Distinct Indications for Adjuvant Therapy in Resected Invasive Mucinous Cystic Neoplasms of the Pancreas Compared with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Surgical and adjuvant management of mucinous cystic neoplasms (MCNs) lacks formal guidelines and data is limited to institutional studies. Factors associated with receipt of adjuvant therapy and any associated impact on survival remain to be clarified. In the absence of other data, guidelines that recommend adjuvant chemotherapy for invasive pancreatic adenocarcinoma have been extrapolated to MCN. PATIENTS AND METHODS: The National Cancer Database (2004-2019) was utilized to identify all patients that underwent pancreatic resection for invasive MCNs. Patients that received neoadjuvant therapy or did not undergo lymphadenectomy were excluded. Patient, tumor, and treatment factors associated with survival were assessed. RESULTS: For 161 patients with invasive MCN, median overall survival (OS) was 133 months and 45% of patients received adjuvant therapy. Multivariable analysis demonstrated that poorly differentiated tumors [odds ratio (OR) 4.19, 95% confidence interval (CI) 1.47-11.98; p = 0.008] and positive lymph node status (OR 2.67, 95% CI 1.02-6.98; p = 0.042) were independent predictors of receiving adjuvant therapy. Lymph node positivity [hazard ratio (HR) 2.90, 95% CI 1.47-5.73; p = 0.002], positive margins (HR 5.28, 95% CI 2.28-12.27; p < 0.001), and stage III disease (HR 12.46, 95% CI 1.40-111.05; p = 0.024) were associated with worse OS. Receipt of adjuvant systemic therapy was independently associated with decreased risk of mortality in node positive patients (HR 0.23, 95% CI 0.10-0.69; p = 0.002). Survival was not associated with adjuvant therapy in patients with negative lymph nodes or margin negative status. CONCLUSION: In contrast to pancreatic ductal adenocarcinoma (PDAC), where adjuvant therapy improves OS for every tumor stage, surgery alone for invasive MCN is not associated with improved OS compared with surgery plus adjuvant therapy in node-negative patients. Surgery alone is likely sufficient for a subset of invasive MCN.

Long-Duration Neoadjuvant Therapy with FOLFIRINOX Yields Favorable Outcomes for Patients Who Undergo Surgery for Pancreatic Cancer.

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

Improved survival of patients receiving immunotherapy and chemotherapy following curative-intent resection of colorectal liver metastases.

BACKGROUND: Despite significant advancements in the treatment of patients with colorectal liver metastases (CRLMs), only a minority will experience long-term survival. This study aimed to determine the effect of chemotherapy (CT) and immunotherapy (IT) compared with that of CT alone on patient survival after surgical resection. METHODS: Patients undergoing curative-intent liver resection followed by adjuvant systemic therapy for stage IV colon cancer were identified using the National Cancer Database. Patients were stratified into type of therapy (CT alone vs CT + IT) and microsatellite status. Propensity score-weighted analysis was performed through 1:1 matching based on the nearest neighbor method. RESULTS: Of 9943 patients who underwent resection of CRLMs, 7971 (80%) received systemic adjuvant therapy. Of 7971 patients, 1432 (18%) received a combination of CT and IT. Microsatellite status was not associated with overall survival (OS). Adjuvant CT + IT was associated with increased 3-year OS compared with that of CT alone in both the unmatched cohort (55% vs 48%, respectively; P < .001) and matched cohort (52% vs 48%, respectively; P = .050). On multivariate analysis, older age, positive resection margins, and KRAS mutation were independent predictors of poor survival, whereas the administration of adjuvant CT + IT was an independent predictor of improved survival. CONCLUSION: IT combined with CT was associated with improved survival compared with that of CT alone after curative-intent resection of CRLMs, regardless of microsatellite instability status. Clinical trials to determine optimal patient selection, IT regimen, and long-term efficacy to improve outcomes of patients with CRLMs are warranted.

Robotic-assisted endoluminal gastric leiomyoma resection: a novel surgical technique for benign gastroesophageal junction tumors.

Gastric leiomyomas are rare, benign smooth muscle tumors that arise from the muscularis propria and can be found in any part of the stomach. The American College of Gastroenterologists recommends resection only for symptomatic leiomyomas, which can often present with bleeding, abdominal pain, or dyspepsia. Notably, symptomatic leiomyomas that arise at the gastroesophageal (GE) junction, especially those that are large, pose unique challenges. Specifically, total gastrectomy with esophagojejunostomy is often necessary, which can be associated with a compromised quality of life and possible complications such as anastomotic stricture or reflux esophagitis. In this context, we present the case of a young, male patient with a large symptomatic leiomyoma at the GE junction who was offered a robotic-assisted endoluminal leiomyoma resection. By placing endoluminal trocars and utilizing the Da Vinci® robot, we were able to carefully excise the tumor without perforating the stomach or causing GE junction stenosis. This allowed the patient to preserve his stomach and avoid a high-risk anastomosis. Another notable highlight of the case included the use of the endoscope as both a bougie and a source of insufflation. The patient had an uncomplicated postoperative course and a rapid recovery, highlighting the feasibility of this approach for patients with benign GE junction tumors.

A Novel Machine Learning Approach to Predict Textbook Outcome in Colectomy.

BACKGROUND: Several calculators exist to predict risk of postoperative complications. However, in low-risk procedures such as colectomy, a tool to determine the probability of achieving the ideal outcome could better aid clinical decision-making, especially for high-risk patients. A textbook outcome is a composite measure that serves as a surrogate for the ideal surgical outcome. OBJECTIVE: To identify the most important factors for predicting textbook outcomes in patients with nonmetastatic colon cancer undergoing colectomy and to create a textbook outcome decision support tool using machine learning algorithms. DESIGN: This was a retrospective analysis study. SETTINGS: Data were collected from the American College of Surgeons National Surgical Quality Improvement Program database. PATIENTS: Adult patients undergoing elective colectomy for nonmetastatic colon cancer (2014-2020) were included. MAIN OUTCOME MEASURES: Textbook outcome was the main outcome, defined as no mortality, no 30-day readmission, no postoperative complications, no 30-day reinterventions, and a hospital length of stay of ≤5 days. Four models (logistic regression, decision tree, random forest, and eXtreme Gradient Boosting) were trained and validated. Ultimately, a web-based calculator was developed as proof of concept for clinical application. RESULTS: A total of 20,498 patients who underwent colectomy for nonmetastatic colon cancer were included. Overall, textbook outcome was achieved in 66% of patients. Textbook outcome was more frequently achieved after robotic colectomy (77%), followed by laparoscopic colectomy (68%) and open colectomy (39%, p < 0.001). eXtreme Gradient Boosting was the best performing model (area under the curve = 0.72). The top 5 preoperative variables to predict textbook outcome were surgical approach, patient age, preoperative hematocrit, preoperative oral antibiotic bowel preparation, and patient sex. LIMITATIONS: This study was limited by its retrospective nature of the analysis. CONCLUSIONS: Using textbook outcome as the preferred outcome may be a useful tool in relatively low-risk procedures such as colectomy, and the proposed web-based calculator may aid surgeons in preoperative evaluation and counseling, especially for high-risk patients. See Video Abstract . UN NUEVO ENFOQUE DE APRENDIZAJE AUTOMTICO PARA PREDECIR EL RESULTADO DE LOS LIBROS DE TEXTO EN COLECTOMA: ANTECEDENTES:Existen varias calculadoras para predecir el riesgo de complicaciones posoperatorias. Sin embargo, en procedimientos de bajo riesgo como la colectomía, una herramienta para determinar la probabilidad de lograr el resultado ideal podría ayudar mejor a la toma de decisiones clínicas, especialmente para pacientes de alto riesgo. Un resultado de libro de texto es una medida compuesta que sirve como sustituto del resultado quirúrgico ideal.OBJETIVO:Identificar los factores más importantes para predecir el resultado de los libros de texto en pacientes con cáncer de colon no metastásico sometidos a colectomía y crear una herramienta de apoyo a la toma de decisiones sobre los resultados de los libros de texto utilizando algoritmos de aprendizaje automático.DISEÑO:Este fue un estudio de análisis retrospectivo.AJUSTES:Los datos se obtuvieron de la base de datos del Programa Nacional de Mejora de la Calidad del Colegio Americano de Cirujanos.PACIENTES:Se incluyeron pacientes adultos sometidos a colectomía electiva por cáncer de colon no metastásico (2014-2020).MEDIDAS PRINCIPALES DE RESULTADO:El resultado de los libros de texto fue el resultado principal, definido como ausencia de mortalidad, reingreso a los 30 días, complicaciones posoperatorias, reintervenciones a los 30 días y una estancia hospitalaria ≤5 días. Se entrenaron y validaron cuatro modelos (regresión logística, árbol de decisión, bosque aleatorio y XGBoost). Finalmente, se desarrolló una calculadora basada en la web como prueba de concepto para su aplicación clínica.RESULTADOS:Se incluyeron un total de 20.498 pacientes sometidos a colectomía por cáncer de colon no metastásico. En general, el resultado de los libros de texto se logró en el 66% de los pacientes. Los resultados de los libros de texto se lograron con mayor frecuencia después de la colectomía robótica (77%), seguida de la colectomía laparoscópica (68%) y la colectomía abierta (39%) (p<0,001). XGBoost fue el modelo con mejor rendimiento (AUC=0,72). Los cinco principales variables preoperatorias para predecir el resultado en los libros de texto fueron el abordaje quirúrgico, la edad del paciente, el hematocrito preoperatorio, la preparación intestinal con antibióticos orales preoperatorios y el sexo femenino.LIMITACIONES:Este estudio estuvo limitado por la naturaleza retrospectiva del análisis.CONCLUSIONES:El uso de los resultados de los libros de texto como resultado preferido puede ser una herramienta útil en procedimientos de riesgo relativamente bajo, como la colectomía, y la calculadora basada en la web propuesta puede ayudar a los cirujanos en la evaluación y el asesoramiento preoperatorios, especialmente para pacientes de alto riesgo. (Traducción-Yesenia Rojas-Khalil ).

Inadequate Lymph Node Yield: An Inadequate Indication for Adjuvant Chemotherapy in Stage II Colon Cancer.

Background: Optimal therapy for stage II colon cancer remains unclear, and national guidelines recommend "consideration" of adjuvant chemotherapy (ACT) in the presence of high-risk features, including inadequate lymph node yield (LNY, <12 nodes). This study aims to determine whether the survival benefit of ACT in stage II disease varies based on the adequacy of LNY. Methods: We used the National Cancer Database (NCDB) to identify adults who underwent resection for a single primary T3 or T4 colon cancer between 2006 and 2018. Multivariable logistic regression tested for associations between ACT and prespecified demographic and clinical characteristics, including the adequacy of LNY. We used Cox proportional hazards models to assess overall survival and restricted cubic splines to estimate the optimal LNY threshold to dichotomize patients based on overall survival. Results: Unadjusted 5- and 10-year survival rates were 84% and 75%, respectively, among patients who received ACT and 70% and 50% among patients who did not (log-rank P < 0.01). Inadequate LNY was independently associated with both receipt of ACT (odds ratios, 1.50; P < 0.01) and decreased overall survival [hazard ratio (HR), 1.56; P < 0.01]. ACT was independently associated with improved survival (HR, 0.67; P < 0.01); this effect size did not change based on the adequacy of LNY (interaction P = 0.41). Results were robust to re-analysis with our cohort-optimized threshold of 18 lymph nodes. Conclusions: Consistent with contemporary guidelines, patients with inadequate LNY are more likely to receive ACT. LNY adequacy is an independent prognostic factor but, in isolation, should not dictate whether patients receive ACT.

A Machine Learning Approach to Predict Postoperative Pancreatic Fistula After Pancreaticoduodenectomy Using Only Preoperatively Known Data.

BACKGROUND: Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables. METHODS: Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed. RESULTS: Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78. CONCLUSIONS: In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling.

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.

Exploring the complexity and spectrum of racial/ethnic disparities in colon cancer management.

BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality across U.S. racial/ethnic groups. Existing studies often focus on a particular race/ethnicity or single domain within the care continuum. Granular exploration of disparities among different racial/ethnic groups across the entire colon cancer care continuum is needed. We aimed to characterize differences in colon cancer outcomes by race/ethnicity across each stage of the care continuum. METHODS: We used the 2010-2017 National Cancer Database to examine differences in outcomes by race/ethnicity across six domains: clinical stage at presentation; timing of surgery; access to minimally invasive surgery; post-operative outcomes; utilization of chemotherapy; and cumulative incidence of death. Analysis was via multivariable logistic or median regression, with select demographics, hospital factors, and treatment details as covariates. RESULTS: 326,003 patients (49.6% female, 24.0% non-White, including 12.7% Black, 6.1% Hispanic/Spanish, 1.3% East Asian, 0.9% Southeast Asian, 0.4% South Asian, 0.3% AIAE, and 0.2% NHOPI) met inclusion criteria. Relative to non-Hispanic White patients: Southeast Asian (OR 1.39, p < 0.01), Hispanic/Spanish (OR 1.11 p < 0.01), and Black (OR 1.09, p < 0.01) patients had increased odds of presenting with advanced clinical stage. Southeast Asian (OR 1.37, p < 0.01), East Asian (OR 1.27, p = 0.05), Hispanic/Spanish (OR 1.05 p = 0.02), and Black (OR 1.05, p < 0.01) patients had increased odds of advanced pathologic stage. Black patients had increased odds of experiencing a surgical delay (OR 1.33, p < 0.01); receiving non-robotic surgery (OR 1.12, p < 0.01); having post-surgical complications (OR 1.29, p < 0.01); initiating chemotherapy more than 90 days post-surgery (OR 1.24, p < 0.01); and omitting chemotherapy altogether (OR 1.12, p = 0.05). Black patients had significantly higher cumulative incidence of death at every pathologic stage relative to non-Hispanic White patients when adjusting for non-modifiable patient factors (p < 0.05, all stages), but these differences were no longer statistically significant when also adjusting for modifiable factors such as insurance status and income. CONCLUSIONS: Non-White patients disproportionately experience advanced stage at presentation. Disparities for Black patients are seen across the entire colon cancer care continuum. Targeted interventions may be appropriate for some groups; however, major system-level transformation is needed to address disparities experienced by Black patients.

Hypertension Requiring Medication Use: a Silent Predictor of Poor Outcomes After Pancreaticoduodenectomy.

BACKGROUND: Although hypertension requiring medication (HTNm) is a well-known cardiovascular comorbidity, its association with postoperative outcomes is understudied. This study aimed to evaluate whether preoperative HTNm is independently associated with specific complications after pancreaticoduodenectomy. STUDY DESIGN: Adults undergoing elective pancreaticoduodenectomy were included from the 2014-2019 NSQIP-targeted pancreatectomy dataset. Multivariable regression models compared outcomes between patients with and without HTNm. Endpoints included significant complications, any complication, unplanned readmissions, length of stay (LOS), clinically relevant postoperative pancreatic fistula (CR-POPF), and cardiovascular and renal complications. A subgroup analysis excluded patients with diabetes, heart failure, chronic obstructive pulmonary disease, estimated glomerular filtration rate from serum creatinine (eGFRCr) < 60 ml/min per 1.73 m2, bleeding disorder, or steroid use. RESULTS: Among 14,806 patients, 52% had HTNm. HTNm was more common among older male patients with obesity, diabetes, congestive heart failure, chronic obstructive pulmonary disease, functional dependency, hard pancreatic glands, and cancer. After adjusting for demographics, preoperative comorbidities, and laboratory values, HTNm was independently associated with higher odds of significant complications (aOR 1.12, p = 0.020), any complication (aOR 1.11, p = 0.030), cardiovascular (aOR 1.78, p = 0.002) and renal (aOR 1.60, p = 0.020) complications, and unplanned readmissions (aOR 1.14, p = 0.040). In a subgroup analysis of patients without major preoperative comorbidity, HTNm remained associated with higher odds of significant complications (aOR 1.14, p = 0.030) and cardiovascular complications (aOR 1.76, p = 0.033). CONCLUSIONS: HTNm is independently associated with cardiovascular and renal complications after pancreaticoduodenectomy and may need to be considered in preoperative risk stratification. Future studies are necessary to explore associations among underlying hypertension, specific antihypertensive medications, and postoperative outcomes to investigate potential risk mitigation strategies.

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.

Minimally Invasive Distal Pancreatectomy Techniques: A Contemporary Analysis Exploring Trends, Similarities, and Differences to Open Surgery.

Limited contemporary data has compared similarities and differences between total laparoscopic (LDP), hand-assisted (HALDP), and open distal pancreatectomy (ODP). This study aimed to examine similarities and differences in outcomes between these three approaches in a contemporary cohort. Methods: Patients undergoing elective LDP, HALDP, and ODP in the NSQIP dataset (2014−2019) were included. Descriptive statistics and multivariate regression analyses were employed to compare postoperative outcomes. Results: Among 5636 patients, 33.9% underwent LDP, 13.1% HALDP, and 52.9% ODP. Compared with the LDP approach, surgical site infections were more frequent in HALDP and ODP approaches (1.2% vs. 2.6% vs. 2.8%, respectively, p < 0.01). After adjustment, the LDP approach was associated with a significantly lower likelihood of surgical site infection (OR 0.25, p = 0.03) when compared to ODP. There was no difference in the likelihood of surgical site infection when HALDP was compared to ODP (OR 0.59, p = 0.40). Unadjusted operative times were similar between approaches (LDP = 192 min, HALDP = 193 min, ODP = 191 min, p = 0.59). After adjustment, the LDP approach had a longer operative time (+10.3 min, p = 0.04) compared to ODP. There was no difference in the adjusted operative time between HALDP and ODP approaches (+5.4 min, p = 0.80). Conclusions: Compared to ODP, LDP was associated with improved surgical site infection rates and slightly longer operative times. There was no difference in surgical site infection rates between ODP and HALDP. Surgeon comfort and experience should decide the operative approach, but it is important to discuss the differences between these approaches with patients.