The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.
From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases ...at 10 collaborating international institutions with documented KRAS status were surveyed.
A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio HR: 1.58, 95% CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95% CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95% CI 1.22-1.99; codon 13, HR 2.10 95% CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.
While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies, and the majority of patients with PDAC present with metastatic disease, mainly in the liver, at ...the time of diagnosis. Surgical resection is the only treatment that can offer prolonged survival and possible cure. However, the indications for surgery for patients with PDAC metastases remain extremely limited to highly selected patients with localized disease, and metastatic disease is generally regarded as a contraindication to surgery. Recently, however, the advent of more effective chemotherapy has changed the treatment strategy for metastatic PDAC. In fact, cases in which resection of synchronous or metachronous PDAC liver metastases lead to prolonged survival in highly selected patients have been reported. In this review, we provide current data regarding survival outcomes after surgery, and discuss the role of surgical resection and selection criteria for patients with PDAC liver metastases in the modern era.
To examine the impact of surgical margin width on survival following R0 hepatic resection for colorectal metastases (CRLM).
Although negative resection margin is considered of paramount importance ...for the prognosis of patients with colorectal liver metastases, optimal resection margin width remains controversial.
Eligible studies examining the association between margin status after R0 hepatic resection for CRLM and survival, including overall survival (OS) and disease-free survival (DFS) were sought using the Medline, Cochrane, and EMBASE databases. Random-effects models were used for the calculation of pooled relative risks (RRs) with their 95% confidence intervals (95% CIs).
Thirty-four studies were deemed eligible for inclusion representing a cohort of 11,147 hepatic resections. Wider resection margin (>1 vs <1 cm) was significantly associated with improved OS at 3 years (pooled RR = 0.86, 95% CI: 0.79-0.95), 5 years (pooled RR = 0.91, 95% CI: 0.85-0.97), and 10 years (pooled RR = 0.94, 95% CI: 0.88-1.00). Similarly, DFS was positively associated with >1 cm resection margin at 3, 5, and 10 years. Interestingly, >1 mm (vs <1 mm) resection margin was significantly associated with improved OS at all-time points. Meta-regression analyses did not reveal any significant modifying role of the study features under investigation, such as the administration of neoadjuvant/adjuvant therapy.
Importantly, our findings suggest that while a >1 mm margin is associated with better prognosis than a submillimeter margin, achieving a margin >1 cm may result in even better oncologic outcomes and should be considered if possible.
Pancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged ...as an effective tool to localize and stage PNETs.
Patients with PNETs who underwent R0 resections were identified from the 2004–2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy.
Of 16,746 R0 resected PNET patients, 44 % underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p < 0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 % vs. 42 %, p < 0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR = 1.67, p < 0.001).
Despite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy.
•Nearly half of patients with resectable PNET in the USA undergo diagnostic biopsy.•Use of diagnostic biopsy for resectable PNETs has increased between 2004 and 2019.•Diagnosis from 2016 to 2019 is associated with significantly increased odds of biopsy.•Odds of undergoing biopsy differ by geographic region.
Introduction
Peritoneal carcinomatosis is considered a late‐stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS‐HIPEC) can be an ...effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS‐HIPEC using only preoperatively known variables.
Methods
Adult patients with peritoneal carcinomatosis and who underwent CRS‐HIPEC were included from a large, single‐center, prospectively maintained dataset (2001–2020). TO was defined as a hospital length of stay ≤14 days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90 days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user‐friendly risk calculator was then developed.
Results
A total of 1954 CRS‐HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n = 258) achieved TO following CRS‐HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery.
Conclusion
This is a data‐driven study to predict the probability of achieving TO after CRS‐HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.
To compare different criteria for post-hepatectomy liver failure (PHLF) and evaluate the association between International Study Group of Liver Surgery (ISGLS) PHLF and the Comprehensive Complication ...Index (CCI)" and 90-day mortality.
PHLF is a serious complication following hepatic resection. Multiple criteria have been developed to characterize PHLF.
Adults who underwent major hepatectomies at twelve international centers (2010-2020) were included. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) Balzan (INR > 1.7 and bilirubin > 2.92mg/dL) or 3) Mullen (peak bilirubin >7mg/dL). We compared the 90-day mortality and major morbidity predicted by each definition. We then used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grades.
Among 1646 included patients, 19 (1.1%) met Balzan, 68 (4.1%) met Mullen, and 444 (27.0%) met ISGLS criteria for PHLF. Of the three definitions, the ISGLS criteria best predicted 90-day mortality (AUC = 0.72; sensitivity 69.4%). Patients with ISGLS grades B&C were at increased odds of CCI > 40 (grade B OR 4.0; 95% CI: 2.2-7.2; grade C OR 137.0; 95% CI: 59.2-317.4). Patients with ISGLS grade C were at increased odds of 90-day mortality (OR 113.6; 95% CI: 55.6-232.1). Grade A was not associated with CCI> 40 or 90-day mortality.
In this diverse international cohort of major hepatectomies, ISGLS grade A was not associated with 90-day mortality or high CCI, calling into question the current classification of patients in this group as having clinically significant PHLF.
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.
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