The Rise of Patients Declining Rectal Cancer Surgery in the Era of Total Neoadjuvant Therapy.

BACKGROUND: The treatment landscape for rectal cancer is rapidly evolving, particularly with the increasing use of neoadjuvant therapies. Still, up to 50% of patients with stage II-III disease require surgical resection post-neoadjuvant therapy to achieve the best oncologic outcomes. Many patients, however, hope to avoid surgery. This study aimed to assess trends and factors associated with declining recommended oncologic resection after systemic therapy nationally and in our institution. PATIENTS AND METHODS: This is a retrospective analysis using the National Cancer Database from 2009 to 2021 and an institutional cohort at an academic center between 2009 and 2022 including adults with stage I-III rectal adenocarcinoma who underwent neoadjuvant therapy and were suitable for surgery. RESULTS: Of 96,997 patients nationally, the rate of declining surgery increased from 2.3% in 2009 to 6.3% in 2021, a trend mirrored in our institutional cohort of 365 patients (0% in 2009/2010 to approximately 6-12% in 2021/2022). Locally, patients who declined surgery had higher rates of tobacco use, temporary loss to follow-up during therapy, and a more robust, albeit incomplete, tumor response to neoadjuvant therapy compared with controls who underwent surgery. Despite a stoma being the most cited reason for declining surgery, 30.4% of patients who declined oncologic resection died with a stoma. CONCLUSIONS: Our findings underscore a notable trend of patients declining oncologic resections following neoadjuvant therapy for rectal cancer. By shedding light on the outcomes of patients who opt against surgery, we address a critical gap in the literature essential for informing patients about potential risks.

Systematic Review of Neoadjuvant Immunotherapy for Mismatch Repair Deficient Locally Advanced Colon Cancer: An Emerging Strategy.

BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with nonmetastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable nonmetastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published between April 24 and September 26, 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were 1) English language, 2) adults with primary cancer of the colon, 3) nonmetastatic disease, 4) neoadjuvant immunotherapy, and 5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASURES: Safety (grade 3+ treatment-related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7691 studies identified, 6370 were screened and 8 were included. Various agents, dosing regimens, and treatment durations were used, with durations of immunotherapy ranging from 1 to 16 cycles. Complete R0 resections were consistently achieved in 98% to 100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50% to 91% had ypT0N0 pathology. The safety profiles were generally favorable, with grade 1 to 2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2% to 70% of patients. Postoperative complications after neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.

Development and validation of multivariable predictive models for recurrence and mortality following nonoperative management of sigmoid volvulus.

AIM: Sigmoid volvulus is a challenging condition, and deciding between elective surgery or expectant management can be complex. The aim of this study was to develop a tool for predicting the risk of recurrent sigmoid volvulus and all-cause mortality within 1 year following initial nonoperative management. METHOD: This is a retrospective cohort study using Medicare claims data from 2016 to 2018 of beneficiaries admitted urgently/emergently for volvulus, undergoing colonic decompression and discharged alive without surgery (excluding those discharged to hospice). The primary outcomes were recurrent sigmoid volvulus and all-cause mortality within 1 year. Proportional hazards models and logistic regression were employed to identify risk factors and develop prediction equations, which were subsequently validated. RESULTS: Among the 2078 patients managed nonoperatively, 36.1% experienced recurrent sigmoid volvulus and 28.6% died within 1 year. The prediction model for recurrence integrated age, sex, race, palliative care consultations and four comorbidities, achieving area under the curve values of 0.63 in both the training and testing samples. The model for mortality incorporated age, palliative care consultations and nine comorbidities, with area under the curve values of 0.76 in the training and 0.70 in the testing sample. CONCLUSION: This study provides a straightforward predictive tool that utilizes easily accessible data to estimate individualized risks of recurrent sigmoid volvulus and all-cause mortality for older adults initially managed nonoperatively. The tool can assist clinicians and patients in making informed decisions about such risks. While the accuracy of the calculator was validated, further confirmation through external validation and prospective studies would enhance its clinical utility.

Systematic Review of Surgical Care in the Incarcerated Population: Identifying Knowledge Gaps for Future Research.

Objective: This study, examining literature up to December 2023, aims to comprehensively assess surgical care for incarcerated individuals, identifying crucial knowledge gaps for informing future health services research and interventions. Background: The US prison system detains around 2 million individuals, mainly young, indigent males from ethnic and racial minorities. The constitutional right to healthcare does not protect this population from unique health challenges and disparities. The scarcity of literature on surgical care necessitates a systematic review to stimulate research, improve care quality, and address health issues within this marginalized community. Methods: A systematic review, pre-registered with the International Prospective Register of Systematic Reviews (CRD42023454782), involved searches in PubMed, Embase, and Web of Science. Original research on surgical care for incarcerated individuals was included, excluding case reports/series (<10 patients), abstracts, and studies involving prisoners of war, plastic surgeries for recidivism reduction, transplants using organs from incarcerated individuals, and nonconsensual surgical sterilization. Results: Out of 8209 studies screened, 118 met inclusion criteria, with 17 studies from 16 distinct cohorts reporting on surgical care. Predominantly focusing on orthopedic surgeries, supplemented by studies in emergency general, burns, ophthalmology, and kidney transplantation, the review identified delayed hospital presentations, a high incidence of complex cases, and low postoperative follow-up rates. Notable complications, such as nonfusion and postarthroplasty infections, were more prevalent in incarcerated individuals compared with nonincarcerated individuals. Trauma-related mortality rates were similar, despite lower intraabdominal injuries following penetrating abdominal injuries in incarcerated patients. Conclusion: While some evidence suggests inferior surgical care in incarcerated patients, the limited quality of available studies underscores the urgency of addressing knowledge gaps through future research. This is crucial for patients, clinicians, and policymakers aiming to enhance care quality for a population at risk of surgical complications during incarceration and postrelease.

Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy.

BACKGROUND: Cholangiocarcinoma (CCA) features highly desmoplastic stroma that promotes structural and functional resistance to therapy. Lysyl oxidases (LOX, LOXL1-4) catalyze collagen cross-linking, thereby increasing stromal rigidity and facilitating therapeutic resistance. Here, we evaluate the role of lysyl oxidases in stromal desmoplasia and the effects of pan-lysyl oxidase (pan-LOX) inhibition in CCA. METHODS: Resected CCA and normal liver specimens were analyzed from archival tissues. Spontaneous and orthotopic murine models of intrahepatic CCA (iCCA) were used to assess the impact of the pan-LOX inhibitor PXS-5505 in treatment and correlative studies. The functional role of pan-LOX inhibition was interrogated through in vivo and ex vivo assays. RESULTS: All 5 lysyl oxidases are upregulated in CCA and reduced lysyl oxidase expression is correlated with an improved prognosis in resected patients with CCA. Spontaneous and orthotopic murine models of intrahepatic cholangiocarcinoma upregulate all 5 lysyl oxidase isoforms. Pan-LOX inhibition reversed mechanical compression of tumor vasculature, resulting in improved chemotherapeutic penetrance and cytotoxic efficacy. The combination of chemotherapy with pan-LOX inhibition increased damage-associated molecular pattern release, which was associated with improved antitumor T-cell responses. Pan-LOX inhibition downregulated macrophage invasive signatures in vitro, rendering tumor-associated macrophages more susceptible to chemotherapy. Mice bearing orthotopic and spontaneously occurring intrahepatic cholangiocarcinoma tumors exhibited delayed tumor growth and improved survival following a combination of pan-LOX inhibition with chemotherapy. CONCLUSIONS: CCA upregulates all 5 lysyl oxidase isoforms, and pan-LOX inhibition reverses tumor-induced mechanical forces associated with chemotherapy resistance to improve chemotherapeutic efficacy and reprogram antitumor immune responses. Thus, combination therapy with pan-LOX inhibition represents an innovative therapeutic strategy in CCA.