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Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC)., Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified., Results: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03)., Conclusion: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background and Aims: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice., Methods: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD., Results: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001)., Conclusions: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

A 65-year-old woman with HER2-positive gastric cancer with multiple liver metastases underwent first conversion surgery of gastrectomy with D2 lymph nodes dissection and three liver metastases after combination therapy with capecitabine, cisplatin, and trastuzumab. Two years later, she experienced multiple liver metastases that were refractory to combination therapy with paclitaxel albumin-bound nanoparticles and ramucirumab. She participated in the DESTINY-Gastric01 trial and received tri-weekly trastuzumab deruxtecan as third-line treatment for 26 cycles. The recurrent lesions markedly shrank, and this effect continued for 19 months. We then performed partial hepatectomy for the one remaining lesion. No adjuvant chemotherapy was given, and she remains alive without recurrence 18 months after the second conversion surgery. Trastuzumab deruxtecan may generate a notable tumor response and subsequent conversion surgery could be a treatment option for HER2-positive stage IV gastric cancer., (© 2023. Japanese Society of Gastroenterology.)

Combination therapy using multiple antiemetic drugs is recommended for intravenous administration of cisplatin, a highly emetogenic agent, whereas a 5-HT3 receptor antagonist alone is commonly used in hepatic arterial infusion chemotherapy using cisplatin for hepatocellular carcinoma owing to its less toxicity than that in the intravenous administration. Given that optimal antiemetic therapy is not yet established, we retrospectively investigated the efficacy of antiemetic drugs for hepatic arterial infusion chemotherapy using cisplatin. This study enrolled 72 patients with hepatocellular carcinoma who received hepatic arterial infusion chemotherapy using cisplatin at Kurashiki Central Hospital between January 2011 and May 2019. A 5-HT3 receptor antagonist was used in all cases, while aprepitant and/or dexamethasone were used concomitantly in 6 cases. After chemotherapy, a complete response rate for 5 days was achieved in 73.6% of the patients; however, complete control could be achieved only in 29.2%. During these 5 days, both rates were lower on days 2-5 than on day 1. In addition, younger age was associated with worse control rates. Our findings suggest that more effective antiemetic therapy is needed for hepatic arterial infusion chemotherapy using cisplatin, especially in non-elderly patients.

Here, we report the case of a 73-year-oldfemale patient, who previously underwent high anterior resection for rectosigmoidcancer at the age of 63. Her scheduled5 years of follow-up after colorectal surgery hadbeen finished, but she kept undergoing endoscopic mucosal resection for colorectal polyps every 1 or 2 years since then. Blood examination 10 years 6 months after surgery for rectosigmoidcancer revealedthat the value of her serum CEA was 5.5 ng/mL, which was slightly higher than the normal range. Contrast-enhancedCT showedan irregular-shapedtumor with a diameter of 3 cm in which the contrast of the peripheral area was mainly emphasized. When combining the results of MRI and PET-CT examinations, the liver tumor was clinically diagnosed as either intrahepatic cholangiocarcinoma or metastatic liver cancer. Since the first choice of therapy was tumor resection for both diagnoses, S8 subsegmental hepatectomy was performed 10 years 8 months after surgery for rectosigmoidcancer. HE staining of the resectedspecimen showedwell or moderately differentiatedad enocarcinoma, andits immunostaining findings were as follows: CDX-2: positive, CK20: positive, CK7: negative. It was pathologically diagnosed as liver metastasis from rectal cancer. It is rare for colorectal cancer to have metachronous liver metastasis more than 10 years after surgery. However, in any case where a tumor marker for colorectal cancer increases, it is necessary to examine carefully with the possibility of any metastasis in mind.

Background and Aim: Several factors, including proangiogenic cytokines, have been reported as predictive markers for the treatment effect of sorafenib in patients with hepatocellular carcinoma (HCC); however, most of them were determined based on one-time measurements before treatment., Methods: We consecutively recruited 80 advanced HCC patients who were treated with sorafenib prospectively. Serum levels of eight proangiogenic cytokines and the appearance of adverse events were monitored periodically, and their correlations with the prognoses of the patients were evaluated., Results: Among six significant risk factors for overall survival in univariate analyses, high angiopoietin-2 (hazard ratio, 2.06), high hepatocyte growth factor (hazard ratio, 2.08), and poor performance status before the treatment (hazard ratio, 2.48) were determined as independent risk factors. In addition, high angiopoietin-2 at the time of progressive disease was a marker of short post-progression survival (hazard ratio, 4.27). However, there was no significant variable that predicted short progression-free survival except the presence of hepatitis B virus surface antigen., Conclusions: Predictions of overall survival and post-progression survival were possible by periodically measuring serum proangiogenic cytokines, especially angiopoietin-2, in patients with HCC treated with sorafenib., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Here, we report the case of a 66-year-old male patient who previously underwent resection of sigmoid colon cancer and its liver metastasis. His follow-up contrast-enhanced CT scan revealed a mass shadow at around the gastrosplenic ligament, which gradually increased in size. Because it could not be pathologically diagnosed by transgastric EUS-FNA, en bloc resection wasperformed surgically for the tumor in the greater omentum. Hematoxylin-eosin staining of the resected specimen showed fibroblast-like cellswith hyperplasia of bold collagen fibersand spindle-shaped nucleus. While the immunostaining findings denied a diagnosis of mesenchymal neoplasm such as GIST, leiomyosarcoma, or schwannoma, it was pathologically diagnosed as a desmoid tumor. He has been followed up without any recurrence for 2-and-a-half years after the surgical resection. Desmoid tumors tend to be locally invasive; thus, there is the potential for local recurrence, although the frequency of distant metastasis is very low. In cases in which the tumor increases in size, en bloc resection with sufficient surgical margin should be performed. Cases of desmoid tumors originating from the greater omentum are reportedly rare; however, en bloc resection may be useful for both diagnosis and treatment of tumors of the greater omentum showing increased size that are also surgically resectable.

Rationale: Hepatocellular carcinoma has been believed not to produce mucin unless it has biliary differentiation. However, some cases of hepatocellular carcinoma with extracellular myxoid change have been reported recently, raising the possibility that, in rare cases, hepatocellular carcinoma cells produce mucin., Patient Concerns: Here we report a case of hepatocellular carcinoma that contained intracellular and extracellular myxoid matrix without morphological evidence of biliary differentiation, although cells in a portion of the tumor were positive for the epithelial markers cytokeratin 7 and 19. She was brought to our hospital due to abnormal liver tests and a large liver tumor found by ultrasound examination., Diagnoses: The liver tumor showed typical imaging findings of hepatocellular carcinoma., Interventions: The tumor was resected with negative margins, and pathologically diagnosed as hepatocellular carcinoma with mucin production., Outcomes: The patient has been free from recurrence of cancer during two-years' follow-up., Lessons: Our case suggests that hepatocellular carcinoma cells can produce mucin without or before morphological differentiation to biliary phenotypes, an observation that may help elucidate the mechanism for the development of combined hepatocellular and cholangiocarcinoma.

Objective The purpose of this study was to construct nomograms for the disease-free survival (DFS) and overall survival (OS) of post-radiofrequency ablation (RFA) patients with hepatocellular carcinoma (HCC). Furthermore, we compared the prognostic predictive ability of these nomograms for estimating per-patient outcomes with that of traditional staging systems. Methods We retrospectively enrolled 298 patients in the training set and 272 patients in the validation set who underwent RFA for HCC. The nomograms for the DFS and OS were constructed from the training set using the multivariate Cox proportional hazards model. The discriminatory accuracy of the models was compared with traditional staging systems by analyzing the Harrell's C-index. Results The DFS nomogram was developed based on the tumor size, tumor number, aspartate aminotransferase (AST), albumin, age, and α-fetoprotein. The OS nomogram was developed based on the tumor size, the model for end-stage liver disease, AST, and albumin. Our DFS and OS nomograms had good calibration and discriminatory abilities in the training set, with C-indexes of 0.640 and 0.692, respectively, that were greater than those of traditional staging systems. The C-indexes of our DFS and OS nomograms were also greater than those of traditional staging systems in the validation set, with C-indexes of 0.614 and 0.657, respectively. RFA patients were stratified into low- and high-risk groups based on the median nomogram scores. High-risk patients receiving surgical resection (SR) were associated with a better DFS and OS than those undergoing RFA. However, the DFS and OS were similar between the low-risk RFA and SR groups. Conclusion We constructed reliable and useful nomograms that accurately predict the DFS and OS after RFA for early-stage HCC patients. These graphical tools are easy to use and will assist physicians during the therapeutic decision-making process.

Purpose: To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria., Materials and Methods: Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching., Results: After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively)., Conclusion: TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible., (© RSNA, 2013.)

Background: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort., Methods: In the current retrospective cohort study, we measured serum levels of the eight cytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS)., Results: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis., Conclusion: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.

The efficacy and safety of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) were compared between elderly (age≥75 years, n=82) and non-elderly groups (age<75 years, n=158). No significant differences were observed in complications between the two groups. Elderly patients had a lower survival rate compared to the non-elderly patients. Multivariate analysis showed that age was not a significant factor for survival on tumor recurrence. Matching by propensity score revealed no significant differences were observed in survival on tumor recurrence rate. The prognosis of elderly patients undergoing RFA might be considered poorer than that of non-elderly patients. However, when considering the clinical background, RFA might be safe and effective in elderly patients, as well as non-elderly patients.