Metastasectomy in cutaneous melanoma.

Metastasectomy remains the only treatment in malignant melanoma to offer complete pathologic response within a few days of in-hospital stay. It has been historically associated with the highest survival rates in the literature reported for patients of this stage. However, only a minority of patients are amenable to curative resection of distant metastatic disease. This patient group exhibit slow growing oligometastases as indicated by: a. Long disease free interval after treatment of their primary tumours and b. An exhaustive preoperative work up with the use of PET/CT and MRI scans. Only complete resection of all metastases is associated with long term survival and debulking should not be attempted. Metastasectomy has also been shown to offer significant palliation in cases of gastrointestinal bleeding or obstruction. The timing and the sequencing of surgery in the modern multimodal targeted treatment of melanoma is still unclear and warrants further investigation.

Acute appendicitis and carcinoid tumor in Meckel's diverticulum. Three pathologies in one: a case report.

Incidental carcinoid tumor of the Meckel's diverticulum is an uncommon event. Herein, a case of a carcinoid tumor in Meckel's diverticulum that was incidentally found in a patient with acute appendicitis is presented. A 42-year-old Caucasian man presented with acute abdomen and clinical signs of acute appendicitis. A typical appendectomy was performed during which further abdominal exploration revealed a Meckel's diverticulum 60 cm proximal to the ileocecal valve, with an irregular and somewhat indurated serosal region on one side. A stapled diverticulectomy was performed. Pathology revealed an incidental carcinoid tumor measuring 1 cm within the Meckel's diverticulum. CT scan of the abdomen and 24-h urine 5-hydroxyindoleacetic acid results were normal. The patient had an uneventful recovery and was discharged at the 5th postoperative day. He is alive and without evidence of disease 23 months after the operation. Coexistence of acute appendicitis along with an incidental Meckel's diverticulum raises controversies in their surgical management. We discuss the issues in managing patients with two or more of these coexistent pathologies.

Determinants of survival in patients with brain metastases from cutaneous melanoma.

BACKGROUND: This retrospective study aimed to identify prognostic factors in patients with brain metastases from cutaneous melanoma. METHODS: In all, 265 patients under regular screening according to valid national surveillance guidelines were included in the study. Kaplan-Meier analyses were performed to estimate and to compare overall survival. Cox modeling was used to identify independent determinants of the overall survival, which were used in explorative classification and regression tree analysis to define meaningful prognostic groups. RESULTS: In total, 55.5% of our patients presented with two or less brain metastases, 82.6% had concurrent extracranial metastasis and 64% were asymptomatic and diagnosed during surveillance scans. In all, 36.7% were candidates for local treatment (neurosurgery or stereotactic radiosurgery (SRS)). The median overall survival of the entire collective was 5.0 months (95% confidence interval: 4.3-5.7). Favourable independent prognostic factors were: normal pre-treatment level of serum lactate dehydrogenase (P<0.001), administered therapy (neurosurgery or SRS vs other, P=0.002), number of brain metastases (single vs multiple, P=0.032) and presence of bone metastasis (false vs true, P=0.044). Three prognostic groups with significantly different overall survival were identified. Candidates for local treatment (group I) had the longer median survival (9 months). Remaining patients could be further classified in two groups on the basis of serum lactate dehydrogenase. CONCLUSION: Applied treatment and serum lactate dehydrogenase levels were independent predictors of survival of patients with brain metastases from cutaneous melanoma. Patients receiving local therapy have overall survival comparable with general stage IV melanoma patients.

Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment.

BACKGROUND: In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression. OBJECTIVES: In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma. METHODS: Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. RESULTS: Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin. CONCLUSIONS: Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations.

Comparative analysis of incidence and clinical features of cutaneous malignant melanoma in Crete (Greece) and southern Germany (central Baden-Württemberg).

BACKGROUND: Comparative analysis of the incidence rates and epidemiological features of cutaneous malignant melanoma (CMM) between different ethnic groups exposed to varying environmental factors is critical for consideration of the causes of CMM but can also be utilized in a public health approach to control of the disease. OBJECTIVES: To compare incidence rates and clinical features of CMM in a Greek and a central European population (central Baden-Württemberg, Germany). METHODS: Incident cases of CMM were traced in all hospitals of the island of Crete for the period 1999-2002. Age-standardized incidence rates per 100 000 inhabitants per year for the European Standard Population were calculated based on the Cretan population statistics. A comparison was performed between the Cretan findings and those of southern Germany as registered by the hospital-based Central Malignant Melanoma Registry, which likewise documents more clinical features than normally recorded by population-based cancer registries. RESULTS: Mean incidence rates in Crete for 1999-2002 were 4.01 per 100 000 inhabitants per year for males and 4.05 for females as compared with 10.6 for males and 11.1 for females in southern Germany. There were striking differences in the clinical characteristics of CMMs, with significantly higher tumour thickness in Crete (median 1.4 mm vs. 0.7 mm in southern Germany). Correspondingly, significantly more nodular melanomas were observed in Crete (29%) as compared with southern Germany (11%). CONCLUSIONS: Incidence of CMM in Crete, with about four cases per 100 000 inhabitants per year, is clearly higher than previously estimated, and there is an urgent necessity for earlier recognition of CMM in Crete. However, the incidence of CMM in southern Germany is much higher.

Major hepatectomy and right hemicolectomy at the time of primary cytoreductive surgery for advanced ovarian cancer: report of a case.

Major liver involvement at the time of diagnosis is a rare event in patients with ovarian cancer, and the issue of major hepatectomy at the time of primary cytoreductive surgery is controversial. A 61-year-old woman was admitted to our hospital with nonspecific abdominal pain of 2-month duration and weight loss of 5 kg during the last semester. A computed tomography scan demonstrated bilateral ovarian masses, extending to the right iliac fossa, pressing the cecum-ascending colon. In the liver parenchyma, three cystic lesions were found of about 6-cm maximum diameter each, along with pelvic lymphadenopathy. There was no ascites. The diagnosis of advanced ovarian cancer was clinically suspected; the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, right hemicolectomy, omentectomy, left lobectomy, deroofing, and draining of the cystic formation of the right liver lobe along with systematic pelvic and para-aortic lymphadenectomy. Systemic chemotherapy (six cycles of paclitaxel/carboplatin) was subsequently administered, and after 15 months of follow-up period, the patient is still in first remission and alive. Ovarian cancer with concomitant extensive right colon infiltration and hematogenous liver metastases can be successfully managed with aggressive surgical resection and postoperative chemotherapy in carefully selected patients.