Sunitinib is an inhibitor of the vascular endothelial growth factor and platelet-derived growth factor receptors, and it has antitumor activity in metastatic renal cell carcinoma and gastrointestinal stromal tumors. To further investigate the fatigue associated with sunitinib therapy, thyroid function tests were performed on patients with metastatic renal cell carcinoma who were receiving sunitinib. Seventy-three patients with metastatic renal cell carcinoma were treated with sunitinib at the Cleveland Clinic Taussig Cancer Center, and 66 of them had thyroid function test results available. Fifty-six (85%) of the 66 patients had one or more abnormality in their thyroid function test results, consistent with hypothyroidism, and 47 (84%) of the 56 patients with abnormal thyroid function tests had signs and/or symptoms possibly related to hypothyroidism. Thyroid hormone replacement was undertaken in 17 patients, and symptoms improved in nine of them. Thyroid function test abnormalities appear to be common in patients with metastatic renal cell carcinoma treated with sunitinib, and routine monitoring is warranted.

Significant antitumor activity is observed when sorafenib or sunitinib are used in patients who have failed prior therapy with an antiangiogenic agent. Prior response to an antiangiogenic agent does not appear to predict subsequent clinical benefit to either sunitinib or sorafenib.

Background: Sorafenib is an orally bioavailable vascular endothelial growth factor receptor (VEGFR) inhibitor with antitumor activity in metastatic renal cell carcinoma (RCC). Sunitinib, also a VEGFR inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC patients, the majority of whom have signs or symptoms of hypothyroidism. Hence, the incidence of thyroid function test (TFT) abnormalities in patients with metastatic RCC receiving sorafenib was investigated.Patients and methods: Sixty-eight patients with metastatic RCC were treated with sorafenib at the Cleveland Clinic Taussig Cancer Center, and 39 patients had TFTs available.Results: Eight patients (21%) had thyroid dysfunction possibly caused by sorafenib [seven hypothyroidism (18%) and one hyperthyroidism (3%)] and eight additional patients (21%) had findings compatible with nonthyroidal illness. Only two patients had clinical signs and symptoms secondary to thyroid dysfunction and received thyroid hormone replacement.Conclusions: In summary, clinically significant TFT abnormalities were not common in patients treated with sorafenib, and replacement therapy was rarely indicated. TFTs should be measured before sorafenib therapy in RCC patients and subsequently only if clinically indicated.

Most Pasteurella multocida human infections involve skin and soft tissues and invariably develop after a bite or a scratch from a dog or a cat. However, other infections with this organism occur infrequently. Enteric microorganisms are the common cause of spontaneous bacterial peritonitis (SBP). We report a case of SBP in a cirrhotic patient from P. multocida. English literature (Pubmed) review revealed 12 adult cases of SBP in cirrhotic patients with P multocida. Nine patients were exposed to animals, though a break in the skin or a bite was not reported in each case. The SBP was fatal in four of these patients.

BACKGROUND.Caveolin‐1 is a major component of membrane caveolae, which are specialized lipid raft microdomains on cell membrane that are implicated in molecular transport, cell adhesion, and signal transduction. The overexpression of caveolin‐1 recently was associated with a poor outcome in patients with clear‐cell renal cell carcinoma (CCRCC) and was proposed as a useful diagnostic marker. In the current study, the authors used immunohistochemistry to investigate the membranous and cytoplasmic expression of caveolin‐1 and its correlation with other pathologic parameters in different subtypes of renal neoplasms.METHODS.A tissue microarray (TMA) was constructed from 60 normal kidneys, 22 CCRCCs, 20 papillary renal cell carcinomas (PRCCs), 16 chromophobe renal cell carcinomas (ChRCCs), and 19 oncocytomas (ONCs). The TMA was immunostained for caveolin‐1 protein. Both membranous and cytoplasmic caveolin‐1 expression levels were measured and were correlated with tumor size, Fuhrman nuclear grade, and pathologic stage.RESULTS.Caveolin‐1 was expressed normally in distal convoluted tubules, collecting ducts, parietal cells of Bowman capsule, smooth muscle, and vascular endothelial cells. Membranous caveolin‐1 expression was detected in 19 of 22 CCRCCs (86.4%), which was significantly higher than the membranous caveolin‐1 expression detected in PRCCs (1 of 20 tumors; 5%), ChRCCs (0 of 16 tumors; 0%), and ONCs (1 of 19 tumors; 5.3%). Cytoplasmic caveolin‐1 expression was detected in 16 of 22 CCRCCs (72.7%), in 13 of 20 PRCCs (65%), in 8 of 16 ChRCCs, (50%), and in 13 of 19 ONCs (68.4%). The percentage of tumors that expressed cytoplasmic caveolin‐1 did not differ significantly among the different types of renal tumors (P = .1). Only membranous caveolin‐1 expression was correlated with tumor size (Pearson correlation = 0.266; P = .043). There was no correlation between membranous or cytoplasmic caveolin‐1 expression and other pathologic parameters, including Fuhrman nuclear grade and staging according to the American Joint Committee on Cancer tumor, lymph node, metastasis classification system.CONCLUSIONS.Caveolin‐1 expression has 2 distinctive patterns in renal neoplasms: membranous and cytoplasmic. In the current study, membranous caveolin‐1 expression was detected predominantly in CCRCCs and only rarely in other subtypes of renal neoplasms. Thus, the current results indicated that caveolin‐1 expression may have potential both as a diagnostic marker in the differential diagnosis of renal tumors and as a therapeutic target, especially for CCRCC. Cancer 2007. © 2007 American Cancer Society.

Background. The safety of immune checkpoint inhibitors (ICI) in patients with hepatitis C virus infection (HCV) has not been studied in many cancers as these patients were excluded from most ICI trials. This poses a degree of uncertainty when an HCV patient is being considered for ICI in the absence of data to inform potential adverse events (AEs). Methods. Single institution retrospective chart review of patients with active or resolved HCV who were treated with ICI for cancer of any type and stage from January 2012-December 2019 with emphasis on AEs rates. Result. We identified 40 patients. Males 30 and females 10. Median age 64 years. Cancer types; non-small cell lung cancer 18 (45%), hepatocellular carcinoma 12 (30%), head and neck cancer 4(10%), small cell lung cancer 3 (7.5%), renal cell carcinoma 1 (2.5%), colon cancer 1 (2.5%), and melanoma 1 (2.5%). Hepatitis C was untreated in 17 (42.5%), treated in 14 (35%), and spontaneously resolved in 9 (22.5%). AEs observed were; grade 3 pneumonitis in one patient (2.5%) on pembrolizumab, grade 3 colitis in one patient (2.5%) on nivolumab, two patients with hepatotoxicity (5%) on nivolumab; one patient with grade 1 and the other had grade 2, grade 1-2 fatigue in 3 patients (7.5%), and one patient with hypothyroidism (2.5%). Conclusion. Adverse events rates in untreated and resolved HCV patients treated with ICI for a variety of cancers were comparable to AEs rates reported in clinical trials for patients without HCV. The Oncologist 2021;9999:• • Implications for Practice: The safety of immune checkpoint inhibitors (ICI) in cancer patients with hepatitis C virus infection is a major concern due to the lack of prospective safety data for most cancers. HCV is prevalent worldwide, and the occurrence of cancer where ICI is indicated is not uncommon. We retrospectively reviewed all HCV patients who received ICI for a variety of cancers in our institution over eight years, and the results are presented in this article. The results may help inform clinical decisions and the design of future clinical trials.

Renal cell carcinoma (RCC) is a disease with a variable natural history, sometimes presenting with a very indolent course and other times with an aggressive clinical course and unusual sites of metastasis. Surgical resection for stage I-III tumors represents the standard of care and is the only curative option available to patients. However, 40-50% of patients develop metastatic disease. Prior to the advent of targeted therapy, cytokine therapy was the only treatment for RCC. The administration of high-dose, bolus IL-2 has historically produced consistent, durable responses in a small percentage of patients with advanced RCC. The use of IFN-alpha is currently limited to combination therapies. Multiple new agents targeting the VEGF pathway have been tested and approved, including sunitinib, sorafenib and bevacizumab, with others waiting in the wings. In the majority of cases these drugs induce disease stabilization with eventual disease progression. Hence additional new pathways are being targeted and studied. Mechanisms of drug resistance, novel combinations, sequences and schedules are the focus of current clinical investigations. This review provides an updated list of the novel targeted agents in advanced clinical development for metastatic RCC.

The combination of docetaxel and temozolomide was well tolerated and these agents can be safely combined. For phase II trials, docetaxel 35 mg/ m(2) IV day 1, 8 and 15, and daily temozolomide at 100 mg/ m(2) day 1-21 are recommended.