Purpose We examined outcomes in patients with recurrent or de novo renal lesions treated with repeat partial nephrectomy on a solitary kidney. Materials and Methods We reviewed the records of ...patients who underwent nephron sparing surgery at the National Cancer Institute from 1989 to 2008. Patients were included in analysis if they underwent repeat partial nephrectomy on a solitary kidney. Perioperative, functional and oncological outcomes were assessed. Functional outcomes were evaluated using the Modification of Diet in Renal Disease equation for the estimated glomerular filtration rate. Oncological efficacy was examined by the need for subsequent repeat renal surgery and the development of metastatic disease. Results A total of 25 patients were included in the analysis. A median of 4 tumors were resected. Median estimated blood loss was 2,400 ml and median operative time was 8.5 hours. Perioperative complications occurred in 52% of patients, including 1 death and the loss of 3 renal units. There was a decrease in the estimated glomerular filtration rate at followup visit 1 within 3 months after surgery but at 1-year followup the difference was not significant (p <0.01 and 0.12, respectively). Surgical intervention was recommended in 8 patients (38%) for recurrent or de novo tumors at a median of 36 months. The average metastasis-free survival rate in the cohort was 95% at 57 months (median 50, range 3 to 196). Conclusions Repeat partial nephrectomy in patients with solitary kidney is a high risk alternative. The complication rate is high and there is a modest decrease in renal function but most patients remain free of dialysis with acceptable oncological outcomes at intermediate followup.
Purpose We evaluate the incidence and risk factors of parastomal hernia formation in patients undergoing radical cystectomy and ileal conduit urinary diversion. Materials and Methods We ...retrospectively reviewed the Indiana University cystectomy database between 2001 and 2011, and identified 516 patients who underwent radical cystectomy and ileal conduit diversion. Overall 199 patients had a clinical followup of at least 12 months and all underwent postoperative staging computerized tomography to confirm the presence of parastomal hernia. The incidence of parastomal hernia is reported with correlations made to demographic, patient level and perioperative risk factors. Results A parastomal hernia developed in 58 patients (29%) at a median followup of 27 months (range 12 to 125). Of these patients 26 (45%) underwent surgical repair due to abdominal discomfort (58%), acute strangulation or obstruction of the small bowel (15%), partial small bowel obstructions (15%) and elective repair for other intra-abdominal procedures (12%). Prior exploratory laparotomy (adjusted HR 1.98, 95% CI 1.97–3.36, p = 0.011) and severe obesity (adjusted HR 4.26, 95% CI 1.52–11.93, p = 0.006) were predictive of parastomal herniation. The cumulative risk of parastomal hernia formation at 1 and 2 years after cystectomy was 12.2% and 22.5%, respectively. Conclusions We demonstrated that parastomal hernia will develop in nearly a third of patients after radical cystectomy with ileal conduit diversion. Prior laparotomy and severe obesity are independent risk factors. Preoperative counseling and preventative measures regarding parastomal hernia formation should be emphasized, particularly in these at risk patients.
Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the ...impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma.
Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4°C, 22°C, and 37°C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RNA integrity number index. Altered gene expression was assessed by paired, two-sample t test between the zero time point and aliquots from various conditions obtained from the same tumor.
One hundred and forty microarrays were conducted. Some RNA degradation was observed 240 minutes after resection at 37°C. The expression of more than 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions.
RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to preacquisition variables is of paramount importance for accurate tumor profiling.
Purpose We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. Materials and Methods After excluding patients with nonvascular positive margins, ...metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. Results There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34–70 vs 76%, 95% CI 64–85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression-free survival (p=0.5) or cancer specific survival (p=0.2). Conclusions In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal.
Abstract Introduction This study seeks to evaluate the incidence and associated risk factors of Clostridium difficile infection (CDI) in patients undergoing radical cystectomy (RC) for bladder ...cancer. Methods We retrospectively reviewed a single institution׳s bladder cancer database including all patients who underwent RC between 2010 and 2013. CDI was diagnosed by detection of Clostridium difficile toxin B gene using polymerase chain reaction–based stool assay in patients with clinically significant diarrhea within 90 days of the index operation. A multivariable logistic regression model was used to identify demographics and perioperative factors associated with developing CDI. Results Of the 552 patients who underwent RC, postoperative CDI occurred in 49 patients (8.8%) with a median time to diagnosis after RC of 7 days (interquartile range: 5–19). Of the 122 readmissions for postoperative complications, 10% ( n = 12) were related to CDI; 2 patients died of sepsis directly related to severe CDI. On multivariate logistic regression, the use of chronic antacid therapy (odds ratio = 1.9, 95% CI: 1.02–3.68, P = 0.04) and antibiotic exposure greater than 7 days (odds ratio = 2.2, 95% CI: 1.11–4.44, P = 0.02) were independently associated with developing CDI. The use of preoperative antibiotics for positive findings on urine culture within 30 days before surgery was not statistically significantly associated with development of CDI ( P = 0.06). Conclusions The development of CDI occurs in 8.8% of patients undergoing RC. Our study demonstrates that use of chronic antacid therapy and long duration of antimicrobial exposure are associated with development of CDI. Efforts focusing on minimizing antibiotic exposure in patients undergoing RC are needed, and perioperative antimicrobial prophylaxis guidelines should be followed.
Patients with clinically advanced paragangliomas (CA-Para) and pheochromocytomas (CA-Pheo) have limited surgical or systemic treatments. We used comprehensive genomic profiling (CGP) to compare ...genomic alterations (GA) in CA-Para and CA-Pheo to identify potential therapeutic targets. Eighty-three CA-Para and 45 CA-Pheo underwent hybrid-capture-based CGP using a targeted panel of 324 genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined. The GA/tumor frequencies were low for both tumor types (1.9 GA/tumor for CA-Para, 2.3 GA/tumor for CA-Pheo). The most frequent potentially targetable GA in CA-Para were in FGFR1 (7%, primarily amplifications), NF1, PTEN, NF2, and CDK4 (all 2%) and for CA-Pheo in RET (9%, primarily fusions), NF1 (11%) and FGFR1 (7%). Germline mutations in known cancer predisposition genes were predicted in 13 (30%) of CA-Pheo and 38 (45%) of CA-Para cases, predominantly involving SDHA/B genes. Both CA-Para and CA-Para had low median TMB, low PD-L1 expression levels and none had MSI high status. While similar GA frequency is seen in both CA-Para and CA-Para, germline GA were seen more frequently in CA-Para. Low PD-L1 expression levels and no MSI high status argue against strong potential for novel immune checkpoint inhibitors. However, several important potential therapeutic targets in both CA-Para and CA-Para are identified using CGP.
Objective To evaluate the oncologic outcomes of patients with retroperitoneal teratoma only at primary retroperitoneal lymph node dissection (RPLND) who did not receive adjuvant chemotherapy. ...Materials and Methods Between 1979 and 2010, 23 patients with clinical stage (CS) I and II disease underwent primary RPLND at our institution with teratoma only in the retroperitoneum. No patient received adjuvant chemotherapy and the minimum follow-up was 2 years. Results At the initial diagnosis, 13 patients (56.5%) had CS I disease and 10 patients (43.5%) had CS II disease. Pathologic staging demonstrated IIA in 13 patients (56.5%), IIB in 8 patients (34.8%), and IIC in 2 patients (8.7%). The 5-year disease-free survival (DFS) was 100% with a median follow-up of 5.8 years (range, 2.1-25.4). DFS was not significantly different comparing pathologic stage IIA vs IIB/IIC disease ( P = .73). Two patients (14%) developed late relapses. One patient had a pelvic recurrence 11 years after primary RPLND. Final pathology from the pelvic resection demonstrated embryonal carcinoma. He remains disease free after his second surgery. The second patient had a contralateral retroperitoneal recurrence with yolk-sac tumor and teratoma 11 years after primary RPLND. He was treated with chemotherapy followed by postchemotherapy RPLND. Conclusion The relapse rate for patients with teratoma only at primary RPLND is low irrespective of PS. Adjuvant chemotherapy is therefore not recommended in the management of these patients.
PDF
