A Comprehensive Review of the Antitumor Properties and Mechanistic Insights of Duocarmycin Analogs.

The duocarmycin family is a group of potent cytotoxic agents originally isolated from the bacterium Streptomyces. This discovery has spurred significant interest due to duocarmycins' unique chemical structures and powerful mechanism of action. This review comprehensively details the history of the duocarmycin family, the current understanding of their therapeutic potential, and the major clinical trials that have been conducted. Chemically, the duocarmycin family is characterized by a DNA-binding unit that confers specificity, a subunit-linking amide that positions the molecule within the DNA helix, and an alkylating unit that interacts with the DNA. This configuration allows them to bind selectively to the minor groove of DNA and alkylate adenine bases, a notable deviation from the more common guanine targeting performed by other alkylating agents. Duocarmycin's mechanism of action involves the formation of covalent adducts with DNA, leading to the disruption of the DNA architecture and subsequent inhibition of replication and transcription. Recent advancements in drug delivery systems, such as antibody-drug conjugates (ADCs), have further elevated the therapeutic prospects of duocarmycin analogs by providing a promising mechanism for enhancing intracellular concentrations and selective tumor delivery. Preclinical studies have highlighted the efficacy of duocarmycin derivatives in various in vitro models, providing a strong foundation for translational research. However, further biological research is required to fully understand the toxicology of duocarmycin family members before it can be clinically relevant. The major focus of this review is to cache the major biologically relevant findings of different duocarmycin analogs as well as their biological shortcomings to propose next steps in the field of cancer therapy with these potent therapeutics.

Oncologic outcomes and survival of modern surgical approaches for gastric gastrointestinal stromal tumor (GIST).

BACKGROUND: Studies have demonstrated comparable outcomes between laparoscopic and open resection of gastrointestinal stromal tumor (GIST). We sought to compare outcomes among robotic, laparoscopic, and open resection of gastric GIST in the era of expanding minimally invasive surgery. METHODS: A retrospective analysis was performed of adult patients with gastric GIST undergoing definitive surgery using the National Cancer Database from 2010 to 2020, excluding cases converted to open. Patients were stratified into minimally invasive surgery (MIS), (combined robotic (R) and laparoscopic (L)), and open (O). Hospital length of stay (LOS), 30-day mortality, 90-day mortality, and margin status were assessed. Subgroup analysis was performed to evaluate outcomes between R and L cohorts. Entropy balancing was used to adjust for intergroup differences. Kaplan-Meier survival estimates were used to compare unadjusted 5-year survival. RESULTS: Of the 15,022 patients (R = 10.4%, L = 44.3%, O = 45.3%), 63.2% were stage I and 70.6% underwent partial gastrectomy. MIS approach was associated with shorter hospital LOS (ß: - 2.58; 95% CI: - 2.82 to - 2.33) and lower odds of 30-day (OR 0.45; 95% CI: 0.30-0.68) and 90-day mortality (OR 0.54; 95% CI: 0.39-0.74) compared to O. Likelihood of R0 resection similar between groups (OR 1.00; 95% CI: 0.88-1.14). Hospital LOS (ß: + 0.25; 95% CI: - 0.14-0.64), odds of 30-day (OR 0.99; 95% CI: 0.40-2.46) and 90-day mortality (OR 0.89; 95% CI: 0.47-1.70), and rate of R0 resection (OR 1.02; 95% CI: 0.82-1.27) were comparable between R and L cohorts. Compared to O, MIS approach was associated with improved 5-year OS (log rank p < 0.001). Overall survival was not significantly different between R and L (log rank p = 0.44). CONCLUSION: These findings suggest that MIS approach may be considered for resection of gastric GIST in select patients. Among patients receiving an MIS approach, the robotic technique can be considered an oncologically safe alternative to laparoscopic surgery.

Improved survival with immunotherapy for microsatellite unstable colorectal cancer with peritoneal metastases.

BACKGROUND: KEYNOTE-177 demonstrated that immunotherapy was superior to chemotherapy for microsatellite-instability-high (MSI-high) metastatic colorectal cancer. Colorectal cancer with peritoneal metastases (CRPM) has a poorer prognosis than other metastatic sites, with an unclear role of immunotherapy. We evaluated trends in immunotherapy use and overall survival (OS). METHODS: Patients with CRPM and MSI testing were identified in the National Cancer Database (2016-2020). We evaluated immunotherapy use by year and associated patient/hospital factors. OS was compared for immunotherapy versus chemotherapy, cytoreductive surgery (CRS), and immunotherapy plus CRS. RESULTS: Among 15 322 CRPM patients, 7072 (46.2%) patients had documented MSI testing, with 819 (11.6%) MSI-high. Ninety-eight MSI-high patients received immunotherapy alone (12.3%), increasing from 0% in 2016 to 19.1% in 2020 (p < 0.01). On multivariable analysis, only higher comorbidity was associated with immunotherapy (OR: 2.83 [1.22-6.52]). Two-year OS with immunotherapy versus chemotherapy was 64.2% versus 54.1% (p < 0.05). In patients receiving CRS plus systemic therapy (N = 96), 2-year OS was 68.4%. Among patients who underwent immunotherapy and CRS versus immunotherapy alone, 2-year OS was 80.0% versus 60.0% (p = 0.14). CONCLUSIONS: Immunotherapy was associated with significantly better survival compared to chemotherapy in MSI-high CRPM. Two-year OS with systemic + CRS was 68.4%. Despite its role in guiding treatment, MSI testing remains low for these patients.

Laparoscopic Conversion to Open Cholecystectomy: Is Incidental Gallbladder Cancer Any Different?

BACKGROUND: A majority of gallbladder cancers present incidentally. Operative risk factors and outcomes for laparoscopic converted to open cholecystectomy in incidental gallbladder cancer are not well characterized. METHODS: Patients with incidental gallbladder cancer and acute cholecystitis undergoing laparoscopic cholecystectomy and conversion to open cholecystectomy in the National Surgical Quality Improvement Program (NSQIP) database of the American College of Surgeons (ACS) from 2010-2019 were reviewed. The primary endpoint was risk factors for conversion to open cholecystectomy in incidental gallbladder cancer. Chi-squared test or Fisher's exact test was used for categorical variables. Continuous variables were compared using the Mann-Whitney U test. RESULTS: A total of 5,789 patients undergoing laparoscopic cholecystectomy were identified, of which, 50 (0.9%) had incidental gallbladder cancer. For incidental gallbladder cancer patients, there were no differences in preoperative profile and risk factors between laparoscopic and converted to open cholecystectomy groups. Incidental carcinoma patients undergoing conversion to open cholecystectomy had lower preoperative sodium levels than the laparoscopic cholecystectomy group (P=0.007). Hospital length of stay (days) was longer for those with a conversion to open cholecystectomy for incidental carcinoma compared to non-conversion, 14 (10.8, 18.8) vs 2 (0.3, 5) (P=0.004). The patients converted to open cholecystectomy also had higher rates of postoperative sepsis (50% vs 0%, P<0.001) and reoperation than the laparoscopic cohort (50% vs 2.2%, P<0.001). Readmission and mortality rates, among other complications, were not significantly different between both surgical approaches in incidental gallbladder cancer patients. CONCLUSIONS:  Patients with conversion to open cholecystectomy had worse outcomes including longer hospital stays and higher rates of sepsis and reoperation. It remains difficult to predict which incidental gallbladder patients will require a conversion to open surgery. Further study examining whether more complicated recovery results in worse oncologic outcomes is warranted.

Adjuvant Radiotherapy for Surgically Resected Stage III Merkel Cell Carcinoma.

This case-control study evaluates whether adjuvant radiotherapy is associated with overall survival among patients with surgically resected stage III Merkel cell carcinoma.

Spanish-Speaking Status: A Protective Factor in Colorectal Cancer Presentation at a Safety-Net Hospital.

INTRODUCTION: Lower screening rates and poorer outcomes for colorectal cancer have been associated with Hispanic ethnicity and Spanish-speaking status, respectively. METHODS: We reviewed sequential colorectal cancer patients evaluated by the surgical service at a safety-net hospital (SNH) (2016-2019). Insurance type, stage, cancer type, surgery class (elective/urgent), initial surgeon contact setting (outpatient clinic/inpatient consult), operation (resection/diversion), and follow-up were compared by patient-reported primary spoken language. RESULTS: Of 157 patients, 85 (54.1%) were men, 91 (58.0%) had colon cancer, 67 (42.7%) primarily spoke Spanish, and late stage (III or IV) presentations occurred in 83 (52.9%) patients. The median age was 58 y, cancer resection was completed in 48 (30.6%) patients, and 51 (32.5%) patients were initially seen as inpatient consults. On univariate analysis, Spanish-speaking status was significantly associated with female sex, Medicaid insurance, being seen as an outpatient consult, and undergoing elective and resection surgery. On multivariable logistic regression, Spanish-speaking patients had higher odds of having Medicaid insurance (AOR 2.28, P = 0.019), receiving a resection (AOR 3.96, P = 0.006), and undergoing an elective surgery (AOR 3.24, P = 0.025). Spanish-speaking patients also had lower odds of undergoing an initial inpatient consult (AOR 0.34, P = 0.046). CONCLUSIONS: Spanish-speaking status was associated with a lower likelihood of emergent presentation and need for palliative surgery among SNH colorectal cancer patients. Further research is needed to determine if culturally competent infrastructure in the SNH setting translates into Spanish-speaking status as a potentially protective factor.

Laparoscopic resection of gastric schwannoma: A case report.

INTRODUCTION: Gastric schwannomas are an extremely rare presentation of mesenchymal tumors originating from Schwann cells, accounting for 0.2% of all gastric tumors. Patients are usually asymptomatic, so these tumors are frequently detected incidentally. PRESENTATION OF CASE: 68-year old male patient found to have a 5 cm mass in the lesser curvature of the stomach. After a careful preoperative evaluation, complete laparoscopic resection was performed. Pathology review confirmed a completely resected gastric Schwannoma. The patient's recovery was uneventful. At a one-year follow-up he remains asymptomatic and with no evidence of disease. DISCUSSION: We present the uncommon case of a gastric schwannoma that was appropriately treated with a laparoscopic approach and present a current literature review focusing on diagnostic and treatment methods of these rare tumors. CONCLUSION: Schwannomas should be included in the differential diagnosis of gastric tumors and can be appropriately treated with a laparoscopic approach.

Trends in Robotic Pancreaticoduodenectomy and Distal Pancreatectomy.

BACKGROUND: Pancreatic surgery remains a challenge even to the most experienced surgeons. Despite significant advances in the field, morbidity and mortality continue to have elevated rates even in specialized, high-volume centers. The rise of laparoscopy in the past decades has improved outcomes for patients, but remains unused due to the technical complexities involved. METHODS: A literature search was performed using PubMed and Google Scholar databases. Key words used in the search include: "robotic surgery," "robotic pancreas surgery," "pancreas surgery," "minimally invasive pancreas surgery," "robotic pancreaticoduodenectomy," and "robotic distal pancreatectomy." The studies included in our review were summarized in a patient intervention comparison and outcome table. RESULTS: The use of a robotic platform has emerged to counteract the more challenging aspects of laparoscopic pancreatic surgery, but incurs a high cost. Data, however, show a trend toward ever improving outcomes such as operative time, estimated blood loss, and length of stay, while still offering the benefits of minimally invasive surgery. CONCLUSION: There is no question that the use of robots in surgery will continue to expand, and with this, appropriate measures must be taken to ensure patient safety in the form of standardized education and certification for the future generation of surgeons considering robotic surgery. As robotic pancreatic surgery grows, encouraging data have emerged-as surgeons become more skilled and programs gain experience, patients are being benefited by this expanding technology. Larger, prospective cohorts will also provide more definitive evidence of the benefits of robotic surgery.