A Review and Case Discussion on a Rare Cause of Non-cirrhotic Portal Hypertension.

Nodular regenerative hyperplasia (NRH) is a rare cause of non-cirrhotic portal hypertension that should be considered in patients with no risk factors for chronic liver disease or in any unusual presentation of variceal hemorrhage. We present a case of an 82-year-old Chinese female, with a history of previous metastatic sigmoid carcinoma with oxaliplatin use, who presented with melena. A gastroscopy done revealed one column of grade 3 esophageal varix, two columns of grade 2 esophageal varices, and a type 1 gastroesophageal varix with stigmata of recent hemorrhage. Cyanoacrylate glue therapy was performed without any complications. A follow-up computed tomography (CT) imaging of the abdomen did not reveal any significant features of cirrhosis or venous thrombosis, and the decision was made for a transjugular liver biopsy with hepatic venous pressure gradient (HVPG) measurement. The measured HVPG was 6 mmHg, and the liver biopsy showed features consistent with NRH.

Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.

Treatment of gastrointestinal tumor (GIST) of the rectum requiring abdominoperineal resection following neoadjuvant imatinib: a cost-effectiveness analysis.

BACKGROUND: Neoadjuvant imatinib for gastrointestinal stromal tumors (GIST) of the rectum can reduce, but may not eliminate, risk of surgical morbidity from permanent bowel diversion. We sought to evaluate the cost-effectiveness of alternative strategies in rectal GIST patients requiring abdominoperineal resection following neoadjuvant imatinib. METHODS: We developed a Markov model using a healthcare payers' perspective to estimate costs in 2017 Singapore dollars (SGD) and quality adjusted life years (QALYs) for upfront abdominoperineal resection (UAPR) versus continued imatinib until progression (CIUP) following 1 year of neoadjuvant imatinib. Transition probabilities and utilities were obtained from published data, and costs were estimated using data from the National Cancer Centre Singapore. Deterministic and probabilistic sensitivity analyses were conducted to probe model uncertainty. Incremental cost-effectiveness ratio below SGD 50,000 per QALY gained was considered cost-effective. RESULTS: In the base case, UAPR dominates CIUP being both more effective (8.66 QALYS vs 5.43 QALYs) and less expensive (SGD 312,627 vs SGD 339,011). These estimates were most sensitive to 2 variables, utility of abdominoperineal resection and annual recurrence probability post-abdominoperineal resection. However, simultaneously varying the values of these variables to maximally favor CIUP did not render it the more cost effective strategy at willingness to pay (WTP) of SGD 50,000. In probabilistic sensitivity analysis, UAPR had probability of being cost-effective compared with CIUP greater than 95%, reaching 100% at WTP SGD 10,000. CONCLUSION: UAPR is more effective and less costly than CIUP for patients with rectal GIST requiring abdominoperineal resection following neoadjuvant imatinib, and is the strategy of choice in this setting.

Biological significance and prognostic relevance of peripheral blood neutrophil-to-lymphocyte ratio in soft tissue sarcoma.

Peripheral blood indices of systemic inflammation such as the neutrophil-lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We aim to investigate the clinical significance of these indices in patients with soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood counts at diagnosis and/or metastatic relapse were retrospectively examined. An optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was determined using receiver operating curve analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Our results show that NLR was significantly higher in patients with distant metastasis at diagnosis (n = 183) compared to those without (n = 529) (median: 4.36 vs 2.85, p < 0.0001). Progression of localized disease at diagnosis to metastatic relapse within the same patients was associated with an interval increase in NLR (median: 3.21 vs 3.74, p = 0.0003). In multivariate analysis, NLR-high was the only consistent factor independently associated with both worse OS (HR 1.53, 95% CI 1.10-2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95% CI 1.08-1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI 1.16-2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high NLR is an independent marker of poor prognosis among patients with STS.

Treatment and outcomes of melanoma in Asia: Results from the National Cancer Centre Singapore.

BACKGROUND: Acral melanoma (AM) and mucosal melanoma (MM) make up more than half of melanomas in Asia but comprise only 5% of cases in Caucasians, where cutaneous melanoma (CM) predominates. AM and MM are thought to be genetically and biologically distinct from CM. We report the characteristics and outcomes of melanoma patients from the National Cancer Centre Singapore. METHODS: Case records of 210 patients treated between 2002 and 2014 were reviewed. RESULTS: Median follow-up was 2.5 years. CM, AM and MM made up of 37.6%, 33.8% and 16.2% of cases, respectively, with 6.2% each having ocular melanoma and unknown primary. Caucasians made up 16.2% of patients, accounting for 36.7% of CM but only 2.8 of AM and 2.9% of MM. Patients with MM (2.9% stage I, 14.7% stage IV) presented with higher American Joint Committee on Cancer (AJCC) stage than those with AM (16.9% stage I, 5.6% stage IV) or CM (24.1% stage I, 8.9% stage IV) (P = 0.01). Median overall survival (OS) was 5.7 years for all patients, and 1.0 year for metastatic disease. Considering stage I-III disease, multivariable Cox regression analysis demonstrated age ≥60 years and higher stage to be independent adverse prognostic factors for RFS and OS. Sentinel lymph node biopsy, undertaken for 56 stage I-III patients (25 AM, 31 CM) did not influence outcome. CONCLUSION: Our study reinforces the known unique clinicopathologic features of melanomas in Asians where AM and MM predominate. Age and stage remain the most critical prognostic factors across all subtypes.

Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.

Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13.6% (n = 9) amongst 66 patients harbour at least one predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53. The most frequently affected genes are involved in the DNA damage repair pathway, with a germline mutation prevalence of 10.6%. Our findings suggests that genetic predisposition plays a larger role than expected in our Asian cohort of sporadic sarcoma, therefore clinicians should be aware of the possibility that young sarcoma patients may be carriers of inherited mutations in cancer genes and should be considered for genetic testing, regardless of family history. The prevalence of germline mutations in DNA damage repair genes imply that therapeutic strategies exploiting the vulnerabilities resulting from impaired DNA repair may be promising areas for translational research.

Cutaneous versus non-cutaneous angiosarcoma: clinicopathologic features and treatment outcomes in 60 patients at a single Asian cancer centre.

BACKGROUND: Angiosarcoma (AS) is an uncommon soft tissue sarcoma with dismal prognosis that presents either cutaneously (C-AS) or non-cutaneously (NC-AS). We compared the clinical features and treatment outcomes between these 2 groups. METHODS: A single-centre study evaluating 60 AS patients between 2002 and 2012 was performed. RESULTS: The median age was 70 years. C-AS of the scalp or face comprised 66% of patients. C-AS patients were older than NC-AS (median age 74 vs. 56 years; p < 0.001). Proportionately more C-AS patients presented with non-metastatic disease (86 vs. 50%; p = 0.007). Amongst resected C-AS and NC-AS patients, rates of positive surgical margins (53 vs. 50%; p = 1.00) and adjuvant therapy (25 vs. 43%; p = 0.626) were not significantly different, though proportionately fewer C-AS patients relapsed (36 vs. 78%; p = 0.038). Paclitaxel was the most common agent in first line palliative systemic therapy, achieving an objective response rate of 56%. Median overall survival was 11.2 months, with no significant difference between C-AS and NC-AS (11.3 vs. 9.8 months; p = 0.895). CONCLUSION: Distinct from AS in the West, our series demonstrates a clear preponderance of scalp AS. Disparities in clinical characteristics between C-AS and NC-AS did not translate into survival differences.

Concurrent chemoradiotherapy incorporating high-dose rate brachytherapy for locally advanced cervical carcinoma: survival outcomes, patterns of failure, and prognostic factors.

BACKGROUND: This is a retrospective study evaluating the survival outcomes, patterns of failure, and prognostic factors of chemoradiotherapy incorporating high-dose rate brachytherapy in the treatment of locally advanced cervical cancer. METHODS: A review of 120 consecutive patients with Federation Internationale de Gynecologie et d'Obstetrique (FIGO) stages IB2 to IVA cervical cancer treated with concurrent cisplatin-based chemoradiotherapy between April 1999 and January 2005. Overall (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method. RESULTS: The 5-year OS and DFS rates were, respectively, 65.0% (35.0% IB2, 65.7% IIA-B, 71.0% IIIA-B, and 40.0% IVA) and 57.3% (30.0% IB2, 58.2% IIA-B, 64.0% IIIA-B, and 40.0% IVA). Most patients had squamous cell carcinoma (89.2%) and belonged to FIGO stages IIB (40.8%) and IIIB (30.8%). All but 4 patients completed the planned radiotherapy regimen. There were 48 documented recurrences, of which 13 were locoregional only, 26 were distant only, and 9 were both sites. Five patients (4.2%) experienced late grade 3 to 4 gastrointestinal toxicity. On multivariate analysis, a preradiotherapy hemoglobin level of less than 10 g/dL and tumor size of 4 cm or greater or bulky on computed tomography were independently significant variables for OS, whereas a nadir hemoglobin level of less than 10 g/dL and presence of radiologically enlarged pelvic or paraaortic lymph nodes were independently significant variables for DFS. CONCLUSIONS: We conclude that this regimen is efficacious and feasible, but the safety profile about concurrent administration of high-dose rate brachytherapy and chemotherapy should be studied further. Finally, for cervical cancer patients selected for nonsurgical treatment, radiological assessment of tumor size and lymph node status can provide valuable prognostic information over and above FIGO staging alone.

Hyalinizing clear cell carcinoma of the hard palate.

Hyalinizing clear cell carcinoma (HCCC) of the salivary gland is new disease only recognized in recent years. It is rare and the standard treatment is still under investigation. This is a report of a 42-year-old female with HCCC who presented with a painless submucosal hard palatal mass of three years duration. Wide excision of the tumour and the underlying palatal and maxillary bones was performed. Pathological examination revealed typical clear cells arranged in anastomosing trabeculae, cords, nests, or solid sheets with a hyalinizing stroma. These clear cells were positive for the periodic acid-Schiff (PAS) reaction but were negative for the mucin stain. Immunohistochemically, these neoplastic cells were positive for cytokeratin, but negative for actin. No recurrence nor distant metastasis was found during the eight-month follow-up period.