Adnexal smooth muscle hyperplasia resulting in non-traumatic testicular dislocation: A case report.

Tumors of the para-testicular adnexa are very rare and are typically histologically diagnosed as adenomatoid neoplasms, leiomyomata, or smooth muscle hyperplasia. Though these masses are usually benign, the potential for malignancy and mass effect causing intrascrotal discomfort necessitate proper diagnosis and excision. Herein, we describe a unique case of gradual, atraumatic testicular dislocation in a 40-year-old male caused by smooth muscle hyperplasia of the testicular adnexa affecting the epididymis and vas deferens. This case highlights the diagnostic and surgical challenges associated with this presentation.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Surgical and Oncological Outcomes in Patients After Vascularised Flap Reconstruction for Locoregionally Advanced Penile Cancer.

BACKGROUND: Treatment of locoregionally advanced penile squamous cell carcinoma (LAPSCC) is challenging. The exact role (in terms of oncological benefit) of extensive surgery is not well established. Moreover, surgery invariably leads to large defects requiring reconstructive surgery. Rectus abdominis myocutaneous (RAM) and abdominal advancement flaps have an independent and constant blood supply, are easily harvested, and provide substantial skin coverage and soft tissue. OBJECTIVE: To determine the surgical and oncological outcomes in patients with LAPSCC undergoing surgical resection with RAM flaps. DESIGN, SETTING, AND PARTICIPANTS: From 2002 to 2016, a multi-institutional database identified 15 LAPSCC patients undergoing flap reconstructions. INTERVENTION: Local surgical resection with RAM or abdominal advancement flap reconstruction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative and pathologic data were collected. Postoperative complications were identified using the Clavien-Dindo classification for surgical complications. RESULTS AND LIMITATIONS: Fifteen patients (median age 61 yr) were treated, ten with curative intent. Thirteen patients received induction chemotherapy. Thirteen of the 15 patients (87%) experienced wound complications, including five Clavien-Dindo grade III complications. In 11/15 patients (73%), the disease recurred (median recurrence-free interval 106 d). The majority of recurrences (91%) were locoregional, and in four cases the patient also had lesions in distant organs. Ten of the 15 patients (67%) died of their disease. The overall median follow-up interval was 10.5 mo. The study was limited by its retrospective design, the absence of quality-of-life measurements, and the cohort size. CONCLUSIONS: The results of this study show that surgical resection with reconstruction is associated with a risk of perioperative complications, including high-grade Clavien-Dindo complications. With a cure rate of 27%, surgery must be carefully considered and there is a need for alternative treatments. Lack of robust quality-of-life-data is also a serious shortcoming in the decision process for this patient category. PATIENT SUMMARY: Surgery in locoregionally advanced penile cancer has a low cure rate. Reconstruction of defects is surgically feasible, albeit with a high risk of complications. Furthermore, decision-making lacks robust data on quality of life after surgery.

Trends in Insurance Status during Initial Presentation of Testicular Carcinoma: Examining Health Outcomes and Implications of Health Reform for Young Adults in the United States.

INTRODUCTION: We evaluated trends in insurance status, and assessed socioeconomic factors associated with clinically metastatic testicular cancer presentation and potential barriers to treatment in the United States. METHODS: The National Cancer Database was queried for patients with testicular germ cell tumors diagnosed from 2004 to 2014. Temporal trends and forecast of insurance status were examined in the years before and after the ACA (Affordable Care Act) was enacted. Multivariable logistic regression was used to assess predictors of clinically metastatic presentation. RESULTS: A total of 58,348 patients were identified with 37.95% presenting with clinically metastatic disease. The uninsured rate remained relatively unchanged during the years before and after the ACA was enacted (11.7% vs 11.9%, respectively). Predictors for clinically metastatic presentation were Medicaid (OR 2.12, 95% CI 1.80-2.50), Medicare (OR 1.35, 95% CI 1.13-1.60) and uninsured status (OR 1.41, 95% CI 1.22-1.64) compared to privately insured patients. A forecast model revealed no significant changes in the uninsured rate (11.58% to 11.60%) for 2015 through 2017. CONCLUSIONS: Socioeconomic disparities continue to be barriers for young adults presenting with testicular cancer in the United States. Longer prospective followup will be required to assess the impact of payer status with the reportedly increased health coverage fostered by the ACA.

Advancements in staging and imaging for penile cancer.

PURPOSE OF REVIEW: We review recent advancements in staging and imaging of penile cancer, including surveillance after therapy. RECENT FINDINGS: For cN0 patients, the sentinel lymph node biopsy is currently considered the preferred way for invasive staging. It has largely replaced other modalities such as staging inguinal lymphadenectomy. Its diagnostic value increases when combined with other staging modalities such as ultrasound with fine-needle aspiration cytology (US-FNAC) or fluorodeoxyglucose-PET with computed tomography (PET/CT). In patients with palpably suspicious nodes (cN+), imaging is more useful. PET/CT has shown good accuracy in a limited number of small studies. US-FNAC can confirm nodal metastatic disease. A staging inguinal lymphadenectomy is of therapeutic value but is associated with significant morbidity. Omitting staging inguinal lymphadenectomy was recently described; one study showed well tolerated use of sentinel lymph node biopsy combined with intraoperative ultrasound-guided resection of suspicious nodes in cN+ patients. Therapeutic inguinal lymphadenectomy was only performed in the 42% of groins with metastases confirmed by disorder. For M-staging, PET/CT has shown good sensitivity, and its role should be further evaluated. Follow-up and surveillance rely on physical examination and US-FNAC. SUMMARY: Over the past decade, staging and treatment of penile cancer have become less invasive, while survival tends to improve.

Contemporary management of patients with penile cancer and lymph node metastasis.

Penile cancer is a rare disease that causes considerable physical and psychological patient morbidity, especially at advanced stages. Patients with low-stage nodal metastasis can achieve durable survival with surgery alone, but those with extensive locoregional metastasis have overall low survival. Contemporary management strategies for lymph node involvement in penile cancer aim to minimize the morbidity associated with traditional radical inguinal lymphadenectomy through appropriate risk stratification while optimizing oncological outcomes. Modified (or superficial) inguinal lymph node dissection and dynamic sentinel lymph node biopsy are diagnostic modalities that have been recommended in patients with high-risk primary penile tumours and nonpalpable inguinal lymph nodes. In addition, advances in minimally invasive and robot-assisted lymphadenectomy techniques are being investigated in patients with penile cancer and might further decrease lymphadenectomy-related adverse effects. The management of patients with advanced disease has evolved to include multimodal treatment with systemic chemotherapy before surgical intervention and can include adjuvant chemotherapy after pelvic lymphadenectomy. The role of radiotherapy in the neoadjuvant or adjuvant setting remains largely unclear, owing to a lack of high-level evidence of possible benefits. New targeted therapies have shown efficacy in squamous cell carcinomas of other sites and might also prove effective in patients with penile cancer.

Neoadjuvant Chemotherapy in Elderly Patients With Bladder Cancer: Oncologic Outcomes From a Single Institution Experience.

INTRODUCTION: We conducted this study to determine if, in appropriately selected elderly patients receiving neoadjuvant chemotherapy (NAC), clinical outcomes including pathologic complete response/downstaging and overall survival were similar to a younger cohort. METHODS: Chart review was performed on patients receiving NAC for urothelial carcinoma of the bladder (UCB) from 2004 to 2013. A total of 116 patients were identified that underwent NAC from 2004 to 2013 for ≥ cT2N0M0 UCB. Patients were excluded who received 2 cycles or less of chemotherapy (N = 18; 11 patients in the younger cohort, 7 in the elderly group; P = .74). Data was analyzed, and Kaplan-Meir analysis curves were used for survival and recurrence. RESULTS: Forty-six elderly patients (age ≥ 70 years) (67% cisplatin-based regimen) were identified and compared with 70 (93% cisplatin-based regimen) younger patients. The estimated glomerular filtration rate, performance status, preoperative hemoglobin, and body mass index were significantly worse in elderly patients. Dose reduction and pathologic downstaging to non-muscle-invasive disease was not statistically different between older and younger patients Complete pathologic response in older patients (16%) and in the younger cohort (17%) were similar (P = .146). There was no significant difference in follow-up, recurrence, or in median overall survival between patient groups (28 months elderly vs. 35 months younger; P = .78). Age was not an independent predictor of pathologic downstaging, complete response, overall survival, or recurrence-free survival. CONCLUSIONS: NAC in elderly patients (≥ 70 years old) demonstrated equivalent toxicity and oncologic outcomes in our single-institution cohort. Although older patients had significantly poorer performance status and renal function, there were no differences in survival or response to NAC.

Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach.

The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa. However, other than smoking cessation, there is a paucity of research that systematically examines agents for chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism based approach, the goal of this review is to summarize epidemiological, in vitro, and preclinical studies, including data regarding the safety, bioavailability, and efficacy of agents evaluated for bladder cancer chemoprevention. Based on the available studies, phytochemicals, specifically isothiocyanates such as sulforaphane, present in Brassicaceae or "cruciferous" vegetables in the precursor form of glucoraphanin are: (a) available in standardized formulations; (b) bioavailable- both systemically and in the bladder; (c) observed to be potent inhibitors of BC carcinogenesis through multiple mechanisms; and (d) without toxicities at these doses. Based on available evidence from epidemiological, in vitro, preclinical, and early phase trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane (SFN) represent a promising potential chemopreventitive agent in bladder cancer.

Bilateral benign renal oncocytomas and the role of renal biopsy: single institution review.

BACKGROUND: The goal was to assess the natural history and management of patients with pathologically proven bilateral (synchronous) RO after undergoing initial partial nephrectomy (PN). METHODS: All patients underwent either robotic/laparoscopic or open PN by two experienced genitourinary oncologists from 2005-2013. Final pathology was determined by surgical excision, CT-guided percutaneous core biopsy (CT-biopsy) or fine needle aspiration (FNA). Patient demographics, tumor characteristics (pathologic data, location, size) type of surgery, pre/post estimated glomerular filtration rate (eGFR) and surgical complications were recorded. RESULTS: Twelve patients were identified with bilateral RO. Median age at the time of surgery was 68 years (46-77) (Table 1). The median size of the largest tumor(s) resected was 2.75 cm (1.5-5.5 cm) and second largest tumor(s) was 1.75 cm (1.0-4.0 cm). Four patients underwent bilateral staged PN and one patient underwent simultaneous bilateral PN (horseshoe kidney). Two patients underwent RFA at the time of biopsy of the contralateral mass after PN. Five patients underwent CT-bx/FNA (5/5) of the contralateral mass followed by active surveillance. Mean follow up was 34 months. There was no significant change in median creatinine pre- and post-operatively. One patient was lost to follow up and one patient died of unknown causes 5 years post-operatively. eGFR decreased an average of 16.96% post-operatively, including a single patient whose eGFR increased by 7.8% after surgery and a single patient whose eGFR did not change (Table 2). CONCLUSIONS: Patients with bilateral renal masses and pathologically proven RO can be safely managed with active surveillance after biopsy confirmation of the contralateral mass.

Need for Evidence and Consensus on Laser Treatment for Management of Select Primary Penile Tumors.

Laser ablation for low-risk primary penile tumors (Ta, Tis, and T1, preferably of low grade) offers satisfactory oncologic outcomes and excellent functional outcomes. Patients require long-term close surveillance given the substantial likelihood of local recurrence, and must adhere to strict follow-up protocols.

Chemoprevention in African American Men With Prostate Cancer.

BACKGROUND: Recommendations for cancer screening are uncertain for the early detection or prevention of prostate cancer in African American men. Thus, chemoprevention strategies are needed to specifically target African American men. METHODS: The evidence was examined on the biological etiology of disparities in African Americans related to prostate cancer. Possible chemopreventive agents and biomarkers critical to prostate cancer in African American men were also studied. RESULTS: High-grade prostatic intraepithelial neoplasia may be more prevalent in African American men, even after controlling for age, prostate-specific antigen (PSA) level, abnormal results on digital rectal examination, and prostate volume. Prostate cancer in African American men can lead to the overexpression of signaling receptors that may mediate increased proliferation, angiogenesis, and decreased apoptosis. Use of chemopreventive agents may be useful for select populations of men. CONCLUSIONS: Green tea catechins are able to target multiple pathways to address the underlying biology of prostate carcinogenesis in African American men, so they may be ideal as a chemoprevention agent in these men diagnosed with high-grade prostatic intraepithelial neoplasia.

Intravesical Hemostatic Clip Migration After Robotic Prostatectomy: Case Series and Review of the Literature.

INTRODUCTION: The Weck Hem-o-lok™ Ligating clip is a routinely used hemostatic tool in robotic and laparoscopic surgery. It has been the practice in our institution to use such clips for hemostasis of the vascular bundles during robotic prostatectomy. Migration of such clips has been reported in the literature as single case reports. In this study, we present a case series of intravesical Weck clip extrusions presenting as bladder calculi. Such events have led to a change in our practice, and more research is needed to assess the impact of this change. MATERIALS AND METHODS: A retrospective chart review was conducted over the period 2006-2011. Patients included in the study required cystoscopic intervention for removal of encrusted or impacted Weck clips. Primary data points included type of intervention required, time to presentation, and number of presentations. Postoperative anastomotic leak, duration of postoperative hospital stay, and initial operative time were also investigated. RESULTS: Out of 570 total men undergoing robotic-assisted laparoscopic radical prostatectomy (RALRP), eight required return to the operating room for clip extraction (1.4%). Extraction methods included laser lithotripsy, blunt litholapaxy, and grasper extraction. Men experiencing clip migration were hospitalized for a longer period of time (7.6 days vs. 2.1 days, P < .01) and they required more blood transfusions (1.4 units vs. 0.05 units, P < .01) than men who did not experience clip migration. The most common site for clip intrusion was the bladder neck. Average time to presentation was 1.75 years. DISCUSSION: Weck clip migration is a recognized complication of robotic-assisted radical prostatectomy. Men with recurrent urinary tract infection, bothersome voiding symptoms, or hematuria following RALRP should be considered for cystoscopic evaluation. Increased length of hospital stays and the need for a larger volume blood transfusion following prostatectomy were significant predictors of clip migration. More research is needed to determine if implemented changes to our surgical technique have mitigated these risks.

Contemporary Issues Surrounding Small Renal Masses: Evaluation, Diagnostic Biopsy, Nephron Sparing, and Novel Treatment Modalities.

Incidental identification of small renal masses (SRMs) has become increasingly common with widespread adoption of cross-sectional imaging. To date, early detection of SRMs has not translated to a substantial improvement in cancer-specific survival. Guidelines on the management of SRMs are evolving to reflect recent developments in treatment. The major approaches to managing SRMs include active surveillance, partial/radical nephrectomy, and ablative therapies, such as radiofrequency ablation with cryoablation. The goal of treatment is to optimize oncologic and renal function outcomes while avoiding overtreatment and associated morbidity. In this review, we summarize the diagnosis of SRMs, the role of renal mass biopsy, different treatment strategies, and future directions, including emerging molecular biomarkers.

Management of Penile Cancer.

Although rare, penile cancer carries high morbidity and mortality particularly when pertaining to the management of locally advanced or metastatic disease. The current scientific literature lacks level 1 evidence and current guidelines are based largely on retrospective studies and small single center studies. Despite these limitations, there has been paradigm shifts in the management of both local and systemic disease. Current guidelines emphasize penile sparing strategies, minimizing morbidity from surgical management of loco-regional metastasis and multimodal management of bulky inguinal lymph node metastases. The present review highlights the current state of knowledge and recommended treatment strategies of penile carcinoma.

Atypical Small Acinar Proliferation: Repeat Biopsy and Detection of High Grade Prostate Cancer.

Purpose. Atypical small acinar proliferation (ASAP) is diagnosed in 1-2% of prostate biopsies. 30-40% of patients with ASAP may be diagnosed with prostate cancer (PCa) on repeat biopsy. Our objective was to examine the association between ASAP and subsequent diagnosis of intermediate/high risk PCa. Materials and Methods. Ninety-six patients who underwent prostate biopsy from 2000 to 2013 and were diagnosed with ASAP were identified. Clinicopathologic features were analyzed. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. Results. 56/96 (58%) patients had a repeat biopsy. 22/56 (39%) were subsequently diagnosed with PCa. There was no significant difference in patients' characteristics. Presence of HGPIN on initial biopsy was associated with a benign repeat biopsy (68% versus 23%). 17/22 (77%) had Gleason grade (GG) 3+3 disease and only 5/22 (23%) had GG 3+4 disease. Conclusions. 22/56 patients (39%) of patients who underwent a subsequent prostate biopsy following a diagnosis of ASAP were found to have PCa. 77% of these men were diagnosed with GG 3+3 PCa. Only 23% were found to have intermediate risk PCa and no high risk PCa was identified. Immediate repeat prostate biopsy in patients diagnosed with ASAP may be safely delayed. A multi-institutional cohort is being analyzed.

Rectal swab culture-directed antimicrobial prophylaxis for prostate biopsy and risk of postprocedure infection: a cohort study.

OBJECTIVE: To examine the effect of rectal swab culture-directed prophylaxis on the incidence of prostate biopsy-associated infections. Secondary objectives were to determine the rate of fluoroquinolone resistance and extended-spectrum beta-lactamase production in local rectal flora. METHODS: All men receiving prostate biopsies from February 2013 to February 2014 were included in a retrospective institutional review board-approved study. All received either a preprocedural rectal swab and culture-directed antimicrobial prophylaxis or routine fluoroquinolone antibiotics. Clinical information was collected on infectious complications treated within 30 days of biopsy. Chi-square test, Fisher exact test, and Welch t test were used for statistical analysis. Confounding variables were included in a multivariate logistic regression model. RESULTS: Of 487 total patients, 314 received preprocedure rectal cultures and 173 did not. Average ages were 62.7 and 64.1 years, respectively (P = .07). There was no difference in mean prostate-specific antigen value (P = .9), Charlson comorbidity score (P = .8), or ethnicity (P = .1). The rectal swab group was more likely to receive supplemental gentamicin (P < .001) and had fewer infectious complications (1.9% vs 2.9%; P = .5). On multivariate analysis, decreased odds of infection was associated with culture-directed antibiotics (odds ratio, 0.70; 95% confidence interval, 0.20-2.50; P = .6). However, the study was only powered to detect a 97% reduction in infections. The incidence of fluoroquinolone resistance and extended-spectrum beta-lactamase production was 12.1% and 0.64%, respectively. CONCLUSION: Our study was underpowered but suggests that there are lower odds of infection with rectal swab-directed antimicrobial prophylaxis. The local incidence of fluoroquinolone resistance is high. A prospective, randomized, controlled trial is warranted to further evaluate this intervention.

Hand-assisted laparoscopic versus robot-assisted laparoscopic partial nephrectomy: comparison of short-term outcomes and cost.

INTRODUCTION: Robot-assisted laparoscopic partial nephrectomy (RALPN) and laparoscopic partial nephrectomy (LPN) have become standard for the surgical management of small renal masses (SRMs). However, no studies have evaluated the short-term outcomes or cost of RALPN as compared with hand-assisted laparoscopic partial nephrectomy (HALPN) in a standardized fashion. METHODS: A retrospective review of all patients who underwent HALPN or RALPN from 2006 to 2010 were assessed for patient age, body mass index (BMI), American Society of Anesthesiologists (ASA) score, radiographic tumor size, nephrometry (radius, endo/exophytic, nearness to collecting system, anterior/posterior, lines of polarity [RENAL]) scores, operative and room times, hospital length of stay (LOS), estimated blood loss (EBL), requirement of hilar vessel clamping, warm ischemia time (WIT), pre- and postprocedural creatinine and hemoglobin levels, and complications. Total costs of the procedures were estimated based on operating room component (operative staff time, anesthesia, and supply) and hospital stay cost (room and board, pharmacy). A robotic premium cost, estimated based on the yearly overall cost of the da Vinci S surgical system divided by the annual number of cases, was included in the RALPN cost. Cost figures were obtained from hospital administration and applied to the mean HALPN and RALPN patient. RESULTS: Forty-seven patients underwent HALPN since 2006 and 21 patients underwent RALPN since 2008. ASA, BMI, EBL, tumor size, nephrometry score, positive margin rate, change in creatinine, change in hemoglobin, morphine equivalents used, and complication rate were all similar in both groups (p>0.05). Room time and operative time were significantly shorter for the HALPN cohort (p=0.001) whereas LOS was significantly shorter in the RALPN cohort (p=0.019). Despite the shorter LOS, RALPN was associated with a $1165 increased cost, mainly due to increased operating room time and premium cost of the robot. CONCLUSIONS: While early in our experience, RALPN offered no significant advantage in short-term outcomes over HALPN and was associated with an increased cost of over $1150.

How do nonprofit hospitals manage earnings?

We hypothesize that, unlike for-profit firms, nonprofit hospitals have incentives to manage earnings to a range just above zero. We consider two ways managers can achieve this. They can adjust discretionary spending [Hoerger, T.J., 1991. 'Profit' variability in for-profit and not-for-profit hospitals. Journal of Health Economics 10, 259-289.] and/or they can adjust accounting accruals using the flexibility inherent in Generally Accepted Accounting Principles (GAAP). To test our hypothesis we use regressions as well as tests of the distribution of earnings by Burgstahler and Dichev [Burgstahler, D., Dichev, I., 1997. Earnings management to avoid earnings decreases and losses. Journal of Accounting and Economics 24, 99-126.] on a sample of 1,204 hospitals and 8,179 hospital-year observations. Our tests support the use of discretionary spending and accounting accrual management. Like Hoerger (1991), we find evidence that nonprofit hospitals adjust discretionary spending to manage earnings. However, we also find significant use of discretionary accruals (e.g., adjustments to the third-party-allowance, and allowance for doubtful accounts) to meet earnings objectives. These findings have two important implications. First, the previous evidence by Hoerger that nonprofit hospitals show less variation in income may at least partly be explained by an accounting phenomenon. Second, our findings provide guidance to users of these financial statements in predicting the direction of likely bias in reported earnings.

Abnormal returns and the regulation of nonprofit hospital sales and conversions.

During the 1990s, concerns that nonprofit (NP) hospitals were being sold at below-market prices to investor-owned (IO) chains helped to prompt the widespread adoption of state laws regulating the sale and conversion of nonprofits. In this paper, we provide a simple test of under-pricing using the IO acquirer's abnormal stock market returns at the time of the acquisition. Prior to regulation, we find that IO chains did not earn abnormal returns from their acquisitions of NPs and earned greater returns from purchasing other IO and privately owned hospitals. In states that subsequently adopted regulations, acquisition activity slowed significantly and acquirer returns became negative. Efficient markets theory suggests that, absent regulation, expected merger synergies were already being transferred to the NP target and that regulation may have reduced expected synergies or increased the costs of acquiring NP hospitals.