Predicting Severe Complications from Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Data-Driven, Machine Learning Approach to Augment Clinical Judgment.

BACKGROUND: CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are limited. We developed a risk score to predict severity of 90 day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). PATIENTS AND METHODS: Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001-April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90 days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered. RESULTS: For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications. CONCLUSIONS: This study refines our ability to predict severe complications within 90 days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival.

Hand-Assisted Versus Pure Minimally-Invasive Distal Pancreatectomy: Is There a Downside to Lending a Hand?

BACKGROUND: Hand-assisted laparoscopic distal pancreatectomy (HALDP) is suggested to offer similar outcomes to pure laparoscopic distal pancreatectomy (LDP). However, given the longer midline incision, it is unclear whether HALDP increases the risk of postoperative hernia. Our aim was to determine the risk of postoperative incisional hernia development after HALDP. METHODS: We retrospectively collected data from patients undergoing HALDP or LDP at a single center (2012-2020). Primary endpoints were postoperative incisional hernia and operative time. All patients had at minimum six months of follow-up. Outcomes were compared using unadjusted and multivariable regression analyses. RESULTS: Ninety-five patients who underwent laparoscopic distal pancreatectomy were retrospectively identified. Forty-one patients (43%) underwent HALDP. Patients with HALDP were older (median, 67 vs. 61 years, p = 0.02). Sex, race, Body Mass Index (median, 27 vs. 26), receipt of neoadjuvant chemotherapy, gland texture, wound infection rates, postoperative pancreatic fistula, overall complications, and hospital length-of-stay were similar between HALDP and LDP (all p > 0.05). In unadjusted analysis, operative times were shorter for HALDP (164 vs. 276 min, p < 0.001), but after adjustment, did not differ significantly (MR 0.73; 0.49-1.07, p = 0.1). Unadjusted incidence of hernia was higher in HALDP versus LDP (60% vs. 24%, p = 0.004). After adjustment, HALDP was associated with an increased odds of developing hernia (OR 7.52; 95% CI 1.54-36.8, p = 0.014). After propensity score matching, odds of hernia development remained higher for HALDP (OR 4.62; 95% CI 1.28-16.65, p = 0.031) p = 0.03). CONCLUSIONS: Compared with LDP, HALDP was associated with increased likelihood of postoperative hernia with insufficient evidence that HALDP shortens operative times. Our results suggest that HALDP may not be equivalent to LDP.

Effects of Multi-stage Procurement on the Viability and Function of Human Donor Parathyroid Glands.

INTRODUCTION: Parathyroid allotransplantation is an emerging treatment for severe hypoparathyroidism. Ensuring the viability and functional integrity of donor parathyroid glands following procurement is essential for optimal transplantation outcomes. METHODS: Cellular viability, calcium-responsive hormone secretion, and gland xenograft survival were assessed in a series of deceased donor parathyroid glands following a two-stage procurement procedure recently developed by our group (en bloc cadaveric dissection with subsequent gland isolation after transport to the laboratory). RESULTS: Parathyroid glands resected in this manner and stored up to 48 h in 4°C University of Wisconsin (UW) media retained in vitro viability with no induction of hypoxic stress (HIF-1α) or apoptotic (caspase-3) markers. Ex vivo storage did not significantly affect parathyroid gland calcium sensing capacity, with comparable calcium EC50 values and suppression of parathyroid hormone secretion at high ambient calcium concentrations. The isolated glands engrafted readily, vascularizing rapidly in vivo following transplantation into mice. CONCLUSIONS: Parathyroid tissue retains viability, calcium-sensing capacity, and in vivo engraftment capability after en bloc cadaveric resection, ex vivo dissection, and extended cold storage.

Consent to organ offers from public health service "Increased Risk" donors decreases time to transplant and waitlist mortality.

BACKGROUND: The Public Health Service Increased Risk designation identified organ donors at increased risk of transmitting hepatitis B, hepatitis C, and human immunodeficiency virus. Despite clear data demonstrating a low absolute risk of disease transmission from these donors, patients are hesitant to consent to receiving organs from these donors. We hypothesize that patients who consent to receiving offers from these donors have decreased time to transplant and decreased waitlist mortality. METHODS: We performed a single-center retrospective review of all-comers waitlisted for liver transplant from 2013 to 2019. The three competing risk events (transplant, death, and removal from transplant list) were analyzed. 1603 patients were included, of which 1244 (77.6%) consented to offers from increased risk donors. RESULTS: Compared to those who did not consent, those who did had 2.3 times the rate of transplant (SHR 2.29, 95% CI 1.88-2.79, p < 0.0001), with a median time to transplant of 11 months versus 14 months (p < 0.0001), as well as a 44% decrease in the rate of death on the waitlist (SHR 0.56, 95% CI 0.42-0.74, p < 0.0001). All findings remained significant after controlling for the recipient age, race, gender, blood type, and MELD. Of those who did not consent, 63/359 (17.5%) received a transplant, all of which were from standard criteria donors, and of those who did consent, 615/1244 (49.4%) received a transplant, of which 183/615 (29.8%) were from increased risk donors. CONCLUSIONS: The findings of decreased rates of transplantation and increased risk of death on the waiting list by patients who were unwilling to accept risks of viral transmission of 1/300-1/1000 in the worst case scenarios suggests that this consent process may be harmful especially when involving "trigger" words such as HIV. The rigor of the consent process for the use of these organs was recently changed but a broader discussion about informed consent in similar situations is important.

Ileostomy or ileal pouch-anal anastomosis for ulcerative colitis: patient participation and decisional needs.

BACKGROUND: Up to 30% of patients with ulcerative colitis will undergo surgery resulting in an ileal pouch-anal anastomosis (IPAA) or permanent end ileostomy (EI). We aimed to understand how patients decide between these two options. METHODS: We performed semi-structured interviews with ulcerative colitis patients who underwent surgery. Areas of questioning included the degree to which patients participated in decision-making, challenges experienced, and suggestions for improving the decision-making process. We analyzed the data using a directed content and thematic approach. RESULTS: We interviewed 16 patients ranging in age from 28 to 68 years. Nine were male, 10 underwent IPAA, and 6 underwent EI. When it came to participation in decision-making, 11 patients felt independently responsible for decision-making, 3 shared decision-making with the surgeon, and 2 experienced surgeon-led decision-making. Themes regarding challenges during decision-making included lack of support from family, lack of time to discuss options with the surgeon, and the overwhelming complexity of the decision. Themes for ways to improve decision-making included the need for additional information, the desire for peer education, and earlier consultation with a surgeon. Only 3 patients were content with the information used to decide about surgery. CONCLUSIONS: Patients with ulcerative colitis who need surgery largely experience independence when deciding between IPAA and EI, but struggle with inadequate educational information and social support. Patients may benefit from early access to surgeons and peer guidance to enhance independence in decision-making. Preoperative educational materials describing surgical complications and postoperative lifestyle could improve decision-making and facilitate discussions with loved ones.

Molecular basis of infrared detection by snakes.

Snakes possess a unique sensory system for detecting infrared radiation, enabling them to generate a 'thermal image' of predators or prey. Infrared signals are initially received by the pit organ, a highly specialized facial structure that is innervated by nerve fibres of the somatosensory system. How this organ detects and transduces infrared signals into nerve impulses is not known. Here we use an unbiased transcriptional profiling approach to identify TRPA1 channels as infrared receptors on sensory nerve fibres that innervate the pit organ. TRPA1 orthologues from pit-bearing snakes (vipers, pythons and boas) are the most heat-sensitive vertebrate ion channels thus far identified, consistent with their role as primary transducers of infrared stimuli. Thus, snakes detect infrared signals through a mechanism involving radiant heating of the pit organ, rather than photochemical transduction. These findings illustrate the broad evolutionary tuning of transient receptor potential (TRP) channels as thermosensors in the vertebrate nervous system.

An Enhanced Role of Innate Immunity in the Immune Response After Kidney Transplant in People Living With HIV: A Transcriptomic Analysis.

BACKGROUND: Although kidney transplantation (KT) has become the standard of care for people living with HIV (PLWH) suffering from renal failure, early experiences revealed unanticipated higher rejection rates than those observed in HIV- recipients. The cause of increased acute rejection (AR) in PLWH was assessed by performing a transcriptomic analysis of biopsy specimens, comparing HIV+ to HIV- recipients. METHODS: An analysis of 68 (34 HIV+, 34 HIV-) formalin-fixed paraffin-embedded (FFPE) renal biopsies matched for degree of inflammation was performed from KT recipients with acute T cell-mediated rejection (aTCMR), borderline for aTCMR (BL), and normal findings. Gene expression was measured using the NanoString platform on a custom gene panel to assess differential gene expression (DE) and pathway analysis (PA). RESULTS: DE analysis revealed multiple genes with significantly increased expression in the HIV+ cohort in aTCMR and BL relative to the HIV- cohort. PA of these genes showed enrichment of various inflammatory pathways, particularly innate immune pathways associated with Toll-like receptors. CONCLUSIONS: Upregulation of the innate immune pathways in the biopsies of PLWH with aTCMR and BL is suggestive of a unique immune response that may stem from immune dysregulation related to HIV infection. These findings suggest that these unique HIV-driven pathways may in part be contributory to the increased incidence of allograft rejection after renal transplantation in PLWH.

Proof-of-concept for intervention to prevent post-operative ileus in patients undergoing ileostomy formation.

BACKGROUND: Preventing post-operative ileus (POI) is important given its associated morbidity and increased cost of care. The authors' prior work showed that POI in patients with newly created ileostomies is associated with a post-operative day (POD) 2 net fluid balance of > + 800 mL. The purpose of this study was to conduct an initial assessment of the efficacy of a pilot intervention. METHODS: This is a single-institution, pre-post-intervention, proof-of-concept study conducted on the Colorectal Surgery service at the University of California, San Francisco. The study included 58 procedures with ileostomy formation by board-certified colorectal surgeons between August 13, 2020 and June 1, 2021. The intervention included three adjustments to the standard Enhanced Recovery After Surgery protocol: addition of diuresis, delay in advancement to solid food, and earlier stoma intubation. Demographics, intraoperative factors, post-operative fluid balance, and outcomes (POI, post-procedure length of stay [LOS], hospitalization cost, and re-admissions) were compared between patients pre- and post-intervention. RESULTS: Eight (13.8%) of the 58 procedures in the intervention period were associated with POI vs. a baseline POI rate of 32.6% (p = 0.004). Compared to patients without intervention, those with intervention had 67% less odds of POI (OR 0.33, 95% CI 0.15-0.73, p = 0.01). This difference remained significant when adjusted for age, gender, body mass index, procedure duration, and operative approach (adjusted OR 0.32, 95% CI 0.14-0.72, p = 0.01). Average POD2 stoma output was 0.3 L greater (1.1 L vs. 0.8L; p < 0.001) and net fluid balance was 1.8 L lower (+ 0.3 L vs. + 2.1 L; p < 0.00001) for these 58 cases. Average post-procedure LOS was 1.9 days lower (5.3 vs. 7.2 days, p < 0.001) and direct cost was $5561 lower ($21,652 vs. $27,213, p = 0.004), with no difference in 30-day readmissions (p = 0.43). CONCLUSIONS: This pilot intervention shows promise for reduction in POI in patients with newly created ileostomies. Additional assessment is needed to confirm these initial findings.

Procurement of Deceased Donor Parathyroid Glands With the Aid of Near-infrared Autofluorescence Imaging.

Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery. Methods: Research tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal. Results: Thirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34). Conclusions: The use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.

Risk factors and outcomes associated with postoperative ileus following ileostomy formation: a retrospective study.

BACKGROUND: Postoperative ileus (POI) is associated with increased patient discomfort, length of stay (LOS), and healthcare cost. There is a paucity of literature examining POI in patients who have an ileostomy formed at the time of surgery. We aimed to identify risk factors for and outcomes associated with POI following ileostomy formation. METHODS: We included 261 consecutive non-emergent cases that included formation of an ileostomy by a board-certified colorectal surgeon at our institution from July 1, 2015, to June 30, 2020. Demographic, clinical, and intraoperative factors associated with increased odds of POI were evaluated. Post-procedure LOS, hospitalization cost, and re-admissions between patients with and without POI were compared. RESULTS: Out of 261 cases, 85 (32.6%) were associated with POI. Patients with POI had significantly higher body mass index (BMI) than those without POI (26.6 kg/m2 vs. 24.8kg/m2; p = 0.01). Intraoperatively, patients with POI had significantly longer procedure duration than those without POI (313 min vs. 279 min; p = 0.02). Patients with POI had a significantly higher net fluid balance at postoperative day (POD) 2 than those without POI (+ 2.65 L vs. + 1.80 L; p = 0.004), with POD2 fluid balance greater than + 807 mL (determined as the maximum Youden index for sensitivity over 80%) associated with a higher rate of POI (p = 0.006). This difference remained significant when adjusted for age, gender, BMI, pre-operative opioid use, procedure duration, and operative approach (p = 0.01). Patients with POI had significantly longer LOS (11.40 days vs. 5.12 days; p < 0.001) and direct cost of hospitalization ($38K vs. $22K; p < 0.001). CONCLUSIONS: Minimizing fluid overload, particularly in the first 48 h after surgery, may be a strategy to reduce POI in patients undergoing ileostomy formation, and thus decrease postoperative LOS and hospitalization cost. Fluid restriction, diuresis, and changes in diet advancement or early stoma intubation should be considered measures that may improve outcomes and should be studied more intensively.

Emergency general surgery utilization and disparities during COVID-19: an interrupted time-series analysis.

OBJECTIVE: We aimed to compare general surgery emergency (GSE) volume, demographics and disease severity before and during COVID-19. BACKGROUND: Presentations to the emergency department (ED) for GSEs fell during the early COVID-19 pandemic. Barriers to accessing care may be heightened, especially for vulnerable populations, and patients delaying care raises public health concerns. METHODS: We included adult patients with ED presentations for potential GSEs at a single quaternary-care hospital from January 2018 to August 2020. To compare GSE volumes in total and by subgroup, an interrupted time-series analysis was performed using the March shelter-in-place order as the start of the COVID-19 period. Bivariate analysis was used to compare demographics and disease severity. RESULTS: 3255 patients (28/week) presented with potential GSEs before COVID-19, while 546 (23/week) presented during COVID-19. When shelter-in-place started, presentations fell by 8.7/week (31%) from the previous week (p<0.001), driven by decreases in peritonitis (ß=-2.76, p=0.017) and gallbladder disease (ß=-2.91, p=0.016). During COVID-19, patients were younger (54 vs 57, p=0.001), more often privately insured (44% vs 38%, p=0.044), and fewer required interpreters (12% vs 15%, p<0.001). Fewer patients presented with sepsis during the pandemic (15% vs 20%, p=0.009) and the average severity of illness decreased (p<0.001). Length of stay was shorter during the COVID-19 period (3.91 vs 5.50 days, p<0.001). CONCLUSIONS: GSE volumes and severity fell during the pandemic. Patients presenting during the pandemic were less likely to be elderly, publicly insured and have limited English proficiency, potentially exacerbating underlying health disparities and highlighting the need to improve care access for these patients. LEVEL OF EVIDENCE: III.

Impact of Sarcopenia on Simultaneous Pancreas and Kidney Transplantation Outcomes: A Retrospective Observational Cohort Study.

BACKGROUND: Sarcopenia has been identified as a predictive variable for surgical outcomes. We hypothesized that sarcopenia could be a key measure to identify frail patients and potentially predict poorer outcomes among recipients of simultaneous pancreas and kidney (SPK) transplants. METHODS: We estimated sarcopenia by measuring psoas muscle mass index (PMI). PMI was assessed on perioperative computed tomography (CT) scans of SPK recipients. RESULTS: Of the 141 patients identified between 2010 and 2018, 107 had a CT scan available and were included in the study. The median follow-up was 4 years (range, 0.5-9.1 y). Twenty-three patients had a low PMI, and 84 patients had a normal PMI. Patient characteristics were similar between the 2 groups except for body mass index, which was significantly lower in low PMI group (P < 0.001). Patient and kidney graft survival were not statistically different between groups (P = 0.851 and P = 0.357, respectively). A multivariate Cox regression analysis showed that patients with a low PMI were 6 times more likely to lose their pancreas allograft (hazard ratios, 5.4; 95% confidence intervals, 1.4-20.8; P = 0.015). Three out of 6 patients lost their pancreas graft due to rejection in the low PMI group, compared with 1 out of 9 patients in the normal PMI group. Among low PMI patients who had a follow-up CT scan, 62.5% (5/8) of those with a functional pancreas graft either improved or resolved sarcopenia, whereas 75.0% (3/4) of those who lost their pancreas graft continued to lose muscle mass. CONCLUSION: Sarcopenia could represent one of the predictors of pancreas graft failure and should be evaluated and potentially optimized in SPK recipients.