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Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a new therapeutic approach with significant survival benefit for patients with several cancer types. However, their use can be associated with unique immune-related adverse effects as a consequence of impaired self-tolerance due to loss of T-cell inhibition via a nonselective activation of the immune system. Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer patients. We present a 62-year-old Caucasian male with recurrent lung adenocarcinoma and currently under third-line therapy with nivolumab, who was admitted in our hospital with abdominal distension. Radiologic findings were consistent with small bowel ileus. After four days of conservative treatment, the patient underwent exploratory laparotomy where no cause of ileus was discovered. Postoperative the ileus persisted and considering that an adverse effect of the immune checkpoint inhibition therapy occurred, the patient received high-dose prednisone resulting in gradual improvement of symptoms. Immune checkpoint inhibitors may induce adverse effects to unaffected organ systems and tissues including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system. The mainstay treatment consists of immunosuppression with corticosteroids in the majority of cases. As the clinical use of immune checkpoint inhibitors is expanding rapidly, there is an emergence of unique immune-related adverse effects in a growing patient population. Gaining early awareness is essential in these patients in order to ensure prompt diagnosis and management. © The Author(s) 2017.

In the recent Greek ages the most devastating epidemics were plague, smallpox, leprosy and cholera. In 1816 plague struck the Ionian and Aegean Islands, mainland Greece, Constantinople and Smyrna. The Venetians ruling the Ionian Islands effectively combated plague in contrast to the Ottomans ruling all other regions. In 1922, plague appeared in Patras refugees who were expelled by the Turks from Smyrna and Asia Minor. Inoculation against smallpox was first performed in Thessaly by the Greek women, and the Greek doctors Emmanouel Timonis (1713, Oxford) and Jakovos Pylarinos (1715, Venice) made relevant scientific publications. The first leper colony opened in Chios Island. In Crete, Spinalonga was transformed into a leper island, which following the Independence War against Turkish occupation and the unification of Crete with Greece in 1913, was classified as an International Leper Hospital. Cholera struck Greece in 1853-1854 brought by the French troops during the Crimean War, and again during the Balkan Wars (1912-13) when the Bulgarian troops brought cholera to northern Greece. Due to successive wars, medical assistance was not always available, so desperate people turned many times to religion through processions in honor of local saints, for their salvation in epidemics. © 2017, Croatian Scientific Society for the History of Health. All rights reserved.

Aim: In patients with progressive, metastatic neuroendocrine tumors (NET), intra-arterial radionuclide infusions with high activities of 111In-[DTPA]-octreotide and more recently with non-carrier added (nca) 177Lu-[DOTA, Tyr3]-octreotate have been performed with encouraging results. However, the affinity profiles (IC50) of these radiopeptides for human sst2 receptors are markedly different (111In-[DTPA]-octreotide, 22 ± 3.6 nM and nca 177Lu-[DOTA,Tyr3]-octreotate, 1.5 ± 4.0 nM). The total administered activity is determined by organ dose limits (kidneys and bone marrow), and our aim therefore was to compare and evaluate the therapeutic efficacy of both radiopeptides in metastatic NETs. Methods: Thirty patients with gastroenteropancreatic (GEP) somatostatinpositive NETs with liver metastases confirmed on biopsy and 111In-pentetreotide scan were included. They were treated with 111In-[DTPA]-octreotide (n = 17) or nca 177Lu-[DOTA,Tyr3]-octreotate (n = 13). Blood samples were collected 2, 4, 8, and 24 hours postadministration to calculate residence time in blood and in red marrow. The maximum percentage uptake in organs and tumors was estimated by region of interest analysis, and tumor dosimetry calculations were performed using OLINDA/EXM/1.0 software. Results: nca177Lu-[DOTA,Tyr3]-octreotate blood radioactivity, expressed as a percentage of the injected dose, was significantly lower than 111In-[DTPA]-octreotide (P < 0.05), as clearly depicted from the time-activity curves; the background-corrected tumor uptake was significantly higher than 111In-[DTPA]-octreotide but without any significant difference in other organs (spleen, kidneys, and liver). Conclusions: Using 177Lu-[DOTA,Tyr3]-octreotate, a 3-fold higher absorbed dose to tumor tissue was achieved compared with 111In-[DTPA] octreotide. Residence time of nca 177Lu-[DOTA,Tyr3]-octreotate results in a significantly higher absorbed dose to bone marrow compared with 111In-[DTPA]-octreotide. However, a drawback of 111In-[DTPA]-octreotide therapy is that the number of administrations would need to be almost doubled to achieve an equal therapeutic outcome as compared with 177Lu-[DOTA, Tyr3]-octreotate. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Current Perspectives in Metastatic Renal Cell Carcinoma Treatment: The Role of Targeted Therapies

Introduction. Chromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma. Case presentation. We present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. Conclusions: Up to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma. © 2012 Michalaki and Gennatas; licensee BioMed Central Ltd.

Background: Hepatocellular carcinoma is the most common primary tumor of the liver. Disease dissemination occurs through hematogenous routes and frequently involves the lungs, bone, adrenal glands, and pancreas. The patterns of the extrahepatic manifestations are diverse. Soft tissue metastasis is extremely rare and mandates systematic pathological analysis, which may include the use of specific immunohistochemical staining. We report metastasis from a hepatocellular carcinoma, as a discrete subcutaneous mass to the right humerus muscle. Materials and Methods: We detail the approach to diagnosis and management of an unusual case of a patient with hepatocellular carcinoma, in whom we found a metastatic lesion as a subcutaneous mass to the right humerus muscle nine years after right hepatectomy. Conclusion: This condition poses differential diagnostic problems in the settings of clinical and pathological investigations. Metastasis of hepatocellular carcinoma should be included in the differential diagnosis of rapidly growing lesions.

Background: Renal cell carcinoma (RCC) represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs). Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation.Case presentation: We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment.Conclusion: In the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance. © 2010 Michalaki et al; licensee BioMed Central Ltd.

The addition of capecitabine to docetaxel significantly improves overall survival in anthracycline-pretreated metastatic breast cancer. We evaluated a low-dose capecitabine-docetaxel regimen as first-line therapy. Patients who had received adjuvant anthracyclines received docetaxel 75 mg/m2 on day 1 and capecitabine 950 mg/m2 twice daily, days 1-14, every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was time to progression. Forty-five patients were evaluable (median age 56 years, range 35-75). The response rate was 42%, including two complete responses. Nine patients (20%) attained stable disease. Median time to progression was 8 months and median overall survival was 23 months. Five patients (11 %) experienced grade 3 neutropenia but febrile neutropenia was absent. Three patients (7%) experienced grade 3 hand-foot syndrome; there was no significant gastrointestinal toxicity. This capecitabine-docetaxel regimen is an active first-line therapy and appears better tolerated than regimens using a higher capecitabine dose. Data from the randomized trial comparing the registered versus a lower capecitabine dose, both in combination with docetaxel, should definitively answer whether a lower dose provides a better safety profile while maintaining the considerable efficacy of this combination. © 2009 Wolters Kluwer Health|Lippincott Williams & Wilkins.

The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m2 bolus i.v. and 5FU 425 mg/m2 bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m 2 (30-90 min i.v. infusion), followed by LV 20 mg/m2 bolus i.v. and 5FU 425 mg/m2 bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p=0.0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment. © E.S.I.F.T. srl.

Aims and background: The understanding of hormonal therapies in postmenopausal women with metastatic breast cancer has advanced greatly in the past several decades. With the introduction of orally active, potent and selective third-generation aromatase inhibitors (anastrozole, letrozole and exemestane), approaches to the treatment of hormone-sensitive advanced breast cancer are undergoing reevaluation. For treatment of advanced or metastatic disease that has progressed on tamoxifen, all three agents are active. The purpose of the study was to assess the antitumor efficacy and tolerance of exemestane administered as third-line hormonal therapy to postmenopausal women with metastatic breast cancer refractory to letrozole and anastrozole. Study design: Sixty postmenopausal women with stage IV hormone receptor-positive carcinoma of the breast were enrolled in the study. All patients had received two prior hormonal manipulations and had measurable or assessable disease. All adverse events were monitored. Results: Objective tumor response was achieved in 12 (20%) patients (95% CI, 9.6-30.4). The overall clinical benefit was 38.3% (95% CI, 21.2-49.3), and the median duration of objective tumor response was 20 months (range, 9-26). The median time to death was 17.4 months (95% CI, 16.14-18.66). Conclusions: Exemestane represents an active and well-tolerated treatment option in pretreated patients with advanced breast cancer who have received standard first- and second-line hormonal therapies. By extending the sequence of hormonal therapy, disease progression and the need for chemotherapy may be significantly delayed.

Breast cancer patients are known to be at increased risk for developing other chronic diseases including cardiovascular disease. Studies by different investigators have shown a correlation between increased dietary fat or hypercholesterolemia and the occurrence of breast cancer. Since previous studies on lipoprotein subfractions in this type of cancer have been inconsistent, we evaluated the lipids and lipoprotein subtraction levels in postmenopausal patients with breast cancer in an attempt to identify the risk for the development of cardiovascular disease. The study included 132 patients, 56 of which were suffering from breast cancer, 32 from pancreatic and 44 age-matched controls. Total cholesterol (TC), triglycerides and lipoprotein fractions as well as TC/High density lipoprotein (HDL) and HDL2/HDL3 ratios were estimated by standard laboratory techniques. An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subtraction, were observed in patients with breast cancer as compared to the controls (P < 0.05). The maximum changes in TC, and HDL concentrations were observed in patients with advanced disease. Analysis of indexes of atherosclerosis (TC/HDL, and HDL2/HDL3 ratios) demonstrated that breast cancer patients had significantly higher TC/HDL ratio (6.44 +/- 1.24) compared with controls (3.43 +/- 0.57, p = 0.001), and patients with pancreatic cancer (3.79 +/- 0.15, p = 0.027). The results have demonstrated an unfavourable lipid profile in untreated breast cancer patients with high atherosclerosis indexes. This observation is of great importance, considering the potential use of endocrine therapy that could result in further deterioration of lipid indexes. We propose the evaluation and monitoring of lipid profile prior and after the induction of hormonal therapy in breast cancer patients, as a routine in clinical setting.

Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) are important multifunctional cytokines involved in tumour growth and metastasis. In this study, we have measured serial levels of serum IL-6 and TNF-alpha in prostate cancer patients. A total of 80 patients with carcinoma of the prostate and 38 controls were studied. Three patient groups, with small bulk localised, large volume localised and metastatic prostate cancer, were assessed. Serum IL-6 and TNF-alpha levels were measured and correlated with clinicopathological variables and patient survival. Serial changes in these cytokines were also assessed and related to disease progression in 40 patients with recurrent prostate cancer. Serum IL-6 levels in patients with metastatic disease (9.3 +/- 7.8 pg ml(-1)) were higher than those in patients with localised disease ( 1.3 +/- 0.8 pg ml(-1), P