Hybrid Renal Cell Carcinomas Containing Histopathologic Features of Chromophobe Renal Cell Carcinomas and Oncocytomas Have Excellent Oncologic Outcomes

Background

Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe–oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear.

Objective

To determine the clinical course of hybrid RCC.

Design, setting, and participants

Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells).

Interventions

Radical tumor nephrectomy or nephron-sparing surgery.

Measurements

Recurrence-free and tumor-specific survival.

Results and limitations

Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n = 17), pT2 in 23.5% of tumors (n = 8), and pT3a in 26.5% of tumors (n = 9). Low-grade RCC was found in 76.5% of tumors (n = 26), and vascular invasion was found in 11.8% of tumors (n = 4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively.

Conclusions

Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses.     

The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.     

Paraoxonase and arylesterase activities in patients with cardiac syndrome X, and their relationship with oxidative stress markers

OBJECTIVES: Paraoxonase-1 is a high-density lipoprotein-associated enzyme with three activities, which are paraoxonase, arylesterase and dyazoxonase. Paraoxonase-1 was shown to decrease in patients with cardiovascular diseases. We aimed to examine serum paraoxonase and arylesterase activities, and their relation with oxidative stress markers such as lipid hydroperoxide and total antioxidant status in patients with cardiac syndrome X. METHODS: Forty-one consecutive patients with cardiac syndrome X (CSX group), 33 consecutive patients without cardiac syndrome X (non-cardiac syndrome X group) and 20 healthy volunteers as control group were taken into the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Lipid hydroperoxide levels were measured by ferrous oxidation with xylenol orange assay. Total antioxidant status was determined using an automated measurement method. RESULTS: Basal paraoxonase, salt-stimulated paraoxonase and arylesterase activities were significantly lower in patients with cardiac syndrome X than those of the non-cardiac syndrome X and control groups (P<0.001, for both). Moreover, lipid hydroperoxide was found at high level, and total antioxidant status was found at low level in patients with cardiac syndrome X than control and non-cardiac syndrome X groups (P<0.001, for all). In patients with cardiac syndrome X, in multiple linear regression analysis, both paraoxonase and arylesterase activities were independently correlated with lipid hydroperoxide levels (P=0.001, P=0.003, respectively), and also arylesterase activity was independently correlated with magnitude of ST depression (P=0.002). CONCLUSION: Reduced paraoxonase and arylesterase activities and total antioxidant status levels and enhanced lipid hydroperoxide levels in patients with cardiac syndrome X might indicate increased oxidative stress that can play a role in pathogenesis of cardiac syndrome X.     

Association of serum uric acid level and coronary blood flow

OBJECTIVES: Slow coronary flow (SCF) has long since been identified and endothelial dysfunction and atherosclerosis of the epicardial coronary arteries and microvasculature are reported to be associated with SCF. Serum uric acid is an independent biochemical marker of atherosclerosis, oxidative stress and endothelial dysfunction. Consequently, we aimed to investigate the association between coronary blood flow and serum uric acid level by means of thrombolysis in myocardial infarction frame count (TFC) and other laboratory parameters, in patients with SCF compared with control participants. METHODS: Sixty-four patients with SCF and 369 control participants with normal coronary flow were studied after quantifying coronary blood flow according to TFC. Serum uric acid levels were determined using commercially available assay kits. The association between TFC and serum uric acid level and other clinical and laboratory parameters were evaluated. RESULTS: Statistically significant differences were present between SCF and control groups with respect to serum uric acid, and hemoglobin levels, heart rate, cigarette smoking and sex (P<0.05 for all). The mean TFC was significantly correlated with serum uric acid, urea, creatinine, high-density lipoprotein-cholesterol and hemoglobin levels, platelet count, male gender, cigarette smoking, heart rate and systolic blood pressure (P<0.05 for all). Serum uric acid level (chi(2)=22.86, beta=0.54, P<0.001), heart rate (chi(2)=7.42, beta=-0.034, P=0.032) and cigarette smoking (chi(2)=12.343, beta=0.969, P=0.025) were independent predictors of SCF, whereas serum uric acid level was the only independent predictor of the mean TFC (beta=0.298, P<0.001). CONCLUSIONS: These findings have shown that serum uric acid level is significantly associated with coronary blood flow and that elevated uric acid might be an independent predictor for the presence of SCF.     

Clinical Features of Ileal Pouch Polyps in Patients with Underlying Ulcerative Colitis

Purpose Polypoid lesions rarely occur in the ileal pouch in ulcerative colitis patients after restorative proctocolectomy. Clinical features, malignant potential, and management of pouch polyps have not been characterized. Methods We identified 23 ulcerative colitis patients with large polyps (size≥1 cm) of the ileal pouch from our 2,512-case ulcerative colitis pouch database. Demographic, clinical, endoscopic, and histologic data were reviewed. The Pouchitis Disease Activity Index symptom score (range, 0–6) was used to quantify patients’ symptoms before and after polypectomy. Results Of the 23 patients, 95.7 percent (22 patients) had pouch endoscopy indicated for the evaluation of symptoms when polyps were detected, and 60.9 percent of patients had the polyps in the pouch, 26.1 percent in the anal transitional zone, and 21.7 percent in the afferent limb. The mean size of pouch polyps was 1.9 cm ± 1 cm. Twenty-one patients (91.3 percent) had concomitant pouchitis, cuffitis, or Crohn’s disease. On histology, 21 patients (91.3 percent) had inflammatory-type polyps, and 2 (8.7 percent) had dysplastic or malignant polyps. In 18 patients who had endoscopic polypectomy with concurrent medical therapy, the prepolypectomy and postpolypectomy mean symptom scores were 3.4 ± 1.7 and 1.1 ± 1.2 points, respectively (P = 0.015). Two patients (8.7 percent) had pouch excision for malignancy or for concomitant chronic refractory pouchitis. Conclusions The majority of patients with large ileal pouch polyps were symptomatic. These polyps were typically detected on the background of pouchitis, cuffitis, or Crohn’s disease. Although the majority of polyps were inflammatory type, polyps in two patients were dysplastic or malignant. Endoscopic polypectomy with concomitant medical therapy seemed to improve patients’ symptom scores. Supported in part by a NIH grant R03 DK 067275 and an American College of Gastroenterology Clinical Research Award (to B.S.). Poster presentation at meeting of the American College of Gastroenterology, Honolulu, Hawaii, October 30 to November 2, 2005. Reprints are not available.     

Portal Vein Thrombi After Restorative Proctocolectomy: Serious Complication Without Long-Term Sequelae

Purpose Portal vein thrombi have been observed after restorative proctocolectomy and ileal pouch-anal anastomosis, and present as a clinical spectrum of abdominal pain, fever, and leukocytosis. Anticoagulation treatment is usually associated with resolution of symptoms. However, the long-term consequences and effect on pouch function are not known. The purpose of this study was to analyze the long-term functional outcome of patients with confirmed portal vein thrombi after restorative proctocolectomy. Methods A retrospective study of all patients undergoing restorative proctocolectomy from January 1997 to 2000 was performed. A case-control study was designed that matched 37 patients with confirmed portal vein thrombi in this period with 133 patients without portal vein thrombi; the groups were compared with respect to pouch function and quality of life by using the Global Cleveland Clinic Quality of Life Questionnaire for pelvic pouch patients. Results The mean follow-up was 4.73 (range, 4.21–7.28) years. The percentage of male patients was 58.8. The most common diagnosis was ulcerative colitis (62.4 percent). There were no significant differences between portal vein thrombi patients and controls with respect to pouch function (number of bowel movements, urgency, incontinence), episodes of pouchitis, or quality of life. Conclusions Portal vein thrombi can be a serious complication after restorative proctocolectomy that usually resolves with anticoagulation therapy. Long-term pouch function and quality of life are not affected. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 3 to 7, 2006.     

Age-related analysis of functional outcome and quality of life after restorative proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous polyposis

BACKGROUND: The aim of the present study was to evaluate the influence of a younger age at the time of ileal pouch-anal anastomosis (IPAA) on functional outcome and quality of life in patients with familial adenomatous polyposis (FAP). METHOD: A total of 105 patients with FAP who had undergone IPAA were retrieved from a dedicated Institutional Review Board (IRB)-approved IPAA database. Fifty-three patients who had complete follow-up data at 1, 3 and 5 years were included in the study. Patients were categorized into three groups according to their ages at the time of surgery. Group 1, patients < or =20 years of age (n = 9); group 2, patients >20 and < or = 40 years of age (n = 23); and group 3, patients >40 years of age (n = 21). Perioperative characteristics, postoperative complications, quality of life scores and functional outcome at 1, 3 and 5 years of postoperative follow-up were assessed. RESULTS: At any time point, there were no significant differences among the groups in terms of perioperative characteristics, quality of life scores or level of satisfaction with the procedure. However, younger patients had significantly lower nocturnal bowel movements at the first and third years of follow-up and tended to have less bowel movements per day at all stages of follow-up. CONCLUSION: These findings indicate that younger patients with FAP are inclined to have better functional outcome after IPAA in the early postoperative period. This finding may be encouraging for colorectal surgeons who will operate on young patients with FAP.