Sahin Lacin

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

BACKGROUND & AIMS: Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. The authors investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. METHODS: We performed a case–control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls) from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. RESULTS: The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% confidence interval [CI], 0.32–0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5 ± 0.9 years) vs nonusers (mean 59.2 ± 1.1 years; P = .001) and the reduced risk of HCC among long‐term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20–0.63). Users of estrogen also had a reduced risk for hepatitis‐associated HCC: AOR for users, 4.37 (95% CI, 1.67–11.44) vs AOR for nonusers, 17.60 (95% CI, 3.88–79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40–0.77; P = .01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7–41.3 months) and 24.1 months for nonusers (95% CI, 19.02–29.30 months; P = .008). CONCLUSION: In a case–control study of women with HCC vs female control subjects at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

Metastatic medullary thyroid cancer: a dramatic response to a systemic chemotherapy (temozolomide and capecitabine) regimen.

A 40-year-old male patient presented with increasing serum levels of calcitonin and CEA. He underwent potential curative surgery for medullary thyroid carcinoma, 3 years ago and then 7 months later he had metastasectomy and cervical lymph node dissection for recurrent disease. On admission he had multiple metastatic skin nodules on the chest wall and positron emission tomography–computed tomography revealed multiple visceral metastases as well. The patient had not received any systemic treatment up to that time; therefore, we considered systemic treatment with the new tyrosine kinase inhibitors (vandetanib, cabozantinib, etc). However, since these drugs are only available after cytotoxic chemotherapy, we started temozolomide and capecitabine chemotherapy. After two courses of the treatment all skin nodules disappeared and CEA and calcitonin levels normalized, radiological imaging showed a good partial response.

Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway?

The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC. Although many factors are known to play important roles in the progression of inflammation in NASH patients, the role of androgen and AR in the progression of NASH to HCC has been understudied. This review summarizes the evidence for a potential role of androgen and the AR pathway in the development of NASH-related HCC and in the treatment of HCC. It has been proposed that AR plays a role in the progression of HCC: inhibitory roles in early stages of hepatocarcinogenesis and tumor-promoting roles in advanced stages. AR can be activated by several pathways, even in the absence of androgen. While AR has been explored as a potential therapeutic target in HCC, several clinical trials have failed to demonstrate a clinical benefit of antiandrogen drugs in HCC. This review discusses the potential reason for these observations and discuss the potential future trials design in this important setting.

Real world survival data of a rare malignancy: Anal cancer results in HIV negative patients from Turkey

BACKGROUND/AIMS An organ preservation approach using chemoradiotherapy has been established for anal cancer. This retrospective cohort study aimed to define the clinico-demographic characteristics and outcomes of cases of human immunodeficiency virus (HIV)-negative anal carcinoma during a period of 20 years in a single comprehensive cancer institute. MATERIALS AND METHODS This was a single-center retrospective cohort study of patients who were treated between January 1995 and January 2015. The primary outcome measures that were investigated included overall survival (OS), progression-free survival (PFS), colostomy rates, and colostomy-free survival (CFS). RESULTS A total of 28 patients who were principally treated with standard 5-fluorouracil + mitomycin combination chemoradiotherapy were eligible for analysis. The 3- and 5-year PFS rates were 92.4% and 63%, respectively. The lower T stage was found to be associated with a prolonged PFS (p=0.001). The 3- and 5-year CFS rates were 84.3% and 74.9%, respectively. A longer CFS was observed with lower T stages (p=0.05). At the last follow-up, 75% of the patients with anal cancer were alive, and 71.4% of the patients were disease free. The median OS was not reached with a median follow-up of 54 months (range, 6-115 months). The 3- and 5-year OS rates were 82% and 71.1%, respectively. No late toxicity was observed during the follow-up period. DISCUSSION The short- and long-term prognoses of HIV-negative patients with anal squamous cell carcinoma were good, and low-grade toxicity was rare, thereby demonstrating that these patients can be successfully treated in a real-life setting with favorable outcomes.

A case of acanthosis nigricans as a paraneoplastic syndrome with squamous cell lung cancer

A 55-year-old man presented with oral mucosal ulcers, blackening of both hands, and hyperpigmentation on axillary, anal, and inguinal regions for the last 3 months, which were all progressive. The patient was referred to the oncology department with the diagnosis of acanthosis nigricans for investigation of an underlying malignancy. He was a smoker. A computed tomography scan of thorax revealed enlarged mediastinal lymphadenopathies and a lesion on the left upper lobe. Fine-needle aspiration biopsy of the mediastinal lesion was consistent with squamous cell carcinoma, and biopsies of the skin and oral mucosal lesion also further confirmed the diagnosis of acanthosis nigricans. After docetaxel and cisplatin chemotherapy, a significant improvement in his skin and mucosal lesions was observed with almost complete resolution of the pulmonary lesion and the mediastinal lymph nodes.