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INTRODUCTION AND OBJECTIVE:Organ sparing surgery (OSS) for penile cancer has been shown to be a viable option for low-stage disease. However, recurrence rates are higher than non-OSS approaches, an...

Importance Lack of insurance coverage has been associated with delays in seeking care, more complicated diseases at the time of diagnosis, and decreased likelihood of receiving optimal surgical care. The Patient Protection and Affordable Care Act’s (ACA) Medicaid expansion has increased coverage among millions of low-income Americans, but its effect on care for common surgical conditions remains unknown. Objective To evaluate the association of the ACA’s Medicaid expansion with access to timely and recommended care for common and serious surgical conditions. Design, Setting, and Participants This quasi-experimental, difference-in-differences study used hospital administrative data to compare patient-level outcomes in expansion vs nonexpansion states before (2010-2013) vs after (2014-2015) expansion. A total of 293 529 patients aged 18 to 64 years with appendicitis, cholecystitis, diverticulitis, peripheral artery disease (PAD), or aortic aneurysm admitted to an academic medical center or affiliated hospital in 27 Medicaid expansion states and 15 nonexpansion states from January 1, 2010, through September 31, 2015, were included in the study. Data analysis was performed from November 1, 2016, to March 3, 2017. Exposures State adoption of Medicaid expansion. Main Outcomes and Measures Presentation with early uncomplicated disease (diverticulitis without abscess, fistula, or sepsis; nonruptured aortic aneurysm at time of repair; and PAD without ulcerations or gangrene) and receipt of optimal management (cholecystectomy for acute cholecystitis, laparoscopic approach for cholecystectomy or appendectomy, and limb salvage for PAD). Results Of the 293 529 study patients (128 392 [43.7%] female and 165 137 [56.3%] male), 225 572 had admissions in Medicaid expansion states and 67 957 had admissions in nonexpansion states. Medicaid expansion was associated with a 7.5–percentage point decreased probability of patients being uninsured (95% CI, −12.2 to −2.9; P = .002) and an 8.6–percentage point increased probability of having Medicaid (95% CI, 6.1-11.1; P P = .001) and a 2.6–percentage point increase in the probability of receiving optimal management (95% CI, 0.8-4.4; P = .006). Conclusions and Relevance The ACA’s Medicaid expansion was associated with increased insurance coverage and improved receipt of timely care for 5 common surgical conditions. Health care systems and policymakers should be aware of the influence of insurance coverage expansion (or its repeal) on presentation with and management of surgical disease.

The term close surgical margin refers to a tumor extending to the inked margin of the specimen without reaching it. Current guidelines state that a close surgical margin should simply be reported as negative. However, this recommendation remains controversial and relies on limited evidence. We evaluated the impact of close surgical margins on the long-term risk of biochemical recurrence after radical prostatectomy.We identified 1,195 consecutive patients who underwent radical prostatectomy and lymphadenectomy for localized prostate cancer at our institution from 1993 to 1999. In 894 of these patients associations between margin status and location, Gleason score, pathological stage, preoperative prostate specific antigen, prostate weight and age with the risk of biochemical recurrence were examined.Of these 894 patients 644 (72%) had negative margins and of these patients 100 (15.5%) had close surgical margins. In the group with prostate specific antigen failure, median time to recurrence was 3.5 years. In the group without recurrence median followup was 9.9 years. Cumulative recurrence-free survival differed significantly among positive, negative and close surgical margins (p0.001). On multivariate analysis a close surgical margin constituted a significant, independent predictor of recurrence (HR 2.1, 95% CI 1.04-4.33). Gleason score and positive margins were the strongest prognostic factors.In this cohort close surgical margins were independently associated with a twofold risk of postoperative biochemical recurrence. Further evaluation of the clinical significance of close surgical margins is indicated as they might be an indicator of local recurrence and of relevance when considering salvage therapy.

Purpose: Perinephric and renal sinus fat invasion are classified as pT3a renal cell carcinoma (RCC) according to the 2002 American Joint Committee on Cancer. We investigated the prognostic significance of each of these pathological features using a cohort of pT3a patients.Materials and Methods: Between 1970 and 2002, 205 patients without direct adrenal invasion underwent nephrectomy for pT3a clear cell RCC. The associations of fat invasion with death from RCC were evaluated using Cox proportional hazards regression models.Results: Of the 162 patients with perinephric fat invasion and 43 patients with renal sinus fat invasion 95 (59%) and 31 (72%), respectively, died of RCC. Patients with renal sinus fat invasion were 63% more likely to die of RCC compared with those with perinephric fat invasion (RR 1.63, 95% CI 1.09–2.46, p=0.018). In addition, the risk of death persisted in multivariate analysis after adjusting for regional lymph nodes and distant metastases (RR 1.91, 95% CI 1.26–2.89, p=0.002) ...

Purpose: We evaluated lymphotropic nanoparticle enhanced magnetic resonance imaging (LNMRI) with ferumoxtran-10 in determining the presence of regional lymph node metastases in patients with penile cancer.Materials and Methods: Seven patients with squamous cell carcinoma of the penis underwent LNMRI. All patients subsequently underwent groin dissection and the nodal images were correlated with histology.Results: We found that LNMRI had sensitivity, specificity, and positive and negative predictive values of 100%, 97%, 81.2% and 100%, respectively, in predicting the presence of regional lymph node metastases in patients with penile cancer.Conclusions: Lymph node scanning using LNMRI accurately predicts the pathological status of regional lymph nodes in patients with cancer of the penis. LNMRI may accurately triage patients for regional lymphadenectomy.

Stromal-epithelial interactions of growth factors and the androgen receptor may have implications for the pathophysiology of benign and neoplastic transformation of the human adult prostate. We investigated a possible interaction of keratinocyte growth factor with its receptor as well as with the androgen receptor signaling pathway in human prostatic epithelial cells.Human prostatic epithelial cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in keratinocyte serum-free medium with supplements. Epithelial cells were characterized by light and electron microscopy, and immunocytochemical study using epithelial and mesenchymal markers. Androgen receptor, keratinocyte growth factor receptor and keratinocyte growth factor messenger RNA expression was measured by polymerase chain reaction (PCR). The response to 0.01 to 10 nM. dihydrotestosterone, 10 microM. flutamide and 1 to 1,000 ng./ml. keratinocyte growth factor was tested by [3H] thymidine assay. The difference in keratinocyte growth factor receptor and androgen receptor gene expression after treatment with and without keratinocyte growth factor and flutamide were determined by quantitative multiplex PCR and quantitated using densitometry analysis.Immunocytochemical and electron microscopy characterization revealed typical epithelial differentiation. PCR showed keratinocyte growth factor receptor and androgen receptor expression in epithelial cultured cells but no keratinocyte growth factor expression. Epithelial cells showed a significant time and dose dependent stimulation of cell proliferation with keratinocyte growth factor and dihydrotestosterone (p0.05). When combined with the anti-androgen flutamide the effect of 100 ng./ml. keratinocyte growth factor was significantly decreased (p0.05). At 100 ng./ml. keratinocyte growth factor quantitative multiplex PCR revealed stimulated keratinocyte growth factor receptor and androgen receptor messenger RNA expression.These results show that keratinocyte growth factor up-regulates the keratinocyte growth factor and androgen receptors in the absence of androgen. Thus, the androgen signaling pathway may be activated by growth factors such as keratinocyte growth factor in an androgen deficient environment.

Purpose: Urinary nuclear matrix protein (NMP22) was evaluated for detection of new and recurrent bladder tumors in patients with a history of transitional cell carcinoma. Our objective was to determine sensitivity and specificity of this marker for tumors of various stages and grades, as well as its use as an adjunct to or substitute for urinary cytology.Materials and Methods: A total of 231 patients with a history of transitional cell carcinoma provided 288 voided urine samples before cytoscopic examination at 1 of 3 institutions (53 patients were reevaluated at least once). Urine samples were assayed for NMP2 using the NMP22 Test Kit.† †Matritech, Newton, Massachusetts. Select patients underwent biopsy with appropriate additional therapy. Voided urinary cytology was obtained in 200 cases. End points for determination of the absence and presence of tumor were negative cystoscopy and positive biopsy, respectively. A receiver operating characteristics curve was constructed to determine the optimal ...

Purpose: Previous work from our laboratory suggests that one mechanism of ammonium transport across the intestinal membrane may be substitution of ammonium for sodium in the sodium/hydrogen antiport. This study further supports this mechanism by demonstrating an inhibitory role for ammonium in the sodium/hydrogen exchange.Materials and Methods: Whole brush border intestinal enterocytes were studied, incorporating a fluorescent marker for sodium transport. The kinetics of the effect of ammonium on sodium transport were determined.Results: Ammonium is an inhibitor of sodium in the sodium/hydrogen exchanger. Quantitatively, the inhibition appears to be competitive.Conclusions: The inhibitory effect of ammonium on sodium/hydrogen exchange supports a mechanism of ionized ammonium transport where it substitutes for sodium in the sodium/hydrogen exchanger. This is a mechanism by which hyperchloremic metabolic acidosis occurs following urinary intestinal diversion.

Purpose: Standard surgical methods to eradicate invasive squamous cell carcinoma of the penis often result in significant deformities. Wide local excision with skin grafting in select cases results in the preservation of normal phallic appearance and function.Materials and Methods: Seven patients with invasive squamous cell carcinoma of the penis were treated with wide excision and resurfaced by 1 of 3 methods, namely 1) a split-thickness graft, 2) a full-thickness graft or 3) shaft skin advancement.Results: At 1 to 5 years of followup there was 1 local recurrence proximal to the original resection site. Local excision of recurrence resulted in no evidence of disease at 2 years of followup following repeat excision. All other patients had no local recurrence.Conclusions: In select cases wide local excision with grafting or skin advancement results in a normal phallic appearance without jeopardizing cancer control.

INTRODUCTION AND OBJECTIVES: Smaller prostate size is associated with a number of negative prognostic indicators including higher Gleason score and positive surgical margins. We hypothesized that this may be related to a longer time to diagnosis and increased volume of disease for patients with smaller glands. METHODS: A retrospective review was performed of patients with Gleason 6-10 prostate cancer who underwent radical prostatectomy from 2001 through 2010. Patients were identified from a prostatectomy tumor bank database. Univariate and multiple logistic regression were performed to determine association between prostate weight and volume of disease at prostatectomy. Number of quadrants with prostate cancer on surgical pathology was used as a surrogate for volume of disease. RESULTS: A total of 2054 patients underwent radical prostatectomy. Mean age, PSA, and prostate weight were 59.6 6.6 years, 6.0 4.7 ng/ml, and 45.5 17.5 grams, respectively. Gleason score was 6 in 1055 patients (51.4%), 7 in 858 patients (41.8%), and 8-10 in 141 patients (6.9%). Number of quadrants with prostate cancer was distributed as follows: 1 quadrant in 274 patients (13.3%), 2 quadrants in 557 patients (27.1%), 3 quadrants in 464 patients (22.6%), and 4 quadrants in 759 (37.0%). On one-way analysis of variance, increasing number of quadrants with cancer was associated with decreasing prostate weight (p 0.001). On univariate and multiple logistic regression (Table), smaller prostate weight, higher PSA, and higher Gleason score were associated with increasing volume of disease. CONCLUSIONS: Smaller prostate gland size is independently associated with increased volume of disease at prostatectomy. Small gland size is a clinical indicator of disease volume.

Purpose: Large groin defects may be created after inguinal lymphadenectomy for bulky metastatic penile cancer. We describe a new method of primary closure of a large groin skin defect.Materials and Methods: In 3 patients with large volume inguinal lymph node metastases with skin breakdown and secondary infection extensive inguinal lymphadenectomy was done with wide surgical excision of skin and subcutaneous tissue. The procedures resulted in a large groin defect. Sartorius muscle was transferred to cover the femoral vessels. An abdominal advancement cutaneous flap was placed for soft tissue and skin coverage of the wound.Results: Primary closure of a large skin defect was possible using an abdominal advancement flap. In all patients the wound healed primarily with good cosmesis. A single patient underwent postoperative external beam radiation therapy to the flap site with no untoward effect on graft survival.Conclusions: Large groin skin defects can be closed primarily using an abdominal advanceme...

INTRODUCTION AND OBJECTIVES: The choice to terminate active surveillance (AS) for localized prostate cancer in favor of initiating definitive treatment is based on a variety of factors. These may include pathologic change on re-biopsy, progression in PSA or DRE, or patient preference. The relative extent to which each of these factors plays a role in the termination of AS is not clearly established. Our objective was to determine the prevalence of prostate re-biopsy and subsequent pathologic change in an AS cohort. METHODS: Under IRB approved protocol, a historical cohort study of men diagnosed with prostate cancer was performed at a single tertiary-care center between 1991 and 2011. Although AS had been practiced throughout this period, in 2008 our group agreed upon a protocol for repeat biopsy at 12-18 months after diagnosis. Subsequent biopsy was left to the discretion of the treating physician. Only men with active surveillance as the initial management option were included. RESULTS: The median follow-up was 4.5 years for the 623 patients included in the study. Median PSA at diagnosis was 5.1 ng/mL. 96.2% (600/623) of patients were Gleason 6, 3.7% (23/623) were Gleason 7 and 89.9% (561/623) were stage T1c. 378 (60.1%) patients underwent re-biopsy. The number of re-biopsies ranged from 1 – 7 with 125 (33.1%) patients having more than one re-biopsy. Findings on initial re-biopsy revealed prostate cancer in 70.9% (268/378), benign tissue in 21.2% (80/378), PIN in 6.4% (24/378), and atypia in 1.6% (6/378). The Gleason sum increased in 17.9% of patients whose re-biopsy revealed cancer. Cancer volume increased (expressed as percentage of positive cores in quartiles) in 25.7% of patients on re-biopsy. Of 149 patients who required active treatment, 45.0% (67/ 149) was due to pathologic progression. CONCLUSIONS: We identified a significant proportion of Gleason upgrading and volume progression on repeat biopsy in this cohort. Repeat biopsy often resulted in a significant change in management of our AS population. These findings support the critical role of repeat biopsy in an AS protocol.

INTRODUCTION AND OBJECTIVES: Patients with persistently elevated PSA despite multiple negative prostate biopsies pose a difficult clinical problem. We report our experience with the use of transperineal template-guided prostate biopsy for such patients. METHODS: A retrospective review was performed of patients with at least 2 negative prostate biopsies who underwent transperineal template-guided biopsy at the Massachusetts General Hospital. All patients underwent transperineal biopsy using a standard brachytherapy grid and transrectal ultrasound guidance under general anesthesia. Electronic medical records were reviewed to obtain relevant clinical, laboratory, and pathologic data. RESULTS: A total of 16 patients with a mean age of 64.6 4.4 years underwent transperineal template-guided prostate biopsy from 1/2009 through 9/2010. Mean number of prior biopsies per patient was 3.6 1.6 (range 2 – 7), including 5 (31.3%) patients who had prior negative TUR biopsy. Mean PSA, prostate volume, PSA density, and PSA velocity were 23.8 16.1 ng/ml, 62.5 31.3 ml, 0.46 0.42 ng / ml2, and 3.7 3.3 ng/ml/yr, respectively. A mean of 22.8 8.5 cores were obtained at biopsy. Prostate cancer was detected in 9 (56.3%) of the 16 patients. Of these, 8 (88.9%) patients had cancer in the anterior prostate. The distribution of Gleason score was as follows: 3 3 (n 4), 3 4 (n 2), 4 3 (n 1), 5 4 (n 1), focal 3 (n 1). Of the 9 patients with a diagnosis of cancer, 4 underwent radical prostatectomy, 1 elected active surveillance, 2 elected radiation therapy, and 2 were deciding therapy at the time of follow-up. Of the 7 patients with no cancer detected, 5 patients had no clinical change at a mean follow-up of 10.6 months and 2 patients were without follow-up data. One-way analysis of variance (ANOVA) was performed to compare variables between patients with and without detection of cancer (Table 1). Only prostate volume and PSA density were significantly different between the groups. CONCLUSIONS: Transperineal template-guided prostate biopsy is an effective technique for detecting cancer in patients with persistently elevated PSA despite multiple negative biopsies. This may result from improved sampling of the anterior prostate as suggested by the high proportion of such cancers in this series.

INTRODUCTION AND OBJECTIVES: Radiofrequency ablation (RFA) is an effective alternative treatment for renal cell carcinoma (RCC) in patients with significant surgical risk due to comorbidity. Complications due to heat conduction to surrounding tissues are reported in 8–13% of RCC patients undergoing RFA, and result in significant increased risk of morbidity and mortality. The objective of this study is to identify risk factors for complications based on renal tumor characteristics, in an effort to improve patient selection criteria for RFA. METHODS: We retrospectively reviewed the outcomes of 274 consecutive patients who underwent RFA for RCC between 1998 and 2008. A total of 311 tumors were treated. Mean follow-up was 4.1 years (SD 2.4). Baseline patient demographics, tumor characteristics including tumor size, location, and number of treatments were examined. Post-operative complications were graded as 0 (none), 1 (minor deviation from postoperative course), 2 (systemic therapy, including transfusion), 3 (surgical or procedural intervention), 4 (major morbidity) and 5 (fatal) according to the Clavien system of classification based on the most severe complication. RESULTS: The overall complication rate was 19.3% (n 53). A total of 14 (5.1%) of patients had moderate to severe (Clavien 3–5) complications and 39 (14%) patients had minor (Clavien 1–2) complications. Patients with centrally located tumors were more likely to develop Clavien grade 3–5 complications (p 0.016) than patients with exophytic or peripherally located tumors. Increased tumor size was significantly associated with increased risk of complications (p 0.02). Significant complications included bowel injury resulting in a fistula which resulted in a mortality, 7 ureteral strictures or obstructions, 5 cases of bleeding requiring transfusion, and 3 cases of significant RFA access tract or perinephric infections/abscesses. General anesthesia was associated with more severe complications (p 0.0001) in comparison to conscious sedation, including two cases of cardiorespiratory arrest. CONCLUSIONS: We report a 19.3% overall complication rate with a 5.1% rate of Clavien grade 3–5 complications after RFA for RCC. Complication rates from RFA are increased in patients with large, centrally located tumors tumors. In patients with higher surgical risk considering RFA, appropriate tumor selection for thermal ablation remains of paramount importance. The management of large and centrally located tumors should be considered when counseling patients regarding management options.

Editorial Comment: The authors review the current state of medical information referable to pheochromocytoma. Urinary catecholamine levels are often positive when a pheochromocytoma is present. Platelet catecholamine levels may also be helpful in the diagnosis. Rarely, pharmacological tests, such as pentolinium suppression, clonidine suppression and glucagon provocation, are in order when the aforementioned levels are negative. Computerized tomography, magnetic resonance imaging and metaiodobenzylguanidine scanning are the imaging modalities that are most appropriate. All but 2% of pheochromocytomas are abdominal. Associated conditions, such as adrenal cortical stimulation by adrenocorticotropic hormone produced by the pheochromocytoma, renal artery stenosis, cholelithiasis and cardiac myopathy may also be present. Of course, surgical extraction is generally curative. W. Scott McDougal, M.D.

We previously reported that chronic urinary diversion through intestinal segments may have adverse effects on bone and mineral metabolism. This study examined the long-term health of patients managed by urinary diversion (94% by ileal conduit) for neuropathic bladders secondary to myelomeningocele defects and compared them to a control population of myelomeningocele patients managed by intermittent catheterization. Of the patients 93 were studied by personal interview, chart review, morphometric analysis, serum studies and dual-photon bone density determination. Average followup was 23 +/- 6 years in the urinary diversion group and 17 +/- 5 years in the intermittent catheterization group. Fractures occurred in 40% of the patients in both groups. Patients with a urinary diversion had an increased need for surgery to correct spinal curvature (57% versus 40%) and a significantly increased incidence of complications resulting from orthopedic procedures (17% versus 3%, p less than or equal to 0.05). There was also an adverse effect on renal function. The urinary diversion group had an increased incidence of radiographic renal deterioration (57% versus 8%, p less than 0.001), nephrolithiasis (43% versus 2%, p less than 0.001), pyelonephritis (60% versus 21%, p less than 0.001) and intermittent metabolic acidosis (20% versus 5%, p = 0.05). Surgery was required in 37% for stomal complications and in 17% for ureterointestinal stricture. Linear growth was adversely affected by urinary diversion. Patients with urinary diversion had decreased lengths for all morphometric parameters and a greater percentage of them were at or below the 10th percentile standards. Serum electrolytes, liver function studies, vitamin D3 and parahormone showed no differences in the 2 groups. No patient had a significant metabolic acidosis at the time of study. Bone densities were significantly diminished in both groups and not significantly different. This study strongly suggests that urinary diversion through intestinal segments is associated with adverse effects on bone health.

Previous investigators have suggested that urinary tract infections with urea-splitting organisms may be a primary etiologic factor in the acidosis which is seen after urinary diversion. This study employs a model in which small intestinal segments are perfused with an artificial urine solution over a three hour period. Urease is then added in order to determine its effect on acid-base balance and net intestinal electrolyte transport. Urease created no significant increase in acid load (delta HCO3- = -7.5 +/- 2.2 for controls vs. -8.7 +/- 2.9 for urease group), but did increase the osmolality of the intestinal contents and resulted in a 24% increase in free water loss (p = .037). Analysis of sodium and chloride movement following the addition of urease to the perfusate suggests that both ammonium and bicarbonate are absorbed by the intestinal segment. Thus any acidosis resulting from increased ammonium absorption following the addition of urease appears to be offset by concomitant bicarbonate absorption. The azotemia of urinary diversion appears to be primarily the result of urea absorption, partially the result of ammonium absorption, and is not significantly increased by urease.

Purpose: We evaluate the effect of the provision of postgraduate educational material on improving practitioner knowledge base during a 3-year period.Materials and Methods: A total of 210 urologists were provided 67 monographs in a 2-year period. They were given a pretest before and posttest 1 year after receipt of all monographs.Results: There was significant improvement in posttest scores for the group as a whole. Improvement correlated with years post-training and number of monographs read. Multivariate analysis revealed the number of monographs read was the only independent predictor of outcome.Conclusions: Although the improvement in test scores was significant and did correlate with the postgraduate educational material read, it was modest. This finding raises significant concerns about the usefulness of this format for graduate medical education.