Piperacillin-Tazobactam Compared With Cefoxitin as Antimicrobial Prophylaxis for Pancreatoduodenectomy: A Randomized Clinical Trial.

Importance: Despite improvements in perioperative mortality, the incidence of postoperative surgical site infection (SSI) remains high after pancreatoduodenectomy. The effect of broad-spectrum antimicrobial surgical prophylaxis in reducing SSI is poorly understood. Objective: To define the effect of broad-spectrum perioperative antimicrobial prophylaxis on postoperative SSI incidence compared with standard care antibiotics. Design, Setting, and Participants: Pragmatic, open-label, multicenter, randomized phase 3 clinical trial at 26 hospitals across the US and Canada. Participants were enrolled between November 2017 and August 2021, with follow-up through December 2021. Adults undergoing open pancreatoduodenectomy for any indication were eligible. Individuals were excluded if they had allergies to study medications, active infections, chronic steroid use, significant kidney dysfunction, or were pregnant or breastfeeding. Participants were block randomized in a 1:1 ratio and stratified by the presence of a preoperative biliary stent. Participants, investigators, and statisticians analyzing trial data were unblinded to treatment assignment. Intervention: The intervention group received piperacillin-tazobactam (3.375 or 4 g intravenously) as perioperative antimicrobial prophylaxis, while the control group received cefoxitin (2 g intravenously; standard care). Main Outcomes and Measures: The primary outcome was development of postoperative SSI within 30 days. Secondary end points included 30-day mortality, development of clinically relevant postoperative pancreatic fistula, and sepsis. All data were collected as part of the American College of Surgeons National Surgical Quality Improvement Program. Results: The trial was terminated at an interim analysis on the basis of a predefined stopping rule. Of 778 participants (378 in the piperacillin-tazobactam group [median age, 66.8 y; 233 {61.6%} men] and 400 in the cefoxitin group [median age, 68.0 y; 223 {55.8%} men]), the percentage with SSI at 30 days was lower in the perioperative piperacillin-tazobactam vs cefoxitin group (19.8% vs 32.8%; absolute difference, -13.0% [95% CI, -19.1% to -6.9%]; P < .001). Participants treated with piperacillin-tazobactam, vs cefoxitin, had lower rates of postoperative sepsis (4.2% vs 7.5%; difference, -3.3% [95% CI, -6.6% to 0.0%]; P = .02) and clinically relevant postoperative pancreatic fistula (12.7% vs 19.0%; difference, -6.3% [95% CI, -11.4% to -1.2%]; P = .03). Mortality rates at 30 days were 1.3% (5/378) among participants treated with piperacillin-tazobactam and 2.5% (10/400) among those receiving cefoxitin (difference, -1.2% [95% CI, -3.1% to 0.7%]; P = .32). Conclusions and Relevance: In participants undergoing open pancreatoduodenectomy, use of piperacillin-tazobactam as perioperative prophylaxis reduced postoperative SSI, pancreatic fistula, and multiple downstream sequelae of SSI. The findings support the use of piperacillin-tazobactam as standard care for open pancreatoduodenectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03269994.

Hospital-level Variation in Utilization of Surgery for Clinical Stage I-II Pancreatic Adenocarcinoma.

OBJECTIVE: To (1) evaluate rates of surgery for clinical stage I-II pancreatic ductal adenocarcinoma (PDAC), (2) identify predictors of not undergoing surgery, (3) quantify the degree to which patient- and hospital-level factors explain differences in hospital surgery rates, and (4) evaluate the association between adjusted hospital-specific surgery rates and overall survival (OS) of patients treated at different hospitals. BACKGROUND: Curative-intent surgery for potentially resectable PDAC is underutilized in the United States. METHODS: Retrospective cohort study of patients ≤85 years with clinical stage I-II PDAC in the 2004 to 2014 National Cancer Database. Mixed effects multivariable models were used to characterize hospital-level variation across quintiles of hospital surgery rates. Multivariable Cox proportional hazards models were used to estimate the effect of adjusted hospital surgery rates on OS. RESULTS: Of 58,553 patients without contraindications or refusal of surgery, 63.8% underwent surgery, and the rate decreased from 2299/3528 (65.2%) in 2004 to 4412/7092 (62.2%) in 2014 (P < 0.001). Adjusted hospital rates of surgery varied 6-fold (11.4%-70.9%). Patients treated at hospitals with higher rates of surgery had better unadjusted OS (median OS 10.2, 13.3, 14.2, 16.5, and 18.4 months in quintiles 1-5, respectively, P < 0.001, log-rank). Treatment at hospitals in lower surgery rate quintiles 1-3 was independently associated with mortality [Hazard ratio (HR) 1.10 (1.01, 1.21), HR 1.08 (1.02, 1.15), and HR 1.09 (1.04, 1.14) for quintiles 1-3, respectively, compared with quintile 5] after adjusting for patient factors, hospital type, and hospital volume. CONCLUSIONS: Quality improvement efforts are needed to help hospitals with low rates of surgery ensure that their patients have access to appropriate surgery.

Variation in costs among surgeons and hospitals in Pediatric tympanostomy tube placement.

OBJECTIVES/HYPOTHESIS: 1) Identify the major expenses for outpatient pediatric tympanostomy tube placement in a multihospital network. 2) Compare differences for variations in costs among hospitals and surgeons. METHODS: An observational cohort study in a multihospital network using a standardized activity-based accounting system to determine hospital costs for tympanostomy tube placement from February 2011 to January 2015. Children aged 6 months to less than 3 years old who underwent same-day surgery (SDS) for tympanostomy tubes at 15 hospital facilities were included. Subjects with additional procedures were excluded. Hospital costs were subdivided into categories including operating room (OR), SDS preoperative, SDS postoperative, postanesthesia care unit, anesthesia, pharmacy, and OR supplies. RESULTS: The study cohort included 5,623 patients undergoing tympanostomy tube placement by 67 surgeons. Mean cost per surgery was $769 ± $3. Significant variations (P < 0.001) in mean cost per procedure were identified by hospital (range $1212 ± $38 to $509 ± $11) and by surgeon (range $1330 ± $75 to $660 ± $11). Operating room and SDS preoperative were the greatest expenditures; each category accounted for over 30% of overall costs. Pharmacy costs and OR costs were some of the major drivers of cost variation among surgeons. CONCLUSION: This study demonstrates that OR and SDS preoperative costs accounted for the greatest expenditure in tympanostomy tube placement, and significant variation exists among surgeons and hospitals within a multihospital network. Further research is needed to elucidate factors accounting for such variation in cost and the overall impact on patient outcomes. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1935-1939, 2016.

Enhanced recovery after colon surgery in a community hospital system.

BACKGROUND: Enhanced recovery after colon surgery has not been widely adopted in the United States and Europe, despite evidence that postoperative complications and hospital length of stay are decreased. OBJECTIVE: We sought to evaluate the introduction of a comprehensive care process for enhanced recovery after colon surgery in 8 community hospitals. DESIGN: A system-wide, surgeon-directed, multidisciplinary committee developed a comprehensive enhanced-care quality-improvement program. Surgeons and operations leaders in each hospital developed the internal structure to implement the process. PATIENTS: Surgeons had the option of entering or not entering patients in the enhanced-care pathway. Other than trauma patients, there were no exclusion criteria. MAIN OUTCOME MEASURES: To limit selection bias, the study population included all patients undergoing colon resections (those entered and not entered in the care process). Length of stay, postoperative days, hospital costs, 30-day readmission rate, and return to surgery for the study population were compared with a 2-year historical baseline. RESULTS: Forty-two percent of the study population was entered in the enhanced-care process. The average length of stay and the number of postoperative days in the study population decreased by 1.5 (P < .0001) and 1.3 (P < .0001) days. The rate of readmissions and returns to surgery remained stable (P > .05), and the average hospital cost decreased by $1763 (P = .02). Generalized linear regression analysis demonstrated that the enhanced-care process was a more significant variable than was the surgical approach (laparoscopic vs open surgery) in decreasing length of stay. LIMITATIONS: The degree of compliance with care process elements and the relative contribution of each element of the care process are unknown. CONCLUSIONS: A comprehensive enhanced-care colon surgery care process was successfully introduced in a community hospital system, as indicated by the clinical outcome measures.

Role of sentinel lymph node biopsy in the staging of synovial, epithelioid, and clear cell sarcomas.

BACKGROUND: Soft tissue sarcomas generally have a

The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma.

BACKGROUND: Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. METHODS: Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. RESULTS: A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 51% in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). CONCLUSIONS: Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients.

Prognosis and management of extramammary Paget's disease and the association with secondary malignancies.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare clinical entity and can be associated with other malignancies. We analyzed our experience for prognosis and impact of therapy on outcomes. STUDY DESIGN: We conducted a retrospective review of all patients (n = 33) with EMPD treated at a tertiary care center from 1971 to 1998. Pathologic features of EMPD, concurrent secondary malignancies, and the effect of operations on recurrence were analyzed. Overall survival was compared with that of the general population. RESULTS: Male-to-female ratio was 4:29, and median age was 70 years. Median followup was 68 months, and no patient died from EMPD. The lesion was predominantly found on the vulva (76%). Patch-like, nonconfluent growth was present in 45% of patients, and no patient had pathologic lymph nodes. The most common signs and symptoms were irritation or pruritus (73%) and rash (61%). The presence of patches, invasive tumor growth, or a second malignancy were significantly associated with a higher recurrence rate. The type of operation, either local excision or hemivulvectomy, was not related to the time to recurrence. Complete gross resection was achieved in 94% of cases. Fifty-six percent of patients had microscopically positive margin and this correlated with a significantly higher recurrence rate (p = 0.002). The tumor recurred clinically in 14 of 33 patients (42%) after a median of 152 months (range 5 to 209 months). In those patients, between one and six reexcisions were performed. In 14 of 33 patients with EMPD (42%), 16 concurrent secondary malignancies were found. Overall survival rates for EMPD patients were similar to those of the general population. CONCLUSIONS: EMPD is an infrequently diagnosed disease that is preferably managed with complete local excision and reexcisions if needed. A thorough search for frequently occurring secondary malignancies might be beneficial to provide the best outcomes for these patients.

Metastatic patterns of extremity myxoid liposarcoma and their outcome.

BACKGROUND AND OBJECTIVES: Extremity myxoid liposarcomas have a unique extrapulmonary metastatic potential. We studied the metastatic pattern of extremity liposarcomas to determine what types of posttreatment imaging may be of value in the follow-up these patients. METHODS: Twenty-two patients from a total of 128 patients with primary extremity liposarcoma were treated at a tertiary care institution for subsequent metastases from January 1981 to January 2000. Median follow-up was 45 months (range: 6-270 months). Data on these patients was prospectively collected and then retrospectively analyzed for effect of metastatic pattern and treatment on outcome. RESULTS: Of these 22 patients, extrapulmonary metastases developed in 10, combined pulmonary and extrapulmonary metastases developed in 6, and isolated pulmonary metastases developed in 6. Of the 16 patients with extrapulmonary metastases, 13 were of the myxoid subtype. Of the 49 patients with extremity myxoid liposarcomas, metastases developed in 14 (29%). The most common sites of metastases among these 14 patients include: the retroperitoneum, 10 patients (71)%; intra-abdominal extra-hepatic, 7 patients (50%); spinal/paraspinal, 6 patients (43%). Only 3 of the patients are alive and disease free and all 3 of these patients are from the subgroup of 10 patients with only extra-pulmonary metastases (2 intra-abdominal and 1 retroperitoneal). CONCLUSIONS: Extremity myxoid liposarcomas have an unusually high predilection for extra-pulmonary metastases, frequently without any pulmonary metastases. After treatment of the primary tumor, these patients should be followed with periodic chest X-ray and abdominal/pelvic computed tomography (CT) scans. Any back or neurologic complaints should prompt additional imaging of the appropriate spinal area. Consideration should be given to surgical and adjuvant treatment of metastatic disease when appropriate.

The effect of surgery and radiotherapy on outcome of anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is an aggressive rare tumor. We analyzed our experience for prognosis and the effect of surgery and radiotherapy on patients with ATC. METHODS: We conducted a retrospective review of all patients (n = 67) with ATC treated at a tertiary care center from 1969 to 1999. Survivor median follow-up was 51 months. Tumor and patient characteristics and therapy were assessed for effect on survival by multivariate analysis. RESULTS: Patients presented with a neck mass (99%), change of voice (51%), dysphagia (33%), and dyspnea (28%). Surgery was performed in 44 of 67 patients, with 12 complete resections. The 6-month and 1- and 3-year survival rates were 92%, 92%, and 83% after complete resection; 53%, 35%, and 0% after debulking; and 22%, 4%, and 0% after no resection, respectively (P < .0001). A radiation dose of >45 Gy improved survival as compared with a lower dose (P = .02). Multivariate analysis showed that age < or = 70 years, absence of dyspnea or dysphagia at presentation, a tumor size < or = 5 cm, and any surgical resection improved survival (P < .05). CONCLUSIONS: Candidates for surgery with curative intent for ATC are patients < or = 70 years, tumors < or = 5 cm, and no distant disease. Radiotherapy >45 Gy improves outcome.