Purpose
In pancreatic cancer, genetic markers to aid clinical decision making are still lacking. The present study was designed to determine the prognostic role of perioperative serum tumor marker ...carbohydrate antigen 19-9 (CA19-9) in pancreatic adenocarcinoma, with a focus on implications for pre- and postoperative therapeutic consequences.
Methods
Of a total of 1,626 consecutive patients who underwent surgery for primary pancreatic adenocarcinoma, data from 1,543 patients with preoperative serum levels of CA19-9 were evaluated for tumor stage, resectability, and prognosis. Preoperative to postoperative CA19-9 changes were analyzed for long-term survival. A control cohort of 706 patients with chronic pancreatitis was used to assess the predictability of malignancy by CA19-9 and the effects of hyperbilirubinemia on CA19-9 levels.
Results
The more that preoperative CA19-9 increased, the lower were tumor resectability and survival rates. Resectability and 5-year survival varied from 80 to 38 % and from 27 to 0 % for CA19-9 <37 versus ≥4,000 U/ml, respectively. The R0 resection rate was as low as 15 % in all patients with CA19-9 levels ≥1,000 U/ml. CA19-9 increased with the stage of the disease and was highest in AJCC stage IV. Patients with an early postoperative CA19-9 increase had a dismal prognosis. Hyperbilirubinemia did not markedly affect CA19-9 levels (correlation coefficient ≤0.135).
Conclusions
In patients with pancreatic adenocarcinoma, CA19-9 predicts resectability, stage of disease, as well as survival. Highly elevated preoperative or increasing postoperative CA19-9 levels are associated with low resectability and poor survival rates, and demand the adjustment of surgical and perioperative therapy.
MINIWe analyzed prognostic factors after neoadjuvant therapy and resection in 280 patients with initially unresectable pancreatic cancer—the largest single-center study reported. We found that ...preoperative CA 19–9 levels, lymph node status, presence of distant metastases, and vascular involvement were all independent overall survival predictors, but not resection margin status.
OBJECTIVE:To evaluate the impact of clinical and pathological parameters, including resection margin (R) status, on survival in patients undergoing pancreatic surgery after neoadjuvant treatment for initially unresectable pancreatic ductal adenocarcinoma (PDAC).
BACKGROUND:Prognostic factors are well documented for patients with resectable PDAC, but have not been described in detail for patients with initially unresectable PDAC undergoing resection after neoadjuvant therapy.
METHODS:Prospectively collected data of consecutive patients with initially unresectable pancreatic cancer treated by neoadjuvant treatment and resection were analyzed. The R status was categorized as R0 (tumor-free margin >1 mm), R1 ≤1 mm (tumor-free margin ≤1 mm), and R1 direct (microscopic tumor infiltration at margin). Clinicopathological characteristics and outcomes were compared among these groups and tested for survival prediction.
RESULTS:Between January, 2006 and February, 2017, 280 patients with borderline resectable (n = 18), locally advanced (n = 190), or oligometastatic (n = 72) disease underwent tumor resection after neoadjuvant treatment. Median overall survival from the time of surgery was 25.1 months for R0 (n = 82), 15.3 months for R1 ≤1 mm (n = 99), and 16.1 months for R1 direct (n = 99), with 3-year overall survival rates of 35.0%, 20.7%, and 18.5%, respectively (P = 0.0076). The median duration of the neoadjuvant treatment period was 5.1 months. In multivariable analysis, preoperative CA 19–9 levels, lymph node status, metastasis category, and vascular involvement were all significant prognostic factors for overall survival. The R status was not an independent prognostic factor.
CONCLUSIONS:In patients undergoing resection after neoadjuvant therapy for initially unresectable PDAC, preoperative CA 19–9 levels, lymph node involvement, metastasis category, and vascular involvement, but not the R status, were independent prognostic factors of overall survival.
Background Postoperative pancreatic fistula (POPF) is the most important complication after pancreatic surgery. In 2005, the International Study Group of Pancreatic Surgery (ISGPS) introduced a ...standardized POPF definition with severity grading from A to C. In recent years, interventional drainage (ID) has become the standard of care for symptomatic postoperative fluid collections or undrained POPF. From the original definition, it is unclear whether ID is categorized as POPF grade B or C. Therefore, international authors shift ID between grades B and C. The aim of the study was to analyze patients with ID (proposed new grade B) versus patients who underwent reoperation (grade C) for POPF. Methods Between 2005 and 2013, all patients undergoing pancreatic resection were analyzed regarding POPF grade A-C. Demographic data, type of operation, postoperative complications, therapies and outcome were examined with focus on ID versus reoperation. Results Of the 2,955 patients included, 403 developed POPF (13.6%). Among all POPF, 11% were grade A, 17% grade B (clinically symptomatic without ID), and 72% grade C. These patients underwent either ID ( n = 165) or reoperation ( n = 123). Patients with ID had an average hospital stay of 33 days and POPF-associated mortality of 0%. This was strikingly different from patients undergoing reoperation with a hospital stay of 47 days and POPF-associated mortality of 37% ( P < .0001). Conclusion After 10 years of the ISGPS classification, there is a clear-cut outcome difference between patients undergoing POPF-associated ID or reoperation. We propose assigning all patients undergoing ID as POPF grade B. Patients undergoing reoperation should definitely remain within category C.
Pancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein ...(CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.
Objective The purpose of this study was to evaluate the radiation exposure of vascular surgeons' eye lens and fingers during complex endovascular procedures in modern hybrid operating rooms. Methods ...Prospective, nonrandomized multicenter study design. One hundred seventy-one consecutive patients (138 male; median age, 72.5 years interquartile range, 65-77 years) underwent an endovascular procedure in a hybrid operating room between March 2012 and July 2013 in two vascular centers. The dose-area product (DAP), fluoroscopy time, operating time, and amount of contrast dye were registered prospectively. For radiation dose recordings, single-use dosimeters were attached at eye level and to the ring finger of the hand next to the radiation field of the operator for each endovascular procedure. Dose recordings were evaluated by an independent institution. Before the study, precursory investigations were obtained to simulate the radiation dose to eye lens and fingers with an Alderson phantome (RSD, Long Beach, Calif). Results Interventions were classified into six treatment categories: endovascular repair of infrarenal abdominal aneurysm (n = 65), thoracic endovascular aortic repair (n = 32), branched endovascular aortic repair for thoracoabdominal aneurysms (n = 17), fenestrated endovascular aortic repair for complex abdominal aortic aneurysm, (n = 25), iliac branched device (n = 8), and peripheral interventions (n = 24). There was a significant correlation in DAP between both lens ( P < .01; r = 0.55) and finger ( P < .01; r = 0.56) doses. The estimated fluoroscopy time to reach a radiation threshold of 20 mSv/y was 1404.10 minutes (90% confidence limit, 1160, 1650 minutes). According to correlation of the lens dose with the DAP an estimated cumulative DAP of 932,000 mGy/m2 (90% confidence limit, 822,000, 1,039,000) would be critical for a threshold of 20 mSv/y for the eyes. Conclusions Radiation protection is a serious issue for vascular surgeons because most complex endovascular procedures are delivering measurable radiation to the eyes. With the correlation of the DAP obtained in standard endovascular procedures a critical threshold of 20 mSv/y to the eyes can be predicted and thus an estimate of a potential harmful exposure to the eyes can be obtained.
Background For pancreatic cancer, complete macroscopic resection in combination with chemotherapy is the only potentially curative treatment. Many patients present with locally advanced cancers ...deemed unresectable. We sought to assess the results of exploration after neoadjuvant therapy for locally advanced possibly unresectable pancreatic cancer. Methods From a prospective database, all consecutive patients undergoing operation from October 2001 to December 2009 after neoadjuvant therapy for locally advanced pancreatic cancer were identified. Main criteria for “unresectability” were infiltration of the celiac axis or superior mesenteric artery. Resection rates, perioperative results, and survival were analyzed. Results Of 257 patients, 199 (77.4%) had received neoadjuvant chemoradiation, and 58 (22.6%) chemotherapy only. Of 257 patients, 120 (46.7%) underwent successful resection, whereas 137 patients underwent exploration only; 47 (39.2%) multivisceral and 45 (37.5%) vascular resections (12 arterial reconstructions) were performed. There were 6 (5%) ypT0 neoplasms, 36 (30.0%) R0, 61 (50.8%) R1, and 16 (13.3%) R2 resections. The median follow-up of surviving patients ( n = 22) was 22 months. Median postoperative survival was greater after resection (12.7 months) than after exploration alone (8.8 months; P < .0001). Median postoperative survival was 24.6 months after R0, 11.9 months after R1, and 8.9 months after R2 resection. The 3-year survival rate after R0 resection was 24%. To determine survival after start of neoadjuvant therapy, 3.7 months (median) have to be added. Conclusion In locally advanced, unresectable pancreatic cancer, R0/R1 resections can be achieved in up to 40% of patients who undergo operation after neoadjuvant therapy. In these cases, survival rates are similar to those observed for initially resectable pancreatic cancer.
Background Small, asymptomatic, branch-duct intraductal papillary mucinous neoplasms of the pancreas are often kept under surveillance despite their malignant potential. The management of branch-duct ...intraductal papillary mucinous neoplasm is controversial with regard to indications and extent of any operative intervention. The present study aimed to evaluate enucleation as an alternative operative approach for branch-duct intraductal papillary mucinous neoplasms to exclude and prevent malignancy. Methods For branch-duct intraductal papillary mucinous neoplasms of <30 mm in diameter and an acceptable distance from the main pancreatic duct, enucleation was considered as the operative approach of choice. All patients scheduled for enucleation of branch-duct intraductal papillary mucinous neoplasm on the basis of these features between January 2004 and September 2014 were analyzed. Among these, patients with successful enucleation were compared with those who were scheduled for enucleation but converted intraoperatively to pancreatic resection (intention-to-treat analysis). End points were hospital morbidity and mortality as well as histopathology and functional outcome at a mean follow-up of 32 months. Results In the study, 115 patients with presumed branch-duct intraductal papillary mucinous neoplasm and the intention to perform pancreatic enucleation were included; 87 enucleations were performed in 74 patients. In 41 patients, enucleation was converted to a pancreatic resection (procedure-specific success rate 64%); indications for conversion included location or size (46%), presence of multicystic lesions (39%), or involvement of the main pancreatic duct (15%). Of the 74 patients with enucleation, 64 branch-duct intraductal papillary mucinous neoplasms revealed low- (85%), 11% moderate dysplasia-, and 4% high-grade dysplasia on histology. Among converted resections, 6 intraductal papillary mucinous neoplasms revealed high-grade dysplasia or invasive carcinoma (15%). Intention-to-treat analysis with patients converted to pancreatic resection showed that enucleations resulted in less blood loss (100 vs 400 mL) and a shorter operation time (146 vs 255 minutes; P < .001 each). Postoperative morbidity including postoperative pancreatic fistula was similar in both groups. No mortality occurred after enucleation; after formal resection, 1 patient died due to multiorgan failure. Both hospital stay (10 vs 14 days) and rates of postoperative endocrine and exocrine dysfunction rates were less after enucleation ( P < .02 each). Intraductal papillary mucinous neoplasm-specific recurrence rates (3% vs 6%) were similar in both groups. Conclusion Enucleation is a safe procedure that can be performed successfully in a high proportion of branch-duct intraductal papillary mucinous neoplasms and should be considered instead of standard resections as an important function-preserving alternative. Limitations may occur due to malignancy, size, localization, multilocularity, or main-duct involvement requiring conversion to a formal, anatomic resection. Beside the advantages in the short-term course, functional outcome seems to be superior after enucleation, and intraductal papillary mucinous neoplasm-specific recurrence rates are not increased compared with standard resections, at least at a mean follow-up of 32 months.
Preoperative/Neoadjuvant treatment (NT) is increasingly used in unresectable pancreatic cancer (PDAC). However, ∼40% of patients cannot be resected after NT and reliable preoperative response ...evaluation is currently lacking. We investigated CA 19-9 levels and their dynamics during NT for prediction of resectability and survival.
We screened our institution's database for patients who underwent exploration or resection after NT with gemcitabine-based therapy (GEM) or FOLFIRINOX (FOL). Pre- and post-NT CA 19-9, resection rate and survival were analyzed.
Of 318 patients 165 (51.9%) were resected and 153 (48.1%) received exploration. In the FOL group (n = 103; 32.4%), a post-NT CA 19-9 cutoff at 91.8 U/ml had a sensitivity of 75.0% and a specificity of 76.9% for completing resection with an AUC of 0.783 in the ROC analysis (95% CI: 0.692–0.874; p < 0.001. PPV: 84.2%, NPV: 65.2%). Resected patients above the cutoff did not benefit from resection. Post-NT CA 19-9 <91.8 U/ml (OR 11.63, p < 0.001) and CA 19-9 ratio of <0.4 (OR 5.77, p = 0.001) were independent predictors for resectability in FOL patients.
CA 19-9 levels after neoadjuvant treatment with FOLFIRINOX predict resectability and survival of PDAC more accurately than dynamic values and should be incorporated into response evaluation and surgical decision-making.
IMPORTANCE: The natural history of intraductal papillary mucinous neoplasms (IPMNs) remains uncertain. The inconsistencies among published guidelines preclude accurate decision-making. The outcomes ...and potential risks of a conservative watch-and-wait approach vs a surgical approach must be compared. OBJECTIVE: To provide an overview of the surgical management of IPMNs, focusing on the time of resection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted in a single referral center; all patients with pathologically proven IPMN who received a pancreatic resection at the institution between October 2001 and December 2019 were analyzed. Preoperatively obtained images and the medical history were scrutinized for signs of progression and/or malignant features. The timeliness of resection was stratified into too early (adenoma and low-grade dysplasia), timely (intermediate-grade dysplasia and in situ carcinoma), and too late (invasive cancer). The perioperative characteristics and outcomes were compared between these groups. EXPOSURES: Timeliness of resection according to the final pathological findings. MAIN OUTCOMES AND MEASURES: The risk of malignant transformation at the final pathology. RESULTS: Of 1439 patients, 438 (30.4%) were assigned to the too early group, 504 (35.1%) to the timely group, and 497 (34.5%) to the too late group. Radiological criteria for malignant conditions were detected in 53 of 382 patients (13.9%), 149 of 432 patients (34.5%), and 341 of 385 patients (88.6%) in the too early, timely, and too late groups, respectively (P < .001). Patients in the too early group underwent more parenchyma-sparing resections (too early group, 123 of 438 28.1%; timely group, 40 of 504 7.9%; too late group, 5 of 497 1.0%; P < .001), while morbidity (too early group, 112 of 438 25.6%; timely group, 117 of 504 23.2%; too late group, 158 of 497 31.8%; P = .002) and mortality (too early group, 4 patients 0.9%; timely, 4 0.8%; too late, 13 2.6%; P = .03) were highest in the too late group. Of the 497 patients in the too late group, 124 (24.9%) had a previous history of watch-and-wait care. CONCLUSIONS AND RELEVANCE: Until the biology and progression patterns of IPMN are clarified and accurate guidelines established, a watch-and-wait policy should be applied with caution, especially in IPMN bearing a main-duct component. One-third of IPMNs reach the cancer stage before resection. At specialized referral centers, the risks of surgical morbidity and mortality are justifiable.
Background & Aims Chronic pancreatitis (CP) and pancreatic adenocarcinoma (PCa) are characterized by intrapancreatic neural alterations and pain. Our aims were to: (a) Investigate whether neuropathic ...changes like pancreatic neuritis, increased neural density, and hypertrophy are phenomena only in CP or whether they are also evident in other pancreatic disorders as well, (b) study possible variations in neural cancer cell invasion among malignant pancreatic tumors, and (c) explore whether these neuropathic changes contribute to pain sensation. Methods Neuropathic changes were studied in PCa (n = 149), in CP (n = 141), in pancreatic tumors (PTm) including serous/mucinous cystadenomas, invasive/noninvasive intraductal papillary mucinous neoplasias, benign/malignant neuroendocrine tumors, ampullary cancers (n = 196), and in normal pancreas (n = 60). The results were correlated with GAP-43 expression, tissue inflammation, pancreatic neuritis, neural invasion, fibrosis, desmoplasia, pain, and patient survival. Results Increased neural density and hypertrophy were only detected in PCa and CP and were strongly associated with GAP-43 over expression and abdominal pain. The severity of pancreatic neuritis was strongest in PCa and was closely linked to changes in neural density and hypertrophy. The aggressiveness of neural cancer cell invasion was most prominent in PCa and was related to neuropathic changes, desmoplasia, and pain. Severe and enduring pain were strongly associated with poor prognosis in PCa patients. Conclusions Enhanced neural density and hypertrophy are only typical features of CP and PCa among all investigated pancreatic disorders. Such neuropathic changes, including damage to nerves by inflammatory and/or cancer cells, seem to enhance and generate pancreatic neuropathic pain.
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