Revolutionizing Postoperative Ileus Monitoring: Exploring GRU-D's Real-Time Capabilities and Cross-Hospital Transferability.

Background: Postoperative ileus (POI) after colorectal surgery leads to increased morbidity, costs, and hospital stays. Identifying POI risk for early intervention is important for improving surgical outcomes especially given the increasing trend towards early discharge after surgery. While existing studies have assessed POI risk with regression models, the role of deep learning's remains unexplored. Methods: We assessed the performance and transferability (brutal force/instance/parameter transfer) of Gated Recurrent Unit with Decay (GRU-D), a longitudinal deep learning architecture, for real-time risk assessment of POI among 7,349 colorectal surgeries performed across three hospital sites operated by Mayo Clinic with two electronic health records (EHR) systems. The results were compared with atemporal models on a panel of benchmark metrics. Results: GRU-D exhibits robust transferability across different EHR systems and hospital sites, showing enhanced performance by integrating new measurements, even amid the extreme sparsity of real-world longitudinal data. On average, for labs, vitals, and assisted living status, 72.2%, 26.9%, and 49.3% respectively lack measurements within 24 hours after surgery. Over the follow-up period with 4-hour intervals, 98.7%, 84%, and 95.8% of data points are missing, respectively. A maximum of 5% decrease in AUROC was observed in brutal-force transfer between different EHR systems with non-overlapping surgery date frames. Multi-source instance transfer witnessed the best performance, with a maximum of 2.6% improvement in AUROC over local learning. The significant benefit, however, lies in the reduction of variance (a maximum of 86% decrease). The GRU-D model's performance mainly depends on the prediction task's difficulty, especially the case prevalence rate. Whereas the impact of training data and transfer strategy is less crucial, underscoring the challenge of effectively leveraging transfer learning for rare outcomes. While atemporal Logit models show notably superior performance at certain pre-surgical points, their performance fluctuate significantly and generally underperform GRU-D in post-surgical hours. Conclusion: GRU-D demonstrated robust transferability across EHR systems and hospital sites with highly sparse real-world EHR data. Further research on built-in explainability for meaningful intervention would be highly valuable for its integration into clinical practice.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Value of Surgical Cytoreduction in Patients with Small Intestinal Neuroendocrine Tumors Metastatic to the Liver and Peritoneum.

BACKGROUND: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. METHODS: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. RESULTS: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). CONCLUSIONS: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

Outcomes of Neoadjuvant Chemotherapy for Invasive Intraductal Papillary Mucinous Neoplasm Compared with de Novo Pancreatic Adenocarcinoma.

BACKGROUND: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. METHODS: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). RESULTS: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. CONCLUSIONS: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.

Academic Surgery in the Era of Large Language Models: A Review.

Importance: This review aims to assess the benefits and risks of implementing large language model (LLM) solutions in an academic surgical setting. Observations: The integration of LLMs and artificial intelligence (AI) into surgical practice has generated international attention with the emergence of OpenAI's ChatGPT and Google's Bard. From an administrative standpoint, LLMs have the potential to revolutionize academic practices by reducing administrative burdens and improving efficiency. LLMs have the potential to facilitate surgical research by increasing writing efficiency, building predictive models, and aiding in large dataset analysis. From a clinical standpoint, LLMs can enhance efficiency by triaging patient concerns and generating automated responses. However, challenges exist, such as the need for improved LLM generalization performance, validating content, and addressing ethical concerns. In addition, patient privacy, potential bias in training, and legal responsibility are important considerations that require attention. Research and precautionary measures are necessary to ensure safe and unbiased use of LLMs in surgery. Conclusions and Relevance: Although limitations exist, LLMs hold promise for enhancing surgical efficiency while still prioritizing patient care. The authors recommend that the academic surgical community further investigate the potential applications of LLMs while being cautious about potential harms.

Early vs conventional onset pancreatic ductal adenocarcinoma: analysis of surgical and oncologic outcomes in patients undergoing curative intent resection.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) impacts patients in their 60s, but its incidence in younger patients is increasing. We hypothesize that younger patients may have worse oncologic outcomes. METHODS: Patients who underwent curative pancreatic resection for PDAC between January 2011 and December 2021 at a single institution were analyzed. Early-onset pancreatic cancer (EOPC) was defined as pancreatic cancer diagnosed in patients ≤50 years. Clinical and survival outcomes were compared between EOPC and Conventional Onset Pancreas Cancer (COPC). RESULTS: A total of 1133 patients were identified, 65 (5.7%) were EOPC. Preoperative patient characteristics including sex, smoking status, alcohol habitus, diabetes mellitus, CA 19-9, and neoadjuvant therapy were similar between EOPC and COPC (p > 0.05). EOPC patients were more likely non-white (p = 0.03), had lower ASA scores (p = 0.02) and larger median tumor size (33 vs 28 mm, p = 0.04), but had similar pathological stages and rate of R0 resections (p > 0.05). Postoperative outcomes were similar (p > 0.05). There was no statistically significant difference in overall (HR 0.93, CI 0.64, 1.33; p = 0.68) or recurrence free (HR 1.05, CI 0.75, 1.48; p = 0.77) survival between the EOPC and COPC after adjusting for significant factors. CONCLUSION: Patients with EOPC who underwent surgical resection had similar oncological outcomes compared to patients with COPC.

Supply and demand of hepatopancreatobiliary surgeons in the United States.

BACKGROUND: Hepatopancreatobiliary (HPB) surgery requires specialized training and adequate case volumes to maintain procedural proficiency and optimal outcomes. Studies of individual HPB surgeon supply related to annual HPB case demand are sparse. This study assesses the supply and demand of the HPB surgical workforce in the United States (US). METHODS: The National Inpatient Sample (NIS) was queried from 1998-2019 to estimate the number of HPB procedures performed. To approximate the number of HPB surgeons, models based on previous HPB workforce publications were employed. We then calculated the number of HPB surgeons needed to maintain volume-outcome thresholds at current reported levels of centralization. RESULTS: In 2019, approximately 37,335 patients underwent inpatient HPB procedures in the US, while an estimated 905-1191 HPB surgeons were practicing. Assuming 50% centralization and an optimal volume-outcome threshold of 24 HPB cases-per-year, only 778 HPB surgeons were needed. Without adjustment in centralization, by 2030 there will be a demand of fewer than 12 annual cases per HPB surgeon. CONCLUSION: The current supply of HPB surgeons may exceed demand in the United States. Without alteration in training pathways or improved care centralization, by 2030, there will be insufficient HPB case volume per surgeon to maintain published volume-outcome standards.

Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity. METHODS: We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90 min from June 2019 to December 2022. RESULTS: Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4-8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0-4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4-7.5) days. There were six (27%) 90-day major complications (Clavien-Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively. CONCLUSIONS: CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. PATIENTS AND METHODS: Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. RESULTS: In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. CONCLUSIONS: CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).

Checking Our Blind Spots: Examining Characteristics of Interviewees Versus Matriculants to a Hepatopancreatobiliary Surgical Fellowship Program.

OBJECTIVE: Racial and gender biases exist within academic surgery; bias negatively impacts patient care, reimbursement, student training, and staff retention. Few studies have investigated the potential for bias in surgical fellowship recruitment. We aimed to compare the racial and gender diversity at our hepatopancreatobiliary (HPB) surgery fellowship program to nationwide standards. We further aimed to investigate differences in the demographics of resident interviewees versus matriculants to our HPB fellowship. DESIGN: Retrospective review. SETTING: North American HPB fellowship training programs. PARTICIPANTS: Mayo Clinic's HPB surgery fellowship interviewees and North American HPB surgery fellowship graduates from 2013 to 2020. RESULTS: When compared to general surgery residency graduates during the study period (in 2019), a lower proportion of North American HPB surgery fellowship graduates were female (26% HPB fellowship graduates vs. 43.1% residents, p = 0.005), with no difference in proportion of racially under-represented in medicine (rURM) HPB fellowship graduates (10.7%) compared to rURM proportion of general surgery residents nationally (14.5%). There was an upward trend in female representation among North American HPB fellowship graduates from 11% in 2013 to 32% in 2020, but proportions of rURM HPB fellows remained steadily low. When comparing HPB interviewees at our institution to national general surgery residents, no differences were observed in proportions of female (34.4% interviewees vs. 43.1% residents, p = 0.17) or rURM (interviewees = 6.8%, residents = 14.5%, p = 0.09) applicants. Additionally, there was no significant difference between the proportion of female or rURM interviewees and matriculants to our HPB program. CONCLUSIONS: While fewer female graduating surgeons are pursuing HPB fellowship training than male graduates, this gender gap has narrowed over time. In contrast, the national percentage of rURM HPB fellowship graduates has remained low, mirroring stagnant proportions of rURM surgical residency graduates. When comparing HPB fellowship interviewees at our own institution to North American fellowship graduates, we observed similar proportions of female interviewees but lower proportions of rURM interviewees. Locally, these data will drive process change toward more intentional examination of our interview selection process. Nationally, more work is needed to increase the racial diversity of surgical residency and fellowship trainees to best reflect and serve our diverse patient populations.

Survival and Symptomatic Relief After Cytoreductive Hepatectomy for Neuroendocrine Tumor Liver Metastases: Long-Term Follow-up Evaluation of More Than 500 Patients.

BACKGROUND: Distant metastases are the strongest predictor of poor prognosis for patients with neuroendocrine tumors (NETs). Cytoreductive hepatectomy (CRH) can relieve symptoms of hormonal excess and prolong survival for patients with liver metastases (NETLMs), but long-term outcomes are poorly characterized. METHODS: This retrospective single-institution analysis analyzed patients who underwent CRH for well-differentiated NETLMs from 2000 to 2020. Kaplan-Meier analysis estimated symptom-free interval and overall and progression-free survival. Multivariable Cox regression analysis evaluated factors associated with survival. RESULTS: The inclusion criteria were met by 546 patients. The most common primary sites were the small intestine (n = 279) and the pancreas (n = 194). Simultaneous primary tumor resection was performed for 60 % of the cases. Major hepatectomy comprised 27% of the cases, but this rate decreased during the study period (p < 0.001). Major complications occurred in 20%, and the 90-day mortality rate was 1.6%. Functional disease was present in 37 %, and symptomatic relief was achieved in 96%. The median symptom-free interval was 41 months (62 months after complete cytoreduction and 21 months with gross residual disease) (p = 0.021). The median overall survival was 122 months, and progression-free survival was 17 months. In the multivariable analysis, worse overall survival was associated with age, pancreatic primary tumor, Ki-67, number and size of lesions, and extrahepatic metastases, with Ki-67 as the strongest predictor (odds ratio [OR], 1.90 for Ki-67 [3-20%; p = 0.018] and OR, 4.25 for Ki-67 [>20%; p < 0.001]). CONCLUSION: The study showed that CRH for NETLMs is associated with low perioperative morbidity and mortality and excellent overall survival, although the majority will experience recurrence/progression. For patients with functional tumors, CRH can provide durable symptomatic relief.

Yield of Staging Laparoscopy for Pancreatic Cancer in the Modern Era: Analysis of More than 1,000 Consecutive Patients.

BACKGROUND: Accurate staging prior to resection of pancreatic ductal adenocarcinoma (PDAC) is imperative to avoid unnecessary operative morbidity and oncologic futility in patients with occult intra-abdominal distant metastases. We aimed to determine the diagnostic yield of staging laparoscopy (SL) and to identify factors associated with increased risk of positive laparoscopy (PL) in the modern era. STUDY DESIGN: Patients with radiographically localized PDAC who underwent SL from 2017 to 2021 were retrospectively reviewed. The yield of SL was defined as the proportion of patients with PL, including gross metastases and/or positive peritoneal cytology. Factors associated with PL were assessed using univariate analysis and multivariable logistic regression. RESULTS: Of 1,004 patients who underwent SL, 180 (18%) had PL due to gross metastases (n = 140) and/or positive cytology (n = 96). Patients who had neoadjuvant chemotherapy prior to laparoscopy had lower rates of PL (14% vs 22%, p = 0.002). When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had PL. In multivariable analysis, PL was associated with younger (<60) age, indeterminate extrapancreatic lesions on preoperative imaging, body/tail tumor location, larger tumor size, and elevated serum CA 19-9 (all p < 0.05). Among patients with no indeterminate extrapancreatic lesions on preoperative imaging, the rate of PL ranged from 1.6% in patients with no risk factors to 42% in young patients with large body/tail tumors and elevated serum CA 19-9. CONCLUSIONS: The rate of PL in patients with PDAC remains high in the modern era. SL with peritoneal lavage should be considered for the majority of patients prior to resection, specifically those with high-risk features, and ideally prior to neoadjuvant chemotherapy.