarcinoma within the diverticulitis with negative resection margins, indicating curative surgery. The low preoperative diagnostic rate of CRC associated with diverticulitis highlights the need for vigilance. Refractory diverticulitis may indicate the presence of concealed malignancy requiring surgical intervention. In the management of refractory diverticulitis, it is important to consider the potential coexistence of cancer. Even if extensive investigations are performed and a definitive diagnosis remains elusive, surgery must be considered.

A prospective feasibility study of one-year administration of adjuvant S-1 therapy for resected biliary tract cancer in a multi-institutional trial (Tokyo Study Group for Biliary Cancer: TOSBIC01).

BACKGROUND: Although surgery is the definitive curative treatment for biliary tract cancer (BTC), outcomes after surgery alone have not been satisfactory. Adjuvant therapy with S-1 may improve survival in patients with BTC. This study examined the safety and efficacy of 1 year adjuvant S-1 therapy for BTC in a multi-institutional trial. METHODS: The inclusion criteria were as follows: histologically proven BTC, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, R0 or R1 surgery performed, cancer classified as Stage IB to III. Within 10 weeks post-surgery, a 42-day cycle of treatment with S-1 (80 mg/m2/day orally twice daily on days 1-28 of each cycle) was initiated and continued up to 1 year post surgery. The primary endpoint was adjuvant therapy completion rate. The secondary endpoints were toxicities, disease-free survival (DFS), and overall survival (OS). RESULTS: Forty-six patients met the inclusion criteria of whom 19 had extrahepatic cholangiocarcinoma, 10 had gallbladder carcinoma, 9 had ampullary carcinoma, and 8 had intrahepatic cholangiocarcinoma. Overall, 25 patients completed adjuvant chemotherapy, with a 54.3% completion rate while the completion rate without recurrence during the 1 year administration was 62.5%. Seven patients (15%) experienced adverse events (grade 3/4). The median number of courses administered was 7.5. Thirteen patients needed dose reduction or temporary therapy withdrawal. OS and DFS rates at 1/2 years were 91.2/80.0% and 84.3/77.2%, respectively. Among patients who were administered more than 3 courses of S-1, only one patient discontinued because of adverse events. CONCLUSIONS: One-year administration of adjuvant S-1 therapy for resected BTC was feasible and may be a promising treatment for those with resected BTC. Now, a randomized trial to determine the optimal duration of S-1 is ongoing. TRIAL REGISTRATION: UMIN-CTR, UMIN000009029. Registered 5 October 2012-Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000009347.

Harness Traction Technique (HARNESS): Novel Method for Controlling the Transection Plane During Laparoscopic Hepatectomy.

We present our experience using a novel method for controlling the transection plane, which we termed as the Harness Traction Technique (HARNESS) and evaluate its usefulness. From May 2009 to March 2012, laparoscopic hepatectomies using HARNESS were performed on 35 patients. After the superficial hepatic parenchyma on the line was transected at 1 to 2 cm depth, 5 mm tape was placed along the groove of the line and tied to prevent it from slipping off. Tape was tied and pulled using a forceps toward the best direction for minimizing the bleeding, moving the transection point to the appropriate position and creating good tension for parenchymal transection at the transection point. There were no conversions to laparotomy or intraoperative complications. HARNESS is useful for controlling the dissection line during laparoscopic hepatectomy, leading to precise and safe laparoscopic liver parenchymal dissection.

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences.

Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

Evaluation of the usefulness of percutaneous transhepatic portal catheterization for preoperatively diagnosing the localization of insulinomas.

INTRODUCTION: The precise intraoperative localization of insulinoma is essential for successful surgical management. AIMS: To assess the usefulness of measuring insulin levels by preoperative percutaneous transhepatic portal catheterization (PTPC) and intraoperative ultrasonography (US). METHODOLOGY: PTPC and other preoperative procedures (enhanced computed tomography [CT], arteriography, and US) were performed in eight patients with insulinoma based on our experience during the past 18 years. Intraoperative US was performed in six of the eight patients. RESULTS: PTPC was undertaken in all eight patients, and increased levels of insulin at the sites corresponding to tumors were observed in all patients. Intraoperative US was performed in six patients, which made it possible to detect insulinomas as hypoechoic masses in all of these patients. All tumors were found to exist as single entities. CONCLUSION: PTPC showed the highest diagnostic accuracy in detecting the number of and accurately localizing the tumors before surgery. Meanwhile, all findings from intraoperative US were identical to those of the resection samples, suggesting that this method is a highly reliable examination technique. We conclude that a combination of PTPC and intraoperative US may be essential for the successful surgical management of insulinomas.