Preoperative prognostic factors in patients with ductal adenocarcinoma of the head of the pancreas

Objective: To identify preoperative prognostic factors influencing pancreatic cancer survival following curative resection in a single Brazilian institution. Methods: From 2005 to 2018, preoperative clinic demographic and laboratory data were prospectively collected. Survival analysis was performed by the Kaplan-Meier method and the comparison between curves by the log-rank test. For multivariate analysis, the Cox regression model was used. Results: Preoperative factors with significant impact on univariate analysis survival were age equal to or greater than 70 years (p = 0.012) and previous history of cancer (p = 0.026). On multivariate analysis, patients with preoperative serum levels of CA 19.9 from 38 to 554 U / ml had a 3.15 times higher chance of death (HR 3.15; 95% CI 1.01-9.82; p = 0.047), whereas patients with the marker above 554 U / ml evolved 3.96 times more likely than those with the normal dosage (HR 3.96; 95% CI 1.19-13.10; p = 0.024). Patients with previous comorbidities had a 2.90 times higher chance of death than those without associated conditions (HR 2.90; 95% CI 1.10-7.67; p = 0.032). Conclusion: Preoperative factors related to the worsening prognosis of pancreatic ductal adenocarcinoma were advanced age, presence of comorbidities, previous history of cancer, and elevated preoperative serum CA 19.9. Headings: Carcinoma, Pancreatic Ductal. Pancreaticoduodenectomy. Prognosis. Survival Analysis. de 66,0%, 52,8%, 45,8% e 19,1% aos 12, 18, 24 e 36 meses, respectivamente. Apesar dos avanços, o tratamento do câncer pancreático é um dos mais desafiadores da atualidade.


INTRODUCTION
P ancreatic cancer is the fourth leading cause of cancer death in the United States, where the incidence matches mortality 1,2 . In Brazil, it represents 2% of overall cancers and 4% of cancer deaths 3 . The long asymptomatic period contributes to the poor prognosis, which means that the diagnosis is made, in most cases, at an advanced stage. Twothirds of patients have cancer located in the head of the pancreas, while one third in the body or tail 2 .
It predominantly affects individuals between 60 and 80 years of age, it is more frequent in men, and it is related to a component of family origin in about 10% of cases 2,4,5 . In addition to genetic factors, the increased risk among smokers, patients with chronic pancreatitis and type 2 diabetes is well established [6][7][8][9] .
Only 10% to 20% of patients diagnosed with pancreatic cancer have a locoregional disease, which evolves with a global survival of about 30% in five years 1,2 . 52% of pancreatic neoplasms are diagnosed at an advanced stage and with metastasis and present with a 3% overall fiveyear survival 1 . The overall survival for all stages of pancreatic cancer is about 8% in five years 1 .
Surgical resection is the only therapeutic option with a chance of cure 2 .
Original Article

Preoperative prognostic factors in patients with ductal adenocarcinoma of the head of the pancreas
Among the periampular carcinomas, the ductal adenocarcinoma of the head of the pancreas (ADCP) has the worst prognosis. The survival of patients undergoing surgical interventions approximates that observed in patients with neoplasia of the papilla or distal choledochus, and belong to the pancreatobiliary subtype 10,11 .
When assessing surgical and postoperative data, lymph node involvement, larger lesions, undifferentiated tumors, angiolymphatic and perineural invasion as well as the non-association with adjuvant therapy are well-established predictors of a worse prognosis [12][13][14] Figure 2 depicts the survival curve using the Kaplan-Meier method according to age.     were the variables that proved to be independent prognostic factors, with statistical significance (  However, some authors have not identified age as a prognostic factor 12,17 .

RESULT (S)
The coexistence of comorbidities, found in 67.5% of our sample, was an important prognostic factor, with a significant impact on survival. Patients with associated diseases had an almost three times higher chance of early death than the others.
Our sample had a prevalence of comorbidities two to three times higher than that found in the literature, which ranges from 20.0% to 30.0% of patients undergoing pancreatic resection 14,18 . Lim et al. 14 allocated operated pancreatic cancer patients into three groups: without comorbidities, one comorbidity and two or more comorbidities.
Most patients had no comorbidities (77.0%) and, when comparing the groups, this factor did not significantly affect survival. Due to the advancement of cancer treatments and improved survival of these patients, the risk of developing second primary neoplasias is increasing 19,20 . These patients are especially susceptible to it due to genetic issues, exposure to common risk factors, as well as the late effect of chemotherapy and radiotherapy treatments 20 .
Pancreatic cancer, as the second primary neoplasm, had a more aggressive outcome in our series. Despite the current advances, the treatment of pancreatic cancer is still a challenge.