Disseminated pleomorphic rhabdomyosarcoma in a horse.

An 8-y-old National Show Horse mare was presented for evaluation of pneumonia and laminitis. Harsh bronchovesicular sounds were auscultated throughout both lung fields, and the mare had signs of moderately painful laminitis. Thoracic ultrasonography revealed lung consolidation throughout the dorsal aspect of both lungs, and radiography revealed an extensive diffuse-to-patchy bronchointerstitial lung pattern. The mare's clinical condition rapidly deteriorated, and euthanasia was elected. On postmortem examination, the lungs, omentum, spleen, liver, adrenal glands, kidneys, and femur contained 0.5-2.5-cm, firm, tan nodules. Histologically, the lungs, spleen, liver, kidneys, adrenal glands, omentum, left eye, and femur were infiltrated by bundles and nests of pleomorphic polygonal-to-spindloid cells intermixed with frequent multinucleate cells. Lymphatic vessels in the affected tissues were frequently distended with tumor emboli. Neoplastic cells were diffusely positive for vimentin, desmin, sarcomeric actin, myoblastic differentiation protein 1, and myogenin, supportive of the diagnosis of rhabdomyosarcoma (RMS), which is a rare neoplasm in horses. Cross-striations were not evident with H&E or phosphotungstic acid-hematoxylin stains. Markedly pleomorphic neoplastic cells, multinucleate cells, and lack of cross-striations suggested the subclassification of pleomorphic RMS.

Clinical and radiological outcomes with an augmented baseplate for superior glenoid wear in reverse shoulder arthroplasty.

Aims: This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). Methods: From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery. Results: There were no significant differences in demographic data and preoperative characteristics between the two groups. Both groups showed significant improvements in patient-reported outcome measures (visual analogue scale for pain, visual analogue scale for function, American Shoulder and Elbow Surgeons, Constant, and Simple Shoulder Test scores) from preoperative to final assessment (p < 0.001). However, AGB showed no additional benefit. Notably, within range of motion, Group B showed significant postoperative decrease in both external rotation and internal rotation, unlike Group A (p = 0.028 and 0.003, respectively). Both groups demonstrated a significant correction of superior-inclination after surgery, while patients in Group B exhibited a significant decrease in LHO postoperatively (p = 0.001). Regarding complications, Group A experienced more acromial stress fractures (3 cases; 12.5%), whereas Group B had a higher occurrence of scapular notching (24 cases; 33.3%) (p = 0.008). Conclusion: Both eccentric reaming with STB and off-axis reaming with AGB are effective methods for addressing superior glenoid wear in RSA, leading to improved clinical outcomes. However, it is important to be aware of the potential risks associated with eccentric reaming, which include excessive bone loss leading to reduced rotation and scapular notching.

Concurrent chronic lymphocytic leukemia and primary hyperparathyroidism in a mule.

A 26-year-old mule gelding was evaluated for chronic weight loss and decreased appetite. The mule had been losing weight and intermittently hypophagic for approximately 7 months. Laboratory analysis of whole blood and plasma identified severe total hypercalcemia, marked hypophosphatemia, markedly increased parathyroid hormone concentration, and marked lymphocytosis. A sestimibi scan intended to identify parathyroid gland tissue was nondiagnostic. Results of flow cytometry and PCR for antigen receptor rearrangement (PARR) were consistent with a B cell lymphoproliferative disorder, likely chronic lymphocytic leukemia (CLL). Although not previously described concurrently, these conditions may sometimes arise together, complicating definition of the underlying mechanism for weight loss and hypercalcemia in aged equids.

Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats.

There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy-assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross-sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin-1ß expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture.

Black oil sunflower seed ingestion associated with renal azotemia, gastroesophageal ulceration, and a high mortality rate in four alpacas and two llamas.

CASE DESCRIPTION: 4 alpacas and 2 llamas (11 months to 11 years old) from 2 properties were examined for lethargy (6/6), salivation and regurgitation (4/6), and recumbency (3/6). Signs developed approximately 48 to 72 hours after accidental access to black oil sunflower seeds. CLINICAL FINDINGS: 3 alpacas died suddenly prior to treatment and were necropsied. One llama survived, and 1 alpaca and 1 llama died after days of medical treatment. All 3 treated animals had systemic inflammatory signs including tachycardia, fever, and hematologic changes. Biochemical anomalies included azotemia, hyperglycemia, hyponatremia, hypochloremia, and hypoalbuminemia. Necropsy identified numerous sunflower seeds in the gastrointestinal tract of all 5 animals that died, with pulmonary congestion (5/5 animals), mild centrilobular vacuolar hepatic degeneration (4/5), and erosions of the esophagus (3/5) and first (3/5) and third (1/5) compartments of the forestomach. Renal tubular necrosis was found in the 2 animals that died on day 4 of treatment. TREATMENT AND OUTCOME: One llama responded successfully to intensive medical management including supplemented IV fluid therapy, oral and partial parenteral nutrition, and administration of antimicrobials, furosemide, and insulin and was clinically normal with plasma biochemical analysis values within reference range 12 weeks later. Vitamin D, oxalates, heavy metals, and mycotoxins were excluded as the cause of clinical signs on the basis of screening of uneaten seeds and tissue samples and gastric content from the treated llama that died. CLINICAL RELEVANCE: Inadvertent large volume black oil sunflower seed ingestion resulted in a high mortality rate in camelids. A specific toxic principle was not identified. Feeding this product to camelids is not recommended to avoid the risk of accidental overingestion and subsequent disease.

Evaluation of various carbon dioxide laser settings on the time and number of laser beam passes required to make a full-thickness skin incision and amount of laser-induced tissue artifact.

OBJECTIVE: To evaluate the time and number of laser beam passes required to make full-thickness skin incisions and extent of laser-induced tissue artifacts following use of a CO2 laser at various settings. SAMPLE: 24 skin specimens from six 5-month-old porcine carcasses. PROCEDURES: 4 full-thickness skin specimens were harvested from the flank regions of each carcass within 30 minutes after euthanasia and randomly assigned to 4 treatment groups. Three 5-cm-long incisions were made in each specimen with a CO2 laser (beam diameter, 0.4 mm) set to deliver a continuous wave of energy alone (groups 1 and 2) or in superpulse mode (groups 3 and 4) at 10 (groups 1 and 3) or 20 (groups 2 and 4) W of power. The time and number of passes required to achieve a full-thickness incision were recorded, and extent of laser-induced tissue artifact (as determined by histologic evaluation) was compared among the 4 groups. RESULTS: Mean time required to make a full-thickness skin incision for groups 2 and 4 (power, 20 W) was significantly less than that for groups 1 and 3 (power, 10 W). Mean number of passes was lowest for group 2 (continuous wave at 20 W). Extent of laser-induced tissue artifact was greatest for group 4 (superpulse mode at 20 W). CONCLUSIONS AND CLINICAL RELEVANCE: Results provided preliminary information regarding use of CO2 lasers to make skin incisions in veterinary patients. In vivo studies are necessary to evaluate the effect of various CO2 laser settings on tissue healing and patient outcome.

Immune complex glomerulonephritis of suspected iatrogenic origin in five Japanese Black calves.

Five Japanese Black embryo transfer calves from a single embryo flush, 30 to 45-days-old, including 4 live animals for clinical examination and 1 dead for necropsy, were presented with a history of decreased milk intake and hypoproteinemia. Consistent clinicopathological abnormalities in the 4 calves presented for clinical evaluation included hyperkalemia, hyperphosphatemia, hypoproteinemia, hypoalbuminemia, hyperbilirubinemia, increased creatine phosphokinase activity, and proteinuria. Four calves ultimately were necropsied and all had histologic evidence of immune complex glomerulonephritis. Glomerulonephritis in these calves was hypothesized to have resulted from the interaction of passively acquired antibodies at birth and active immunization at 7 and 28 days of age with a Salmonella Typhimurium core antigen vaccine.

Prognosticators and outcomes of patients with renal cell carcinoma and adjacent organ invasion treated with radical nephrectomy.

OBJECTIVE: To study the natural history, prognosticators, and outcomes in patients with renal cell carcinoma (RCC) with extension of tumor beyond Gerota׳s fascia or invading contiguously into the adrenal gland (pT4) or both. PATIENTS AND METHODS: From 1992 to 2012, we identified 61 patients who underwent radical nephrectomy and were found to have pT4 disease. Clinicopathologic variables were queried using univariate analysis to identify relevant prognostic variables. Cox proportional hazards model was used for multivariate analysis of predictors of cancer-specific survival. Survival plots were estimated using Kaplan-Meier method and survival analysis using log-rank test. RESULTS: Median age was 56 years (interquartile range: 49-64) and 49 (81.7%) patients had Eastern Cooperative Oncology Group Performance Status 0 or 1. At diagnosis, 22 (36.1%) patients showed nonmetastatic and 39 (63.9%) patients showed metastatic RCC. Overall, 49 (80.3%) patients had clear cell RCC, 24 (39.3%) patients had sarcomatoid features, and 39 (69.6%) patients had Fuhrman grade 3 to 4. There were 26 (42.6%) patients with pN0, 16 (26.2%) patients with pN1, and 19 (31.1%) patients with pNx. Median cancer-specific survival was 37 months for patients with nonmetastatic and 8 months for patients with metastatic RCC. On multivariate analysis, preoperative lactate dehydrogenase and alkaline phosphatase, M stage, pN stage, and sarcomatoid dedifferentiation were significantly associated with survival. CONCLUSIONS: Survival in patients with pT4 remains poor. The pT4 disease is associated with a locally and regionally invasive biology that requires specific attention and warrants careful study. Understanding the drivers of this unique phenotype would generate therapeutic interventions that can change the behavior of these uniquely aggressive tumors.

A contemporary analysis of Fournier gangrene using the National Surgical Quality Improvement Program.

OBJECTIVE: To determine a nationwide contemporary description of surgical Fournier gangrene (FG) and necrotizing fasciitis of the genitalia (NFG) outcomes because historically reported mortality rates for FG and NFG are based on small single-institution studies from the 1980s and the 1990s. METHODS: The National Surgical Quality Improvement Program is a risk-adjusted surgical database used by nearly 400 hospitals nationwide, which tracks preoperative, intraoperative, and 30-day postoperative clinical variables. Data are extracted from patient charts by an independent surgical clinical reviewer at each hospital. Using the National Surgical Quality Improvement Program data from 2005 to 2009, we calculated 30-day mortality rates and identified preoperative factors associated with increased mortality. RESULTS: A total of 650 patients were identified with surgery for FG or NFG. Fourteen patients with do not resuscitate orders placed preoperatively were excluded from analyses. For the remaining 636 patients, the overall 30-day mortality was 10.1% (64 of 636). Fifty-seven percent of patients (360 of 636) were men, 70% (446 of 636) were white, and 13% (81 of 636) were African American. Multivariate logistic regression indicated that increased age (odds ratio [OR], 1.041; P = .004), body mass index (OR, 1.045; P <.001), and preoperative white blood cell count (OR, 1.061; P = .001), and decreased platelet count (OR, 0.993; P <.001) were all associated with increased risk of death. CONCLUSION: We determined a surgical mortality rate for FG-NFG of 10.1%. This rate is about half of historically published estimates and similar to recent studies. The lower rate may indicate improvements in therapy. Increased age, body mass index, and white blood cell count, and decreased platelet count were all associated with an increased risk of 30-day mortality.

The clinical significance of findings obtained on 3D-FLAIR MR imaging in patients with Ramsay-Hunt syndrome.

OBJECTIVES/HYPOTHESIS: To investigate the clinical significance of three-dimensional-fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) findings in patients with Ramsay-Hunt syndrome (RHS). STUDY DESIGN: Case series. METHODS: We enrolled 28 consecutive patients of RHS with temporal bone MRI. Initial clinical findings and outcome were assessed by House-Brackmann (HB) scales, electroneuronography (ENoG), and pure tone audiometry (PTA). Two radiologists evaluated the presence of abnormalities on pre-/postcontrast 3D-FLAIR for the cranial nerve (CN)-VII, CN-VIII, inner ear (IE), and the posterior fossa by consensus. The relative signal intensity and enhancement degree (rED) of the structures were measured using ImageJ (http://rsbweb.nih.gov/ij/). Statistical test correlated the clinical symptoms and the outcome with the analysis results of 3D-FLAIR images. RESULTS: 3D-FLAIR demonstrated enhancement of CN-VII in all patients. Precontrast hyperintensity and enhancement were seen in eight and 16 patients with IE, and in four and six with CN-VIII, respectively. Precontrast hyperintensity of IE or CN-VIII was significantly associated with the presence of vertigo (P value < 0.05). Precontrast hyperintensity of IE or CN-VIII significantly correlated with clinical symptoms assessed by HB, ENoG, and PTA (P value < 0.05, respectively). rED of the vestibule moderately correlated with initial HB scale (r = 0.391, P = 0.039). There was no correlation between any of the 3D-FLAIR findings and the follow-up HB. CONCLUSIONS: RHS shows frequent abnormalities of IE or CN-VIII, as well as CN-VII on pre-/postcontrast 3D-FLAIR images. Precontrast hyperintensity of IE/CN-VIII on 3D-FLAIR is significantly correlated with the severity of facial palsy, the presence of vertigo, and the degree of hearing impairment but not with clinical outcome.

Effects of coculture with cumulus-derived somatic cells on in vitro maturation of porcine oocytes.

In the process of IVM, cumulus-oocyte complexes (COCs) separate from the follicular microenvironment, leading to the loss of endocrine interactions between follicular mural somatic cells and COCs. To restore the microenvironment, a coculture system was established using cumulus-derived somatic cells (CSCs) for IVM. The CSCs were cultured in Dulbecco's modified Eagle's medium for 48 hours with varying numbers of CSCs (0.0, 2.5 × 10(4), 5.0 × 10(4), and 10.0 × 10(4)) and then cultured in tissue culture medium 199 (TCM 199) for 4 hours before adding the oocytes. Cumulus-oocyte complexes from 3- to 6-mm follicles were matured in 500 µL of TCM 199 with eCG and hCG for 22 hours and then cultured in TCM 199 without hormones for 22 hours. After IVM, the group with 2.5 × 10(4) CSCs showed a significant increase in intracellular glutathione levels compared with the control group. In the evaluation of sperm penetration, efficient fertilization was increased in the groups with 2.5 × 10(4) and 5.0 × 10(4) CSCs compared with controls (44.9 and 46.5 vs. 32.1, respectively). The mRNA expression pattern analysis in matured COCs showed a significant upregulation of PCNA, COX-2, Has2, Ptx3, and Nrf2 in the 2.5 × 10(4) CSC group compared with controls. During COC maturation at 0, 11, 22, 33, and 44 hours, the 2.5 × 10(4) and 5.0 × 10(4) CSC groups showed a significantly altered mRNA expression of BMP15 and GDF9. The developmental competence of the matured oocytes in all groups was evaluated after IVF and parthenogenetic activation (PA). After IVF, the 2.5 × 10(4) CSC group showed significantly higher cleavage, blastocyst formation rate, and total cell numbers compared with controls (60.0%, 35.7%, and 127.3 vs. 43.2%, 21.1%, and 89.3, respectively). After PA, the 2.5 × 10(4) CSC group had significantly higher blastocyst formation rate and total cell number than the control group (52.0% and 120.4 vs. 35.4% and 90.9, respectively). In conclusion, these results suggest that the presence of a population of 2.5 × 10(4) CSCs during IVM synergistically improved the developmental potential of IVF- and PA-derived porcine embryos by increasing the intracellular glutathione level via changing of a specific gene expression pattern during oocyte maturation.

Preoperative predictors of pathological lymph node metastasis in patients with renal cell carcinoma undergoing retroperitoneal lymph node dissection.

PURPOSE: Patients with locally advanced renal cell carcinoma represent a subset that may benefit from retroperitoneal lymph node dissection. We identified preoperative clinical predictors of positive lymph nodes in patients with renal cell carcinoma without distant metastasis who underwent retroperitoneal lymph node dissection. MATERIALS AND METHODS: We retrospectively analyzed data on a consecutive cohort of 1,270 patients with cTany Nany M0 renal cell carcinoma who were treated at a single institution from 1993 to 2012. Multivariate analysis was performed to determine preoperative predictors of pathologically positive lymph nodes in patients who underwent retroperitoneal lymph node dissection. A nomogram was developed to predict the probability of lymph node metastasis. Overall, cancer specific and recurrence-free survival was estimated using the Kaplan-Meier Method. RESULTS: We identified 1,270 patients with renal cell carcinoma without distant metastasis who had (564) or did not have (706) retroperitoneal lymph node dissection performed. Of the 564 patients 131 (23%) and 433 (77%) had pN1 and pN0 disease, and 60 (37%) and 29 (7.2%) had cN1pN0 and cN0pN1 disease, respectively. ECOG PS, cN stage, local symptoms and lactate dehydrogenase were associated with nodal metastasis on multivariable analysis. A nomogram was developed with a C-index of 0.89 that demonstrated excellent calibration. Differences in overall, cancer specific and recurrence-free survival among pNx, pN0 and pN1 cases were statistically significant (p <0.001). CONCLUSIONS: Local symptoms, ECOG PS, cN stage and lactate dehydrogenase were independent predictors of lymph node metastasis in patients who underwent retroperitoneal lymph node dissection. Our predictive nomogram using these factors showed excellent discrimination and calibration.

Frequency of lower urinary tract injury after gastrointestinal surgery in the nationwide inpatient sample database.

Bladder and ureteral injury are serious iatrogenic complications during abdominal and pelvic surgery but are poorly investigated in the general surgery literature. The objective of this study was to examine rates, trends, and patient and surgical characteristics present in lower urinary tract injuries during gastrointestinal surgery using the Nationwide Inpatient Sample (NIS) database. The NIS database was queried from 2002 to 2010 for gastrointestinal surgery procedures including small/large bowel, rectal surgery, and procedures involving a combination of the two. These were crossreferenced with bladder and ureteral injury using International Classification of Diseases, 9th Revision, Clinical Modification codes. Multivariate regression analysis was used to calculate odds ratios for hypothesized risk factors. From 2002 to 2010, total average rates of bladder injury and ureteral injury were 0.15 and 0.06 per cent, respectively. Small/large bowel procedures had lower annual rates of ureteral (0.05 to 0.07%) and bladder (0.12 to 0.14%) injuries compared with ureteral (0.11 to 0.25%) and bladder (0.27 to 0.41%) injuries in rectal procedures. Presence of metastatic disease was associated with the greatest risk for bladder (odds ratio, 2.0; 95% confidence interval, 1.8 to 2.2) and ureteral (2.2; 1.9 to 2.5) injury in small/large bowel surgery, and for bladder (3.1; 2.5 to 3.9) and ureteral (4.0; 3.2 to 5.0) injury in combination procedures. Injury rates were significantly greater in open surgeries compared with laparoscopic procedures for both bladder injury (0.78 vs 0.26%, P < 0.0001) and ureteral injury (0.34 vs 0.06%, P < 0.0001). The incidence of genitourinary (GU) injury in gastrointestinal surgery is rare, less than 1.0 per cent, and is less than the incidence of GU injury reported in gynecologic surgery. This risk is increased by operations on the rectum and the presence of malignancy.

Herbal adaptogens combined with protein fractions from bovine colostrum and hen egg yolk reduce liver TNF-α expression and protein carbonylation in Western diet feeding in rats.

BACKGROUND: We examined if a purported anti-inflammatory supplement (AF) abrogated Western-diet (WD)-induced liver pathology in rats. AF contained: 1) protein concentrates from bovine colostrum and avian egg yolk; 2) herbal adaptogens and antioxidants; and 3) acetyl-L-carnitine. METHODS: Nine month-old male Brown Norway rats were allowed ad libitum access to WD for 41-43 days and randomly assigned to WD + AF feeding twice daily for the last 31-33 days (n = 8), or WD and water-placebo feeding twice daily for the last 31-33 days (n = 8). Rats fed a low-fat/low-sucrose diet (CTL, n = 6) for 41-43 days and administered a water-placebo twice daily for the last 31-33 days were also studied. Twenty-four hours following the last gavage-feed, liver samples were analyzed for: a) select mRNAs (via RT-PCR) as well as genome-wide mRNA expression patterns (via RNA-seq); b) lipid deposition; and, c) protein carbonyl and total antioxidant capacity (TAC). Serum was also examined for TAC, 8-isoprostane and clinical chemistry markers. RESULTS: WD + AF rats experienced a reduction in liver Tnf-α mRNA (-2.8-fold, p < 0.01). Serum and liver TAC was lower in WD + AF versus WD and CTL rats (p < 0.05), likely due to exogenous antioxidant ingredients provided through AF as evidenced by a tendency for mitochondrial SOD2 mRNA to increase in WD + AF versus CTL rats (p = 0.07). Liver fat deposition nor liver protein carbonyl content differed between WD + AF versus WD rats, although liver protein carbonyls tended to be lower in WD + AF versus CTL rats (p = 0.08). RNA-seq revealed that 19 liver mRNAs differed between WD + AF versus WD when both groups were compared with CTL rats (+/- 1.5-fold, p < 0.01). Bioinformatics suggest that AF prevented WD-induced alterations in select genes related to the transport and metabolism of carbohydrates in favor of select genes related to lipid transport and metabolism. Finally, serum clinical safety markers and liver pathology (via lesion counting) suggests that chronic consumption of AF was well tolerated. CONCLUSIONS: AF supplementation elicits select metabolic, anti-inflammatory, and anti-oxidant properties which was in spite of WD feeding and persisted up to 24 hours after receiving a final dose.

Treating the two extremes in renal cell carcinoma: management of small renal masses and cytoreductive nephrectomy in metastatic disease.

The incidental renal mass represents a heterogeneous group that contains both benign and malignant pathologies. The majority of renal cell carcinomas are discovered incidentally, without the presence of symptoms directly related to the mass, and are closely associated with the term small renal masses because of the discovery before the onset of symptoms. In general, small renal masses are defined as 4 cm or smaller, and may account for greater than half of renal cell carcinoma diagnosis. The use of renal mass biopsy may offer additional pathological information but the clinician must be reminded of the technical and diagnostic limitations of renal mass biopsy. Patient-dependent factors, such as life expectancy and comorbidities, guide the management of small renal masses, which include active surveillance, partial nephrectomy, radical nephrectomy, and ablative techniques (cryoablation and radiofrequency ablation). Partial nephrectomy has demonstrated durable oncologic control for small renal masses while preserving renal function and, if feasible, is the current treatment of choice. In the other extreme of the renal cell carcinomas spectrum and in the presence of metastatic disease, the removal of the renal primary tumor is termed cytoreductive nephrectomy. Two randomized trials (SWOG 8949 and EORTC 30947) have demonstrated a survival benefit with cytoreductive nephrectomy before the initiation of immunotherapy. These two studies have also been the motivation to perform cytoreductive nephrectomy in the targeted therapy era. Currently, there are two ongoing randomized prospective trials accruing to investigate the timing and relevance of cytoreductive nephrectomy in the contemporary setting of targeted therapy.

Role of metastasectomy for metastatic renal cell carcinoma in the era of targeted therapy.

Numerous biological pathways are affected in renal cell carcinoma and the introduction of targeted agents has improved the survival of patients with advanced and metastatic disease. Durable and long-lasting cure is rarely achieved, and in select cases, the excision of metastatic deposits has shown to increase survival. Clinical trials of targeted agents are being explored as neoadjuvant and adjuvant therapies with the role of metastasectomy evolving in the treatment paradigm. This review examines published reports of metastasectomy and its developing role in the era of targeted therapy. A Medline search was conducted using keywords "metastasectomy," "renal cell carcinoma," and "targeted therapy," and selected articles are discussed by examining prognostic stratification and metastasectomy in major anatomic regions. Most published reports span earlier periods of immunotherapy and chemotherapy, and henceforth, discussions are in historical context in this review. Although there is lack of Level 1 evidence, reports have suggested the prognostic value and survival benefit for metastasectomy in lesions that are amenable to complete resection after longer disease-free intervals in carefully selected patients with adequate performance status. Therefore, the role of metastasectomy must be further elucidated in the era of targeted therapy.