Dataset Information

Preoperative Predictors for 90-Day Mortality after Pancreaticoduodenectomy in Patients with Adenocarcinoma of the Ampulla of Vater: A Single-Centre Retrospective Cohort Study.

ABSTRACT:

Background

The standard treatment for ampullary adenocarcinoma is pancreaticoduodenectomy. Identification of preoperative risk factors might help the clinician to select patients fit for resection and potentially decrease morbidity and mortality after PD. We conducted a cohort study to determine the preoperative factors related to 90-day severe morbidity and mortality after PD.

Methods

We conducted a retrospective cohort study in patients with a diagnosis of ampullary adenocarcinoma who underwent an open PD between January 2010 and December 2019 at our tertiary centre.

Results

Independent preoperative predictors of mortality were the albumin-bilirubin (ALBI) grade 3 (OR: 21.7; CI 95: 2.1-226.9; p=0.01) and the estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m² (OR: 17.7; CI 95: 1.8-172.6; p=0.013). The eGFR <90 mL/min/1.73 m² (OR = 6.6; CI 95: 1.9-23.4; p=0.003) and prothrombin time (OR = 1.5; CI 95; 1.1-2.1; p=0.005) were independent predictors for severe morbidity.

Conclusion

These findings suggest that baseline renal function measured by the eGFR and liver function categorized with the ALBI grading are predictors of severe morbidity and mortality. Thus, they should be considered when selecting patients for PD or the use of neoadjuvant treatments. Further research is warranted.

SUBMITTER: Fernandez-Placencia R

PROVIDER: S-EPMC7937469 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Preoperative Predictors for 90-Day Mortality after Pancreaticoduodenectomy in Patients with Adenocarcinoma of the Ampulla of Vater: A Single-Centre Retrospective Cohort Study.

Fernandez-Placencia Ramiro R Berrospi-Espinoza Francisco F Uribe-Rivera Karla K Medina-Cana Jose J Chavez-Passiuri Ivan I Sanchez-Bartra Nestor N Paredes-Galvez Kori K Luque-Vasquez Vasquez Carlos C Celis-Zapata Juan J Ruiz-Figueroa Eloy E

Surgery research and practice 20210227

<h4>Background</h4>The standard treatment for ampullary adenocarcinoma is pancreaticoduodenectomy. Identification of preoperative risk factors might help the clinician to select patients fit for resection and potentially decrease morbidity and mortality after PD. We conducted a cohort study to determine the preoperative factors related to 90-day severe morbidity and mortality after PD.<h4>Methods</h4>We conducted a retrospective cohort study in patients with a diagnosis of ampullary adenocarcino ...[more]

PMID: 33728373

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Project description:LESSONS LEARNED:Panitumumab has no clinical activity in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC), possibly due to the foregut and midgut derivation of small bowel and ampulla.These results, along with findings from genomic characterization of SBA, suggest that SBA represents a unique intestinal malignancy and treatments should not be habitually extrapolated from colorectal cancer.Further studies evaluating the benefit of targeted therapies exclusively in SBA and AAC are warranted. BACKGROUND:Given the benefit of epidermal growth factor receptor (EGFR) monoclonal antibodies in colorectal cancer (CRC), we sought to evaluate the efficacy of panitumumab in metastatic RAS wild-type small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (AAC). METHODS:We conducted a single-center, open-label, single-arm, Bayesian phase II trial. The primary objective was response rate (RR). Panitumumab was administered at a dose of 6 mg/kg intravenously (IV) every 14 days. RESULTS:Nine patients (male/female 7:2, median age: 61 years [range: 40-74], Eastern Cooperative Oncology Group [ECOG] performance status 0/1: 2/7) were enrolled from September 2013 to October 2015. One patient had AAC (pancreaticobiliary subtype) and eight patients had SBA (three duodenal, five jejunal/ileal). Acneiform rash was the most common toxicity. The study was stopped early due to futility with no responses, stable disease (SD) in two patients, and progression of disease (PD) in seven patients. Median progression-free survival (PFS) and overall survival (OS) were 2.4 and 5.7 months, respectively. No patients had extended RAS mutations (exons 2/3/4), but two patients had BRAF G469A and one patient had PIK3CA H1074R mutations. CONCLUSION:Panitumumab had no clinically meaningful activity in patients with metastatic RAS wild-type SBA and AAC. Our findings may relate to the primarily midgut and foregut derivation of the small bowel and ampulla.

Project description:Patients with ampulla of Vater adenocarcinoma exhibit diverse outcomes, likely since these malignancies can originate from any of the three converging epithelia at this site. Such variability presents difficulties in clinical decision-making processes and in devising therapeutic approaches. In this study, the potential clinical value of histomolecular phenotypes was determined by integrating histopathological analysis with protein expression (MUC1, CDX2, CK20, and MUC2), in a cohort of 87 patients diagnosed with stage IB to III ampulla of Vater adenocarcinoma who underwent curative surgical resection. Of the 87 patients, 54 were classified as pancreato-biliary (PB) subtype and 33 as intestinal subtype. The median follow-up time for all patients was 32.8 months (95% CI, 25.3-49.2). Patients with a histomolecular PB phenotype (CDX2 negative, MUC1 positive, MUC2 negative, and irrespective of the CK20 results) were associated with poor prognostic outcomes in both disease-free survival (DFS) (HR = 1.81; 95% CI, 1.04-3.17; p = 0.054) and overall survival (OS) (HR = 2.01; 95% CI, 1.11-3.66; p = 0.039) compared to those with histomolecular intestinal carcinomas. Patients with the PB subtype were more likely to have local recurrence alone (11 of 37, 29.7%) compared to those with the intestinal subtype (1 of 15, 6.7%). In the context of systemic disease, a notably greater proportion of patients exhibiting elevated carbohydrate antigen 19-9 levels were observed in the PB subtype compared to the intestinal subtype (p = 0.024). In the cohort of 38 patients who received first-line palliative chemotherapy, a diminished median overall survival (OS) was observed in the PB group compared to the intestinal group (10.3 vs. 28.3 months, HR = 2.47; 95% CI, 1.23-4.95; p = 0.025). By integrating histopathologic and molecular criteria, we can identify distinct and clinically relevant histomolecular phenotypes in adenocarcinomas of the ampulla of Vater, which could have considerable impact on existing therapeutic approaches.

Project description:Tumors of the pancreas, the ampulla of Vater, and the extrahepatic and intrahepatic bile ducts have significant histological similarities due to the common embryonic origin of the pancreatobiliary system. This obviates the need for discovery of biomarkers with diagnostic and prognostic value for these tumors. Mucins, especially MUC-1, -2, -4 and -5AC, are important candidates for developing into such reliable biomarkers. Increased expression of MUC1 occurs in pancreatic ductal adenocarcinomas and is associated with increased degrees of dysplasia in pancreatic intraepithelial neoplasia (PanIN). Positive expression of MUC2 in intraductal papillary mucinus neoplasms (IPMN) of the intestinal type indicates high potential progression to invasive carcinoma with de novo expression of MUC1, while absence of MUC2 expression in IPMNs of gastric type implies low potential to malignant evolution. De novo MUC4 expression correlates to the severity of dysplasia in PanIN and is associated with a poor prognosis in patients with pancreatic ductal adenocarcinomas. In biliary intraepithelial neoplasia (BilIN), increased expression of MUC1 is associated with higher degrees of dysplasia. Intrahepatic cholangiocarcinomas (ICC) are characterized by increased expression of all glycoforms of MUC1. Positive MUC2 expression in intraductal papillary neoplasm of the bile ducts (IPNB) of the intestinal type indicates high malignant potential with de novo expression of MUC1 in the invasive element. Absent MUC2 expression in any degree of BilIN may prove useful in differentiating them from IPNB. De novo expression of MUC4 is associated with poor prognosis in patients with ICC or carcinoma of the extrahepatic bile ducts (EHBDC). High de novo expression of MUC5AC is found in all degrees of BilIN and all types of IPNB and ICC. The MUC5AC is useful in the detection of neoplastic lesions of the bile duct at an early stage. Increased expression of mucin MUC1 in carcinoma of the ampulla of Vater associated with unfavorable behavior of the tumor, such as lymph node metastasis, infiltration of the pancreas and duodenum, advanced TNM classification and worse prognosis. Patients with intra-ampullary papillary-tubular neoplasm (IAPN) of the pancreatobiliary immunophenotype did not show MUC2, while those of the intestinal immunophenotype are MUC2 positive. The expression of MUC4 is associated with poor prognosis in patients with carcinoma of the ampulla of Vater favoring metastasis and making them resistant to apoptosis. Moreover, it appears that MUC4 positivity correlates with recurrence of the tumor. Expression of MUC5AC is associated with the invasive potential of the tumor.

Project description:BackgroundThere is controversial evidence regarding the impact of clinically relevant postoperative intra-abdominal collections (CR-IC) on the clinical course after pancreaticoduodenectomy. C-reactive Protein (CRP) has been validated as a predictor of postoperative pancreatic fistula (POPF). Still, its role in predicting CR-IC has not been studied.MethodsA retrospective analysis was conducted on patients who underwent PD at a tertiary hospital between October 2012 and October 2017. The incidence of CR-IC, clinically relevant POPF and other complications, as well as mortality and length of hospitalisation, was retrieved. The impact of CR-IR on mortality and major complications was analysed. The serum CRP levels were retrieved on the third and fifth postoperative days (POD3 and POD5), followed by an analysis of sensitivity, specificity, and area under the curve to predict CR-IC using CRP.ResultsOne hundred forty patients were enrolled following inclusion and exclusion criteria. The mean age was 66.5 years (15-83). The incidence of CR-IC was 33.7% (47), and CR-POPF was 24.3%. Pancreatic duct diameter ≤ 4 mm was identified as a risk factor related to CR-IC occurrence. The group of patients who developed CR-IC after PD exhibited a higher rate of complications Clavien-Dindo ≥ III compared to patients without CR-IC (40.4% vs 7.5%, p < 0.001), as well as other events such as admission to the intensive care unit (25.5% vs 4.3%, p < 0.001), the incidence of CR-POPF (66% vs 3.2%, p < 0.001), prolonged hospital stay (32 vs 13 days, p < 0.001), postoperative haemorrhage (23.4 vs 5.4%, p = 0.002), and delayed gastric empty (38.8% vs 11.8%, p < 0.001) respectively. Logistic regression analysis identified CR-IC related to POPF as a risk factor for Clavien-Dindo > III: OR = 10.6 (95% CI: 3.90-28.7). No differences in mortality were reported between the CR-IC group and non-CR-IC group. CRP at postoperative day 3 (POD3) > 17.55 mg/dl and CRP at postoperative day 5 (POD5) > 13.46 mg/dl were predictors of CR-IC (AUC: 0.731 and AUC:0.821, respectively).ConclusionsCR-IC has a significant impact after pancreaticoduodenectomy and is associated with a higher incidence of Clavien-Dindo ≥ III complications. Additionally, CRP levels at POD3 and POD5 play a role in predicting CR-IC. Prospective studies are essential to explore strategies for mitigating the occurrence of CR-IC after PD.

Dataset Information

Preoperative Predictors for 90-Day Mortality after Pancreaticoduodenectomy in Patients with Adenocarcinoma of the Ampulla of Vater: A Single-Centre Retrospective Cohort Study.

Background

Methods

Results

Conclusion

Publications

Preoperative Predictors for 90-Day Mortality after Pancreaticoduodenectomy in Patients with Adenocarcinoma of the Ampulla of Vater: A Single-Centre Retrospective Cohort Study.

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