Annals of surgery最新文献

Objective: We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC).

Background: Data are limited on how modern multimodality therapy affects PDAC recurrence and postrecurrence survival.

Methods: Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy during 1998-2004, 2005-2011, and 2012-2018.

Results: The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). The use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared with earlier cohorts, the 2012-2018 cohort had a lower conditional risk of recurrence in postoperative year 1 and a higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7 mo, P < 0.005), driven by improved postrecurrence overall survival (median, 7.8, 12.5, and 12.6 mo; 3-year rate, 7%, 10%, and 20%; P < 0.005).

Conclusions: We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and postrecurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.

Objective: To assess whether long-term survivors of pancreatic surgery show increased risk to develop impaired bone mineral density, osteoporosis, and vitamin D deficiency.

Background: Pancreatic resection poses a risk for malabsorption of fat-soluble vitamins and other micronutrients essential for bone mineralization. Here, we evaluated the long-term effects of pancreatic resection on bone mineral density (BMD) and its clinical sequelae.

Methods: This was a 2-pronged analysis of postpancreatectomy patients with a follow-up period >3 years comprising (1) a large, propensity score matched, cohort study based on a multinational federated research network (FRN) and (2) a retrospective single institution review of clinical and radiographic patient data. In the FRN analysis, an initial cohort of 8423 postpancreatectomy patients were identified and propensity score matched with normal controls. The primary endpoint was the 10-year risk of developing osteoporotic pathologic fractures and secondary endpoints included diagnosis of osteoporosis, vitamin D deficiency, and related therapies. The single institution retrospective analysis identified 224 patients who underwent pancreatic resection between 2005 and 2019. BMD was quantified in CT images acquired before and after surgery. BMD trends and related factors were assessed in a time-series mixed-effect linear regression model.

Results: A total of 8080 propensity score-matched pairs were included in the FRN analysis. The analysis revealed a 2.4-fold increase in pathologic fractures ( P <0.0001) and 1.4- to 1.5-fold increase in osteoporosis/osteomalacia ( P <0.0001) and vitamin D deficiency ( P <0.0001) in postpancreatectomy patients. Vitamin D supplements were more common in the pancreatectomy group (OR=1.4, 95% CI: 1.28-1.53, P <0.0001), as were specific osteoporosis/osteomalacia treatments such as calcitonin, denosumab, romosozumab, abaloparatide, and teriparatide (OR=2.24, 95% CI: 1.69-2.95, P <0.0001). Retrospective analysis of CT imaging revealed that BMD declined more rapidly following pancreatic resection compared with normal historical controls ( P =0.015). Older age, pancreatic cancer, and pancreaticoduodenectomy were associated with increased rates of BMD loss ( P <0.05, each).

Conclusions: After pancreatic resection, patients are at higher risk for BMD loss and subsequent fractures. As the cohort of pancreatic resection survivorship grows, attention will need to be paid to focused prevention efforts to reduce BMD loss, osteoporosis, and fractures in these vulnerable patients, with specific attention to the pancreatic cancer population.

Objective: To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-pN2, respectively).

Background: Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling.

Methods: A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathologic features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratios (HRs) with corresponding 95% CIs.

Results: In total, 1630 patients were included with a median follow-up of 43 (interquartile range: 33-58) months. PNI was independently associated with worse OS in both R0 patients [HR: 1.49 (95% CI: 1.18-1.88); P < 0.001] and R1 patients [HR: 1.39 (95% CI: 1.06-1.83); P = 0.02], as well as in pN0 patients [HR: 1.75 (95% CI: 1.27-2.41); P < 0.001] and pN1-N2 patients [HR: 1.35 (95% CI: 1.10-1.67); P < 0.01]. In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS [HR: 2.24 (95% CI: 1.52-3.30); P < 0.001].

Conclusions: PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathologic features. These findings may aid patient stratification and counseling and help guide treatment strategies.

Objective: The aim of the present study was to compare long-term postresection oncological outcomes between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC).

Background: Knowledge of long-term oncological outcomes (e.g. recurrence and survival) comparing A-IPMN and PDAC is scarce.

Methods: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centers and compared with PDAC patients from the same time period. Propensity-score matching was performed, and survival and recurrence were compared between A-IPMN and PDAC.

Results: In all, 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4% vs. 75.6%), perineural invasion (55.8% vs. 71.2%), lymph node positivity (47.3% vs. 72.3%) and R1 resection (38.6% vs. 56.3%) compared with PDAC ( P <0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus 19.5 months ( P <0.001) and 33.1 versus 14.8 months ( P <0.001), respectively (median follow-up, 78 vs. 73 months). Ten-year overall survival for A-IPMN was 34.6% (27/78) and PDAC was 9% (6/67). A-IPMN had higher rates of peritoneal (23.0% vs. 9.1%, P <0.001) and lung recurrence (27.8% vs. 15.6%, P <0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P <0.001). The matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival ( P =0.003), and higher locoregional recurrence ( P <0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates ( P =0.695).

Conclusions: PDACs have inferior survival and higher recurrence rates compared with A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC, but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Objective: To evaluate the rate of unplanned surgery among dually eligible beneficiaries for surgical conditions that should be treated electively.

Summary background data: Access-sensitive surgical conditions (eg, abdominal aortic aneurysm repair, colectomy for colon cancer, and ventral hernia repair) are ideally treated with elective surgery, but when left untreated have a natural history leading to unplanned surgery. Dually eligible beneficiaries may face systematic barriers to accessing surgical care.

Methods: Cross-sectional retrospective study of all beneficiaries who were eligible for both Medicare and Medicaid and underwent surgery for an access-sensitive surgical condition between 2016 and 2020. We compared the rate of unplanned surgery as well as 30-day mortality, complications, and readmissions for dually eligible versus non-dually eligible beneficiaries. Gender, age, race/ethnicity, comorbidities, teaching status, nursing ratio, hospital region and bed size, and surgery year were included in the risk-adjustment model.

Results: Out of 853,500 beneficiaries, 118,812 were dually eligible, with an average age (SD) of 75.2(7.7) years. Compared with nondually eligible beneficiaries, dually eligible beneficiaries had higher rates of unplanned surgery for access-sensitive surgical conditions (45.1% vs. 31.8%, P <0.001), 30-day mortality (2.9% vs. 2.6%, aOR=1.10 (1.07-1.14), P <0.001), complications (23.6% vs. 20.1%, aOR=1.23 (1.20-1.25), P <0.001), and 30-day readmissions (15.5% vs. 12.9%, aOR=1.24 (1.22-1.27), P <0.001). These differences narrowed significantly when evaluating elective procedures only.

Conclusions: Dually eligible beneficiaries were more likely to undergo unplanned surgery for access-sensitive surgical conditions, leading to worse rates of mortality, complications, and readmissions. Our findings suggest that improving rates of elective surgery for these conditions represents an actionable target to narrow the difference in postoperative outcomes between dually eligible and non-dually eligible beneficiaries.

Objective: Compare radioactive seed localization (RSL) and wire-guided localization (WL) for nonpalpable malignant breast disease.

Background: While WL has been the most common approach for localization of nonpalpable breast tumors, other techniques such as RSL, intraoperative ultrasound, radioactive intraoperative occult lesion localization, hematoma localization, radar localization, and magnetic seed localization have been suggested as safe and efficacious alternatives. However, very few randomized controlled trials have compared these localization techniques.

Methods: Between July 2015 and January 2021, 400 women with nonpalpable malignant breast disease were randomized 1:1 to RSL or WL, stratified by the surgeon and invasive disease status. The primary outcome was initial resection negative margin rates. Secondary outcomes included time efficiencies, cost, and satisfaction.

Results: There was no significant difference in negative margin rates between RSL and WL [RSL 0.80 (95% CI: 0.75-0.86) vs WL 0.85 (95% CI: 0.80-0.89); P=0.29]. RSL received better patient scores for anxiety [OR=2.62 (95% CI: 1.79-3.84); P<0.01], pain [OR=2.50 (95% CI: 1.69-3.71); P<0.01], and overall satisfaction [OR=3.24 (95% CI: 1.70-6.22); P<0.01] compared with WL. Radiologists and surgeons associated RSL with better convenience [OR=3.32 (95% CI: 1.65-6.69); P<0.01] and satisfaction of surgical procedure conduct [OR=1.67 (95% CI: 1.09-2.58); P=0.02]. Time in radiology did not differ [RSL mean (SD) 12.8±9.5 min vs. WL 11.4±6.0 min; P=0.18]. RSL incurred a $600 higher cost than WL.

Conclusions: The results of the largest randomized controlled trial in the United States support RSL as an acceptable alternative to WL in the treatment of nonpalpable malignant breast disease. While RSL was not superior to WL in achievement of negative margins, patients and providers reported improved satisfaction scores.

Objective: To evaluate the 1-year clinical outcomes of patients enrolled in the #HOPE4LIVER trial of hepatic histotripsy.

Background: Histotripsy is a novel noninvasive, non-thermal-focused ultrasound therapy that liquefies tissue at the focal point of the transducer. Following diagnostic ultrasound targeting, an automated treatment is performed through a robotic arm to treat a user-defined volume of tissue.

Methods: Forty-seven patients were enrolled at 14 sites in the United States and Europe. Included patients were ineligible for or had opted out of standard therapies. Tumor control was evaluated through a core laboratory with a primary assessment at each time point and a post hoc assessment performed following the completion of each time point to allow for a learning curve of interpreting imaging findings of this novel therapy. Overall survival and freedom from local tumor progression were evaluated through the Kaplan-Meier method.

Results: Nineteen patients with hepatocellular carcinoma and 28 with metastatic disease were enrolled, of whom 89.5% (17/19) and 96.4% (27/28) had multifocal hepatic tumors at the time of treatment. Fifty-two tumors were treated. The 1-year local control rate was 63.4% using the primary assessment method and 90% using the post hoc method. There were 6 serious adverse device-related effects within 30 days of treatment. Only one nonserious adverse device-related effect was observed after 30 days of treatment. Overall survival at 1-year was 73.3% for patients with hepatocellular carcinoma and 48.6% for patients with metastatic disease.

Conclusions: Histotripsy results in local control of liver tumors at 1 year, which is consistent with current locoregional therapies. The safety profile is favorable, and survival at 1 year is comparable with other therapies for similar disease stages.

Objective: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry.

Background: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge.

Methods: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy, and completion colectomy. The primary outcome was the proportion of patients diagnosed with LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival.

Results: A total of 1749 patients were included, and 1022 patients (58.4%) underwent initial LE. The rate of R1 margins after the initial LE was 31.0%. Colectomy was performed in 1160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P = 0.392) and in patients with any single histopathological risk factor compared with those with none (8.9% vs 10.6%, P = 0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found in multivariable analysis.

Conclusions: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to complete surgery appear insufficient, and more robust predictors are needed.

Objective: To optimize the management strategies of delayed postpancreaticoduodenectomy hemorrhage (PPH) by evaluating data from a high-volume pancreatic center.

Background: Delayed PPH is a potentially lethal complication. The management of delayed PPH remains controversial.

Methods: Patients who underwent pancreaticoduodenectomy between July 2018 and June 2023 were identified from an institutional database. The clinical scenarios, management, and outcomes of patients with delayed PPH (>5 days postoperatively) were analyzed.

Results: Of the 2013 patients who underwent elective pancreaticoduodenectomy, 130 (6.5%) with delayed PPH were identified. The overall mortality was 15.4%. The success rates of endoscopy, angiographic intervention, and relaparotomy in treating delayed PPH were 54.5%, 56.5%, and 68.8%, respectively. For PPH from the hepatic arteries or their branches, complete blockade of the common or proper hepatic artery (C/PHA) was performed in 17 patients, either by coil embolization (n=7) or surgical ligation (n=10). Coil embolization of the C/PHA resulted in significant infarction of the left liver in 2 patients. No postoperative liver infarction occurred in patients who underwent ligation of the C/PHA during relaparotomy. Ten patients underwent suture repair of the C/PHA 13 times during relaparotomy. Arterial ligation achieved a significantly higher success rate of hemostasis than suture repair of the C/PHA during relaparotomy (100% vs 30.8%, P <0.001).

Conclusions: Angiography should be attempted first in managing hemodynamically stable delayed PPH. Arterial ligation was preferred for bleeding from the hepatic arteries during relaparotomy with minor consequences for the liver.