A 62-Year-Old Woman With Nodules, Cysts, and Activated Bone Marrow.

CASE PRESENTATION: A 62-year-old woman with a long-term smoking history was evaluated at our lung cancer clinic for a new 2.5-cm lung nodule. She had a history of well-controlled COPD and hypertension. She was in overall good health until 3 weeks before her evaluation in an ED for new-onset exertional dyspnea. Her physical examination was unremarkable, except for diffuse hyperpigmented scaly scalp lesions that coalesced into plaques. Her subjective symptoms were nonproductive cough, exertional dyspnea, unintentional weight loss of 10 lb, and fatigue that had started 2 months earlier. She did not have fever or night sweats.

A 51-year-old man with chronic cough and left hilar prominence.

What is the diagnosis of this man with a chronic dry cough and left hilar prominence on chest radiography? https://bit.ly/3fL7QMx.

Safety of Immune Checkpoint Inhibitors in Patients with Cancer and Hepatitis C Virus Infection.

BACKGROUND: The safety of immune checkpoint inhibitors (ICIs) in patients with hepatitis C virus (HCV) infection has not been studied in many cancers, as these patients were excluded from most ICI trials. This poses a degree of uncertainty when a patient with HCV is being considered for ICIs in the absence of data to inform potential adverse events (AEs). MATERIALS AND METHODS: This was a single-institution retrospective chart review of patients with active or resolved HCV who were treated with ICIs for cancer of any type and stage from January 2012 to December 2019, with emphasis on AE rates. RESULTS: We identified 40 patients, 30 men and 10 women. Median age was 64 years. Cancer types were 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 (12.5%). Hepatitis C was untreated in 17 patients (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; hepatotoxicity in two patients (5%) on nivolumab: one patient with grade 1 and the other with grade 2; grade 1-2 fatigue in three patients (7.5%); and hypothyroidism in one patient (2.5%). CONCLUSION: Adverse events rates in patients with untreated and resolved HCV treated with ICI for a variety of cancers were comparable with AEs rates reported in clinical trials for patients without HCV. IMPLICATIONS FOR PRACTICE: The safety of immune checkpoint inhibitors (ICIs) in patients with cancer with hepatitis C virus (HCV) infection is a major concern because of 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. This study was a retrospective review of all patients with HCV who received ICI for a variety of cancers in the authors' institution over 8 years, and the results are presented in this article. The results may help inform clinical decisions and the design of future clinical trials.

Resistance to angiogenesis inhibitors in renal cell carcinoma.

Antiangiogenic drugs are now available for treatment of renal cell carcinoma and are utilized sequentially to prolong clinical benefit in patients with recurrent disease. These antiangiogenic agents are disease stabilizing in most cases, and resistance eventually develops over time. Because different combinations and sequences are tested in clinical trials, resistance patterns and mechanisms should be investigated. Much effort has been devoted to understanding the biology and elucidating the pathways and additional targets during tumorigenesis and metastasis. Resistance appears to be either primary nonresponsiveness, or it is acquired over time and related to various evasive/escape mechanisms that the tumor develops in response to therapy. Primary resistance is less common, but may be due to an intrinsic redundancy of available angiogenic signals for the tumor, causing unresponsiveness to vascular endothelial growth factor (VEGF)-targeted therapies. During acquired resistance, tumors may activate an "angiogenic switch," which leads to either upregulation of the existing VEGF pathway or recruitment of alternative factors responsible for tumor revascularization. Rationally designed preclinical and clinical trials will shed additional light on our understanding of the potential mechanisms of resistance to antiangiogenic drugs.

KRAS status and clinical outcome in metastatic colorectal cancer patients treated with first-line FOLFOX chemotherapy.

BACKGROUND: Two previous first-line studies showed an improved trend in response rate (RR) and progression free survival (PFS) in metastatic colorectal cancer (CRC) patients with KRAS mutation. Others have reported a worsened outlook for metastatic CRC patients with KRAS mutation and a higher likelihood of metastatic disease to the lungs. In this study, we aimed to address the impact of KRAS on the pattern of metastatic disease at presentation and on RR and PFS with first-line 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. METHODS: Patients with CRC who underwent KRAS testing using DxS assay at Roswell Park Cancer Institute (RPCI) were identified. Patients with metastatic CRC treated with first-line FOLFOX +/- bevacizumab were assessed for response and survival using RECIST 1.1 guidelines. A two-sided Fisher's exact test was used to determine the statistical significance. RESULTS: 181 patients with metastatic CRC and KRAS testing were identified. 83/181 patients were treated with FOLFOX (+/- bevacizumab) in the first-line setting at RPCI and were evaluable as per study guidelines. KRAS mutation (MT) occurred in 40.31% cases. There was no difference in organ-metastases distribution, RR (56.60% in KRAS wild-type (WT) and 50% in KRAS mutant) or PFS (9.3 months KRAS WT and 8.7 months in KRAS MT) based on KRAS status. CONCLUSION: In this single institute study, our findings do not support any predictive role for KRAS-MT in terms of response to FOLFOX first-line chemotherapy, or in terms of sites of metastatic disease at mCRC presentation.

Update on novel agents in renal cell carcinoma.

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.

Clinical implications of caveolins in malignancy and their potential as therapeutic targets.

Caveolae are cell membrane invaginations that were first described in the early 1950s. Since then, researchers have undertaken numerous studies to define their role in normal physiology and disease. The caveolin proteins, particularly caveolin-1, are the major structural and functional components of caveolae, which are involved in a plethora of cellular functions. This review briefly describes the role of caveolae and caveolin proteins in these cellular processes and in different types of human cancers. In addition, it also discusses the use of caveolin-1 as a potential diagnostic and prognostic marker and therapeutic target.

Antitumor effects of sunitinib or sorafenib in patients with metastatic renal cell carcinoma who received prior antiangiogenic therapy.

PURPOSE: Antiangiogenic therapy with sunitinib and sorafenib has become the standard of care for patients with advanced renal cell carcinoma. However, the clinical benefit of these agents after prior antiangiogenic therapy has not been defined. Currently, several agents with a putative antiangiogenic mechanism exist and they are often being used in sequence with little to no data regarding activity in a second line or later setting. MATERIALS AND METHODS: Patients with advanced renal cell carcinoma currently being treated with either sunitinib or sorafenib after receiving 1 or more prior antiangiogenic agent(s) were investigated in a retrospective analysis. Time to progression and the overall response rate by Response Evaluation Criteria in Solid Tumors were evaluated. RESULTS: Thirty patients receiving current sunitinib (16 patients) or sorafenib (14 patients) were identified. Patients received 1 or more prior antiangiogenic therapies: thalidomide, lenalidomide, bevacizumab, volociximab, AG13736, sorafenib or sunitinib. Of 16 patients treated with sunitinib 13 had some degree of tumor shrinkage, including 9 with a partial response by Response Evaluation Criteria in Solid Tumors. Of 14 patients treated with sorafenib 10 had some degree of tumor shrinkage, including 1 with a partial response. The median time to progression for the entire cohort was 10.4 months. CONCLUSIONS: 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.

Differential expression of caveolin-1 in renal neoplasms.

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.

Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib.

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.

Spontaneous bacterial peritonitis with Pasteurella multocida in cirrhosis: case report and review of literature.

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.