Search

Background: Low-grade appendiceal mucinous neoplasms (LAMNs) can progress to pseudomyxoma peritonei (PMP). The incidence and risk factors for recurrence are unclear, and there is a lack of consensus on the need and duration of surveillance imaging., Methods: Patients at the Mayo Clinic in Rochester, Minnesota, with a histologic diagnosis of LAMNs confined to the appendix and limited involvement of the right lower quadrant from 1992 to 2023 were included. Associations between recurrence and risk factors were assessed using Kaplan-Meier curves and Cox proportional hazards regression., Results: A total of 125 patients with LAMNs underwent abdominal imaging surveillance for a median of 51.2 months (IQR, 26-92). Of note, 5 patients (4%) recurred, all of which were PMP. Overall, the 5- and 10-year cumulative recurrence incidence rates were 3% and 6%, respectively. The median time to recurrence was 24 months (IQR, 23-87). Only LAMNs limited to the right lower quadrant and LAMN tumor size of <2 cm were associated with recurrence (P < .05). The 5- and 10-year cumulative recurrence risks were 12% and 30%, respectively, for the 21 patients with either risk factor. Only 1% of patients without these 2 risk factors developed a recurrence at 10 years., Conclusion: The overall recurrence risk of LAMN after resection is low. Appendectomy is sufficient for LAMN. Select patients with acellular mucin confined to the right lower quadrant and a tumor size of <2 cm are at higher risk of recurrence. Thus, long-term surveillance is recommended for high-risk individuals. Conversely, LAMNs without risk factors can be safely observed expectantly., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

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., (© 2023. Society of Surgical Oncology.)

Background: Intrahepatic Cholangiocarcinoma (iCCA) is an aggressive cancer with diverse mutational profiles. An important molecular subtype is fibroblast growth factor receptor 2 (FGFR2) fusion. The effect of FGFR2 fusions on prognosis is unknown. Our aim was to assess the outcomes in resected CCA patients in relation to FGFR2 status., Methods: Surgically treated CCA patients from a single institution were retrospectively reviewed between 2008 and 2014. FGFR rearrangements were detected by fluorescence in situ hybridization (FISH). Data included patient demographics, tumor pathology, disease-free survival (DFS) and overall survival (OS)., Results: Ninety-five patients underwent surgical resection for iCCA. Twelve (13%) of these were found to have FGFR2 fusion, none of which were treated with FGFR targeted therapy. Patients with FGFR2 fusions were found to have a longer 5-year (83 vs. 32%, p = 0.01) and 10-year (46 vs. 22%, p = 0.04) OS. Five and 10-year DFS was also increased (68 vs. 33% p = 0.04) and (68 vs. 25 %, p = 0.02,). FGFR2 fusion status was the strongest independent factor associated with improved OS (HR 0.23, 0.09-0.62, p=0.003) and DFS (HR 0.18, 0.05-0.67, p=0.01)., Conclusion: Patients with CCA FGFR2 fusion have improved OS and DFS following surgical resection., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

In the current endovascular era, open repair of complex aortic aneurysms is becoming a rare, but indispensable, part of vascular surgeons' skill set in specific scenarios. For young, low-risk patients and patients with connective tissue disorders, early target vessel bifurcation, a horseshoe kidney, or pedunculated intraluminal aortic thrombus, fenestrated-branched stent graft technology will not be applicable without significant risks. Thus, an open surgical approach has been recommended for these patients. Most vascular surgeons will be familiar with a transperitoneal approach or a retroperitoneal approach with a lateral incision. For patients with a horseshoe kidney, an inflammatory aneurysm, or a history of multiple intraperitoneal procedures, a retroperitoneal approach should be preferred. In the present report, we have described in detail the optimization of a retroperitoneal approach through a midline incision that provides excellent exposure to the paravisceral aorta, improves exposure to the right renal artery and right iliac artery bifurcation (which is limited using the left flank retroperitoneal approach), and avoids division of the lateral abdominal wall muscles, which has often been associated with iatrogenic muscle denervation and postoperative bulging for four patients who had required complex aortic reconstruction., (© 2022 The Author(s).)

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics. Desmoplastic malignancies, such as cholangiocarcinoma (CCA), have an abundant tumor immune microenvironment (TIME). However, to date, ICB monotherapy in such malignancies has been ineffective. Herein, we identify tumor-associated macrophages (TAMs) as the primary source of programmed death-ligand 1 (PD-L1) in human and murine CCA. In a murine model of CCA, recruited PD-L1+ TAMs facilitated CCA progression. However, TAM blockade failed to decrease tumor progression due to a compensatory emergence of granulocytic myeloid-derived suppressor cells (G-MDSCs) that mediated immune escape by impairing T cell response. Single-cell RNA sequencing (scRNA-Seq) of murine tumor G-MDSCs highlighted a unique ApoE G-MDSC subset enriched with TAM blockade; further analysis of a human scRNA-Seq data set demonstrated the presence of a similar G-MDSC subset in human CCA. Finally, dual inhibition of TAMs and G-MDSCs potentiated ICB. In summary, our findings highlight the therapeutic potential of coupling ICB with immunotherapies targeting immunosuppressive myeloid cells in CCA.

Background: Preoperative opioid use in patients undergoing low complexity operations has been associated with increased complications, but its relationship to procedures of greater complexity is unclear. We aimed to assess this impact on outcomes following pancreaticoduodenectomy (PD)., Methods: A single institution, retrospective cohort of adults undergoing elective PD for cancer (1/2009-9/2015). Preoperative opioid users were defined as patients documented as taking opioids up to 90 days preoperatively. Discharge prescriptions were converted into Oral Morphine Equivalents (OME) and ten-point pain scores were abstracted. Univariate and multivariable analyses compared outcomes of naïve and preoperative opioid users overall and for laparoscopic vs open surgery., Results: Of 661 PD patients, 131 (19.8%) were preoperative opioid users. These patients had greater mean pain scores over the first three days after surgery (3.4 ± 1.6, vs 2.8 ± 1.4, p < 0.001), max pain (7.9 ± 1.9 vs 7.2 ± 2.0, p < 0.001), and discharge pain (2.3 ± 1.9 vs 1.8 ± 1.6, p = 0.01) than naïve patients. Preoperative opioid users received more opioids at discharge (mean 496 ± 764 OME) than naïve (320 ± 489 OME, p = 0.03). Thirty-day refill rates were 12.6% (19.1% preoperative vs 10.9% naïve, p = 0.02). After controlling for tumor type, pancreas texture, and duct size, naïve patients had similar odds of clinically significant post-operative pancreatic fistulas (grade B or C) (OR 1.13, p = 0.68) and delayed gastric emptying (OR 1.05, p = 0.87). After controlling for age and complications, preoperative opioid use was associated with increased odds of LOS ≥9 days (OR 1.59, p = 0.04)., Conclusion: Following PD, preoperative opioid users had worse pain scores, received more opioids at discharge, refilled prescriptions more frequently, and were more likely to have prolonged LOS. As most opioid utilization research has been focused on low complexity surgery, additional work aimed at optimizing opioid use in complex oncologic operations is warranted., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Treatment of cardiovascular implantable device pocket infections (CIDPIs) requires a multimodal approach that includes antimicrobials, device explantation, and local wound care. Our institution implemented a practice management guideline (PMG) to standardize the care of CIDPIs and engage our acute care surgeons in 2013. Our PMG includes wound culture, complete capsulectomy, pulse lavage, and the placement of a negative pressure wound therapy appliance at the time of device extraction. Forty-eight hours later, wounds are irrigated and closed in a delayed primary fashion over drains. Our objective was to compare the outcomes of patients who underwent device extraction before and after the implementation of the PMG for the treatment of CIDPIs., Methods: An IRB-approved retrospective review of 155 patients at our institution from 2012 to 2015 who underwent device explantation. Evaluated outcomes measured included days from device explant to wound closure, and postoperative complications. Outcomes data were analyzed before (pre-PMG) and after (post-PMG) enactment of the PMG., Results: Fifty-eight patients (42 males; mean age 68 years) were managed prior to PMG implementation; 97 (72 males; mean age 67) were managed after. Mean days from device explantation to wound closure were compared (pre-PMG 6 ± 3.5 and post-PMG 2.8 ± 1.8), and time to closure was reduced by 3-d post-PMG implementation (P < 0.05). No increase in surgical site infection, hematoma, or unplanned return to operating room was demonstrated between groups (P < 0.05)., Conclusions: The implementation of a PMG for the management of CIDPIs is effective in reducing the number of days to pocket wound closure; acute care surgeons are well equipped to participate in this practice and improve patient outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Endoscopic totally extraperitoneal inguinal hernia repair (TEP-IHR) requires practice and training to perform well. We developed a simple, low-cost, inanimate model to teach surgical residents inguinal anatomy and the technique of mesh insertion for a safe, endoscopic TEP-IHR. The objective of this study was to compare our model vs cadaveric dissection for teaching anatomy and mesh insertion., Methods: A total of 14 general surgery residents participated in an institutional review board approved, prospective, and randomized study. Participants received a timed, web-based, interactive pretest assessing relevant anatomy and operative-based techniques. They then performed endoscopic TEP-IHRs on either a cadaver or our low-cost model. Participants then received a timed, web-based interactive posttest consisting of the same questions. Participants were surveyed anonymously regarding the degree to which either the model or the cadaver was educationally effective., Results: Both groups of trainees (cadaver = 7, low-cost model = 7) scored higher on the posttest (p<0.05) with similar improvement (cadaver group: pretest = 78% correct, posttest = 87%; low-cost model group: 77% vs 86%). Survey results revealed the trainees preferred for both initial learning and understanding of mesh placement using low-cost models (5 out of 5, 4.8/5, respectively) over cadavers (4.0/5, 3.8/5, respectively; p<0.05). Trainees preferred the cadaver (4.7) over the low-cost model (3.9, p<0.05) in overall experience. No differences were found in the trainees' preference between the cadaver (4.5) and low-cost model (4.7) in the overall educational value., Conclusion: While the overall educational experience of 14 learners favored a cadaver experience to learn TEP-IHR, initial anatomical learning and placing the mesh was better with an inanimate model. Given the educational value of the 2 methods was equivalent, the $1500 cost for cadavers make the inexpensive and repeatable inanimate model an attractive early resource for learning TEP-IHR., (Published by Elsevier Inc.)