Curative Resection For Pancreatic Adenocarcinoma Research Articles

HPB P27 Prognostication for Patterns of Recurrence After Surgical Resection for Pancreatic Adenocarcinoma

Abstract Background This study aims to investigate patterns and factors affecting recurrence after curative resection for pancreatic adenocarcinoma (PDAC). Methods Consecutive patients who underwent curative resection for PDAC (2011-21) and consented to data and tissue collection (Barts Pancreas Tissue Bank) Were followed up till May 2023. Clinico-pathological variables were analysed using Cox proportional hazards model. Results Some 91 people (median age 71 years) had a median follow-up of 51 months, with a recurrence rate of 72.5% (n=66: 12 loco-regional alone, 11 liver alone, 5 lung alone, 3 peritoneal alone, 29 simultaneous loco-regional and distant metastases and 6 multi-focal distant metastases at first recurrence diagnosis). The median time to recurrence was 8.5 months (95% CI: 6.6-10.5) and median survival after recurrence was 5.8 months (95% CI: 4.2-7.3). Stratification by recurrence location revealed no differences in time to recurrence. Significant predictors for recurrence by multivariate analysis were lymph node ratio, adjuvant chemotherapy and systemic inflammation index. Conclusions No significant patterns of recurrence were found. Lymph node ratio, adjuvant chemotherapy and systemic inflammation index were predictors of PDAC recurrence. More research is needed to investigate predictive factors for PDAC recurrence after curative resection in large prospective national cohorts.

The role of natural killer cell activity as a milestone in oncologic outcome after curative resection of pancreatic adenocarcinoma.

The objective of this study was to investigate differences in oncologic outcomes of patients with pancreas cancer according to natural killer cell activity (NKA). A total of 118 patients who underwent curative resection for primary pancreas cancer in two hospitals were analyzed. NKA change pattern was analyzed. Difference in disease-free survival or overall survival was investigated by dividing subjects into two groups based on a normal NKA value for each period. NKA value decreased after surgery compared to the value measured at admission. It recovered to normal levels at 5 weeks postoperatively. The low NKA (less than 250 pg/mL) group at admission, 5 weeks postoperatively, and before 1st chemotherapy had significantly poorer disease-free survival than the normal NKA group. In multivariate analysis, NKA values less than 250 pg/mL at admission (odds ratio = 2.267, p = 0.023) and N 1 or N2 category (odds ratio = 2.478, p = 0.023) were significant factors associated with recurrence after curative resection. NKA in patients with pancreatic cancer demonstrated noticeable changes after surgery. Immunologically predisposed patients with a low NKA value had a high risk of early recurrence and a poor prognosis, although pancreatic cancer was surgically removed.

795 Predictors and Timing of Recurrence After Surgical Resection of Pancreatic Adenocarcinoma

Abstract Aim To investigate the predictors and timing of recurrence after curative resection for pancreatic adenocarcinoma (PDAC). Method Consecutive patients who underwent curative resection for PDAC (2011-21) and consented to data and tissue collection, were followed up prospectively in a single institution. Clinico-pathological variables were analysed using the Cox proportional hazards model. Results 91 patients (median age 71 years (range 43 – 86)) had a median follow-up of 51 (95% CI 40–61) months. 66 (72.5%) patients experienced recurrence (12 locoregional, 11 liver, 5 lung, 3 peritoneal, 29 simultaneous locoregional and distant and 6 multi-focal distant). Median time to recurrence was 8.5 (95% CI 6.6-10.5) months and median survival after recurrence was 5.8 (95% CI 4.2-7.3) months. Stratification by recurrence location revealed no significant differences in time to recurrence (p = 0.24). Significant predictors for any recurrence were lymph node ratio ≥0.33 (p = 0.005, HR 2.8, 95% CI 1.4 – 5.8), adjuvant chemotherapy (p = 0.002, HR 0.4, 95% CI 0.2 – 0.7) and systemic inflammation score ≥500 (p = 0.01, HR 4.5, 95% CI 1.4 – 14.3). Conclusions Lymph node ratio, adjuvant chemotherapy and systemic inflammation score were significant predictors for recurrence after curative resection for PDAC: this needs validation in large national cohorts.

Survival benefit of adjuvant chemoradiotherapy for positive or close resection margin after curative resection of pancreatic adenocarcinoma

BackgroundThis study was conducted to identify patients who may benefit from adjuvant chemoradiotherapy (CRT) for positive or close resection margin (RM) after curative resection of pancreatic adenocarcinoma. MethodsFrom 2004 to 2015, total of 472 patients with pancreatic adenocarcinoma underwent curative resection. After excluding patients with RM > 2 mm or unknown, remaining 217 patients were retrospectively analyzed. Forty-six (21.2%) patients were treated with adjuvant chemotherapy alone (CTx; mainly gemcitabine-based), 142 (65.4%) with adjuvant CRT (mainly upfront), and 29 (13.4%) patients didn’t receive any adjuvant therapy (noTx group). ResultsLocoregional recurrence rate was significantly lower in the CRT group (43.7%) than in the CTx group (71.7%) or noTx group (65.5%) (p = 0.001). Significant survival benefits of CRT over CTx (HR 0.602, p = 0.020 for overall survival (OS); HR 0.599, p = 0.016 for time to any recurrence (TTR)) were demonstrated in multivariate analysis. CRT group had more 5-year survivors than other groups. In the subgroup analysis, such benefits of adjuvant CRT over CTx was observed only in patients with head tumor & vascular RM > 0.5 mm, but not in patients with body/tail tumor or vascular RM ≤ 0.5 mm. In the CRT group, radiation dose≥54 Gy was significantly associated with better TTR and OS. ConclusionsAdjuvant CRT could improve TTR and OS compared to adjuvant CTx alone in patients with close RM under 2 mm. Radiation dose escalation may be beneficial when feasible. Modern CRT regimen–based randomized evidence is needed for these high-risk patients.

Resected Pancreatic Cancer With N2 Node Involvement Is Refractory to Gemcitabine-Based Adjuvant Chemotherapy.

Lymphatic metastasis is a major determinant of the outcome of resected pancreatic cancer. Gemcitabine-based adjuvant chemotherapy can improve the outcome of resected pancreatic cancer. However, the efficacy of gemcitabine against pancreatic cancer stratified by nodal involvement is unclear. In this study, patients who had undergone curative resection of pancreatic adenocarcinoma (612 cases) were included. The efficacy of adjuvant gemcitabine-based regimen, stratified by nodal status (negative, positive) or N substage (N0, no nodal involvement; N1, 1-3-node involvement; N2, ≥4-node involvement), was examined. Both the node-negative (hazard ratio [HR] = 0.62, 95% confidence interval [CI], 0.44-0.87, P = .006) and node-positive subgroups (HR = 0.45, 95% CI, 0.33-0.62, P < .001) benefited from gemcitabine-based adjuvant chemotherapy. Patients with N0 (ie, the node-negative subgroup) or N1 (HR = 0.36, 95% CI, 0.25-0.52, P < .001) disease benefited from gemcitabine-based chemotherapy. However, patients with N2 tumors (HR = 0.95, 95% CI, 0.50-1.78, P = .867) had poor response to gemcitabine-based treatment. Therefore, we postulate that resected pancreatic cancer with N2 node involvement is refractory to gemcitabine-based adjuvant chemotherapy. A more intensive adjuvant regimen may be required for N2 subgroup patients.

Percutaneous Radiofrequency Ablation for Metachronous Hepatic Metastases after Curative Resection of Pancreatic Adenocarcinoma

ObjectiveTo retrospectively evaluate the safety and efficacy of percutaneous radiofrequency ablation (RFA) in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma who had previously received curative surgery.Materials and MethodsBetween 2002 and 2017, percutaneous RFA was performed on 94 metachronous hepatic metastases (median diameter, 1.5 cm) arising from pancreatic cancer in 60 patients (mean age, 60.5 years). Patients were included if they had fewer than five metastases, a maximum tumor diameter of ≤ 5 cm, and disease confined to the liver or stable extrahepatic disease. For comparisons during the same period, we included 66 patients who received chemotherapy only and met the same eligibility criteria described.ResultsTechnical success was achieved in all hepatic metastasis without any procedure-related mortality. During follow-up, local tumor progression of treated lesions was observed in 38.3% of the tumors. Overall median survival and 3-year survival rates were 12 months and 0%, respectively from initial RFA, and 14.7 months and 2.1%, respectively from the first diagnosis of liver metastasis. Multivariate analysis showed that a large tumor diameter of > 1.5 cm, a late TNM stage (≥ IIB) before curative surgery, a time from surgery to recurrence of < 1 year, and the presence of extrahepatic metastasis, were all prognostic of reduced overall survival after RFA. Median overall (12 months vs. 9.1 months, p = 0.094) and progression-free survival (5 months vs. 3.3 months, p = 0.068) were higher in the RFA group than in the chemotherapy group with borderline statistical difference.ConclusionRFA is safe and may offer successful local tumor control in patients with metachronous hepatic metastases arising from pancreatic adenocarcinoma. Patients with a small diameter tumor, early TNM stage before curative surgery, late hepatic recurrence, and liver-only metastasis benefit most from RFA treatment. RFA provided better survival outcomes than chemotherapy for this specific group with borderline statistical difference.

Preoperative CA19-9 levels predict disease-free survival and overall survival in pancreatic adenocarcinoma patients after resection

Background: This study investigates the association between the preoperative serum CA19-9 and the effects of adjuvant chemotherapy (CT), and its impact on survival in patients undergoing curative resection for pancreatic adenocarcinoma (PAC). Methods: From January 01, 2015 to June 30, 2017, we retrospectively reviewed 421 PAC patients who underwent radical resection. The association between preoperative CA19-9 and disease-free survival (DFS), and overall survival (OS) was analyzed using Kaplan-Meier method and Cox proportional hazards model. Results: A total of 354 patients eligible for this study were classified into three groups according to preoperative CA19-9: G1 (≤87 U/mL), G2 (87–322 U/mL) and G3 (>322 U/mL), in tertiles. Multivariable analysis showed preoperative CA19-9 and adjuvant CT were both independent predictors of DFS and OS. Subgroup analyses showed the multivariable-adjusted hazard ratios (HR) of DFS for patients treated with adjuvant CT were 0.54 (95% CI, 0.33–0.86), 0.63 (95% CI, 0.40–0.97) and 0.32 (95% CI, 0.21–0.49) in G1, G2 and G3, respectively. A trend of decreasing HR of recurrence risk was observed in the higher preoperative CA 19-9 group treated with CT. Conclusions: High preoperative CA19-9 is an emerging biomarker that identifies a more aggressive PAC subgroup, which might benefit more from postoperative CT.

Preoperative CA19-9 levels predict disease-free survival and overall survival in pancreatic adenocarcinoma patients after resection.

BackgroundThis study investigates the association between the preoperative serum CA19-9 and the effects of adjuvant chemotherapy (CT), and its impact on survival in patients undergoing curative resection for pancreatic adenocarcinoma (PAC).MethodsFrom January 01, 2015 to June 30, 2017, we retrospectively reviewed 421 PAC patients who underwent radical resection. The association between preoperative CA19-9 and disease-free survival (DFS), and overall survival (OS) was analyzed using Kaplan-Meier method and Cox proportional hazards model.ResultsA total of 354 patients eligible for this study were classified into three groups according to preoperative CA19-9: G1 (≤87 U/mL), G2 (87–322 U/mL) and G3 (>322 U/mL), in tertiles. Multivariable analysis showed preoperative CA19-9 and adjuvant CT were both independent predictors of DFS and OS. Subgroup analyses showed the multivariable-adjusted hazard ratios (HR) of DFS for patients treated with adjuvant CT were 0.54 (95% CI, 0.33–0.86), 0.63 (95% CI, 0.40–0.97) and 0.32 (95% CI, 0.21–0.49) in G1, G2 and G3, respectively. A trend of decreasing HR of recurrence risk was observed in the higher preoperative CA 19-9 group treated with CT.ConclusionsHigh preoperative CA19-9 is an emerging biomarker that identifies a more aggressive PAC subgroup, which might benefit more from postoperative CT.

Impact of the controlling nutritional status (CONUT) score on the prognosis after curative resection of pancreatic adenocarcinoma

Introduction: The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to retrospectively investigate the impact of the CONUT score on short- and long-term outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Methods: Between April 2002 and April 2016, 344 consecutive patients who underwent curative resection of PDAC without neoadjuvant therapy were analysed. After the best predictive value of the CONUT score for survival was explored, predictors of overall survival (OS) were identified using Kaplan-Meier analyses, the log-rank test and Cox multivariable analysis. Correlations between the CONUT score and postoperative complications were analysed using the Mann-Whitney U test and Spearman`s rank correlation. Results: The median survival times of patients with high and low CONUT scores were 18.0 and 26.8 months, respectively. The high CONUT score group showed significantly lower OS than that of the low CONUT score group in the univariate analysis (P = 0.002). In contrast, no significant difference in recurrence-free survival was found (P = 0.43). The multivariate analysis demonstrated that a high CONUT score was an independent prognostic risk factor for OS (hazard ratio: 1.64, P = 0.003). The CONUT score showed no association with postoperative pancreatic fistula, the Clavien-Dindo grade or the postoperative hospital stay. Conclusion: The CONUT score, which is a measure of immune-nutritional status, was an independent prognostic risk factor for OS in patients with PDAC after pancreatectomy and was not associated with RFS or postoperative complications.

Adjuvant FOLFOX-Nab-paclitaxel (FOLFOX-A) for pancreatic cancer: A phase II Brown University Oncology Research Group (BrUOG) trial.

TPS550 Background: The FOLFOX-A regimen was developed by BrUOG, in response to the activity of nab-paclitaxel (nP) in metastatic pancreatic cancer (mPC), by substituting nP for irinotecan in FOLFIRINOX. In a phase I/II study of FOLFOX-A in mPC, median overall survival (OS) was 15 months (Safran H, et al. Am J Clin Oncol, 2016 Dec;39(6):619-622), which motivated evaluation of the tolerability and efficacy of this aggressive regimen in the adjuvant setting. Therefore, a phase II study of FOLFOX-A was initiated for patients with resected pancreatic cancer. Methods: Eligibility criteria included potentially curative resection of pancreatic adenocarcinoma (positive margins allowed if all gross tumor was removed), pathologic stages T1-3/N0-1/M0, interval between surgery and registration of 21-70 days and post resection serum CA19-9 ≤ 180 units/mL. All patients received nab-paclitaxel 150mg/m2, oxaliplatin 85mg/m2 and leucovorin 400mg/m2, followed by fluorouracil 2400mg/m2 infused over 46 hours. Cycles were repeated every 2 weeks. The primary objective is to assess the feasibility of administering at least 10 of 12 planned cycles of FOLFOX-A without unacceptable toxicity in 25 patients. Secondary endpoints include progression-free survival and OS. Results: Between June 2014-August 2017, 19 patients have been enrolled, 8 male and 11 female. Median age is 63 (43-68). Fifteen patients had positive lymph nodes on pathology with stages T1N0(n = 2), T3N0(n = 2), T1N1(n = 1), T3N1(n = 14) [AJCC Cancer Staging Manual, 7th Edition (2010)]. Conclusions: This study is testing the tolerability of administering adjuvant FOLFOX-A to patients with resected pancreatic cancer. Accrual is expected to be complete by January 2018. Clinical trial information: NCT02022033.

Analysis of 300 consecutive cases of pancreatic adenocarcinoma in a single-center in China

Most of the reports on the prognostic indicators of patients with pancreatic adenocarcinoma are from developed countries. The present study focused on the prognostic indicators of Chinese patients with pancreatic adenocarcinoma. A total of 300 patients with pancreatic adenocarcinoma who had undergone curative resection were included. The resection and R0/R1 resection rates for adenocarcinomas from different parts of the pancreas were calculated and clinical characteristics were analyzed. In 3427 patients diagnosed with pancreatic adenocarcinomas, only 300 (8.8%) were eligible for radical resection. The total median survival of these patients was 19 months, and their 1-, 3-, and 5-year survival rates were 72.5%, 28.0% and 23.4%, respectively. The prognostic factors included socioeconomic status, smoking history, symptoms, high blood glucose, and various tumor characteristics, including perineural and vascular invasion, lymph node metastases, and CA19-9 levels before and after operation. Operation-associated prognostic indicators included operation time, blood loss and transfusions, pancreatic fistula, and complications. Independent predictors of mortality included poor socioeconomic status, smoking history, symptoms, CA19-9, perineural invasion and lymph node metastasis, grade of fistula and complications. Patient survival was not correlated with either resection margin or adjuvant chemotherapy in multivariate analysis. The survival rates of patients with curative resection for pancreatic adenocarcinoma in China are close to those in developed countries, but curative resection rate is far below. Socioeconomic status, symptoms, and CA19-9 are the three most prominent prognostic factors, which are helpful in patient selection and perioperative care.

Impact Total Psoas Volume on Short- and Long-Term Outcomes in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma: a New Tool to Assess Sarcopenia

BackgroundWhile sarcopenia is typically defined using total psoas area (TPA), characterizing sarcopenia using only a single axial cross-sectional image may be inadequate. We sought to evaluate total psoas volume (TPV) as a new tool to define sarcopenia and compare patient outcomes relative to TPA and TPV. MethodSarcopenia was assessed in 763 patients who underwent pancreatectomy for pancreatic adenocarcinoma between 1996 and 2014. It was defined as the TPA and TPV in the lowest sex-specific quartile. The impact of sarcopenia defined by TPA and TPV on overall morbidity and mortality was assessed using multivariable analysis. ResultMedian TPA and TPV were both lower in women versus men (both P < 0.001). TPA identified 192 (25.1 %) patients as sarcopenic, while TPV identified 152 patients (19.9 %). Three hundred sixty-nine (48.4 %) patients experienced a postoperative complication. While TPA-sarcopenia was not associated with higher risk of postoperative complications (OR 1.06; P = 0.72), sarcopenia defined by TPV was associated with morbidity (OR 1.79; P = 0.002). On multivariable analysis, TPV-sarcopenia remained independently associated with an increased risk of postoperative complications (OR 1.69; P = 0.006), as well as long-term survival (HR 1.46; P = 0.006). ConclusionThe use of TPV to define sarcopenia was associated with both short- and long-term outcomes following resection of pancreatic cancer. Assessment of the entire volume of the psoas muscle (TPV) may be a better means to define sarcopenia rather than a single axial image.

Mo1659 Neutrophil to Lymphocyte Ratio Correlates With Pre-Operative CA 19-9 and Predicts Overall Survival in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma

Mo1659 Neutrophil to Lymphocyte Ratio Correlates With Pre-Operative CA 19-9 and Predicts Overall Survival in Patients Undergoing Curative Resection for Pancreatic Adenocarcinoma

Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P&lt;0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.

Surgical Management of Adenocarcinoma of the Pancreatic Uncinate Process in a Cancer Hospital in Egypt

INTRODUCTIONPancreatic carcinoma affecting the uncinate process is a challenging surgical condition. Several considerations affect the management plan, including the need for vascular resection and the ability to achieve a clear margin.METHODSThe data of 19 patients who had curative resection for pancreatic adenocarcinoma of the uncinate process were reviewed. Operative mortality and morbidity, and disease-free survival (DFS) were calculated.RESULTSThe study population included 13 male and 6 female patients with a mean age of 55 years. Nine patients (47.4%) had stage I disease, seven patients (36.8%) had stage II disease, and three patients (15.8%) had stage III disease. A total of 12 patients had Whipple procedure and 7 patients had total pancreatectomy. In total, there were 9 R0 and 10 R1 resections. Operative mortality rate was 10.5% (2/19), postoperative leakage rate was 21.1% (4/19), and wound sepsis rate was 21.1%. Median DFS was 19.2 months. Survival was superior in the Whipple procedure group than in the total pancreatectomy group (median survival 19 months vs 4 months, respectively). Vascular resection and retroperitoneal safety margin status did not affect disease relapse.CONCLUSIONNon-metastatic pancreatic adenocarcinoma of the uncinate process should be offered R0 or R1 resection whenever technically feasible.

Adjuvant Therapy in Pancreatic Cancer

Adjuvant treatment following curative resection for pancreatic cancer is now well established. Historically, the role of adjuvant therapy post resection was uncertain, as was the best form of adjuvant, the choices lying between adjuvant chemotherapy, chemoradiation or a combination of these. The landmark randomized controlled European Study Group for Pancreatic Cancer (ESPAC)-1 trial, provided the strongest evidence for the benefit of adjuvant therapy. ESPAC-1 showed a strong survival advantage for chemotherapy comprising 5-fluorouracil (5-FU) with folinic acid (FA), but no support for the use of chemoradiation. The CONKO-001 trial showed that gemcitabine was also superior to surgery alone. The ESPAC-3 trial showed no superiority for gemcitabine over 5-FU/FA although gemcitabine was less toxic. The effects of adding biological agents or combining agents within regimens are being investigated as well as neo-adjuvant therapies being compared with adjuvant therapy. A network meta-analysis has confirmed reduced survival and increased toxicity with adjuvant chemoradiotherapy. Adjuvant systemic chemotherapy with either gemcitabine or 5-FU/FA following curative resection for pancreatic adenocarcinoma continues as the mainstay of treatment. The five-year survival rates are around 25% with chemotherapy compared to resection alone, with a significant survival benefit also shown for patients with R1 positive resection margins.

Clinical and pathological features of five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

BackgroundClinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma.MethodsThe clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed.ResultsOf 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P = 0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P = 0.0018), an absence of intrapancreatic nerve invasion (P = 0.028), and undergoing an R0 resection (P = 0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P = 0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P = 0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P = 0.0316).ConclusionsWe conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

Impact of Preoperative Diabetes on Long-Term Survival After Curative Resection of Pancreatic Adenocarcinoma: A Systematic Review and Meta-Analysis

Diabetes mellitus (DM) is coupled to the risk and symptomatic onset of pancreatic ductal adenocarcinoma (PDAC). The important question whether DM influences the prognosis of resected PDAC has not been systematically evaluated in the literature. We therefore performed a systematic review and meta-analysis evaluating the impact of preoperative DM on survival after curative surgery. The databases Medline, Embase, Web of Science, and the Cochrane Library were searched for studies reporting on the impact of preoperative DM on survival after PDAC resection. Hazard ratios and 95 % confidence intervals (CI) were extracted. The meta-analysis was calculated using the random-effects model. The data search identified 4,365 abstracts that were screened for relevant articles. Ten retrospective studies with a cumulative sample size of 4,471 patients were included in the qualitative review. The mean prevalence of preoperative DM was 26.7 % (1,067 patients), and all types of pancreatic resections were considered. The meta-analysis included 8 studies and demonstrated that preoperative DM is associated with a worse overall survival after curative resection of PDAC (hazard ratio 1.32, 95 % CI 1.46-1.60, P = 0.004). Only 2 studies reported separate data for new-onset and long-standing DM. To our knowledge, this is the first meta-analysis evaluating long-term survival after PDAC resection in normoglycemic and diabetic patients, demonstrating a significantly worse outcome in the latter group. The mechanism behind this observation and the question whether different antidiabetic medications or early control of DM can improve survival in PDAC should be evaluated in further studies.

Metachronous double cancer after curative resection for pancreatic adenocarcinoma: report of four cases.

We experienced four cases of metachronous double cancer after curative resection for pancreatic adenocarcinoma without the background of intraductal papillary mucinous neoplasm. Case 1, a 67-year-old Japanese female developed tongue cancer 53months after a pylorus-preserving Whipple resection for pancreatic head adenocarcinoma. Case 2, a 66-year-old female developed multiple breast cancers 52months after a pylorus-preserving pancreaticoduodenectomy for pancreatic head adenocarcinoma. Case 3, a 59-year-old male developed an adenocarcinoma in the remnant pancreatic head 63months after a distal pancreatectomy for pancreatic body cancer. Case 4, a 68-year-old male developed lung cancer 92months after a Whipple procedure for pancreatic head adenocarcinoma. Gemcitabine was administered to three patients as adjuvant chemotherapy at an average administrated dose of 38,199mg per body surface area. Since primary pancreatic ductal adenocarcinoma is aggressive and always associated with a devastating outcome, metachronous double cancer is scarcely seen. All four cases received curative-intent surgery for each metachronous cancer and were alive for at least 20months.

Preoperative Neutrophil‐to‐Lymphocyte Ratio (NLR) is Associated with Reduced Disease‐free Survival Following Curative Resection of Pancreatic Adenocarcinoma

Serological proinflammatory markers such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been associated with reduced survival for many different types of cancer. This study determined the prognostic value of the preoperative value of these markers in patients with resectable pancreatic adenocarcinoma. Consecutive patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma were entered into our database from 2001 to the present day. CRP, NLR, and PLR at the time of presentation were recorded as well as overall and disease-free survival. Seventy-four patients were identified. Overall median survival was 35.0 months and median disease-free survival was 27.0 months. Follow-up ranged from 1 to 125.8 months. Preoperative NLR was significantly greater in those patients who developed recurrence in the follow-up period (4.5 vs. 3.1). CRP and PLR were not found to differ significantly between the two groups. Kaplan-Meier survival analysis of patients with NLR > 5 demonstrated a disease-free survival of 12 months compared with 52 months for those patients with NLR < 5 (p < 0.001). Preoperative NLR offers important prognostic information regarding disease-free survival following curative resection of pancreatic ductal adenocarcinoma.