Mohamed Shama

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic with high prevalence in Western countries. Genome-wide association studies had reported that a variation in the patatin-like phospholipase domain containing 3 (PNPLA3) gene is associated with high susceptibility to NAFLD. However, the relationship between this variation and hepatocellular carcinoma (HCC) has not been well established. We investigated the impact of PNPLA3 genetic variation (rs738409: C>G) on HCC risk and prognosis in the United States by conducting a case-control study that included 257 newly diagnosed and pathologically confirmed Caucasian patients with HCC (cases) and 494 healthy controls. Multivariate logistics and Cox regression models were used to control for the confounding effects of HCC risk and prognostic factors. We observed higher risk of HCC for subjects with a homozygous GG genotype than for those with CC or CG genotypes, the adjusted odds ratio (OR) was 3.21 (95% confidence interval [CI], 1.68-6.41). We observed risk modification among individuals with diabetes mellitus (OR = 19.11; 95% CI, 5.13-71.20). The PNPLA3 GG genotype was significantly associated with underlying cirrhosis in HCC patients (OR = 2.48; 95% CI, 1.05-5.87). Moreover, GG allele represents an independent risk factor for death. The adjusted hazard ratio of the GG genotype was 2.11 (95% CI, 1.26-3.52) compared with CC and CG genotypes. PNPLA3 genetic variation (rs738409: C>G) may determine individual susceptibility to HCC development and poor prognosis. Further experimental investigations are necessary for thorough assessment of the hepatocarcinogenic role of PNPLA3.

OBJECTIVE: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of HCC. We report an analysis of the clinicopathologic features, treatment outcomes, and prognostic indicators of 94 cases.

METHODS: We retrospectively collected clinicopathologic and treatment outcome data from 94 FLHCC patients (48 males and 46 females). Median overall survival (OS) and recurrence-free survival (RFS) were calculated using Kaplan-Meier curves, and survival rates were compared by the log-rank test. The Cox proportional hazard model was used for univariate and multivariate estimation of hazard risk ratios and 95% confidence intervals (CI) for factors that correlated with survival and disease recurrence after resection.

RESULTS: Median age was 23 years (14-75); median OS was 57.2 months (95% CI, 36.4-77.9), and median RFS was 13.9 months (95% CI, 8.8-18.9). White race, female gender, early tumor stage, and tumor resection including metastasectomy were positively associated with longer OS, while female gender was the only significant positive predictor of longer RFS. Finally, the 5-fluorouracil-interferon combination was the most frequently used systemic therapy.

CONCLUSIONS: Our analyses indicate that surgical approaches including metastasectomy as the first-line treatment in FLHCC correlated with better outcome. Multimodality approaches, including neoadjuvant and adjuvant therapies, prolonged patient survival.

Diabetes and perineural invasion are frequently observed in pancreatic cancer. In this study, we tested possible relations between diabetes and perineural invasion in patients with resected pancreatic cancer. We conducted a retrospective study in 544 cases of resected pancreatic adenocarcinoma seen at the University of Texas MD Anderson Cancer Center during 1996-2011. Information on tumor characteristics, diabetes history, and survival time was collected by personal interview and medical record review. Patients with diabetes before or at the time of the pancreatic cancer diagnosis were considered diabetes only. Pearson χ(2) test was used to compare categorical variables in diabetic and nondiabetic groups. Kaplan-Meier plot, log-rank test, and Cox proportional regression models were applied in survival analysis. The prevalence of diabetes and perineural invasion was 26.5% and 86.9%, respectively, in this study population. Patients with diabetes had a significantly higher prevalence of perineural invasion (92.4%) than those without diabetes (85%) (P = 0.025, χ(2) test). Diabetes was not associated with other pathological characteristics of the tumor, such as tumor size, lymphovascular invasion, tumor grade, lymph node metastasis, and resection margin status. Diabetic patients had a significantly lower frequency of abdominal pain (P = 0.01), but a slightly higher frequency of weight loss (P = 0.078) as early symptoms of their cancer. Both diabetes and perineural invasion were related to worse survival and increased risk of death after adjusting for tumor grade and margin and node status (P = 0.036 and 0.019, respectively). The observed associations of diabetes and perineural invasion as well as reduced frequency of pain as early symptom of pancreatic cancer support the hypothesis that diabetes may contribute to pancreatic progression via the mechanism of nerve damage.

Purpose: Isolated neck recurrence occurs in about 5–7% of patients after radical treatment of head and neck cancer. Limited information is available on the clinical outcome of such patients due to lack of randomized clinical trials. In addition, controversy still exists on the ideal technique of neck dissection required. This retrospective study is discussing the different options of salvage neck dissections for patients with isolated neck recurrence and its effectiveness on controlling disease progression.

Methods: At the National Cancer Institute, University of Cairo, Egypt, we identified 27 patients underwent salvage neck dissection for neck recurrence diagnosed between 2002 and 2011. We reviewed their medical records and retrieved their treatment history, pathologic and clinical characteristics, type of neck dissection, technique of reconstruction and outcome were analyzed.

Results: A total of 27 patients underwent salvage neck dissection for regional neck failure after their primary treatment. The primary treatment was surgery in 4 cases, combined with other modality in 15 cases, radiotherapy in 2 cases and combined with chemotherapy in 6 cases. The median time elapsed after primary treatment to diagnosis of cervical nodal recurrence was13 months. Nodal recurrences occurred on the ipsilateral (22), contralateral (4), and bilateral sides (3). The primary tumor sites included oral cavity (6), oropharynx (3), larynx and hypopharynx (6) and the rest of cases were in thyroid, salivary gland, eye, nasopharynx and one case of unknown origin. Types of neck dissection included RND (9), extended RND (9), MRND (7) and SND (4). Seventeen cases were staged N2 at the time of recurrence, 3 cases at N1 and 7 cases at N3. Five cases needed reconstructive surgery in the form of pectoralis myocutaneous flap or deltopectoral flap. One patient died postoperatively from pneumonia. Complications included wound infection (7), chylous fistula (2) and seroma in one case. Post operative adjuvant treatment was chemo radiation in 9, radiation in 4, radioactive iodine in 3, and chemotherapy in one patient. Ten patients developed recurrences after surgery. The recurrence was loco regional in 5, regional in 2, local in 2 cases and one patient developed lung metastasis. Disease free survival ranged from 4 to 18 months, seventeen were alive and free of disease at the last time of follow up, while 4 patients were alive with regional recurrence. Loco regional recurrence was the main cause of death accounting for 66% of cases.

Conclusion: Patients with resectable isolated neck recurrence following comprehensive neck management should be offered salvage neck dissection as it offers the best chance of cure. However, every effort should be made to make sure that that the primary site is controlled.