Surgical resection for gastrointestinal metastatic melanoma

AIM: Metastases of melanoma are frequent. On the gastro-intestinal tract, commonest localizations are small bowel, stomach and colon. Surgical treatment of digestive metastases from melanoma is not well known and its value is still debated. PATIENTS AND METHODS: Medical records of 10 patients (six female and four male) operated for metastatic melanoma to gastro-intestinal tract were reviewed to determine results of surgery. RESULTS: Gastro-intestinal metastases were symptomatic in eight patients (abdominal pain in three, bowel obstruction in three, abdominal mass and obstructive jaundice in one each). Two patients had anemia. Diagnosis has been suggested by imaging in seven patients and endoscopy in three. All patients were operated on by laparotomy for resection of metastases located on small bowel in four patients, gallbladder in two, stomach in two and colon in two. Complete resection suppressed symptoms in nine cases. In one patient, resection was incomplete but provided satisfying symptomatic relief. One patient died at day 3; in other patients, median survival was 18 months (range: 3-120). CONCLUSION: In a patient with previous history of melanoma, digestive symptoms indicate morphological explorations due to suspicion of metastases to gastro-intestinal tract. Surgical treatment of these metastases is usually palliative but, in some cases, allows long-term survival.     

Isolated pelvic metastasis of thyroid cancer

Thyroid cancer rarely metastasizes to the pelvis. We report a case where the metastasis was found two years before the thyroid cancer. Treatment included initial surgery with resection of the metastatic tumor and reconstruction of the acetabulum with bone cement, and secondly total thyroidectomy, node dissection and I131. Surgical treatment of locoregional recurrence had no influence on the clinical course leading to the patient's death. Early diagnosis of unique metastasis of a thyroid cancer is important in terms of prognosis and quality of life. This case is exceptional due to the unique bone metastasis and treatment options for acetabular metastases. Therapeutic options should be adapted according to algorithms reported in the literature.     

The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis

The proto-oncogene RAS, coding for a 21 kDa protein (p21), is mutated in 20% of lung cancer. However, the literature remains controversial on its prognostic significance for survival in lung cancer. We performed a systematic review of the literature with meta-analysis to assess its possible prognostic value on survival. Published studies on lung cancer assessing prognostic value of RAS mutation or p21 overexpression on survival were identified by an electronic search. After a methodological assessment, we estimated individual hazard ratios (HR) estimating RAS protein alteration or RAS mutation effect on survival and combined them using meta-analytic methods. In total, 53 studies were found eligible, with 10 concerning the same cohorts of patients. Among the 43 remaining studies, the revelation method was immunohistochemistry (IHC) in nine and polymerase chain reaction (PCR) in 34. Results in terms of survival were significantly pejorative, significantly favourable, not significant and not conclusive in 9, 1, 31, 2, respectively. In total, 29 studies were evaluable for meta-analysis but we aggregated only the 28 dealing with non-small-cell lung cancer (NSCLC) and not the only one dealing with small-cell-lung cancer (SCLC). The quality scores were not statistically significantly different between studies with or without significant results in terms of survival, allowing us to perform a quantitative aggregation. The combined HR was 1.35 (95% CI: 1.16-1.56), showing a worse survival for NSCLC with KRAS2 mutations or p21 overexpression and, particularly, in adenocarcinomas (ADC) (HR 1.59; 95% CI 1.26-2.02) and in studies using PCR (HR 1.40; 95% CI 1.18-1.65) but not in studies using IHC (HR 1.08; 95% CI 0.86-1.34). RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR.     

Thyrotropin stimulates the generation of inositol 1,4,5-trisphosphate in human thyroid cells

CONTEXT: Dual activation by TSH of the phospholipase C and cAMP cascades has been reported in human thyroid cells. In contrast, Singh et al. reported convincing data in FRTL-5 thyrocytes arguing against such an effect in this model. Their data in FRTL-5 cells indicated no increase in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in response to TSH. Therefore, the authors questioned results previously obtained on human cells by cruder methodology. OBJECTIVE: We investigated the formation of inositol phosphates by HPLC techniques in human thyroid slices to separate the inositol phosphate isomers. RESULTS: Ins(1,4,5)P3, inositol 1,3,4-trisphosphate, and inositol 1,3,4,5-tetrakisphosphate were increased after TSH stimulation. The effect of TSH in human thyroid cells was reproduced by recombinant TSH and prevented by antibodies blocking the TSH receptor. Thyroid-stimulating antibodies at concentrations eliciting a cAMP response equivalent to TSH failed to stimulate inositol phosphate generation. CONCLUSIONS: TSH, but not thyroid-stimulating antibodies, activates both cAMP and the phospholipase C cascade in human thyroid as now demonstrated by an increase in Ins(1,4,5)P3 and its inositol phosphate metabolites. Therefore, this effect cannot be extrapolated to the FRTL-5 cell line. The apparent discrepancy may be due to a difference between species (human vs. rat) or to the loss of the fresh tissue properties in a cell line. The dual effect of TSH in human cells, through cAMP on secretion of thyroid hormones and through the diacylglycerol, Ins(1,4,5)P3 Ca2+ pathway on thyroid hormone synthesis, implies the possible separation of these effects in thyroid disease.     

Severe Pericardial Effusion in Patients with Concurrent Malignancy: A Retrospective Analysis of Prognostic Factors Influencing Survival

Background  The treatment of massive and/or symptomatic pericardial effusion in patients with cancer remains a subject of discussion. Medical and surgical management have been proposed. In the present study, we aimed to determine the prognostic factors influencing survival of cancer patients admitted in intensive care unit (ICU) with severe pericardial effusion to better select the treatment strategies. Methods  All patients with cancer and massive or symptomatic pericardial effusion were retrospectively analyzed. Patients were followed up until death or last time known to be alive. Univariate and multivariate analyses were performed to determine prognostic factors influencing survival. Results  Between January 1999 and August 2004, 55 eligible patients were admitted in the ICU for pericardial effusion, including 30 with lung cancer, 9 with breast cancer, 5 with hematological malignancies, and 11 patients with other types of solid tumors. Forty-three patients underwent a surgical drainage. No operative death occurred. Four patients presented with an asymptomatic recurrence. Median survival of the entire group was 112 days. Survival rates for 1, 2, and 3 years were 27%, 17%, and 12%, respectively. In univariate analysis, the following variables were significantly associated with a reduced survival: histopathological diagnosis of malignant pericardial effusion, age (>60 years), the volume of pericardial effusion (<550 cc), and the cancer status (complete or partial response). After multivariate analysis, the cancer status was the only statistically significant clinical factor influencing overall survival (P = .005). Conclusion  In this series of patients presenting with severe pericardial effusion, the control of the underlying neoplasm was the only significant factor influencing survival and could be helpful in making decision to the optimal (invasive) treatment that should balance treatment efficacy with life expectancy.     

Ki-67 expression and patients survival in lung cancer: systematic review of the literature with meta-analysis

Among new biological markers that could become useful prognostic factors for lung carcinoma, Ki-67 is a nuclear protein involved in cell proliferation regulation. Some studies have suggested an association between Ki-67 and poor survival in lung cancer patients. In order to clarify this point, we have performed a systematic review of the literature, using the methodology already described by our Group, the European Lung Cancer Working Party. In total, 37 studies, including 3983 patients, were found to be eligible. In total, 49% of the patients were considered as having a tumour positive for the expression of Ki-67 according to the authors cutoff. In all, 29 of the studies dealt with non-small-cell lung carcinoma (NSCLC), one with small-cell carcinoma (SCLC), two with carcinoid tumours and five with any histology. In terms of survival results, Ki-67 was a bad prognosis factor for survival in 15 studies while it was not in 22. As there was no statistical difference in quality scores between the significant and nonsignificant studies evaluable for the meta-analysis, we were allowed to aggregate the survival results. The combined hazard ratio for NSCLC, calculated using a random-effects model was 1.56 (95% CI: 1.30-1.87), showing a worse survival when Ki-67 expression is increased. In conclusion, our meta-analysis shows that the expression of Ki-67 is a factor of poor prognosis for survival in NSCLC.