Short-course radiation with consolidation chemotherapy does not increase operative morbidity compared to long-course chemoradiation: A retrospective study of the US rectal cancer consortium.

BACKGROUND AND OBJECTIVES: Neoadjuvant short-course radiation and consolidation chemotherapy (SC TNT) remains less widely used for rectal cancer in the United States than long-course chemoradiation (LCRT). SC TNT may improve compliance and downstaging; however, a longer radiation-to-surgery interval may worsen pelvic fibrosis and morbidity with total mesorectal excision (TME). A single, US-center retrospective analysis has shown comparable risk of morbidity after neoadjuvant short-course radiation with consolidation chemotherapy (SC TNT) and long-course chemoradiation (LCRT). Validation by a multi-institutional study is needed. METHODS: The US Rectal Cancer Consortium database (2010-2018) was retrospectively reviewed for patients with nonmetastatic, rectal adenocarcinoma treated with neoadjuvant LCRT or SC TNT before TME. The primary endpoint was severe postoperative morbidity. Cohorts were compared by univariate analysis. Multivariable logistic regression modeled the odds of severe complication. RESULTS: Of 788 included patients, 151 (19%) received SC TNT and 637 (81%) LCRT. The SC TNT group had fewer distal tumors (33.8% vs. 50.2%, p < 0.0001) and more clinical node-positive disease (74.2% vs. 47.6%, p < 0.0001). The intraoperative complication rate was similar (SC TNT 5.3% vs. 4.4%, p = 0.65). There was no difference in overall postoperative morbidity (38.4% vs. 46.3%, p = 0.08). Severe morbidity was similar with low anterior resection (9.1% vs. 15.3%, p = 0.10) and abdominoperineal resection (24.4% vs. 29.7%, p = 0.49). SC TNT did not increase the odds of severe morbidity relative to LCRT on multivariable analysis (OR 0.64, 95% CI 0.37-1.10). CONCLUSIONS: SC TNT does not increase morbidity after TME for rectal cancer relative to LCRT. Concern for surgical complications should not discourage the use of SC TNT when aiming to increase the likelihood of complete clinical response.

Is There a Role for Adjuvant Chemotherapy in Pathologic Node-Negative Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiation Therapy?

BACKGROUND: Neoadjuvant chemoradiation therapy (NCRT, 5-fluorouracil and radiation) followed by resection and adjuvant chemotherapy (AC) is one of the standard treatment paradigms for locally advanced rectal adenocarcinoma. However, the utility of AC in patients with pathologic lymph node (pLN)-negative disease is unclear. Our aim is to assess the value of AC stratified by pLN status. METHODS: The US Rectal Cancer Consortium database (2007-2017) was retrospectively reviewed for patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation (NACR) and curative-intent resection. Those who received neoadjuvant systemic chemotherapy or underwent local resection were excluded. Patients were categorized by pLN status. Primary outcome was overall survival (OS). RESULTS: Of 213 patients, 70% had pLN-negative disease and 30% pLN-positive disease. Median age was 57 years, 65% were male, and median follow-up was 31 months. Among patients with pLN-negative disease, 74% received AC. Receipt of AC was not associated with improved 5-year OS (82% versus 74%, respectively; p = 0.16). This finding persisted on multivariable analysis. Of patients with pLN-positive disease, 83% received AC. Patients with pLN-positive disease demonstrated improved 5-year OS with receipt of AC (72% compared with 0% with no adjuvant chemotherapy, p = 0.04). CONCLUSION: After receiving neoadjuvant chemoradiation, adjuvant chemotherapy for patients with pLN-negative disease does not appear to be associated with improved survival. Further validation and prospective studies are needed to evaluate the utility of adjuvant chemotherapy in this setting.

Patient Perspectives on Defining Textbook Outcomes Following Major Abdominal Surgery.

BACKGROUND: The composite metric textbook outcome (TO) has recently gained interest as a novel quality measure. However, the criteria for defining a TO have not been rigorously defined and patient perspectives on the characteristics of TO are unknown. METHODS: Patients who underwent major abdominal surgery at a single tertiary care center were administered a customized survey designed to ascertain their perspectives on defining TOs. The relationship between patient-reported and clinically defined TO rates was compared. RESULTS: Among 79 patients who underwent gastrointestinal (51%), pancreatic (29%), hepatic (18%), or other major abdominal (3%) operations, 57% were female and 86% had an ASA class ≥3. Most patients underwent surgery for malignancy (87%) with 60% undergoing an open operation. Patients most commonly valued no mortality following surgery (96%), no reoperation (75%), and having a margin negative resection (73%) as "extremely important." In contrast, those outcomes that were most commonly valued as "not important at all" or "minimally important" were receiving a blood transfusion (24%) and not having any complications (13%). Using previously published criteria for TOs, 47 (60%) patients were classified as having a clinically defined TO; in contrast, 68 patients (86%) self-reported their outcome was textbook. Self-reported responses were concordant with clinically defined TO criteria 63% of the time (McNemar's test: S=15.2, p<0.01, evidence of disagreement). CONCLUSION: There was significant discordance between patient-reported versus clinically defined measures of TOs, suggesting patients value other considerations beyond traditional factors when evaluating the success of their surgery. Future studies should delineate these relationships and incorporate these factors to refine TO definitions.

Radiological assessment of persistent retroperitoneal and lateral pelvic lymph nodes after neoadjuvant therapy for rectal cancer: An analysis of the United States Rectal Cancer Consortium.

INTRODUCTION: Management of retroperitoneal and lateral pelvic lymph nodes (RLPN) in rectal cancer remains unclear. With total neoadjuvant therapy (TNT), more patients have radiologic complete clinical response (rCR). We sought to evaluate the impact of radiographic persistent RLPN after neoadjuvant therapy on survival. MATERIALS AND METHODS: Patients with rectal adenocarcinoma with isolated RLPN metastasis, who received neoadjuvant therapy before surgery were included from the United States Rectal Cancer Consortium database. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 77 patients, all received neoadjuvant therapy, with 35 (46%) receiving TNT. Posttreatment, 33 (43%) had rCR while 44 (57%) had radiographic persistent RLPN. Median number of radiographic positive RLPN was 1 (IQR 1-2). Receipt of TNT was associated with radiographic RLPN rCR (OR 4.77, 95% CI 1.81-12.60, p < .01). However, there was no difference in RFS and OS between patients who achieved rCR or with persistent RLPN (all p > .05). CONCLUSIONS: Radiographic persistence of RLPN was not associated with worse survival in well-selected patients and may not be a reliable indicator of pathological response. TNT may be the preferred management strategy to select patients given its association with rCR. Radiographic persistence of RLPN after preoperative therapy should not necessarily preclude surgery.

Hemoglobin A1c Is a Predictor of New Insulin Dependence After Partial Pancreatectomy: A Multi-Institutional Analysis.

BACKGROUND: Pancreatic diseases have long been associated with impaired glucose control. This study sought to identify the incidence of new insulin-dependent diabetes mellitus (IDDM) after pancreatectomy and the predictive accuracy of hemoglobin A1c (HbA1c) or blood glucose. METHODS: Patients who underwent partial pancreatectomy and had preoperative HbA1c available at two academic institutions were assessed for new IDDM on discharge in relation to complication rates and survival. RESULTS: Of the 267 patients analyzed, 67% had abnormal HbA1c levels prior to surgery (mean 6.8%, glucose 135 mg/dL). Two hundred eight (77.9%) were not insulin-dependent prior to surgery, and 35 (16.8%) developed new IDDM after resection. On multivariable regression, increasing HbA1c and preoperative glucose were the only significant predictors for new IDDM. Optimal predictive cutoffs (HbA1c of 6.25% and glucose of 121 mg/dL) were determined in a discovery group (n = 143) and confirmed in a validation group (n = 124) with a diagnostic sensitivity of 72.7% and specificity of 84.8%. Patients with new IDDM after resection had higher rates of severe complications (OR 3.39), increased TPN at discharge (OR 4.32), and increased rates of discharge to nursing facilities (OR 2.57) (all P < 0.05). New IDDM was also associated with a decreased cancer-specific survival. CONCLUSION: Preoperative HbA1c ≥ 6.25% and blood glucose ≥ 121 mg/dL can accurately identify patients at increased risk of IDDM. These diagnostics may help identify patients in a preoperative setting that may benefit from interventions such as diabetes education or enhanced glucose control preoperatively.

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies.

BACKGROUND: While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM). STUDY DESIGN: All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge. RESULTS: Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01). CONCLUSION: Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

Impact of Postoperative Complications on Oncologic Outcomes After Rectal Cancer Surgery: An Analysis of the US Rectal Cancer Consortium.

BACKGROUND: Postoperative complications (POCs) are associated with worse oncologic outcomes in several cancer types. The implications of complications after rectal cancer surgery are not well studied. METHODS: The United States Rectal Cancer Consortium (2007-2017) was reviewed for primary rectal adenocarcinoma patients who underwent R0/R1 resection. Ninety-day POCs were categorized as major or minor and were grouped into infectious, cardiopulmonary, thromboembolic, renal, or intestinal dysmotility. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Among 1136 patients, the POC rate was 46% (n = 527), with 63% classified as minor and 32% classified as major. Of all POCs, infectious complications comprised 20%, cardiopulmonary 3%, thromboembolic 5%, renal 9%, and intestinal dysmotility 19%. Compared with minor or no POCs, major POCs were associated with both worse RFS and worse OS (both p < 0.01). Compared with no POCs, a single POC was associated with worse RFS (p < 0.01), while multiple POCs were associated with worse OS (p = 0.02). Regardless of complication grade, infectious POCs were associated with worse RFS (p < 0.01), while cardiopulmonary and thromboembolic POCs were associated with worse OS (both p < 0.01). Renal POCs were associated with both worse RFS (p < 0.001) and worse OS (p = 0.01). After accounting for pathologic stage, neoadjuvant therapy, and final margin status, Multivariable analysis (MVA) demonstrated worse outcomes with cardiopulmonary, thromboembolic, and renal POCs for OS (cardiopulmonary: hazard ratio [HR] 3.6, p = 0.01; thromboembolic: HR 19.4, p < 0.01; renal: HR 2.4, p = 0.01), and renal and infectious POCs for RFS (infectious: HR 2.1, p < 0.01; renal: HR 3.2, p < 0.01). CONCLUSIONS: Major complications after proctectomy for cancer are associated with decreased RFS and OS. Given the association of infectious complications and postoperative renal dysfunction with earlier recurrence of disease, efforts must be directed towards defining best practices and standardizing care.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

Surgical management of pancreatic neuroendocrine liver metastases.

Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of neoplasms that vary in their clinical presentation, behavior and prognosis. The most common site of metastasis is the liver. Surgical resection of neuroendocrine liver metastases (NELM) is thought to afford the best long-term outcomes when feasible. Initial preoperative workup should include surveillance for carcinoid syndrome, screening for evidence of liver insufficiency, and performance of imaging specific to neuroendocrine tumors such as a somatostatin receptor positron emission tomography scan. Standard surgical principles apply to hepatic surgery for NELM, namely prioritizing low central venous pressure anesthesia, minimizing blood loss, knowledge of liver anatomy, generous use of intraoperative ultrasound, as well as safe parenchymal transection techniques and practices to avoid bile leakage. Knowledge of established prognostic factors may assist with patient selection, which is important for optimizing short- and long-term outcomes of hepatic resection. Adjunct therapies such as concomitant liver ablation are used frequently and are generally safe when used appropriately. For patients with synchronous resectable NELM, resection of the primary either in a staged or combined fashion is recommended. Primary tumor resection in the setting of unresectable metastatic disease is more controversial, however generally recommended if morbidity is acceptable. For patients who are not surgical candidates, due to either patient performance status or burden of liver disease, several liver-directed therapies such as transarterial embolization, chemoembolization, and radioembolization are available to assist with locoregional control, extend progression-free survival (PFS), and improve symptoms of carcinoid syndrome. Multiple systemic therapy options exist for patients with metastatic PNET which are often prioritized for those patients with advanced or progressive disease. A systematic approach in a multi-disciplinary setting is likely to result in the best long-term outcomes for patients with pancreatic NELM. Ongoing research is needed to determine the optimal patient selection for hepatic surgery as well as the ideal treatment sequencing for those patients with NELM.

Analysis of textbook outcomes among patients undergoing resection of retroperitoneal sarcoma: A multi-institutional analysis of the US Sarcoma Collaborative.

BACKGROUND: The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data. METHODS: All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed. RESULTS: Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size <20 cm and low tumor grade, while ASA class ≥3, history of a prior cardiac event, resection of left colon/rectum, distal pancreatic resection, major venous resection and drain placement were associated with not achieving a TO (all P < .05). Achievement of a TO was associated with improved survival (median:12.7 vs 5.9 years, P < .01). CONCLUSIONS: Among patients undergoing resection for RPS, failure to achieve TO is common and associated with significantly worse survival. The use of TO may inform patient expectations and serve as a measure for patient-level hospital performance.

Location, Location, Location: Approaches to Retroperitoneal Vascular Leiomyosarcoma.

Leiomyosarcoma, one of the most common soft tissue sarcomas, can occur anywhere in the body, but it is frequently found in the abdomen and retroperitoneum. When arising in the retroperitoneum, anatomic constraints can have a profound effect on treatment, particularly when these tumors abut or involve the inferior vena cava. Although there have been improvements in systemic and locoregional therapies for leiomyosarcomas, surgery remains the mainstay for management. Herein describes our approach to these tumors.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis.

BACKGROUND: The role of neoadjuvant chemotherapy in the management of colorectal liver metastases remains controversial. We sought to investigate whether neoadjuvant systemic chemotherapy contributes to clinically significant increases in postoperative morbidity and mortality using a population-based cohort. STUDY DESIGN: The American College of Surgeons NSQIP Targeted Hepatectomy Participant Use Files were queried from 2014 to 2016 to identify patients with colorectal liver metastases who underwent liver resection. Patients were stratified by receipt of neoadjuvant chemotherapy using propensity score matching. Univariate and multivariable analyses were used to characterize the effect of neoadjuvant chemotherapy on perioperative morbidity and mortality. RESULTS: After propensity score matching, 1,416 (50%) patients received neoadjuvant chemotherapy before hepatectomy and 1,416 (50%) underwent liver resection without neoadjuvant chemotherapy. There were no differences in age (60 vs 61 years), maximum tumor size (≤5 cm: 79% vs 80%, >5 cm: 21% vs 20%), resection type (partial hepatectomy: 69% vs 70%), simultaneous colectomy (9% vs 9%), or use of preoperative portal vein embolization (5% vs 5%) in those undergoing neoadjuvant chemotherapy compared with those who did not (all, p > 0.05). Overall 30-day postoperative morbidity (34% vs 33%), including rates of biliary fistula (6% vs 5%), post-hepatectomy liver failure (5% vs 5%), and mortality rates (0.8% vs 0.7%), were similar among patients who received neoadjuvant chemotherapy vs those who did not (all, p > 0.05). On multivariable analysis, receipt of neoadjuvant chemotherapy was not associated with increased morbidity (odds ratio 1.07; 95% CI 0.90 to 1.27; p = 0.43) or mortality (odds ratio 1.09; 95% CI 0.44 to 2.72; p = 0.85). CONCLUSIONS: In this propensity-matched population-based cohort study, the use of neoadjuvant systemic chemotherapy was not associated with higher rates of complications, biliary fistula, post-hepatectomy liver failure, or mortality among patients with colorectal liver metastases undergoing liver resection.

Predictors of mortality in the elderly after open repair for perforated peptic ulcer disease.

BACKGROUND: As the U.S. population ages and the number of emergent surgical repairs for perforated peptic ulcer disease (PUD) rise, contemporary national data evaluating operative outcomes for open surgical repair for perforated PUD among the elderly are lacking. MATERIALS AND METHODS: The National Surgical Quality Improvement Program (2007-2014) was queried for patients ≥65 y who underwent open surgical repair for perforated PUD. The primary outcome was 30-d mortality. Secondary outcomes included 30-d postoperative complications. Univariate and multivariable regression analyses were performed. RESULTS: Overall, 2131 patients underwent open surgical repair for perforated PUD. Among those who died, more used steroids preoperatively (15% versus 9%, P = 0.001) and fewer were independent preoperatively (55% versus 83%, P < 0.0001) compared to those who were alive 30-d postoperatively. Common postoperative complications were septic shock (15%) and pneumonia (12%). The overall 30-d mortality rate was 17.7%, with more deaths in subsequent decades of life (65-75 y 13% versus 75-84 y 18% versus >85 y 24%, P < 0.0001). After adjustment for other factors, mortality was significantly associated with older age (85+ versus 65-74 y) (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.8, 1.7), dependent functional status preoperatively ([OR], 0.2; 95% CI, 0.2, 0.3), and American Society of Anesthesiologist classification ≥4 (OR, 3.2; 95% CI, 2.4, 4.3). CONCLUSIONS: At U.S. hospitals, open surgical repair, the accepted treatment of perforated PUD, among the elderly is associated with significant 30-d morbidity and mortality rates that are unacceptably high in our contemporary era. Furthermore, mortality rates are associated with older age. Therefore, as the elderly population continues to increase in the United States, preoperative, perioperative, and postoperative measures must be taken to reduce this high morbidity and mortality rates.

Location is everything: The role of splenic flexure mobilization during colon resection for diverticulitis.

INTRODUCTION: Routine splenic flexure mobilization (SFM) has been previously recommended to ensure an adequate length for a tension free anastomosis during resection for diverticulitis. We sought to evaluate the role of selective SFM for diverticulitis, and its impact on outcomes. MATERIALS AND METHODS: Retrospective review of elective colectomies at a tertiary care center (2007-2015) for left-sided diverticulitis were identified from the National Surgical Quality Improvement Program. Demographics and perioperative characteristics were compared; and 30-day risk-adjusted outcomes were assessed. RESULTS: We identified 208 sigmoid/left colectomy cases. A laparoscopic approach predominated (71%), and SFM was performed in 54% of cases (n = 113). Demographics and comorbidities were similar. Median operative time was greater in the SFM group [226; interquartile range (IQR): (190-267) minutes] compared to no mobilization [180; IQR: (153-209) minutes] (p < 0.01). After risk adjustment, SFM was associated with a trend towards an increased rate of a minor morbidity (OR: 2.8; p = 0.05). CONCLUSION: Splenic flexure mobilization was performed selectively in half of colectomies evaluated. This technique was associated with a trend towards an increased rate of minor complications, with no difference in major adverse events, including organ space infections. These findings suggest that for patient with diverticulitis, SFM should be performed in an individualized fashion.

Endovascular Versus Open Revascularization for Peripheral Arterial Disease.

OBJECTIVE: The aim of this study was to determine whether endovascular or open revascularization provides an advantageous approach to symptomatic peripheral arterial disease (PAD) over the longer term. SUMMARY OF BACKGROUND DATA: The optimal revascularization strategy for symptomatic lower extremity PAD is not established. METHODS: We evaluated amputation-free survival, overall survival, and relative rate of subsequent vascular intervention after endovascular or open lower extremity revascularization for propensity-score matched cohorts of Medicare beneficiaries with PAD from 2006 through 2009. RESULTS: Among 14,685 eligible patients, 5928 endovascular and 5928 open revascularization patients were included in matched analysis. Patients undergoing endovascular repair had improved amputation-free survival compared with open repair at 30 days (7.4 vs 8.9%, P = 0.002). This benefit persisted over the long term: At 4 years, 49% of endovascular patients had died or received major amputation compared with 54% of open patients (P < 0.001). An endovascular procedure was associated with a risk-adjusted 16% decreased risk of amputation or death compared with open over the study period (hazard ratio: 0.84; 95% confidence interval, 0.79-0.89; P < 0.001). The amputation-free survival benefit associated with an endovascular revascularization was more pronounced in patients with congestive heart failure or ischemic heart disease than in those without (P = 0.021 for interaction term). The rate of subsequent intervention at 30 days was 7.4% greater for the endovascular vs the open revascularization cohort. At 4 years, this difference remained stable at 8.6%. CONCLUSIONS: Using population-based data, we demonstrate that an endovascular approach is associated with improved amputation-free survival over the long term with only a modest relative increased risk of subsequent intervention.

Decreased Numbers of Somatostatin-Expressing Neurons in the Amygdala of Subjects With Bipolar Disorder or Schizophrenia: Relationship to Circadian Rhythms.

BACKGROUND: Growing evidence points to a key role for somatostatin (SST) in schizophrenia (SZ) and bipolar disorder (BD). In the amygdala, neurons expressing SST play an important role in the regulation of anxiety, which is often comorbid in these disorders. We tested the hypothesis that SST-immunoreactive (IR) neurons are decreased in the amygdala of subjects with SZ and BD. Evidence for circadian SST expression in the amygdala and disrupted circadian rhythms and rhythmic peaks of anxiety in BD suggest a disruption of rhythmic expression of SST in this disorder. METHODS: Amygdala sections from 12 SZ, 15 BD, and 15 control subjects were processed for immunocytochemistry for SST and neuropeptide Y, a neuropeptide partially coexpressed in SST-IR neurons. Total numbers (Nt) of IR neurons were measured. Time of death was used to test associations with circadian rhythms. RESULTS: SST-IR neurons were decreased in the lateral amygdala nucleus in BD (Nt, p = .003) and SZ (Nt, p = .02). In normal control subjects, Nt of SST-IR neurons varied according to time of death. This pattern was altered in BD subjects, characterized by decreases of SST-IR neurons selectively in subjects with time of death corresponding to the day (6:00 am to 5:59 pm). Numbers of neuropeptide Y-IR neurons were not affected. CONCLUSIONS: Decreased SST-IR neurons in the amygdala of patients with SZ and BD, interpreted here as decreased SST expression, may disrupt responses to fear and anxiety regulation in these individuals. In BD, our findings raise the possibility that morning peaks of anxiety depend on a disruption of circadian regulation of SST expression in the amygdala.