SEOM clinical guideline for the management of malignant melanoma (2017).

All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy. Up to 10 years follow up is reasonable for melanoma patients with dermatologic examinations and physical exams.

SEOM guidelines for the management of Malignant Melanoma 2015.

All melanoma patients must be confirmed histologically and resected according to Breslow. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon must be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 therapy. Up to 10 years follow up is recommended for melanoma patients with dermatologic examinations and physical exams.

Immunotherapy of distant metastatic disease.

Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm. The ongoing effort to develop melanoma vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) or CD137 are discussed. Recent advances of intratumour gene transfer technologies and adoptive immunotherapy, which represents a promising although technically challenging direction, are also discussed.

Clinical trials with anticoagulant and antiplatelet therapies.

Clinical trials of drugs that influence coagulation and fibrinolysis pathways have been undertaken in patients with malignancy because these pathways are capable of influencing malignant progression. The validity of this concept was originally confirmed in experimental animal models of malignancy. Earlier pilot studies in human disease have been succeeded by definitive prospective randomized clinical trials that have revealed heterogeneity of responsiveness to anticoagulant and fibrinolytic agents that may be attributable to differences in mechanisms of interaction of the tumor cells of various types of malignancy with these pathways in vivo. In certain tumor types studied thus far, increased tumor response rates and prolongation of survival have been observed that suggest the possibility that substantial benefit may be realized from this treatment approach in patients with malignancy. In addition, the availability of newer and potentially more effective therapeutic agents holds promise for even greater gains in previously tested tumor types. The ability to design treatment regimens that correspond to defined mechanisms that pertain to specific tumor types should permit future studies to be designed rationally. Current data suggest that anticoagulant and fibrinolytic agents might reasonably be tested in tumor types characterized by the existence of a tumor cell-associated coagulation pathway with thrombin generation and conversion of fibrinogen to fibrin (such as small cell carcinoma of the lung). By contrast, protease inhibitors might reasonably be tested in tumor types characterized by expression of tumor cell plasminogen activators. Expansion of current views on the possible role of antithrombic drugs in cancer therapy is justified. For example, antithrombotic drugs classified as non-steroidal anti-inflammatory agents may inhibit carcinogenesis while polyanionic drugs with anticoagulant properties, such as suramin and heparin, may inhibit growth factor interactions with cells. Intriguing new opportunities clearly exist for interactions between clinical and basic investigators that may provide both novel biologic insights and improved patient care.

Intraoperative radiotherapy for recurrent and/or residual colorectal cancer.

Intraoperative radiotherapy (IORT) is an attractive boosting modality in the combined treatment of recurrent and/or residual colorectal cancer. Twenty seven patients treated with IORT are analysed. Residual disease following resection of the primary tumor was treated in 11 cases (group I). Localized recurrent disease without previous radiotherapy was treated in 11 cases (group II). IORT was used in five additional patients with local recurrences in previously irradiated areas (group III). The treatment program consisted of maximal tumor resection, IORT (10-30 Gy) to the area of residual disease and external beam radiotherapy (46-50 Gy). The median follow-up time for the entire series of patients is 11 months. Local tumor control rates are 90% in group I, 63% in group II and 60% in group III. Toxicity and complications related to IORT observed in this initial experience have been pelvic pain (29%) and lower extremity neuropathy (3%). These early clinical results suggest that the IORT combined with surgery and external beam radiotherapy is feasible in primary and recurrent disease. Local control rates obtained in patients not suitable for curative surgery are encouraging.

Oat cell carcinoma of the larynx. A study of six new cases.

Clinicopathological details of six oat cell carcinomas of the larynx are presented. Five patients were male and heavy smokers. Only two patients had lymph node metastases at diagnosis. Only one tumour was unequivocally Grimelius stain positive. Immunostaining for neurone-specific enolase was negative in all cases. Neurosecretory granules were found in two tumours studied electron microscopically. Three tumours had areas of squamous carcinoma. Laryngectomy was the treatment of choice. Two patients are alive without evidence of disease 21 and 25 months after diagnosis.

Undifferentiated epithelial-rich invasive malignant thymoma: complete response to cisplatin, vinblastine, and bleomycin therapy.

Two cases of complete remission plus one almost complete and another partial response of undifferentiated, invasive epithelial malignant thymoma using the combination of cisplatin, vinblastine, and bleomycin (PVB), are reported in four patients treated with this combination. Radiotherapy was instituted after completing the fourth course of chemotherapy in three patients. One patient died from intercurrent infection after the fourth cycle of combination chemotherapy. Three patients remain free of disease at the end of the treatment program. PVB appears to be highly active in this disease and deserves more extensive evaluation in multicenter clinical trials.

Combination chemotherapy of cisplatin and 5-FU in advanced colorectal carcinoma.

Thirty-two patients with advanced colorectal carcinoma were treated with cisplatin (100 mg/m2) by infusion over 24 hours on Day 1 and 5-FU (1000 mg/m2/day) by infusion over 24 hours on Days 2-6 every 28 days. Ten of the 32 patients had received prior chemotherapy consisting of either 5-FU alone or 5-FU combination regimens. Objective response was observed in 13 patients (two complete and 11 partial responses). Another 11 patients had stabilization of disease. The overall median survival time in this study was 9.53 months. Toxicity was generally mild and tolerable. The response rate found in this study indicated that continuous infusion of cisplatin-5-FU administered at this dose and schedule was moderately active in advanced colorectal carcinoma.

Functional and ultrastructural studies of granulocyte adherence in the newborn.

Polymorphonuclear leukocyte (PMN) adherence to nylon was studied in the umbilical cord blood of 33 full-term, healthy newborns (NBs) during delivery. The results were compared to the adherence of PMN of peripheral blood in 50 healthy adult blood bank donors. PMN adherence in the NBs (56.64 +/- 3.24) was found to be significantly higher (p less than or equal to 0.01) than in the adults (47.03 +/- 2.01). PMN adherence, either in adults or NBs, is not related to leukocytes, platelets or hematocrit values. It was found to be related only to the percentage of total leukocyte adherence. Also using scanning electron microscopy (SEM), the ultrastructure of the adherence process was analyzed. In these studies we observed a higher tendency to adopt fusiform disposition in the PMN of the adult population. These results suggest that NB PMNs are hyperadherent and that they show a cellular rigidity and a resistance to deformation that could be responsible for the chemotactic alterations previously described in neonates.