Surgical and local control outcomes after sequential short-course radiation therapy and chemotherapy for rectal cancer.

Background: Total neoadjuvant therapy (TNT) is an accepted approach for the management of locally advanced rectal cancer (LARC) and is associated with a decreased risk of development of metastatic disease compared to standard neoadjuvant therapy. However, questions remain regarding surgical outcomes and local control in patients who proceed to surgery, particularly when radiation is given first in the neoadjuvant sequence. We report on our institution's experience with patients who underwent short-course radiation therapy, consolidation chemotherapy, and surgery. Methods: We retrospectively reviewed surgical specimen outcomes, postoperative complications, and local/pelvic control in a large cohort of patients with LARC who underwent neoadjuvant therapy incorporating upfront short-course radiation therapy followed by consolidation chemotherapy. Results: In our cohort of 83 patients who proceeded to surgery, a complete/near-complete mesorectal specimen was achieved in 90 % of patients. This outcome was not associated with the time interval from completion of radiation to surgery. Postoperative complications were acceptably low. Local control at two years was 93.4 % for all patients- 97.6 % for those with low-risk disease and 90.4 % for high-risk disease. Conclusion: Upfront short-course radiation therapy and consolidation chemotherapy is an effective treatment course. Extended interval from completion of short-course radiation therapy did not impact surgical specimen quality.

Short-Stay Left Colectomy for Colon Cancer: Is It Safe?

BACKGROUND: Advances in surgical practices have decreased hospital length of stay (LOS) after surgery. This study aimed to determine the safety of short-stay (≤24-hour) left colectomy for colon cancer patients in the US. STUDY DESIGN: Adult colon cancer patients who underwent elective left colectomies were identified using the American College of Surgeons NSQIP database (2012 to 2021). Patients were categorized into 4 LOS groups: LOS 1 day or less (≤24-hour short stay), 2 to 4, 5 to 6, and 7 or more. Primary outcomes were 30-day postoperative overall and serious morbidity. Secondary outcomes were 30-day mortality and readmission. Multivariable logistic regression was performed to explore the association between LOS and overall and serious morbidity. RESULTS: A total of 15,745 patients who underwent left colectomies for colon cancer were identified with 294 (1.87%) patients undergoing short stay. Short-stay patients were generally younger and healthier with lower 30-day overall morbidity rates (LOS ≤1 day: 3.74%, 2 to 4: 7.38%, 5 to 6: 16.12%, and ≥7: 37.64%, p < 0.001). Compared with patients with LOS 2 to 4 days, no differences in mortality and readmission rates were observed. On adjusted analysis, there was no statistical difference in the odds of overall (LOS 2 to 4 days: odds ratio 1.90, 95% CI 1.01 to 3.60, p = 0.049) and serious morbidity (LOS 2 to 4 days: odds ratio 0.86, 95% CI 1.42 to 1.76, p = 0.672) between the short-stay and LOS 2 to 4 days groups. CONCLUSIONS: Although currently performed at low rates in the US, short-stay left colectomy is safe for a select group of patients. Attention to patient selection, refinement of clinical pathways, and close follow-up may enable short-stay colectomies to become a more feasible reality.

Anorectal Anatomy Quiz: Practical Review.

Understanding anorectal and pelvic floor anatomy can be challenging but is paramount for every physician managing patients with anorectal pathology. Knowledge of anorectal anatomy is essential for managing benign, malignant, traumatic, and infectious diseases affecting the anorectum. This quiz is intended to provide a practical teaching guide for medical students, medical and surgical residents, and may serve as a review for practicing general surgeons and specialists.

National trends and feasibility of a robotic surgical approach in the management of patients with inflammatory bowel disease.

BACKGROUND: Research on the utilization of robotic surgical approaches in the management of inflammatory bowel disease (IBD) is limited. The aims of this study were to identify temporal trends in robotic utilization and compare the safety of a robotic to laparoscopic operative approach in patients with IBD. METHODS: Patients who underwent minimally invasive surgery (MIS) for IBD were identified using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2013-2021). Temporal trends of robotic utilization were assessed from 2013 to 2021. Primary (30-day overall and serious morbidity) and secondary (unplanned conversion to open) outcomes were assessed between 2019 and 2021, when robotic utilization was highest. Multivariable logistic regression was performed. RESULTS: The use of a robotic approach for colectomies and proctectomies increased significantly between 2013 and 2021 (p < 0.001), regardless of disease type. A total of 6016 patients underwent MIS for IBD between 2019 and 2021. 2234 (37%) patients had surgery for UC [robotic 430 (19.3%), lap 1804 (80%)] and 3782 (63%) had surgery for CD [robotic 500 (13.2%), lap 3282 (86.8%)]. For patients with UC, there was no difference in rates of overall morbidity (22.6% vs. 20.7%, p = 0.39), serious morbidity (11.4% vs. 12.3%, p = 0.60) or conversion to open (1.5% vs. 2.1%, p = 0.38) between the laparoscopic and robotic approaches, respectively. There was no difference in overall morbidity between the two groups in patients with CD (lap 14.0% vs robotic 16.4%, p = 0.15), however the robotic group exhibited higher rates of serious morbidity (7.3% vs. 11.2%, p < 0.01), shorter LOS (3 vs. 4 days, p < 0.001) and lower rates of conversion to an open procedure (3.8% vs. 1.6%, p = 0.02). Adjusted analysis showed similar results. CONCLUSION: The use of the robotic platform in the surgical management of IBD is increasing and is not associated with an increase in 30-day overall morbidity compared to a laparoscopic approach.

Academic Global Surgery Curricula: Current Status and a Call for a More Equitable Approach.

INTRODUCTION: We aimed to search the literature for global surgical curricula, assess if published resources align with existing competency frameworks in global health and surgical education, and determine if there is consensus around a fundamental set of competencies for the developing field of academic global surgery. METHODS: We reviewed SciVerse SCOPUS, PubMed, African Medicus Index, African Journals Online (AJOL), SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) and Bioline for manuscripts on global surgery curricula and evaluated the results using existing competency frameworks in global health and surgical education from Consortium of the Universities for Global Health (CUGH) and Accreditation Council for Graduate Medical Education (ACGME) professional competencies. RESULTS: Our search generated 250 publications, of which 18 were eligible: (1) a total of 10 reported existing competency-based curricula that were concurrent with international experiences, (2) two reported existing pre-departure competency-based curricula, (3) six proposed theoretical competency-based curricula for future global surgery education. All, but one, were based in high-income countries (HICs) and focused on the needs of HIC trainees. None met all 17 competencies, none cited the CUGH competency on "Health Equity and Social Justice" and only one mentioned "Social and Environmental Determinants of Health." Only 22% (n = 4) were available as open-access. CONCLUSION: Currently, there is no universally accepted set of competencies on the fundamentals of academic global surgery. Existing literature are predominantly by and for HIC institutions and trainees. Current frameworks are inadequate for this emerging academic field. The field needs competencies with explicit input from LMIC experts to ensure creation of educational resources that are accessible and relevant to trainees from around the world.

Special Considerations in the GI Bleeding Patient.

Lower gastrointestinal bleeding (LGIB) is an increasingly common problem in patients with comorbid medical conditions that place them at higher bleeding risk. This discussion of some special considerations in the GI bleeding patient encompasses an overview of the elderly patient, and selects comorbid conditions that place patients at higher risk of developing intestinal bleeding. The discussion lends itself to exploring the challenges of and new advancements in anticoagulation therapy. Radiation induced proctitis and rectal varices as sources of LGIB will also be addressed.

Normothermic extracorporeal liver perfusion for donation after cardiac death (DCD) livers.

BACKGROUND: The susceptibility of extended criteria livers to ischemia reperfusion injury is a major obstacle in organ cold preservation. Normothermic extracorporeal liver perfusion (NELP) has been investigated to reduce ischemic damage, restore physiologic function, and assess viability of the liver prior to transplant. The goal of this study is to compare physiological parameters of livers maintained continuously on NELP to those preserved in cold solution. METHODS: Livers from 9 female landrace pigs were subjected to either 20 minutes (W20-NELP), 40 minutes (W40-NELP), or 60 minutes (W60-NELP) of warm ischemia followed by 6 hours of NELP followed by a 2-hour NELP evaluation phase. This was compared with 3 livers subjected to 40 minutes of warm ischemia time followed by 6 hours of cold storage (W40-Cold) and a 2-hour NELP evaluation phase. Groups were compared with the 2-way analysis of variance test. RESULTS: NELP stabilized transaminases accompanied by significant improvement in bile production and decline in lactate and INR values in all W-NELP groups. Histologic analysis demonstrated significant improvement from 0 hour (mild-to-moderate sinusoidal dilation and zone 3 necrosis) to the end of the NELP run (minimal necrosis and mild IRI). Comparison of W40-NELP and W40-Cold revealed greater bile production and oxygen extraction ratio in W40-NELP. In contrast, markers of cellular and functional damage were increased in the W40-Cold group. CONCLUSION: NELP improves metabolic and functional parameters of livers with either short or extended warm ischemia times compared with livers subjected to comparable cold ischemia times.

Surgical treatment of hepatocellular carcinoma in North America: can hepatic resection still be justified?

BACKGROUND: The incidence of hepatocellular cancer (HCC) is increasing dramatically worldwide. Optimal management remains undefined, especially for well-compensated cirrhosis and HCC. STUDY DESIGN: This retrospective analysis included 5 US liver cancer centers. Patients with surgically treated HCC between 1990 and 2011 were analyzed; demographics, tumor characteristics, and survival rates were included. RESULTS: There were 1,765 patients who underwent resection (n = 884, 50.1%) or transplantation (n = 881, 49.9%). Overall, 248 (28.1%) resected patients were transplant eligible (1 tumor <5 cm or 2 to 3 tumors all <3 cm, no major vascular invasion); these were compared with 496 transplant patients, matched based on year of transplantation and tumor status. Overall survivals at 5 and 10 years were significantly improved for transplantation patients (74.3% vs 52.8% and 53.7% vs 21.7% respectively, p < 0.001), with greater differences in disease-free survival (71.8% vs 30.1% at 5 years and 53.4% vs 11.7% at 10 years, p < 0.001). Ninety-seven of the 884 (11%) resected patients were within Milan criteria and had cirrhosis; these were compared with the 496 transplantation patients, with similar results to the overall group. On multivariate analysis, type of surgery was an independent variable affecting all survival outcomes. CONCLUSIONS: The increasing incidence of HCC stresses limited resources. Although transplantation results in better long-term survival, limited donor availability precludes widespread application. Hepatic resection will likely remain a standard therapy in selected patients with HCC. In this large series, only about 10% of patients with cirrhosis were transplant-eligible based on tumor status. Although liver transplantation results are significantly improved compared with resection, transplantation is available only for a minority of patients with HCC.

Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.

Liver transplantation for metastatic neuroendocrine tumors.

The ideal management of NET must be addressed on a case-by-case basis, with consideration given to patient factors, disease burden, and clinical tumor activity. Outcome improvement for LT in the setting of metastatic disease requires better characterization of the biological behavior of NETs and further identification of factors to be included in the selection criteria. Box 3 summarizes the many areas that have been, and are currently, undergoing investigation. LT as an attempt for cure rather than palliation is a justified treatment option for well-selected patients with metastatic neuroendocrine tumors of the pancreas and GI system. Optimization of pretransplantation staging and patient management algorithms, patient selection, and posttransplant management options are areas that need to be better defined. Further investigations for defining reproducible prognostic factors, consistent histopathologic evaluation, and uniform preoperative staging and site-specific data are needed. With the advancement of newer treatment modalities, it is necessary to define the role of LT along with the optimal perioperative management of existing and recurrent disease.

Liver transplantation for hepatocellular carcinoma: how far have we come and what is the future?

Liver transplantation is the best treatment for hepatocellular carcinoma in the setting of chronic liver disease, completely removing malignancy and underlying diseased liver tissue. Technical aspects of liver transplantation have improved over the years, along with outcomes. But challenges continue in the areas of expanding existing indications for transplant with limited organ supply, calling for optimization of patient selection and the development of alternative or adjunctive treatment options. Expansion of existing transplant criteria will help identify patients most likely to have good outcomes. Locoregional and systemic treatments showing therapeutic promise are being investigated for use in achieving acceptable oncologic effect. Improvements in post-transplant treatment and continued attempts to enlarge the donor pool will continue to provide avenues for further improvements in outcomes.

Hepatic epithelioid hemangioendothelioma: MR imaging findings.

We report the MRI findings in three patients with pathologically proven hepatic epithelioid hemangioendothelioma, a rare tumor of the liver that is not well described in the MR imaging literature. The recognition of the imaging features of this rare malignancy may help further early detection and surgical treatment of this potentially curable disease.

IFNgamma restores breast cancer sensitivity to fulvestrant by regulating STAT1, IFN regulatory factor 1, NF-kappaB, BCL2 family members, and signaling to caspase-dependent apoptosis.

Antiestrogens are effective therapies for the management of many estrogen receptor-alpha (ER)-positive breast cancers. Nonetheless, both de novo and acquired resistance occur and remain major problems in the clinical setting. IFNgamma is an inflammatory cytokine that induces the expression and function of IFN regulatory factor 1 (IRF1), a tumor suppressor gene that can increase antiestrogen responsiveness. We show that IFNgamma, but not IFNalpha, IFNbeta, or fulvestrant (ICI; ICI 182,780; Faslodex), induces IRF1 expression in antiestrogen-resistant MCF7/LCC9 and LY2 cells. Moreover, IFNgamma restores the responsiveness of these cells to fulvestrant. Increased IRF1 activation suppresses NF-kappaB p65 (RELA) activity, inhibits the expression of prosurvival (BCL2, BCL-W), and induces the expression of proapoptotic members (BAK, mitochondrial BAX) of the BCL2 family. This molecular signaling is associated with the activation of signal transducer and activator of transcription 1 and leads to increased mitochondrial membrane permeability; activation of caspase-7 (CASP7), CASP8, and CASP9; and induction of apoptosis but not autophagy. Whereas antiestrogen-resistant cells are capable of inducing autophagy through IFN-mediated signaling, their ability to do so through antiestrogen-regulated signaling is lost. The abilities of IFNgamma to activate CASP8, induce apoptosis, and restore antiestrogen sensitivity are prevented by siRNA targeting IRF1, whereas transient overexpression of IRF1 mimics the effects of IFNgamma treatment. These observations support the exploration of clinical trials combining antiestrogens and compounds that can induce IRF1, such as IFNgamma, for the treatment of some ER-positive breast cancers.