Orbital Metastasis as the First Manifestation of Hepatocellular Carcinoma, and Its Effective Treatment with Combined Dual Immunotherapy: A Case Report and Review of the Literature.

BACKGROUND Orbital metastasis originating from hepatocellular carcinoma (HCC), particularly as an initial manifestation in patients without a known history of HCC, is rare. Few reports exist on the treatment of patients having HCC with orbital metastasis using targeted therapy or immunotherapy. CASE REPORT We report a case of advanced-stage HCC in a 65-year-old man who first presented with progressive, painless blurred vision and proptosis of the right eye for 2 weeks. The patient had no history of chronic liver disease or cancer. Computed tomography revealed an enhancing hyperdense extraconal mass in the right orbit; a biopsy revealed metastatic HCC. Abdominal CT, which was performed to investigate the primary cancer, revealed a 1.2×1.6-cm arterial-enhancing nodule with venous washout in hepatic segment 5, associated with liver cirrhosis. The patient's serum alpha-fetoprotein level was 70.27 ng/dL. Chest computed tomography revealed lung metastasis. Thus, first-line systemic therapy combining durvalumab and tremelimumab was initiated alongside palliative radiotherapy targeting the right orbit, which began 1 week after the first dose of dual immunotherapy. The patient had significant clinical improvement, reduced proptosis, and serum alpha-fetoprotein levels. CONCLUSIONS Although orbital metastasis is a rare manifestation of HCC, physicians should recognize and consider aggressive investigations for early diagnosis, especially in patients with existing risk factors for HCC. Dual immunotherapy with durvalumab and tremelimumab in combination with radiotherapy can be considered a potential treatment option for managing advanced HCC with orbital metastasis.

The Performance of a Survival Nomogram and Albumin-Bilirubin Grade as Prognostic Tools in Advanced Hepatocellular Carcinoma Treated with FOLFOX4.

BACKGROUND: The ability of the survival nomogram developed in the EACH study and albumin-bilirubin (ALBI) grade to predict the survival of advanced hepatocellular carcinoma (HCC) patients receiving oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) remains unvalidated. Here, we comprehensively evaluated these prognostic tools. METHODS: The survival nomogram and ALBI grade of each patient were assessed, and the area under the receiver operating curve (AUROC) and Harrell's C-index for the risk classification model were calculated. RESULTS: Overall, 76 HCC patients who received FOLFOX4 between August 2017 and June 2023 were included. The survival nomogram classified patients into low-, intermediate-, and high-risk groups, with a median overall survival (OS) of 9.82, 10.64, and 3.70 months, respectively (p = 0.23). The AUROC was 0.621 and Harrell's C-index was 0.589. However, the ALBI grade categorized all patients into grade 1, 2, and 3, with a median OS of 9.82, 6.83, and 1.58 months, respectively (p = 0.00024). The AUROC was 0.663 and Harrell's C-index was 0.663. CONCLUSION: The ALBI grade can be a potential prognostic tool. However, the survival nomogram does not provide clear discrimination. Therefore, FOLFOX4 should be an option for patients with ALBI grade 1 who cannot receive immunotherapy or targeted therapy. Additional prospective studies with a larger cohort are warranted to validate the survival nomogram and ALBI grade as prognostic tools.

LABS score- a prognostic tool for FOLFOX4-treated advanced hepatocellular carcinoma and real-world efficacy: a single-center retrospective study.

BACKGROUND: No widely used prognostic tool exists to demonstrate the benefit of oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX4) in patients with advanced hepatocellular carcinoma (HCC). We aimed to establish a prognostic score and demonstrate the real-world efficacy of FOLFOX4 chemotherapy in Thai patients. METHODS: Between August 2017 and December 2021, we identified 58 FOLFOX4-treated patients with HCC. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were assessed. The prognostic score was constructed by stepwise Cox proportional hazards regression analysis to select variables for the best model with the lowest Akaike information criterion from all potential variables. RESULTS: Forty-four patients (76%) received FOLFOX4 as first-line therapy. The ORR in the entire cohort was 8.6%, and the disease control rate was 29.3%. The PFS and OS were 3.7 and 4.8 months, respectively. Four clinically relevant variables were included in the new prognostic score to predict 6-month OS: L, the presence of lung metastasis; A, alcoholic cirrhosis; B, elevated total bilirubin level; and S, sorafenib-naïve status. Using the LABS score, patients were classified into low-, intermediate-, and high-risk groups, demonstrating OS values of 9.3, 4.2, and 2.1 months, respectively (p < 0.0001). The C-index and area under the receiver-operating characteristic curve of the score were 0.71 and 0.73, respectively. CONCLUSIONS: The proposed LABS score could discriminate patients who would derive benefit from FOLFOX4 chemotherapy. FOLFOX4 chemotherapy is an option for patients who cannot receive immunotherapy and targeted therapy, particularly those with a low-risk score. However, further validation of this model via larger cohorts is warranted.

Comparing the Efficacy of Carboplatin plus 5-Fluorouracil, Cisplatin plus 5-Fluorouracil, and Best Supportive Care for Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Analysis from a Tertiary Hospital in Southern Thailand.

Background: Although cisplatin plus 5-fluorouracil (5-FU) is the standard first-line treatment for advanced-stage esophageal squamous cell carcinoma (ESCC), carboplatin was substituted for cisplatin in cisplatin-ineligible patients. The efficacy of carboplatin plus 5-FU for advanced-stage ESCC remains unreported. Methods: This retrospective study analyzed first-line treatment-carboplatin plus 5-FU, cisplatin plus 5-FU, or best supportive care (BSC)-in advanced-stage ESCC patients at a tertiary hospital in Thailand (2012-2022). Survival was assessed using the Kaplan-Meier method, compared via the log-rank test, and adjusted through propensity score matching. Significance was set at p < 0.05. Results: Of 256 patients, 39.9% received carboplatin plus 5-FU, 27.7% cisplatin plus 5-FU, and 32.4% BSC. Carboplatin was significantly associated with older age, poorer performance status, more comorbidities, chronic kidney disease, and lower creatinine clearance. Median overall survival (OS) for carboplatin plus 5-FU, cisplatin plus 5-FU, and BSC was 8.05 (HR 0.31 [0.23, 0.43] vs. BSC, p < 0.001; HR 1.06 [0.78, 1.44] vs. cisplatin plus 5-FU, p = 0.7), 8.43, and 3.64 months, respectively. No significant OS difference was observed between carboplatin and cisplatin treatments after propensity score matching. Median progression-free survival (PFS) and objective response rates (ORR) showed no significant difference between carboplatin and cisplatin treatments. Conclusions: Despite less favorable baseline characteristics of patients receiving carboplatin plus 5-FU, this combination exhibited comparable OS, PFS, and ORR to cisplatin plus 5-FU in real-world scenarios. Furthermore, it significantly improved OS over BSC. Consequently, carboplatin plus 5-FU should be considered as an alternative regimen, particularly for advanced-stage ESCC patients who are ineligible for cisplatin.

Nineteen-year, real-world experience of first-line combination chemotherapy in patients with metastatic colorectal cancer: a propensity score analysis from southern Thailand.

OBJECTIVE: Combination fluoropyrimidine-based chemotherapy is the standard first-line treatment for metastatic colorectal cancer (CRC). We performed a propensity score (PS)-based analysis to report our real-world experience with long-term follow-up of this regimen for metastatic CRC. METHODS: In this retrospective study, 170 patients with newly diagnosed metastatic CRC treated with first-line combination chemotherapy between January 2003 and March 2021 were identified. Cox proportional hazards regression analysis and PS-based approaches with the logistic regression model were adopted, and the results were compared. RESULTS: The hazard ratio for overall survival (OS) in the oxaliplatin- and irinotecan-based groups was 0.79 (95% confidence interval = 0.56-1.11), and the median OS times in these groups were 16.8 and 13.0 months, respectively. The median time to progression (TTP) for these regimens were 9.0 and 8.9 months, respectively. The objective response rates for the oxaliplatin- and irinotecan-based groups were 42.7% and 34.6%, respectively. OS and TTP did not differ between these regimens in all PS matching models. CONCLUSIONS: First-line treatment using fluoropyrimidine-based chemotherapy regimens in combination with oxaliplatin or irinotecan in patients with metastatic CRC provided comparable efficacy and tolerable toxicity profiles in a real-world setting with long-term follow-up.

Metastatic Primary Testicular Neuroendocrine Carcinoma Associated with Somatic Malignant Transformation of Teratoma: A Rare Case Report.

Testicular neuroendocrine tumor associated with teratoma is a rare disease. Very few cases have been reported in the literature, particularly cases involving visceral metastasis. Teratoma with somatic malignant transformation (SMT) is associated with a worse prognosis compared to teratoma without SMT. Previous data have suggested that chemotherapy regimens should be directed toward the transformed histology; however, those suggestions were based on patients with rhabdomyosarcoma, adenocarcinoma, and primitive neuroectodermal subtypes. To the best of our knowledge, only 2 cases with visceral metastasis have been reported, and a better outcome with the bleomycin/etoposide/cisplatin regimen, which responds strongly to germ cell tumors, has been reported in these cases. In contrast, 2 others with lymph node metastasis did not respond to these regimens. Here, we report a case of a patient with testicular neuroendocrine carcinoma associated with teratoma who achieved a good response to chemotherapy.

Re-bleeding and its predictors after capsule endoscopy in patients with obscure gastrointestinal bleeding in long-term follow-up.

BACKGROUND: Capsule endoscopy (CE) is the preferred diagnostic test of choice in the investigation of obscure gastrointestinal bleeding (OGIB). Although, a conservative strategy is recommended in the short-term, for cases with a negative result from CE, the impact of CE on long-term re-bleeding still remains unclear. Hence, the aim of this study was to determine the long-term re-bleeding rate along with predictors after CE in patients with OGIB. METHODS: We retrospectively reviewed 216 patients with OGIB, whom had received a CE examination, so as to investigate the cause of obscure GI bleeding; between July 2008 and March 2018. The patient's characteristics, medication use, CE finding, treatments strategy, re-bleeding episodes and follow-up information were collected from the institutional electronic medical chart and CE database. Re-bleeding free survival was evaluated using Kaplan-Meier curves with log rank test, whilst predictors associated with the re-bleeding episodes were analyzed via the use of Cox proportional hazard model. RESULTS: One hundred and thirty-three patients with OGIB, having received CE were enrolled in the analysis. The pool rate of re-bleeding was 26.3% (35/133) during a follow-up duration of 26 months after CE. Patients with positive CE study, without specific treatment, had higher rates of re-bleeding (47.6%) than those with positive study whom received specific treatment (25.7%), and negative study (20.8%) (p = 0.042). Although, the re-bleeding free survival was not significantly different among the groups (log rank test; P = 0.10). Re-bleeding events occurring within 6, 12, and 24 months after CE were 36, 64 and 92%, respectively. The high-frequency re-bleeding etiologies were the small bowel angiodysplasias and abnormal vascular lesions. Furthermore, independent predictors for re-bleeding after CE were patients with cirrhosis (hazard ratio, HR 4.06), incomplete CE visualization (HR 2.97), and a history of previous GI bleeding (HR 2.80). CONCLUSIONS: The likelihood of re-bleeding after CE was higher in patients with positive CE study than those with negative study. Specific treatments, or therapeutic interventions for patients with detectable lesions reduced the probability of re-bleeding episodes in long-term follow-up. Close follow-up for recurrent bleeding is recommeded for at least 2 years after CE.