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Background/aims : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC. Methods We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias. Results Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis. Conclusions We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

Introduction Pancreatic ductal adenocarcinoma cancer (PDAC) remains a challenging diagnosis. The likelihood of long-term survival is limited even for patients who undergo maximal medical therapy with systemic chemotherapy and surgical resection. Within this intensive process, there remains limited understanding of patients' pretreatment expectations of PDAC treatment experience and their decision-making process. Methods PDAC patients who underwent chemotherapy and surgical resection were retrospectively identified. Semi-structured phone interviews were completed regarding patient experience with therapy. Qualitative descriptive analysis was performed, and categories, subcategories, and themes were determined. Results Fifteen patients were interviewed regarding their experience with PDAC treatment. An overall personal disease trajectory experience was identified with two phases. The first phase encompassed the patients' treatment. In this phase, patients expressed a choice, non-choice regarding therapy decisions, viewing therapy as the only option. Misconceptions about the roles of therapies and expected experience of treatment were observed. The second phase focused on life after therapy. Patients reported persistent physical changes secondary to therapy. An overall realistic understanding of the patient's limited prognosis was observed, with patients expressing appreciation of the life time gained as a benefit of treatment. Conclusions There remains critical areas for improvement in communication and care of patients with PDAC. Physicians should continue to ensure that patient's goals and wishes are respected when making treatment decisions and confirm that patients understand the roles and limitations of prescribed therapies. Additionally, patients continue to have significant physical changes post treatment which should be assessed for and managed as appropriate to maintain quality of life.

Background and Aim Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the standard of care in advanced pancreatic cancer. Its role in resectable disease, however, is controversial. This meta-analysis aims to ascertain the clinical outcomes of patients with resectable pancreatic cancer undergoing preoperative EUS-FNA compared to those going directly to surgery. Methods A literature search was performed from 1996 to April 2019 using MEDLINE, EMBASE, and ISI Web of Knowledge for studies comparing preoperative EUS-FNA to EUS without FNA in resectable pancreatic cancer for clinical outcomes. The primary outcome is overall survival (OS). Secondary outcomes include cancer-free survival, tumor recurrence and peritoneal carcinomatosis, and post-FNA-pancreatitis rate. Results Six retrospective studies were included. Preoperative EUS-FNA had better OS than the non-FNA group (WMD, 4.40 months [0.02 to 8.78]). Cancer-free survival did not differ significantly between the two groups (WMD, 2.08 months [−2.22 to 6.38]). EUS with FNA was not associated with increased rates of tumor recurrence or peritoneal carcinomatosis. Conclusion Preoperative EUS-FNA in resectable pancreatic cancer may be associated with significantly greater OS when compared to the non-FNA group, with no significant difference in the rates of tumor recurrence or peritoneal seeding. Important limitations of our meta-analysis include the lack of prospective controlled data, which are unlikely to emerge given feasible constraints.

Following high-quality imaging studies for staging, endoscopic ultrasound examination fine needle aspiration/biopsy is the preferred modality for tissue diagnosis of pancreatic cancer. Endoscopic retrograde cholangiopancreatography with metal stent placement is used for palliation of malignant biliary obstruction. Metal stents can be placed in patients with resectable pancreatic cancer in whom surgery is going to be delayed. For palliation of gastric outlet obstruction, endoscopic enteral stenting is often selected because of its less invasiveness. Endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction or gastrojejunostomy for gastric outlet obstruction are emerging less invasive techniques as compared with palliative surgery.

Objective The aim of this study was to pool data from randomized controlled trials (RCT) limited to resectable pancreatic ductal adenocarcinoma (PDAC) to determine whether a neoadjuvant therapy impacts on disease-free survival (DFS) and surgical outcome. Summary background data Few underpowered studies have suggested benefits from neoadjuvant chemo (± radiation) for strictly resectable PDAC without offering conclusive recommendations. Methods Three RCTs were identified comparing neoadjuvant chemo (± radio) therapy vs. upfront surgery followed by adjuvant therapy in all cases. Data were pooled targeting DFS as primary endpoint, whereas overall survival (OS), postoperative morbidity, and mortality were investigated as secondary endpoints. Survival endpoints DFS and OS were compared using Cox proportional hazards regression with study-specific baseline hazards. Results A total of 130 patients were randomized (56 in the neoadjuvant and 74 in the control group). DFS was significantly longer in the neoadjuvant treatment group compared to surgery only [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.4-0.9] (P = 0.01). Furthermore, DFS for the subgroup of R0 resections was similarly longer in the neoadjuvant treated group (HR 0.6, 95% CI 0.35-0.9, P = 0.045). Although postoperative complications (Comprehensive Complication Index, CCI®) occurred less frequently (P = 0.008), patients after neoadjuvant therapy experienced a higher toxicity, but without negative impact on oncological or surgical outcome parameters. Conclusion Neoadjuvant therapy can be offered as an acceptable standard of care for patients with purely resectable PDAC. Future research with the advances of precision oncology should now focus on the definition of the optimal regimen.

While patients with clinico-radiologically diagnosed resectable pancreatic cancer usually undergo surgery without preoperative cytological or histopathological diagnostics, patients with inoperable tumors or ambiguous findings in imaging often undergo EUS-FNA or EUS-FNB (endoscopic ultrasound-guided fine-needle aspiration or endoscopic ultrasound-guided fine-needle biopsy). In many cases, this concerns pancreatic cystic lesions, which can range from benign inflammatory pseudocysts to invasive pancreatic cancer emerging from intraductal papillary mucinous neoplasms (IPMNs) or mucinous cystic neoplasms (MCNs). However, the evaluation of EUS-FNA material can be especially hampered by contamination with gastric or enteric cells or mucin, degenerative changes, or low or even no cellularity of the sample. Next-generation-sequencing-based molecular analyses, especially of cystic lesions, can significantly increase the accuracy of EUS-FNA diagnostics of the pancreas. Interpretation of morphological and molecular data considering each case's clinico-radiological context is crucial. While reliable molecular markers for the detection of mucinous and specific nonmucinous pancreatic neoplasms already exist, establishing valid markers for the detection of high-grade lesions is an urgent future goal.

Aim: The prognosis of resectable pancreatic cancer patients with the same stage of disease is highly variable. The purpose of this study is to establish a scoring system for preoperative screening of resectable patients. Materials & methods: The clinical information and laboratory tests of 105 resectable patients with pancreatic cancer were enrolled and analyzed. Results: The consistency of clinical stage and pathological stage was poor (κ = 0.193; p mut KRAS ctDNA) for the resectable patients. Patients with higher scores were more prone to early postoperative recurrence and poorer prognosis. Conclusion: The scoring system can help preoperatively screen out resectable patients who are prone to early postoperative recurrence.

Background In pancreatic cancer surgery, accurate identification and resection of intrapancreatic residual tumors are quite difficult. We have developed a novel open-typed PET system (called 'OpenPET'), which enables high-resolution PET-guided surgery in real time, and demonstrated that OpenPET-guided surgery with intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab is useful to detect and resect primary pancreatic cancer. Here, we investigated applicability of OpenPET-guided surgery for unexpected residual intrapancreatic tumors and examined its survival benefit over conventional surgery. Methods A mouse model with large (>1 cm) resectable pancreatic cancer of xPA-1-DC cells expressing red fluorescent protein was used. OpenPET-guided surgery was conducted 24 h after intraperitoneal administration of 64Cu-labeled cetuximab (7.4 MBq/mouse). For comparison, similar surgical procedures were conducted, and conventional tumor resection was attempted using only the naked eye (control). Survival rate after OpenPET-guided surgery was compared to that after control operations. Results Intraoperative OpenPET guidance enabled detection and resection of small residual tumors. Ten residual tumor specimens (3-10 mm in diameter) were intraoperatively isolated with OpenPET guidance (n = 7 mice). All isolated specimens showed tumor RFP signals. No resection of tumor tissue was performed in control group because the tumor could not be clearly detected with the naked eye alone. Mice after OpenPET-guided surgery showed significantly longer survival rates than those in control group. Conclusions OpenPET-guided surgery with 64Cu-labeled-cetuximab enabled intraoperative identification and resection of intrapancreatic small residual tumors. This technology could be useful to prevent tumor residuals during surgery and improve pancreatic cancer survival.

In the last two decades, pancreatic cancer has been undergoing important changes in its perioperative management due to the great interest in multidisciplinary management and preoperative multimodal therapy, which in numerous studies have shown promising clinical results. Although the standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC) today is surgery followed by adjuvant therapy, as it is a biologically aggressive disease, even with complete resection, it has high rates of local and distant relapse. Several retrospective and prospective phase I/II studies have opened the window for neoadjuvant therapy with chemotherapy (CT), chemoradiotherapy (CRT), or both, as an alternative treatment for resectable pancreatic cancer, with promising results. Neoadjuvant therapy could has some advantages, including early administration of systemic treatment, in vivo assessment of response to treatment, increase resectability rate in borderline patients, increase resection rate with negative margin and survival benefit. While it seems clear that even potentially resectable disease would benefit from preoperative multimodal therapy, the optimal neoadjuvant therapeutic strategy is still controversial and currently there are only recommendations for neoadjuvant treatment, in clinical guidelines such as the NCCN and ESMO, for borderline and/or locally advanced PDAC. This review provides an overview of recent studies available and how they relate to systemic treatment of resectable PDAC in the neoadjuvant setting.

BACKGROUND Neoadjuvant treatment has become a standard of care for borderline or locally advanced pancreatic cancer and is increasingly considered even for up-front resectable disease. The aim of this article is to present the case of a 62-year-old patient with locally advanced pancreatic adenocarcinoma who was successfully treated with gemcitabine plus nab-paclitaxel after the failure of the first line treatment. CASE SUMMARY Computerized tomography scan and magnetic resonance imaging demonstrated a nodular lesion of ill-defined limits in the body of the pancreas, measuring approximately 4.2 cm × 2.7 cm, with an infiltrative aspect. The tumor had contact with the superior mesenteric vein, splenomesenteric junction and the proximal segment of the splenic artery, causing focal reduction of its lumens. Due to vascular involvement, neoadjuvant chemotherapy treatment with eight cycles of “folinic acid, 5-fluorouracil, irinotecan and oxaliplatine” (FOLFIRINOX) were performed. At the end of the cycles, surgery was performed, but the procedure was interrupted due to finding of lesions suspected of metastasis. Gemcitabine plus nab-paclitaxel was then successfully used for neoadjuvant treatment with subsequent R0 surgical resection. CONCLUSION Gemcitabine plus nab-paclitaxel may be effective as an alternative regimen when FOLFIRINOX fails as the first line of treatment, suggesting the need for further studies to identify which patients would benefit from each type of therapeutic approach.

While the use of neoadjuvant therapy is well-accepted in the treatment of borderline resectable and locally advanced pancreatic cancers, the benefit of neoadjuvant chemotherapy in patients with resectable disease has been a topic of debate. Recently, key trials evaluating neoadjuvant chemotherapy for resectable pancreatic cancer have reported results. This review describes key clinical trials evaluating the use of preoperative therapy in patients with technically resectable pancreatic cancer with a focus on their contribution to the available evidence.

Although the efficacy of neoadjuvant therapies for pancreatic cancer (PDAC) is reported in recent years, ideal neoadjuvant treatment for patients with potentially resectable (R) PDAC remains uncertain. We conducted the retrospective study about the effect of short-term neoadjuvant chemoradiotherapy (sNACRT) on R PDAC. The 94 patients received curative intent pancreatectomy for R PDAC between 2000 and 2016. Among them, 31 patients received sNACRT (S1 60 mg/m2/day for 2w and RTx 30 Gy/2w). Clinical outcomes of the 31 patients with sNACRT were analyzed in comparison with 63 patients without sNACRT. The 1-, 3-, and 5-year overall survival (OS) rates were 93, 71, and 62% in the patients with sNACRT and 78, 35, and 26% in the patients without sNACRT ( P = .0007), respectively. Lymph node metastasis was found in 41.9% of patients with sNACRT and 56.5% of patients without sNACRT ( P = .09). Microscopic tumor infiltration at resection margins (R1) was found in no patient with sNACRT and 5 patients (7.9%) without sNACRT ( P=.042). Retropancreatic infiltration ( P = .04), lymphatic invasion ( P = .002), plexus invasion ( P = .042), and main pancreatic duct extension ( P = .004) were significantly fewer in patients with sNACRT than the patients without sNACRT. The recurrences were found in 64% of patients with sNACRT (39% distant, 16% local, and 10% mix pattern) and 68% in patients without sNACRT (28% distant, 21% local, and 19% mix pattern). The recurrence patterns were significantly different ( P = .008) between the groups. Short-term neoadjuvant chemoradiotherapy decreased R1 resection rate and improved OS. Short-term neoadjuvant chemoradiotherapy may provide ideal local control during the short term and improve clinical outcome of R PDAC.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of malignant tumors with the worst prognosis. Surgery and adjuvant chemotherapy are the main treatments for resectable pancreatic cancer. For borderline resectable PDAC, neoadjuvant chemotherapy has been advised. For clearly resectable PDAC, neoadjuvant chemotherapy also might be considered for the patients with high-risk features, but with no precise quantitative criteria to define these features. So, this study aimed to re-evaluate the relationship between high-risk features and prognosis of clearly resectable pancreatic cancer, and to define the precise criteria for these high-risk features. Methods Data from 211 patients with clearly resectable pancreatic cancer were reviewed to assess the relationship between overall survival (OS) after surgery and high-risk features, and cut-off values were determined for high-risk features that were associated with poor prognosis of clearly resectable pancreatic cancer. Results Lymph node metastasis (LNM), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and primary tumor size ≥6 cm were significant variables related to OS. CA19-9 ≥1,000 U/mL was statistically related to prognosis, as was CA19-9 ≥500 U/mL without obstructive jaundice. There was no significant relationship between abdominal and/or back pain and OS, but patients with moderate or severe pain accompanied by tumor size ≥4 cm or 10 times higher CA19-9 levels had worse prognosis. Conclusions For clearly resectable pancreatic cancer with R0 resection, the high-risk features were clarified. Abdominal and/or back pain may not be used as a prognostic indicator alone, though combined with CA19-9 or tumor size it may be more valuable for predicting prognosis.

Background Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC. Methods We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR). Results Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group. Conclusions It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.

Background : The C-reactive protein (CRP)-albumin ratio (CAR) was reported as a prognostic factor of resectable hepatocellular carcinoma. The aim of this study was to analyse the significance of CAR in resectable pancreatic cancer. Patients and Methods : 163 patients with curative resection for pancreatic cancer were enrolled in this retrospective study. Cases of non-curative resection were excluded. The CAR was calculated with the preoperative plasma CRP and albumin values, with a cut-off value of 0.06, as calculated in a previous report. Results : Patients in the low CAR group had significantly better overall survival (OS) and disease-free survival (DFS) compared with the high CAR group (P 0.05). On multivariate analysis, for high CAR, CA19-9 300 U / ml and receipt of adjuvant chemotherapy were independent risk factors for OS and DFS. High CAR was significantly associated with advanced T stage. Conclusion : The CAR might be a prognostic factor for patients with resectable pancreatic cancer. J. Med. Invest. 68 : 244-248, August, 2021.

Background The aim of this study was to evaluate the prognostic impact of simultaneous venous resection during pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) that was preoperatively staged resectable according to NCCN guidelines. Methods A retrospective analysis of 153 patients who underwent PD for PDAC was performed. Patients were divided into standard PD and PD with simultaneous vein resection (PDVR). Groups were compared to each other in terms of postoperative morbidity and mortality, disease free (DFS) and overall survival (OS). Results 114 patients received PD while 39 patients received PDVR. No differences in terms of postoperative morbidity and mortality between both groups were detected. Patients in the VR group presented with a significantly shorter OS in the median (13 vs. 21 months, P = 0.011). In subgroup analysis, resection status did not influence OS in the PDVR group (R0 13 vs. R1 12 months, P = 0.471) but in the PD group (R0 23 vs. R1 14 months, P = 0.043). PDVR was a risk factor of OS in univariate but not multivariable analysis. Conclusion PDVR for PDAC preoperatively staged resectable resulted in significantly shorter OS regardless of resection status. Patients who require PDVR should be considered for adjuvant chemotherapy in addition to other oncological indications.

BACKGROUND Preoperative neoadjuvant chemoradiation therapy (NACRT) is applied for resectable pancreatic cancer (RPC). To maximize the efficacy of NACRT, it is essential to ensure the accurate placement of fiducial markers for image-guided radiation. However, no standard method for delivering fiducial markers has been established to date, and the nature of RPC during NACRT remains unclear. AIM To determine the feasibility, safety and benefits of endoscopic ultrasound-guided (EUS) fiducial marker placement in patients with RPC. METHODS This was a prospective case series of 29 patients (mean age, 67.5 years; 62.1% male) with RPC referred to our facility for NACRT. Under EUS guidance, a single gold marker was placed into the tumor using either a 19- or 22-gauge fine-needle aspiration needle. The differences in daily marker positioning were measured by comparing simulation computed tomography and treatment computed tomography. RESULTS In all 29 patients (100%) who underwent EUS fiducial marker placement, fiducials were placed successfully with only minor, self-limiting bleeding during puncture observed in 2 patients (6.9%). NACRT was subsequently administered to all patients and completed in 28/29 (96.6%) cases, with one patient experiencing repeat cholangitis. Spontaneous migration of gold markers was observed in 1 patient. Twenty-four patients (82.8%) had surgery with 91.7% (22/24) R0 resection, and two patients experienced complete remission. No inflammatory changes around the marker were observed in the surgical specimen. The daily position of gold markers showed large positional changes, particularly in the superior-inferior direction. Moreover, tumor location was affected by food and fluid intake as well as bowel gas, which changes daily. CONCLUSION EUS fiducial marker placement following NACRT for RPC is feasible and safe. The RPC is mobile and is affected by not only aspiration, but also food and fluid intake and bowel condition.

Although upfront surgery has been the gold standard for pancreatic adenocarcinoma that is planned for resection, it should be compared with the alternative strategy of neoadjuvant therapy. Despite the many reports of the efficacy of neoadjuvant therapy, most of them were not comparative. Recently Prep‐02/JSAP05 study clearly demonstrated the significant survival benefit of neoadjuvant chemotherapy over upfront surgery for pancreatic adenocarcinoma that is planned for resection. These findings opened a new chapter of neoadjuvant therapy. Ongoing trials are expected to confirm the evidence. This review summarizes the past, present, and future perspectives of neoadjuvant therapy and its optimization., Recently, Prep‐02/JSAP05 study demonstrated the significant survival benefit of neoadjuvant chemotherapy over upfront surgery for pancreatic adenocarcinoma that is planned for resection. This review summarizes the past, present, and future perspectives of neoadjuvant and its optimization.

Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ≥3 mm. In contrast, neither OpenPET with intravenous-administered 64Cu-cetuximab nor intraperitoneal/intravenous-administered 18F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.

Background: Optimal patient selection for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) is unestablished. Molecular profiling may select patients at high risk for locoregional recurrence (LRR) who would benefit from radiation. Methods: We included resectable pancreatic cancer (R-PDAC) patients, divided into training and validation cohorts, treated among three institutions with surgery and adjuvant chemotherapy, and borderline resectable or locally advanced pancreatic cancer (BR/LA-PDAC) patients treated with chemotherapy with or without radiation at the primary study institution. We isolated RNA from R-PDAC surgical specimens. Using NanoString, we identified miRNAs differentially expressed between normal and malignant pancreatic tissue. ElasticNet regression identified two miRNAs most predictive of LRR in the training cohort, miR-181b/d and miR-575, which were used to generate a risk score (RS). We evaluated the association of the median-dichotomized RS with recurrence and overall survival (OS). Results: We identified 183 R-PDAC and 77 BR/LA-PDAC patients with median follow up of 37 months treated between 2001 and 2014. On multivariable analysis of the R-PDAC training cohort (n = 90), RS was associated with worse LRR (HR = 1.34, 95%CI 1.27–11.38, p = 0.017) and OS (HR = 2.89, 95%CI 1.10–4.76, p = 0.027). In the R-PDAC validation cohort, RS was associated with worse LRR (HR = 2.39, 95%CI 1.03–5.54, p = 0.042), but not OS (p = 0.087). For BR/LA-PDAC, RS was associated with worse LRR (HR = 2.71, 95%CI 1.14–6.48, p = 0.025), DR (HR = 1.93, 95%CI 1.10–3.38, p = 0.022), and OS (HR = 1.97, 95%CI 1.17–3.34, p = 0.011). Additionally, after stratifying by RS and receipt of radiation in BR/LA-PDAC patients, high RS patients who did not receive radiation had worse LRR (p = 0.018), DR (p = 0.006), and OS (p &lt, 0.001) compared to patients with either low RS or patients who received radiation, irrespective of RS. Conclusions: RS predicted worse LRR and OS in R-PDAC and worse LRR, DR, and OS in BR/LA-PDAC. This may select patients who would benefit from radiation and should be validated prospectively.

Background/aim In cases where neoadjuvant treatment (NAT) is administered, research on short-term postoperative outcomes appears to be insufficient. We compared short-term outcomes of upfront surgery (UpS) cases and NAT cases for pancreatic ductal adenocarcinoma (PDAC). Patients and methods We retrospectively reviewed 1,228 cases that had elective pancreatectomy at Samsung Medical Center from 2010 to 2020. All cases were classified into resectable pancreatic cancer (RPC) and locally advanced pancreatic cancer (LAPC) according to NCCN guidelines 2017. In each group, factors were compared between the UpS and NAT groups. Results Rate of vascular resection was higher in the NAT group in RPC, compared to that in the NAT group in LAPC. Short-term postoperative outcomes had no significant differences between the UpS and NAT groups in both RPC and LAPC. Conclusion In the NAT group, there were no significant differences from UpS in terms of short-term postoperative outcomes. Conversion surgery following NAT is a favorable strategy.

Objectives To explore the associations among clinical characteristics, fatigue, diabetes mellitus (DM) self-care activities, and quality of life (QOL) in individuals with resectable pancreatic cancer and DM. Sample & setting 57 individuals with resectable pancreatic cancer and DM from an outpatient pancreatic surgical department in Taiwan were included in the final analysis. Methods & variables A cross-sectional, correlational design was used. QOL, fatigue, and DM self-care were measured by the European Organisation for Research and Treatment of Cancer QOL Questionnaire-Core 30, the Fatigue Symptom Inventory, and the Summary of Diabetes Self-Care Activities. Results Participants who had a shorter duration of DM and higher levels of fatigue (including intensity, duration, and interference) reported lower QOL scores. Participants who performed more DM self-care activities and physical activity per week had higher QOL scores. Fatigue, DM self-care activities, and DM duration were significant factors related to QOL. Implications for nursing Shorter DM duration, increased fatigue, and fewer DM self-care activities were determinants of worse QOL in individuals with resectable pancreatic cancer and DM.

The results of treatment of localized (early) pancreatic cancer are unsatisfactory despite all achievements of modern clinical and surgical oncology. Nevertheless, certain success was achieved even in these extremely unfavorable patients regarding their prognosis. The authors analyzed evolution of adjuvant therapy, as well as new concepts in the treatment of borderline resectable and resectable pancreatic cancer. Modern anticancer therapy with acceptable toxicity profile significantly improved the outcomes. However, further research is needed to improve the effectiveness of treatment despite favorable current results.

Surgery with adjuvant or neoadjuvant treatment vs surgery alone for resectable pancreatic cancer: A network meta-analysis

Background: Upfront surgery is recommended in patients with potentially resectable pancreatic ductal adenocarcinoma (R-PDAC) by National Comprehensive Center Network (NCCN) guidelines. However, even among R-PDACs, there is a subset that demonstrates extremely poor prognosis. The purpose of this study was to identify preoperative prognostic factors for upfront surgical resection of R-PDACs. Methods: The records of 278 consecutive patients with PDAC who underwent curative resection between 2001 and 2015 in a single institution were retrospectively reviewed. Preoperative factors to predict prognosis in patients with R-PDAC according to the NCCN guidelines were analyzed. Results: Of the 278 patients who underwent resection, 153 R-PDACs received upfront surgery with a median survival time (MST) of 26.4months. Tumor location (pancreatic head) (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.14-3.40; P=0.015), preoperative cancer antigen 19-9 (CA19-9) >100U/mL (OR 1.92, 1.31-2.80; P=0.0009), and tumor size >20mm (OR 1.50, 1.02-2.19; P=0.038) were identified as preoperative independent predictive risk factors for poor prognosis in patients with R-PDACs. In the patients with R-PDAC, 5-year survival was 60.7%, 21.5%, and 0% in patients with 0, 1 or 2, and 3 risk factors, respectively. There were significant differences in overall survival between the three groups (P

Background The aim of this study was to evaluate health disparities in the outcomes of patients with resectable pancreatic adenocarcinoma. Methods We retrospectively analyzed 280,935 patients from the National Cancer Data Base (NCDB), from 1998 to 2012 to compare the differences in patient characteristics, refusal of offered surgical treatment and overall survival after pancreatic adenocarcinoma resection between white vs. black patients. Results Black patients did not undergo and refused offered surgical treatment more frequently. Race and insurance were the most important factors independently associated with not receiving the offered resection. Having private insurance, Hispanic ethnic background, geographic location, higher income, residing in urban/metropolitan area and systemic treatment were independently associated with improved survival. Race was associated with overall worse survival in an unadjusted model but not in multivariable analysis. The association between race and survival was removed when adjusting for facility location, income, education, tumor size, tumor stage or systemic treatment. Conclusion Disparities exist at various levels in resectable pancreatic cancers. These findings help developing targeted interventions and quality improvement initiatives.

Objective The role of neoadjuvant therapy (NAT) in resectable pancreatic cancer (RPC) remains controversial. Therefore, this meta-analysis was performed to compare the clinical differences between NAT and upfront surgery in RPC. Materials and methods A systematic literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Register of Controlled Trials databases. Only patients with RPC who underwent tumor resection and received adjuvant or neoadjuvant treatment were enrolled. The OR or HR and 95% CIs were calculated employing fixed-effects or random-effects models. The HR and its 95% CI were extracted from each article that provided survival curve. Publication bias was estimated using funnel plots and Egger's regression test. Results In total, eleven studies were included with 9,386 patients. Of these patients, 2,508 (26.7%) received NAT. For patients with RPC, NAT resulted in an increased R0 resection rate (OR=1.89; 95% CI=1.26-2.83) and a reduced positive lymph node rate (OR=0.34; 95% CI=0.31-0.37) compared with upfront surgery. Nevertheless, patients receiving NAT did not exhibit a significantly increased overall survival (OS) time (HR=0.91; 95% CI=0.79-1.05). Conclusion In patients with RPC, R0 resection rate and positive lymph node rate after NAT were superior to those of patients with upfront surgery. The NAT group exhibited no significant effect on OS time when compared with the upfront surgery group. However, this conclusion requires more clinical evidence to improve its credibility.

Objectives Surgery is the curative treatment for pancreatic ductal adenocarcinoma (PDA). Guidelines recommend utilizing a multidisciplinary pancreatic cancer conference (MDPC) in treatment; however, data are limited. The objective of this study was to assess the accuracy of an MDPC. Methods Patients with PDA presented at an MDPC were prospectively collected from April 2013 to August 2016. Patients were included if the MDPC predicted them to have resectable PDA and underwent upfront surgery. Secondary aims were to compare differences in tumor characteristics, time to surgery, and resection rates with patients prior to MDPC implementation (pre-MDPC). Results A total of 278 patients were presented at the MDPC. After excluding borderline and nonresectable cases, 91 patients were predicted as resectable on evaluation, and 70 were fit for surgery. The MDPC predicted resection in 91.4%. The MDPC had larger tumor size (32.6 vs 24.0 mm), greater proportion of stage II tumor, and a shorter time from diagnosis to resection (27.3 vs 35.5 days) compared with the pre-MDPC. Microscopically negative resections were similar between MDPC and pre-MDPC (85.9% vs 88.0%) despite advanced tumor size and stage. Conclusions The MDPC demonstrates a high resection rate. Compared with a pre-MDPC, MDPC provides shorter time to surgery and selects for advanced tumors.

To describe, in patients with resectable pancreatic ductal adenocarcinoma (PDAC), the laparotomy findings, treatments and outcomes before (period 1) and after 2010 (period 2).From 2000 to 2015, patients newly diagnosed with resectable PDAC at Paoli-Calmettes Institute, France, were evaluated. Survival was examined using the Kaplan-Meier method, and statistical comparisons were conducted using log rank tests.Among 1175 patients diagnosed with pancreatic mass, 164 underwent laparotomy with an intention of pancreatic resection. Some of them did not undergo pancreatic resection due to peroperative discovery of advanced disease. For those who were finally resected (n = 119), there were fewer pancreaticoduodenectomies (p = 0.045), shorter operation times (p 0.01), lower mortality rates (p = 0.02), more advanced-stage tumors (T3), more frequent perineural invasion and R1 resection in period 2. This group had a trend of better outcomes after 2010 (51 months vs. 36 months (p = 0.065)).Improvement in surgical procedures and postoperative management led to prolonged survival of those who underwent surgery for resectable pancreatic cancer since 2010, despite a higher frequency of advanced tumors at the diagnosis in our institution.

Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in all patients suffering from obstructive jaundice before pancreatic surgery. The severity of jaundice that mandates PBD has yet to be defined. The evaluated paper examines the impact of PBD on intra-operative, and post-operative outcomes in patients initially presenting with severe obstructive jaundice (bilirubin ≥250 μmol/L). In this key paper evaluation, the impact of PBD versus a direct surgery (DS) approach is discussed. The arguments for and against each approach are considered with regards to drainage associated morbidity and mortality, resection rates, survival and the impact of chemotherapy and malnutrition. Concentrating on resectable head of pancreas tumors, this mini-review aims to scrutinize the authors' recommendations, alongside those of prominent papers in the field.

Background: In pancreatic cancer clinical practice guideline 2016, it is recommended to perform pathological diagnosis as much as possible, but priorities and algorithms for diagnostic methods have not yet been established. In recent years, EUS-FNA has become mainstream as a method of collecting tissues from pancreatic disease, but the effect of EUS-FNA on surgical results and prognosis has not been clarified.Aims: To evaluate the diagnostic ability of EUS-FNA and preoperative diagnosis affects surgical outcome and prognosis of pancreatic cancer.Methods: Between January 2005 and June 2017, 293 patients who had surgical resection for pancreatic cancer were retrospectively evaluated. The interested outcomes were diagnostic ability of EUS-FNA and the influence for surgical result and prognosis.Results: The diagnostic sensitivity of EUS-FNA was 94.4%, which was significantly higher than ERCP (45.5%) (pp=0.001). Patients were divided into FNA group (N=160) and non-FNA group (N=133) for each preoperative diagnostic method. In the study of surgical curability R0 between two groups, there was no significant difference in FNA group: 65.0% (104/160) and non-FNA group: 64.7% (86/133), (p=1.000). In the prognostic study, the total of 256 patients with curability R0 or R1, the recurrence rate was 54.3% (70/129) in the FNA group and 57.4% (73/127) in non-FNA group. Moreover peritoneal dissemination occurred 34.3% (24/70) in the FNA group and 21.9% (16/73) in the non-FNA group, neither of which showed significant difference. The median survival time of FNA group and non-FNA group were 955 days and 799 days, respectively, and there was no significant difference between the two groups (Log rank p=0.735). In the Cox proportional hazards model examining factors influencing prognosis, staging, curability and adjuvant chemotherapy were dominant factors, but preoperative diagnostic method(EUS-FNA) itself was not.Conclusions: As a preoperative examination of pancreatic cancer, EUS-FNA was shown to be a safe procedure with high diagnostic ability. It was considered to be the first choice without the influence of surgical curability, postoperative recurrence, peritoneal dissemination and prognosis.

Radiologically identified para-aortic lymph node (PALN) metastasis is contraindicated for pancreatic cancer (PC) surgery. There is no clinical consensus for unexpected intraoperative PALN enlargement. To analyze the prognostic role of unexpected PALN enlargement in resectable PC, we retrospectively reviewed data of 1953 PC patients in a single tertiary center. Patients with unexpected intraoperative PALN enlargement (group A1, negative pathology, n = 59, group A2, positive pathology, n = 13) showed median overall survival (OS) of 24.6 (95% CI: 15.2–33.2) and 13.0 (95% CI: 4.9–19.7) months, respectively. Patients with radiological PALN metastasis without other metastases (group B, n = 91) showed median OS of 8.6 months (95% CI: 7.4–11.6). Compared with group A1, groups A2 and B had hazard ratios (HRs) of 2.79 (95% CI, 1.4–5.7) and 2.67 (95% CI: 1.8–4.0), respectively. Compared with group A2, group B had HR of 0.96 (95% CI: 0.5–1.9). Multivariable analysis also showed positive PALN as a negative prognostic factor (HR 2.57, 95% CI: 1.2–5.3), whereas positive regional lymph node did not (HR 1.32 95% CI: 0.8–2.3). Thus, unexpected malignant PALN has a negative prognostic impact comparable to radiological PALN metastasis. This results suggests prompt pathologic evaluation for unexpected PALN enlargements is needed and on-site modification of surgical strategy would be considered.

Background: The time-trend in the survival of elderly pancreatic cancer patients was still unclear. Thus, the aim of this study was to compare the survival benefit of young and elderly pancreatic cancer patients by a time-trend analysis. Methods: From 2004-2013, we obtained 5,341 of young patients (< 80 years) and 569 elderly patients (≥ 80 years) from the Surveillance, Epidemiology, and End Results (SEER) database, and the overall survival of these patients were analyzed by Kaplan-Meier estimator. The independent factors which could predict the survival of patients were determined by cox proportional hazards model.Results: We observed that the median overall survival of the young patients in 2004-2008 cohort was significantly (P < 0.001) increased when compared to that in the 2009-2013 cohort. However, we did not observe the survival benefit for the elderly patients. The Cox proportional hazards model demonstrated that the tumor size, lymph node ratio, grade, and AJCC TNM stage were independent factors of survival. Conclusions: This study demonstrated that compared to 2004-2008, the survival of elderly patients in 2009-2013 was not significantly improved. Thus, the clinicians still need to administer more care to elderly patients.

Adjuvant chemotherapy is the standard treatment for patients with resectable pancreatic ductal carcinoma. Perioperative chemotherapy has been given in less than 50% of patients with potentially resectable pancreatic cancer in Japan. A modified combination regimen of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX; oxaliplatin 85 mg/m(2), leucovorin 400 mg/m(2), irinotecan 150 mg/m(2) on day 1, and 5-fluorouracil 2,400 mg/m(2) over 46 hours every 14 days for 12 cycles) is now preferred worldwide because it mitigates concerns regarding toxicity and tolerance. Adjuvant chemotherapeutic regimens employ S-1 in East Asia, whereas other areas use FOLFIRINOX, capecitabine plus gemcitabine, or gemcitabine monotherapy. Adjuvant chemoradiotherapy is not recommended because randomized controlled trials and meta-analyses revealed no survival benefit compared with chemotherapy. Preoperative chemotherapy with S-1 and gemcitabine combination chemotherapy for patients with resectable/borderline resectable pancreatic cancer significantly increased survival compared to upfront surgery in a recent clinical trial. Perioperative outcomes, including R0 resection rate and post-operative morbidity, were not significantly different between groups. When compared to upfront surgery, neoadjuvant S-1 and gemcitabine treatment significantly reduced the number of pathological nodal metastases in patients who underwent resection. Japanese guidelines therefore recommend neoadjuvant chemotherapy for patients with resectable pancreatic cancer. Preoperative chemotherapy can increase R0 cases by down-staging with higher relative dose intensity of chemotherapy. In contrast, patients who do not respond to chemotherapy may miss resection opportunities and would therefore be at a disadvantage. Therefore, it is critical for both patients and doctors that predictive markers for the response to chemotherapy are identified.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is frequently used for the preoperative histologic diagnosis of pancreatic cancer. However, debate continues regarding the clinical merits of preoperative EUS-FNA for the management of resectable pancreatic cancer. We aimed to evaluate the benefits and safety of preoperative EUS-FNA for resectable distal pancreatic cancer. The medical records of 304 consecutive patients with suspected distal pancreatic cancer who underwent EUS-FNA were retrospectively reviewed to evaluate the clinical benefits of preoperative EUS-FNA. We also reviewed the medical records of 528 patients diagnosed with distal pancreatic cancer who underwent distal pancreatectomy with or without EUS-FNA. The recurrence rates and cancer-free survival periods of patients who did or did not undergo preoperative EUS-FNA were compared. The diagnostic accuracy of preoperative EUS-FNA was high (sensitivity, 87.5%; specificity, 100%; positive predictive value 100%; accuracy, 90.7%; negative predictive value, 73.8%). Among patients, 26.7% (79/304) avoided surgery based on the preoperative EUS-FNA findings. Of the 528 patients who underwent distal pancreatectomy, 193 patients received EUS-FNA and 335 did not. During follow-up (median 21.7 months), the recurrence rate was similar in the two groups (EUS-FNA, 72.7%; non-EUS-FNA, 75%; P = 0.58). The median cancer-free survival was also similar (P = 0.58); however, gastric wall recurrence was only encountered in the patients with EUS-FNA (n = 2). Preoperative EUS-FNA is not associated with increased risks of cancer-specific or overall survival. However, clinicians must consider the potential risks of needle tract seeding, and care should be taken when selecting patients.

Well-defined outcome measures enable comparisons between clinical trials. However, the reporting of baseline and prognostic characteristics largely vary in studies investigating potentially resectable pancreatic cancer patients. This makes accurate comparisons between studies challenging. By standardization of the reporting of mandatory baseline and prognostic characteristics, possible confounders can be identified, which will allow for a better comparison of outcomes across studies. We created a structured overview describing the reporting frequencies of baseline characteristics and the clinical relevance of these factors. This chapter is the first to describe a set of mandatory baseline and prognostic variables for patients with potentially resectable pancreatic cancer.

Pancreatoduodenectomy offers at present the only chance for a cure for cancer of the pancreatic head. A meticulous surgical technique, proper patient selection, an all-inclusive perioperative care and multimodal treatment approaches are essential to achieving the best possible clinical and oncologic outcomes. Open pancreatoduodenectomy is the standard surgical procedure for pancreatic head carcinoma, which can be broken down into several steps, with the three major phases exploratory, resection and the reconstruction phase. Despite numerous trials that compared diverse steps of pancreatoduodenectomy, no specific technique can reproducibly lower the relatively high morbidity and mortality rates of this complex procedure. In particular, the prevention of a clinically relevant postoperative pancreatic fistula, the most troublesome complication after pancreatoduodenectomy, remains a challenge to date. This chapter will focus on the open technique of pancreatoduodenectomy and describe the essential steps as well as variations for performing a safe resection of a cancer of the pancreatic head. Relevant references will give direction to further details, to help guide the reader through the extensive literature on this topic.

Simple Summary Pancreatic cancer is known to be one of the most lethal malignant diseases in gastrointestinal tract. Margin-negative pancreatectomy followed by postoperative adjuvant chemotherapy is essential treatment for long-term survival. Due to anatomical complexity and technical difficulty, laparoscopic pancreaticoduodenectomy is still controversial. However, with the advance of laparoscopic surgery, laparoscopic pancreatic resection of pancreatic head cancer has been carefully applied in well selected patients. The accumulating data are suggesting its technical feasibility, safety, and potential equivalent long-term oncologic outcome. In this review, the current status of laparoscopic pancreaticoduodenectomy for pancreatic head cancer is summarized. In addition, potential surgical indications and future perspectives of laparoscopic pancreaticoduodenectomy for pancreatic cancer are discussed for safe implementation in our clinical practice. Abstract Margin-negative radical pancreatectomy is the essential condition to obtain long-term survival of patients with pancreatic cancer. With the investigation for early diagnosis, introduction of potent chemotherapeutic agents, application of neoadjuvnat chemotherapy, advancement of open and laparoscopic surgical techniques, mature perioperative management, and patients’ improved general conditions, survival of the resected pancreatic cancer is expected to be further improved. According to the literatures, laparoscopic pancreaticoduodenectomy (LPD) is also thought to be good alternative strategy in managing well-selected resectable pancreatic cancer. LPD with combined vascular resection is also feasible, but only expert surgeons should handle these challenging cases. LPD for pancreatic cancer should be determined based on surgeons’ proficiency to fulfil the goals of the patient’s safety and oncologic principles.

Background Although genes have been previously detected in pancreatic cancer (PC), aberrant genes that play roles in resectable pancreatic cancer should be further assessed. Methods Messenger RNA samples and clinicopathological data corrected with PC were downloaded from The Cancer Genome Atlas (TCGA). Resectable PC patients were randomly divided into a primary set and a validation set. Univariable Cox regression analysis, lasso-penalized Cox regression analysis, and multivariable Cox analysis were implemented to distinguish survival-related genes (SRGs). A risk score based on the SRGs was calculated by univariable Cox regression analysis. A genomic-clinical nomogram was established by integrating the risk score and clinicopathological data to predict overall survival (OS) in resectable PC. Results Five survival-related genes (AADAC, DEF8, HIST1H1C, MET, and CHFR) were significantly correlated with OS in resectable PC. The resectable PC patients, based on risk score, were sorted into a high-risk group that showed considerably unfavorable OS (p Conclusion Our study identified five prognostic gene biomarkers for OS prediction and which facilitate postoperative molecular target therapy for the resectable PC, especially the nomic-clinical nomogram which may be used as an effective model for the postoperative OS evaluation and also an optimal therapeutic tool for the resectable PC.

Background Neoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT. Methods Between 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses. Results The postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively). Conclusions CY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.

Purpose Several studies investigating the role of intraoperative radiotherapy (IORT) in the treatment of resectable pancreatic cancer (PC) have been published; however, their results remain inconsistent. By conducting a systematic review and meta-analysis, this study aimed to compare clinical outcomes in patients with resectable PC who underwent surgery with or without IORT. Methods and materials The MEDLINE/PubMed, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to February 28, 2019. The main outcome measures included median survival time (MST), local recurrence (LR), postoperative complications, and operation-related mortality. Pooled effect estimates were obtained by performing a random-effects meta-analysis. Results A total of 1095 studies were screened for inclusion, of which 15 studies with 834 patients were included in the meta-analysis. Overall, 401 patients underwent pancreatic resection with IORT and 433 underwent surgery without IORT. The pooled analysis revealed that IORT group experienced favorable overall survival (median survival rate [MSR], 1.20; 95% confidence interval [CI], 1.06–1.37, P = 0.005), compared with patients who did not receive IORT. Additionally, the pooled data showed a significantly reduced LR rate in the IORT group compared with that in the non-IORT group (relative risk [RR], 0.70; 95% CI, 0.51–0.97, P = 0.03). The incidences of postoperative complications (RR, 0.95; 95% CI, 0.73–1.23) and operation-related mortality (RR, 1.07; 95% CI, 0.44–2.63) were similar between the IORT and non-IORT groups. Conclusion IORT significantly improved locoregional control and overall survival in patients with resectable PC, without increasing postoperative complications and operation-related mortality rates.