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Renal cell carcinoma accounts for 85% of all solid renal tumors in adults. Nearly one quarter of patients has distant metastasis at presentation while another 50% develop metastasis during follow-up. A small percentage of these are solitary metastasis. We report here a case of solitary bone sternal metastasis as an initial presentation of clear-cell renal cell carcinoma in a 56-year-old woman. The prognosis for patients with metastasized renal cell carcinoma is poor; treatment of metastasis is usually palliative and designed to provide comfort and pain relief. Palliative nephrectomy may be considered for control of symptoms. Radical nephrectomy associated with metastatic bone tumor resection is being tested to improve functional status and survival, especially when metastasis involves supporting bones.

Introduction. Partial nephrectomy (PN) is playing an increasingly important role in localized renal cell carcinoma (RCC) as a true alternative to radical nephrectomy. With the greater experience and expertise of surgical teams, it has become an alternative to radical nephrectomy in young patients when the tumor diameter is 4 cm or less in almost all hospitals since cancer-specific survival outcomes are similar to those obtained with radical nephrectomy. Materials and Methods. The authors comment on their own experience and review the literature, reporting current indications and outcomes including complications. The surgical technique of open partial nephrectomy is outlined. Conclusions. Nowadays, open PN is the gold standard technique to treat small renal masses, and all nonablative techniques must pass the test of time to be compared to PN. It is not ethical for patients to undergo radical surgery just because the urologists involved do not have adequate experience with PN. Patients should be involved in the final treatment decision and, when appropriate, referred to specialized centers with experience in open or laparoscopic partial nephrectomies.

Purpose

To assess the validity of the 2009 TNM classification for renal cell carcinoma (RCC) and compare its ability to predict survival relative to the 2002 classification.

Materials and Methods

We identified 1,691 patients who underwent radical nephrectomy or partial nephrectomy for unilateral, sporadic RCC between 1989 and 2007. Cancer-specific survival was estimated by the Kaplan-Meier method and was compared among groups by the log-rank test. Associations of the 2002 and 2009 TNM classifications with death from RCC were evaluated by Cox proportional hazards regression models. The predictive abilities of the two classifications were compared by using Harrell's concordance (c) index.

Results

There were 234 deaths from RCC a mean of 38 months after nephrectomy. According to the 2002 primary tumor classification, 5-year cancer-specific survival was 97.6% in T1a, 92.0% in T1b, 83.3% in T2, 61.9% in T3a, 51.1% in T3b, 40.0% in T3c, and 33.6% in T4 (p for trend<0.001). According to the 2009 classification, 5-year cancer-specific survival was 83.2% in T2a, 83.8% in T2b, 62.6% in T3a, 41.1% in T3b, 50.0% in T3c, and 26.1% in T4 (p for trend<0.001). The c index for the 2002 primary tumor classification was 0.810 in the univariate analysis and increased to 0.906 in the multivariate analysis. The c index for the 2009 primary tumor classification was 0.808 in the univariate analysis and increased to 0.904 in the multivariate analysis.

Conclusions

Our data suggest that the predictive ability the 2009 TNM classification is not superior to that of the 2002 classification.

Background

The surgical management of renal cell carcinoma with invasion of the renal vein or inferior vena cava is associated with significant rates of perioperative morbidity and mortality. In this report we propose a surgical checklist aimed at reducing adverse events associated with the resection of these tumors.

Methods

This review describes the development of an evidence- and experience-based surgical checklist aimed at improving the perioperative safety of patients undergoing radical nephrectomy and tumor thrombectomy.

Results

Reducing the risk of complications during the surgical management of renal tumors with venous invasion begins with appropriate pre-operative imaging aimed at defining the cranial extent of the tumor thrombus, thus facilitating accurate preoperative planning. Other key elements of the checklist are aimed at ensuring clear and precise pre-, intra- and postoperative communication between members of the multidisciplinary-care team.

Conclusion

A standardized surgical checklist may help to increase the perioperative safety of patients undergoing radical nephrectomy and tumor thrombectomy. Future validation studies are required to determine the clinical feasibility and post-implementation safety profile of this new checklist.

Renal cell carcinoma (RCC) is often detected incidentally and early. Currently, open partial nephrectomy and laparoscopic total nephrectomy form competing technologies. The former is invasive, but nephron-sparing; the other is considered less invasive but with more loss of renal mass. Traditionally, emphasis has been placed on oncologic outcomes. However, a patient with an excellent oncologic outcome may suffer from morbidity and mortality related to renal failure. Animal models with hypertension and diabetic renal disease indicate accelerated progression of pre-existing disease after nephrectomy. Patients with RCC are older and they have a high prevalence of diabetes and hypertension. The progression of renal failure may also be accelerated after a nephrectomy. Our analysis of the available literature indicates that renal outcomes in RCC patients after surgery are relatively poorly defined. A strategy to systematically evaluate the renal function of patients with RCC, with joint discussion between the nephrologist and the oncologic team, is strongly advocated.

The standard treatment for a small mass has shifted from radical nephrectomy to partial nephrectomy. The benefits of partial nephrectomy, including preserving renal function, prolonging overall survival, preventing postoperative chronic kidney disease, and reducing cardiovascular events, have been discussed in many studies. With the accumulation of surgeons' experience and simplification of the operative procedures, the warm ischemic time has become shorter despite the indication of tumor size becoming larger. With the help of intraoperative ultrasound, partial nephrectomy can be performed for an endophytic renal mass. Recently, laparoscopic partial nephrectomy has become well indicated for most renal tumors in many centers with advanced laparoscopic expertise. Open partial nephrectomy remains indicated for complex tumors. With technical innovation, robotic partial nephrectomy shows at least comparable perioperative outcomes with a benefit for challenging cases. Laparoendoscopic single-site partial nephrectomy has recently been tried in limited indications and seems to be feasible.

Background

By combining trocar sites and extraction incision, Laparo-endoscopic Single-site Surgery (LESS) may provide less morbidity than traditional laparoscopy. Concerns continue about LESS for locally advanced tumors. We present our experience with LESS-radical nephrectomy with renal vein thrombectomy (LESS-RN-RVT)

Case Presentation

Between 5-6/2009, 2 patients underwent LESS-RN-RVT (1 right-/1 left-side). Standard steps of multi-site laparoscopic radical nephrectomy were performed, including stapled renal vein thrombectomy and intact specimen extraction. Both cases were successfully completed by LESS without complications. Mean tumor size was 7.8 cm, incision size 4.5 cm, operative time 152 min, EBL 100 ml, and hospital stay 2.5 days. Both patients had negative margins, and are alive at time of last follow-up. One did not require postoperative opiates.

Conclusions

LESS-RN-RVT is safe and feasible in selected patients with renal vein thrombi. Further accumulation of data and comparison to multiport laparoscopic technique are requisite.

Introduction

In this case series and short review of the literature, we underline the impact of nephrectomy combined with sequential therapy based on cytokines, antiangiogenic factors, and mammalian target of rapamycin inhibitors along with metastasectomy on overall survival and quality of life in patients with metastatic clear cell renal carcinoma.

Case presentation

In the first of two cases reported here, a 53-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer and relapsed with a bone metastasis in his right humerus. He was treated with closed nailing and cytokine-based chemotherapy. For 5 years, the disease was stable and he had great improvement in quality of life. Subsequently, the disease relapsed in his lymph nodes, lung, and thorax soft tissue. He was then treated with antiangiogenic factors and mammalian target of rapamycin inhibitors. The disease progressed until September 2009, when he died of allergic shock during a blood transfusion, 9 years after the initial diagnosis of renal cell cancer.

In the second case, a 54-year-old Caucasian man underwent a radical left nephrectomy for renal cell cancer. A year later, the disease progressed to his neck lymph nodes, and cytokine-based chemotherapy was initiated. While he was on cytokines, a solitary pulmonary nodule appeared and he underwent a metastasectomy. Nine months later, magnetic resonance imaging of his brain revealed a focal right occipitoparietal lesion, which was resected. After two years of active surveillance, the disease relapsed as a pulmonary metastasis and he was treated with an antiangiogenic factor. Further progressions presenting as enlarged axillary lymph nodes, chest soft tissue lesions, and thoracic spine bone metastases were sequentially observed. He then received a first-generation mammalian target of rapamycin inhibitor, an antiangiogenic factor, and later a second-generation mammalian target of rapamycin inhibitor and palliative radiotherapy. Ten years after the initial diagnosis of renal cell cancer, his disease is stable and he is on a third antiangiogenic factor and leads an active life.

Conclusions

One multidisciplinary approach to patients with metastatic renal cell cancer combines nephrectomy, metastasectomy, and radiotherapy (when feasible) with medical therapy based on cytokines and targeted treatment employing agents inhibiting angiogenesis, other receptor tyrosine kinases, and mammalian target of rapamycin. This approach could prolong survival and improve quality of life.

Nephron-sparing surgery (partial nephrectomy) results are similar to those of radical nephrectomy for small (<4 cm) renal tumors. However, in patients with end-stage renal disease, radical nephrectomy emerges as a more efficient treatment for localized renal cell cancer. Laparoscopic radical nephrectomy (LRN) increasingly is being performed. The objective of the present study was to present a case of a patient under hemodialysis who was submitted to LRN for a small renal mass and discuss the current issues concerning this approach. It appears that radical nephrectomy should be the standard treatment in dialysis patients even for small tumors. The laparoscopic technique is associated with acceptable cancer-specific survival and recurrence rate along with shorter hospital stay, less postoperative pain and earlier return to normal activities.

Although more sophisticated ways exist to analyze TG-MS than that applied in our study, the approach was able to identify the TG species sufficiently to emphasize the importance of TG structure. The criticism that differences in dietary fat saturation alone would explain the lipoprotein response across diets is not supported by careful scrutiny of the facts. Nor does fat saturation per se address the observed impact that fat structure had on insulin/glucose metabolism.

Renal cell carcinoma is the most lethal urologic malignancy. Up to 30% of patients with kidney cancer have metastatic disease and 30% of those treated for local or locally advanced disease will progress to metastases. Radical nephrectomy is the standard treatment for the management of nondisseminated kidney cancer, but the role of cytoreductive nephrectomy for patients with metastatic disease is controversial. In this paper, the rationale for cytoreductive nephrectomy is described and the currently available evidence for and against it is evaluated. The different approaches to defining prognostic factors to select which patients will benefit from cytoreductive nephrectomy will also be described. Finally, the role of cytoreductive nephrectomy in the era of new targeted therapies is discussed.

Renal cell carcinoma (RCC) diagnosis and management have undergone significant shifts in the recent past. The increasing rate of diagnosis of small renal masses, often in patients at high risk of morbidity with operative treatment, has led to studies, trials and discoveries in renal mass biopsy, active surveillance and minimally invasive thermal ablation. At the other end of the disease spectrum, targeted systemic therapies for metastatic RCC have supplanted cytokine-based treatment, with significant benefits to progression and survival. Recent reviews and trials have also cemented the role of partial nephrectomy as standard surgical management for most low-stage masses, and the roles of regional lymphadenectomy and adrenalectomy concomitant with nephrectomy have been clarified. This review aims to highlight recent evidence that has emerged in the management of this complicated oncologic issue.

SUMMARY

OBJECTIVE

Prospective randomized trials have demonstrated a survival benefit for nephrectomy in patients with metastatic renal cell carcinoma treated with immunotherapy. These data have been extrapolated to support cytoreductive nephrectomy in the targeted therapy era as well. However, the likelihood that patients with metastatic kidney cancer who undergo nephrectomy will receive systemic treatment postoperatively remains poorly defined. We present a multi-institutional experience evaluating the utilization of systemic therapy in patients undergoing cytoreductive nephrectomy.

PATIENTS AND METHODS

141 patients who underwent cytoreductive nephrectomy between 1990 and 2008 were identified from our Institutional Kidney Cancer Registries. Kaplan Meier analyses and Cox regression models were used to assess the impact of clinicopathological and perioperative variables on patients’ subsequent receipt of systemic therapy and postoperative survival.

RESULTS

Overall, 98/141 patients (69.5%) received postoperative systemic treatment, at a median of 2.5 months (range 0.1–61.5) after nephrectomy. In this group, 52 (53%) patients received immunotherapy, 34 (35%) targeted agents, and 12 (12%) other regimens. By contrast, 43 patients (30.5%) did not receive systemic therapy, because of rapid disease progression (n=13, 30%), decision for surveillance by medical oncology (n=9, 21%), patient refusal (n=10, 23%), perioperative mortality (n=8, 19%), and unknown reasons in three patients (7.0%). Median survival following cytoreductive nephrectomy was 16.7 months (range 0–120). The risk of death after surgery correlated with the number of metastatic sites (p=0.012) and symptoms (p=0.001) at presentation, poor performance status (p=0.001), high tumor grade (p=0.006), and presence of sarcomatoid features (p<0.024).

CONCLUSION

Nearly one-third of patients undergoing cytoreductive nephrectomy did not receive systemic treatment. While some were electively observed or declined therapy, others did not receive treatment due to rapidly progressive disease. Further investigation is warranted to identify those patients at highest risk for rapid post-operative disease progression who might benefit instead from an initial approach to treatment with systemic therapy.

Purpose

We analyzed a series of patients who had undergone laparoscopic partial nephrectomies (LPNs) and open partial nephrectomies (OPNs) to compare outcomes of the two procedures in patients with pathologic T1a renal cell carcinomas (RCCs).

Materials and Methods

From January 1998 to May 2009, 417 LPNs and 345 OPNs were performed on patients with small renal tumors in 15 institutions in Korea. Of the patients, 273 and 279 patients, respectively, were confirmed to have pT1a RCC. The cohorts were compared with respect to demographics, peri-operative data, and oncologic and functional outcomes.

Results

The demographic data were similar between the groups. Although the tumor location was more exophytic (51% vs. 44%, p=0.047) and smaller (2.1 cm vs. 2.3 cm, p=0.026) in the LPN cohort, the OPN cohort demonstrated shorter ischemia times (23.4 min vs. 33.3 min, p<0.001). The LPN cohort was associated with less blood loss than the OPN cohort (293 ml vs. 418 ml, p<0.001). Of note, two patients who underwent LPNs had open conversions and nephrectomies were performed because of intra-operative hemorrhage. The decline in the glomerular filtration rate at the last available follow-up (LPN, 10.9%; and OPN, 10.6%) was similar in both groups (p=0.8). Kaplan-Meier estimates of 5-year local recurrence-free survival (RFS) were 96% after LPN and 94% after OPN (p=0.8).

Conclusions

The LPN group demonstrated similar rates of recurrence-free survival, complications, and postoperative GFR change compared with OPN group. The LPN may be an acceptable surgical option in patients with small RCC in Korea.

Purpose

To evaluate the prognostic roles of metastasectomy and an established risk stratification system for patients experiencing a disease recurrence following nephrectomy for non-metastatic renal cell carcinoma (RCC).

Methods

A retrospective analysis was performed on 129 patients with localized RCC treated by partial or radical nephrectomy and subsequently diagnosed with disease recurrence. At the time of recurrence, a previously validated risk score based on Karnofsky performance status, interval from nephrectomy, and serum hemoglobin, calcium, and lactate dehydrogenase levels was used to categorize patients as favorable, intermediate, or poor-risk. Survival from recurrence was assessed based on risk categorization and metastasectomy

Results

Median time from nephrectomy to recurrence was 16 months. Median and two-year survival rates were strongly associated with the risk score (favorable-risk: 73 months and 81%; intermediate-risk: 28 months and 54%; poor-risk: 6 months and 11%; log-rank<0.001). Metastasectomy was performed in 44 patients (34%) and found to be of clinical benefit across the various risk categories (interaction analysis, p=0.8). On multivariate analysis, a better risk category (p<0.001) and undergoing a metastasectomy (p<0.001) were each independently associated with a more favorable survival and when combined provided six different risk categories with an estimated two-year survival ranging from 0 – 93%.

Conclusions

The clinical course for patients with an RCC recurrence following nephrectomy can be variable and is independently impacted by an objectively obtained risk score and whether the patient undergoes a metastasectomy.

Here, we present a case in which cytoreductive surgery, like left radical nephrectomy, was effective in the treatment of pulmonary metastases and para-aortic metastases from renal cell carcinoma. A 28-year-old man underwent left radical nephrectomy with pulmonary metastasectomy for the diagnosis of metastatic left renal cell carcinoma. The histologic diagnosis was clear cell carcinoma G2, pT3N1M1. He subsequently underwent i.m. administration of IFN-α, 5 million units per day for 30 days. The nasal oxygen mask was weaned gradually, and the chest tube was removable due to cessation of the continuous production of pleural fluid. The patient was well until one year after operation.

Objective:

To report our operative experience and oncologic outcomes for the laparoscopic management of large renal tumors.

Methods:

All laparoscopic and hand-assisted laparoscopic radical nephrectomies performed at our institution were reviewed. Thirty patients with tumors ≥7cm and a pathologic diagnosis of renal cell carcinoma were included.

Results:

Mean operative time was 175.7±24.5 minutes, and mean estimated blood loss was 275.5±165.8 mL. No case required conversion to open radical nephrectomy. The mean hospital stay was 2.4±1.6 days. Four patients (13%) had minor complications. Of the 30 tumors, 18 were pathologic stage T2, 9 were stage T3a, 2 were stage T3b, and one was stage T4. At a mean follow-up of 30 months (range, 10 to 70), 22 patients (73%) were alive without evidence of recurrence, and 5 patients (17%) were alive with disease. One patient (3%) died of complications related to renal cell carcinoma, and 2 patients (7%) died from other causes. Overall survival was 90%, cancer-specific survival was 97%, and recurrence-free survival was 80%.

Conclusion:

Laparoscopic radical nephrectomy for large tumors is a technically challenging operation. However, in experienced hands, it is a reasonable therapeutic option for the management of larger RCC neoplasms.

Introduction

We report a case of pulmonary metastatic recurrence of renal adenocarcinoma soon after radical nephrectomy that was followed by renal transplant and immunosuppressive medication. Increased risk of metastatic recurrence of renal cell carcinoma should be considered in the immediate post-transplant period when immunosuppressive medication is administered, even if nephrectomy had been performed many years earlier.

Case presentation

In 1986 the patient demonstrated renal insufficiency secondary to mesangial glomerulonephritis. In 1992 he underwent left side radical nephrectomy with histopathological diagnosis of clear cell adenocarcinoma. Mesangial glomerulonephritis in the remaining right kidney progressed to end-stage renal failure. In October 2000 he received a kidney transplant from a cadaver and commenced immunosuppressive medication. Two months later, several nodules were found in his lungs, which were identified as metastases from the primary renal tumor that had been removed with the diseased kidney 8 years earlier.

Conclusion

Recurrence of renal cell carcinoma metastases points to tumor dormancy and reflects a misbalance between effective tumor immune surveillance and immune escape. This case demonstrates that a state of tumor dormancy can be interrupted soon after administration of immunosuppressant medication.

Introduction:

The cost of surveillance strategies in patients after radical nephrectomy for localized primary renal cell carcinoma (RCC) has not been evaluated. We compared the costs of 2 different surveillance strategies, the new Canadian Urological Association (CUA) guidelines and the old strategy implemented in our institution.

Methods:

Seventy-five patients who underwent radical nephrectomy for primary non-metastatic renal cancer were retrospectively reviewed. The direct cost of surveillance was determined and compared with the theoretical cost which would have been accrued using the CUA guidelines.

Results:

Our mean follow-up was 31.1 (SD ± 20.4) months. The overall and disease-free survival endpoints were 87.7% and 85.2%, respectively. Total medical costs were higher for our old institutional surveillance strategy than the CUA guidelines ($181 861 vs. $135 054). For the complete follow-up of 75 patients, a cost-savings of $46 806 could have been achieved following the CUA guidelines (p = 0.002). Of recurrences, 7 of 8 were detected by routine screening, only 1 recurrence was identified by symptoms. The cost per recurrence detected in our old protocol was $9 812.92. The increased cost of our institution was due to more visits with basic testing, symptomatic investigation, and follow-up of imaging tests. The median percent cost attributable to these extra tests was 15% (range 0 to 59).

Conclusion:

Based on our results, we endorse the new CUA surveillance strategy in RCC follow-up as appropriate and cost effective in comparison with previous follow-up strategies used at our institution.

Introduction

Chylous ascites may result from diverse pathologies. Ascites results either due to blockage of the lymphatics or leak secondary to inadvertent trauma during surgery.

Case presentation

We report the first case of chylous ascites following radical nephrectomy for a renal cell carcinoma involving the right half of a crossed fused renal ectopia. The patient was managed conservatively.

Conclusion

Post-operative chylous ascites is a rare complication of retroperitoneal and mediastinal surgery. Most cases resolve with conservative treatment which aims at decreasing lymph production and optimizing nutritional requirements along with palliative measures. Refractory cases need either open or laparoscopic ligation of the leaking lymphatic channels. A review of the current literature on the management of post-operative chylous ascites is presented.

Paraneoplastic syndromes are often associated with renal parenchymal tumours. This report describes a case of renal-cell carcinoma with kappa-chain nephropathy. The patient, a 60-year-old man, had renal tubular dysfunction, shown by low serum concentrations of urate and phosphate. Kappa-chains were found in both serum and urine, but no lambda-chains were found. Investigations showed a clear-cell carcinoma, and the patient underwent a radical nephrectomy. Two years after operation serum phosphate and urate concentrations had returned to normal, and kappa-chains were undetectable in serum or urine. The absence of lambda-chains indicates that the light-chain proteinuria was due to overproduction of the M component, and the disappearance of kappa-chains after the operation suggests a causal relation between the renal tumour and the overproduction of the M component.

The association of body mass index, smoking, and blood pressure, which are related to the three well-established risk factors of renal cell carcinoma, and survival in patients with renal cell carcinoma is not much studied. Our objective was to evaluate this association. A cohort of 1,036 patients with low stage (pT1 and pT2) renal cell carcinoma who underwent radical or partial nephrectomy were enrolled. We retrospectively reviewed medical records and collected survival data. The body mass index, smoking status, and blood pressure at the time of surgery were recorded. Patients were grouped according to their obesity grade, smoking status, and hypertension stage. Survival analysis showed a significant decrease in overall (P = 0.001) and cancer-specific survival (P < 0.001) with being underweight, with no differences of smoking status or perioperative blood pressure. On multivariate analysis, perioperative blood pressure ≥ 160/100 mmHg (HR, 2.642; 95% CI, 1.221-5.720) and being underweight (HR, 4.320; 95% CI, 1.557-11.984) were independent predictors of overall and cancer-specific mortality, respectively. Therefore, it is concluded that being underweight and perioperative blood pressure ≥ 160/100 mmHg negatively affect cancer-specific and overall survival, respectively, while smoking status does not influence survivals in patients with renal cell carcinoma.

Purpose

Laparoscopic radical nephrectomy (LRN) has become the standard technique for radical nephrectomies for T1 renal tumors (7 cm or less). We extended our experience with LRN to T2 renal tumors (greater than 7 cm) and compared the efficacy and long-term oncologic outcomes with those of open radical nephrectomy (ORN) for T2 clear renal cell carcinoma (RCC) in the same period.

Materials and Methods

We retrospectively analyzed the data from 33 patients who underwent LRN and 35 patients who underwent ORN in our institution from January 2003 to June 2006 for T2N0M0 RCC. We compared long-term oncologic outcomes between the two groups.

Results

The median follow-up periods were 60.0 months (range, 48.0-77.0 months) and 65.6 months (range, 56.0-77.0 months) in the LRN and ORN groups, respectively. There were no statistically significant differences between the two groups in the patients' demographic data. There were no significant differences in the 5-year overall survival rate, the cancer-specific survival rate, or the recurrence-free survival rate.

Conclusions

Our results suggest that LRN for the management of T2 RCC is feasible and efficacious and that the long-term oncologic outcomes of LRN are comparable to those of ORN.

Laparoscopic renal surgery is associated with reduced blood loss, shorter hospital stay, enhanced cosmesis, and more rapid convalescence relative to open renal surgery. Laparoscopic partial nephrectomy (LPN) is a minimally invasive, nephron-sparing alternative to laparoscopic radical nephrectomy (RN) for the management of small renal masses. While offering similar oncological outcomes to laparoscopic RN, the technical challenges and prolonged learning curve associated with LPN limit its wider dissemination. Robot-assisted partial nephrectomy (RAPN), although still an evolving procedure with no long-term data, has emerged as a viable alternative to LPN, with favorable preliminary outcomes. This article provides an overview of the role of RAPN in the management of renal cell carcinoma. The clinical indications and principles of surgical technique for this procedure are discussed. The oncological, renal functional, and perioperative outcomes of RAPN are also evaluated, as are complication rates.

Elevated Dicer and Drosha mRNA levels have been documented across a range of tumor types (including ovarian carcinoma) by a number of investigators without any demonstrable correlation with patient survival nor evidence of interference with shRNA processing. A recent publication by Merritt et al. (NEJM 359(25):2641-50, 2008) reporting their findings in patients with ovarian carcinoma reach opposite conclusions. Further study will be needed to resolve this issue.