Arterial Abutment Research Articles

Development of Nomograms for Predicting Prognosis of Pancreatic Cancer after Pancreatectomy: A Multicenter Study.

Surgical resection is the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). Currently, the TNM classification system is considered the standard for predicting prognosis after surgery. However, the prognostic accuracy of the system remains limited. This study aimed to develop new predictive nomograms for resected PDAC. The clinicopathological data of patients who underwent surgery for PDAC between 2006 and 2015 at five major institutions were retrospectively reviewed; 885 patients were included in the analysis. Cox regression analysis was performed to investigate prognostic factors for recurrence and survival, and statistically significant factors were used for creating nomograms. The nomogram for predicting recurrence-free survival included nine factors: sarcopenic obesity, elevated carbohydrate antigen 19–9, platelet-to-lymphocyte ratio, preoperatively-identified arterial abutment, estimated blood loss (EBL), tumor differentiation, size, lymph node ratio, and tumor necrosis. The nomogram for predicting overall survival included 10 variables: age, underlying liver disease, chronic kidney disease, preoperatively found portal vein invasion, portal vein resection, EBL, tumor differentiation, size, lymph node metastasis, and tumor necrosis. The time-dependent area under the receiver operating characteristic curve for both nomograms exceeded 0.70. Nomograms were developed for predicting survival after resection of PDAC, and the platforms showed fair predictive performance. These new comprehensive nomograms provide information on disease status and are useful for determining further treatment for PDAC patients.

Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution

BackgroundBorderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A).MethodsA total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT.ResultsTwenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19–9 (CA19-9) > 400 U/ml before NACIMRT.ConclusionsNACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment.Trial RegistrationUMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776Registration number: UMIN000010113.Date of first registration: 01/03/2013,

Pre-operative/Neoadjuvant Therapy and Vascular Debranching Followed by Resection for Locally Advanced Pancreatic Cancer (PREVADER): Clinical Feasibility Trial.

Introduction: Pancreatic cancer continues to have a poor outcome. Many patients are diagnosed with advanced disease, and in a considerable proportion, abutment or invasion of visceral arteries is present. Moreover, some patients have anatomical variations or stenosis of major visceral arteries requiring arterial reconstruction upon pancreatic cancer resection to avoid organ ischemia. Simultaneous arterial reconstruction during resection is associated with relevant morbidity and mortality. This trial evaluates the approach of visceral debranching, that is, arterial reconstruction, prior to neoadjuvant chemotherapy and tumor resection in patients with locally advanced, unresectable pancreatic cancer.Methods and Analysis: The trial includes patients with locally advanced, non-metastatic pancreatic cancer with arterial abutment or invasion (deemed primarily unresectable), variations in vascular anatomy, or stenosis of visceral arteries. The participants undergo visceral debranching, followed by current standard neoadjuvant chemotherapy (mFOLFIRINOX, gemcitabine–nab-paclitaxel, or other) and potential subsequent tumor resection. The primary outcome is feasibility, measured as the proportion of patients who start neoadjuvant therapy within 6 weeks of visceral debranching. The trial has an exact single-stage design. The proportion below which the treatment is considered ineffective is set at 0.7 (H0). The proportion above which the treatment warrants further exploration in a phase III trial is set at 0.9 (H1). With a power (1-beta) of 0.8 and a type 1 mistake (alpha) of 0.05, the required sample size is 28 patients. Feasibility of the approach will be assumed if 24 of the enrolled 28 patients proceed to neoadjuvant chemotherapy within 6 weeks from visceral debranching.Discussion: This trial evaluates a new treatment sequence, that is, visceral debranching followed by chemotherapy and resection, for pancreatic cancer with invasion or abutment of visceral arteries. The primary objective of the trial is to evaluate feasibility. Trial results will allow for estimating treatment effects and calculating the sample size of a randomized controlled trial, in which the approach will be tested if the feasibility endpoint is met.Clinical Trial Registration: clinicaltrials.gov, identifier: NCT04136769.

Inoue plane 3 evaluated by endoscopic ultrasound predicts resectability without arterial resection in borderline resectable or locally advanced pancreatic adenocarcinoma

Introduction: Arterial invasion in borderline resectable (BR) and locally advanced (LA) pancreatic adenocarcinoma (PDAC) remains a challenge for tumor resection. After neoadjuvant therapies (NT), cross sectional imaging does not adequately reflect the extent of tumoral response, therefore difficulting resectability judgment. Alongside with mesopancreatic knowledge, Inoue et al. describes 3 levels of dissection: the level 3 plane approached by arterial divestment technique can achieve a tumor resection in BR and LA PDAC settings. Having a preoperative imaging technique that will enable to determine the indemnity of this plane would help in patient’s selection for surgery. EUS and elastography (EUS-EG) has been found to have high diagnostic ability in evaluating relative movement/consistency of tissues and might be of value when defining the type of vascular involvement. We present our first case series following this novel approach for BR and LA PDAC. Methods: We included PDAC patients with diagnostic of BR or LA who received NT in which a critical arterial encasement suspicion of infiltration was diagnosed. We reviewed all cases in our multidisciplinary committee, and only patients with RECIST (Response Evaluation Criteria in Solid Tumors) criteria of regression or stable disease were eligible to intent of resectability. The day prior to the surgery an EUS + EUS-EG was done to evaluate arterial involvement. Results: In total 73 BR and LA were evaluated. After NT, 25 cases of BR and 6 LA were proposed for surgery. 27 patients had venous infiltration alone and less complex arterial involvement on CT and were not EUS eligible; 2 BR and 2 LA were candidates for preoperative EUS. After NT (3 received FOLFIRINOX and 1 NALIRINOX), arterial abutment was still radiologically evident. A preoperative EUS and EUS-EG was performed the day prior to surgery in which a hyperechoic line (theoretical dissection plane) was found, with no vascular infiltration on EUS-EG. All patients were explored by artery first approach technique. In every case, the plane 3 of Inoue was reached, and tumor was removed from artery, corroborating the EUS findings. A complex venous vascular resection was needed in all surgeries; no arterial resection was performed. R0 margins were achieved for all patients (Figure 1). Conclusion: Preoperative EUS and EUS-EG should guide surgeons toward sparing arterial procedures and help to accomplish negative surgical margins in selected patients.

Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma \u2013 results of the Conko-007 multicenter trial

BackgroundOne critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer.MethodsPretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared.ResultsOne hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05).ConclusionExcellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors.Trial registrationEudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).

Phase II Trial of Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy (SBRT) for Resectable and Borderline Resectable (BLR) Pancreas Cancer

There is emerging interest in the role of SBRT in locally advanced pancreas cancer, however little prospective data exists examining the safety, efficacy, and optimal target volumes for SBRT in the neoadjuvant setting for resectable or BLR pancreatic cancer. The durability of local control and failure patterns following SBRT in the neoadjuvant setting are not well described. A phase II prospective trial was conducted in resectable and BLR pancreatic patients. Eighteen patients were enrolled from 11/2014-6/2017. All patients received 3 cycles of chemotherapy and restaging prior to radiation. SBRT was delivered to the tumor and abutting vessel with fiducials/compression and a 3 mm PTV margin to 33 Gy (6.6 Gyx5fxn) with an optional elective PTV to 25 Gy (5 Gyx5fxn) customized to the nodal space and mesenteric vessels. Patients without progression underwent surgery 4-6 weeks following SBRT. The primary endpoint is ≥ Grade 3 acute and late GI toxicity. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and cumulative incidence of local failure (LF). LF is defined as recurrence within conventional RT volumes from the time of resection to local failure or last CT with no progression. Local failures were fused to planning CTs for dose quantification. Thirteen patients had BLR tumors due to arterial abutment (n = 7) or SMV encasement (n = 6); 3 patients had resectable tumors. All patients received 4 months of gemcitabine/nab-paclitaxel (n = 13) or FOLFIRNOX (n = 5) prior to SBRT. There were no ≥ Grade 3 acute or late GI events. Following completion of SBRT, 6 patients progressed (33%) at restaging or surgery with liver metastases (n=5, 28%) or local disease (n=1, 5%). Surgery was performed in 12 patients (67%) with 11 (92%) R0 resections (median margin distance 1.75 mm [0-9mm]). Lymph nodes were involved in 4 (33%) patients. Median OS was 21 months for all patients. In patients undergoing resection median OS was 31 months compared to 9 months without resection (p=0.003). The median PFS was 11 months. Progression occurred in 75% (9/12) of resected patients with first site of failure as distant (n = 4, 44%), local only (n = 4, 44%), and local and distant (n = 1,11%). The cumulative incidence of LF at 12 months from resection was 56% with one patient surviving 15 months without LF. All LF were outside to the PTV33 with median D90 of 11.5 Gy (4-25 Gy), V25 Gy of 51% (0-90%), and V33 Gy of 45% (0-52%). In resected patients, LF occurred in 4/8(50%) patients treated with a 25 Gy elective PTV and in 4/5(80%) of patients treated to the primary only (p=0.56). SBRT as a component of neoadjuvant therapy was well tolerated. However, local failures were predominantly observed outside the PTV33 volume within conventional RT volumes. Therefore, the durability of local control after SBRT in the neoadjuvant setting using target volumes and dose as described merits close examination relative to chemoradiation prior to incorporation into routine practice.

Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment

Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment

Development and multicentre validation of a prognostic model to predict resectability of pancreatic head malignancy.

BackgroundAt the time of planned pancreatoduodenectomy patients frequently undergo exploratory laparotomy without resection, leading to delayed systemic therapy. This study aimed to develop and validate a prognostic model for the preoperative prediction of resectability of pancreatic head tumours.MethodsThis was a retrospective study of patients undergoing attempted resection for confirmed malignant tumours of the pancreatic head in a university hospital in Hannover, Germany. The prognostic value of patient and tumour characteristics was investigated in a multivariable logistic regression model. External validation was performed using data from two other centres.ResultsSome 109 patients were included in the development cohort, with 51 and 175 patients in the two validation cohorts. Eighty patients (73·4 per cent) in the development cohort underwent resection, and 37 (73 per cent) and 141 (80·6 per cent) in the validation cohorts. The main reasons for performing no resection in the development cohort were: local invasion of vasculature or arterial abutment (15 patients, 52 per cent), and liver (12, 41 per cent), peritoneal (8, 28 per cent) and aortocaval lymph node (6, 21 per cent) metastases. The final model contained the following variables: time to surgery (odds ratio (OR) 0·99, 95 per cent c.i. 0·98 to 0·99), carbohydrate antigen 19‐9 concentration (OR 0·99, 0·99 to 0·99), jaundice (OR 4·45, 1·21 to 16·36) and back pain (OR 0·02, 0·00 to 0·22), with an area under the receiver operating characteristic (ROC) curve (AUROC) of 0·918 in the development cohort. AUROC values were 0·813 and 0·761 in the validation cohorts. The positive predictive value of the final model for prediction of resectability was 98·0 per cent in the development cohort, and 91·7 and 94·7 per cent in the two external validation cohorts. [Corrections added on 18 July 2018, after first online publication: The figures for OR of the variables time to surgery and CA19‐9 in the abstract and in Table 3 and Table 4 were amended from 1·00 to 0·99]ConclusionFor preoperative prediction of the likelihood of resectability of pancreatic head tumours, this validated model is a valuable addition to CT findings.

Patterns of failure in a phase II trial of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) for resectable and borderline resectable (BLR) pancreatic cancer.

482 Background: There is emerging interest in the role of SBRT in locally advanced pancreas cancer, however little prospective data exists examining the safety, efficacy, and optimal target volumes for SBRT in the neoadjuvant setting for resectable or BLR pancreatic cancer. Methods: Eighteen patients were enrolled from 11/2014-6/2017. SBRT was delivered to the tumor and abutting vessel with fiducials/compression and a 3 mm PTV margin to 33 Gy (6.6 Gyx5fxn) with an optional elective PTV to 25 Gy (5 Gyx5fxn) customized to the nodal space and mesenteric vessels. Patients without progression underwent surgery 4-6 weeks following SBRT. The primary endpoint is ≥ Grade 3 acute and late GI toxicity. Secondary endpoints included overall survival (OS), progression-free survival (PFS),and cumulative incidence of local failure (LF). LF is defined as recurrence within conventional RT volumes from the time of resection to local failure or last CT with no progression. Local failures were fused to planning CTs for dose quantification. Results: Thirteen patients had BLR tumors due to arterial abutment (n = 7) or SMV encasement (n = 8); 3 patients had resectable tumors. All patients received 4 months of gemcitabine/nab-paclitaxel (n = 13) or FOLFIRNOX (n = 5) prior to SBRT. There were no ≥ Grade 3 acute or late GI events. Metastases were noted in 6 patients (33%) at restaging or surgery. Surgery was performed in 12 patients (67%) with 11 (92%) R0 resections. Median OS and PFS are 21 months and 11 months, respectively. Progression occurred in 67% (8/12) of resected patients with first site of failure as distant (n = 3, 38%), local only (n = 4, 50%), and local and distant (n = 1,13%). The cumulative incidence of LF at 12 months from resection was 50%. All LF were outside to the PTV33 with median D90 of 11.5 Gy (4-25 Gy), V25 Gy of 51% (0-90%), and V33 Gy of 45% (0-52%). Conclusions: SBRT as a component of neoadjuvant therapy was well tolerated. However, local failures were predominantly observed outside the PTV33 volume within conventional RT volumes. Therefore, the durability of local control after SBRT in the neoadjuvant setting relative to chemoradiation merits close examination. Clinical trial information: NCT02208024.

Common Hepatic Artery Abutment or Encasement Is an Adverse Prognostic Factor in Patients with Borderline and Unresectable Pancreatic Cancer

BackgroundLocalized and unresectable pancreatic ductal adenocarcinoma (PDA) comprises one third of new diagnoses and includes borderline resectable (BR) and locally advanced (LA) unresectable disease. In a cohort of patients who were treated and followed at a single institution, we assessed clinical and radiographic predictors of outcome. MethodsThe study included 69 consecutive patients with BR or LA PDA. Serial imaging studies were reviewed by both a pancreatic surgeon and a radiologist for vascular abutment or encasement by cancer, and they were recorded. ResultsThe cohort included 25 patients with BR and 44 patients with LA PDA, with median overall survivals (OS) of 15 and 14 months, respectively (p = 0.802). Fifteen patients were resected (22%), with a median OS of 21 months from diagnosis (HR 2.50, p = 0.006) and 13 months from resection. Median OS from diagnosis was 33 months in patients without lymph node metastases at resection (n = 10), but just 17 months with lymph node metastases (n = 5, HR = 8.95, p = 0.011). There were 12 two-year survivors in the total cohort (17%), and seven of them never underwent resection. First-line treatments consisted of gemcitabine (n = 13), modern first-line combinations (FOLFIRNOX or gemcitabine/nab-paclitaxel, n = 24), or alternative multi-agent therapies (n = 32); there were no statistical differences between treatment subgroups (OS of 10, 13, and 16 months, respectively). Common hepatic artery (CHA) abutment or encasement at diagnosis was associated with poor survival (adjusted hazard ratio, CHA abutment = 2.47 (p = 0.015) and CHA encasement = 2.16 (p = 0.036)). ConclusionIn this cohort, common hepatic arterial abutment or encasement and residual lymph node disease at resection portended a particularly poor outcome in patients with localized, unresectable PDA.

Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment

For the products that provide not only intrinsic value from their functions but also stylish consumption experience, there often exist both Veblen and network effects. Some customers are more likely to purchase the product if fewer customers can afford it, while others might appreciate the existence of more peers. Focusing on these products, we study the market equilibrium under rational expectations. The optimal pricing and quantity decisions reveal interesting insights about the effects of such mixed consumption externalities.

Inverse Probability of Treatment Weighting Analysis of Upfront Surgery Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Pancreatic Adenocarcinoma with Arterial Abutment

Pancreatic ductal adenocarcinomas (PDACs) are aggressive with frequent lymphatic spread. By analysis of data from The Cancer Genome Atlas, we determined that ~35% of PDACs have a pro-angiogenic gene signature. We now show that the same PDACs exhibit increased expression of lymphangiogenic genes and lymphatic endothelial cell (LEC) markers, and that LEC abundance in human PDACs correlates with endothelial cell microvessel density. Lymphangiogenic genes and LECs are also elevated in murine PDACs arising in the KRC (mutated Kras; deleted RB) and KIC (mutated Kras; deleted INK4a) genetic models. Moreover, pancreatic cancer cells (PCCs) derived from KRC tumors express and secrete high levels of lymphangiogenic factors, including the EGF receptor ligand, amphiregulin. Importantly, TGF-β1 increases lymphangiogenic genes and amphiregulin expression in KRC PCCs but not in murine PCCs that lack SMAD4, and combinatorial targeting of the TGF-β type I receptor (TβRI) with LY2157299 and EGFR/HER2 with lapatinib suppresses tumor growth and metastasis in a syngeneic orthotopic model, and attenuates tumor lymphangiogenesis and angiogenesis while reducing lymphangiogenic genes and amphiregulin and enhancing apoptosis. Therefore, this combination could be beneficial in PDACs with lymphangiogenic or angiogenic gene signatures.

Inverse probability of treatment weighting analysis of upfront surgery versus neoadjuvant chemoradiotherapy followed by surgery for pancreatic adenocarcinoma with arterial abutment.

440 Background: Combined arterial resection during pancreatectomy can be a challenging treatment, and outcome would be more favorable if the tumor becomes technically removable from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve locoregional control and enable margin-negative resection. To investigate the effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were deemed borderline resectable through preoperative imaging due to abutment of the major artery, including the superior mesenteric artery (SMA) or common hepatic artery (CHA), but were still considered to be technically removable. Methods: Comparisons were make between 71 patients who underwent upfront surgery and 21 patients who underwent NACRT followed by surgery in the strategy to preserve the artery, using unmatched and inverse probability of treatment weighting analysis (UMIN000017115). Results: Fifty patients in the upfront surgery group and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively; P = 0.1609). The results of the propensity score weighted logistic regressions indicated that the incidences of pathological lymph node metastasis and a pathological positive resection margin were significantly lower in the NACRT group (odds ratio, 0.006; P &lt; 0.0001 and odds ratio, 0.007; P = 0.0005, respectively). Among the propensity-score matched patients, the estimated 1- and 2-year survival rates in the upfront surgery group were 66.7% and 16.0%, respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. Conclusions: It was suggested that chemoradiotherapy followed by surgery provided clinical benefits in patients with PDACs in contact with the SMA or CHA. Clinical trial information: 000017115.

A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.

TPS516 Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / &lt; 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.

Inverse Probability of Treatment Weighting Analysis of Upfront Surgery Versus Neoadjuvant Chemoradiotherapy Followed by Surgery for Pancreatic Adenocarcinoma with Arterial Abutment.

Combined arterial resection during pancreatectomy can be a challenging treatment, and outcome would be more favorable if the tumor becomes technically removable from the artery. Neoadjuvant chemoradiotherapy (NACRT) is expected to achieve locoregional control and enable margin-negative resection. To investigate the effects of NACRT in patients with pancreatic adenocarcinoma (PDAC) which were deemed borderline resectable through preoperative imaging due to abutment of the major artery, including the superior mesenteric artery (SMA) or common hepatic artery (CHA), but were still considered to be technically removable. In the current study, comparisons were make between 71 patients who underwent upfront surgery and 21 patients who underwent NACRT followed by surgery in the strategy to preserve the artery, using unmatched and inverse probability of treatment weighting analysis (UMIN000017115). Fifty patients in the upfront surgery group and 18 in the NACRT group underwent curative resection (70% vs 86%, respectively; P = 0.16). The results of the propensity score weighted logistic regressions indicated that the incidences of pathological lymph node metastasis and a pathological positive resection margin were significantly lower in the NACRT group (odds ratio, 0.006; P < 0.001 and odds ratio, 0.007; P < 0.001, respectively). Among the propensity-score matched patients, the estimated 1- and 2-year survival rates in the upfront surgery group were 66.7% and 16.0%, respectively, and those in the NACRT group were 80.0% and 65.2%, respectively. In conclusion, it was suggested that chemoradiotherapy followed by surgery provided clinical benefits in patients with PDACs in contact with the SMA or CHA.

Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma

The aim of this study was to determine the added value of portal or superior mesenteric vein (PV/SMV) resection during pancreatoduodenectomy for pancreatic head carcinoma. A multicentre observational study was conducted in patients with pancreatic head carcinoma who underwent pancreatoduodenectomy in seven Japanese hospitals between 2001 and 2012. Clinicopathological factors were compared between patients who did and did not undergo PV/SMV resection. Those with an impact on survival were identified by univariable and multivariable analysis. Of the 937 patients who underwent pancreatoduodenectomy, 435 (46·4 per cent) had PV/SMV resection, whereas the remaining 502 (53·6 per cent) did not. Some 71·5 and 63·9 per cent of patients with and without PV/SMV resection respectively had lymph node-positive disease. Patients who underwent PV/SMV resection had more advanced tumours. Perioperative mortality and morbidity rates did not differ between the two groups. Multivariable analysis revealed that PV/SMV resection was not an independent prognostic factor for overall survival (P = 0·268). Among the 435 patients in whom the PV/SMV was resected, borderline resectable tumours with arterial abutment (P = 0·021) and absence of adjuvant chemotherapy (P < 0·001) were independent predictors of poor survival in multivariable analysis. Patients with resectable or borderline resectable tumours with PV/SMV involvement had a median survival time with additional adjuvant chemotherapy of 43·7 and 29·7 months respectively. Median survival time in patients with borderline resectable tumours with arterial abutment was 18·6 months despite adjuvant chemotherapy. Pancreatoduodenectomy with PV/SMV resection and adjuvant chemotherapy in patients with pancreatic head carcinoma may provide good survival without increased mortality and morbidity.

Neoadjuvant chemoradiation with IMRT in resectable and borderline resectable pancreatic cancer

PurposeNeoadjuvant chemoradiation is an alternative to the surgery-first approach for resectable pancreatic cancer (PDA) and represents the standard of care for borderline resectable (BLR). Materials and methodsAll patients with resectable and BLR PDA treated with neoadjuvant chemoradiation using IMRT between 1/2009 and 11/2011 were reviewed. Patients were treated to a customized CTV which included the primary mass and regional vessels. ResultsNeoadjuvant chemoradiation was completed in 69 patients (39 BLR and 30 resectable). Induction chemotherapy was used in 32 (82%) of the 39 patients with BLR disease prior to chemoXRT. All resectable patients were treated with chemoXRT alone. Following neoadjuvant treatment, 48 (70%) of the 69 patients underwent successful pancreatic resection with 47 (98%) being margin negative (RO). In 30 of the BLR patients who had arterial abutment or SMV occlusion, 19 (63%) were surgically resected and all had RO resections. The cumulative incidence of local failure at 1 and 2years was 2% (95% CI 0–6%) and 9% (95% CI 0.6–17%) respectively. The median overall survival for all patients, patients undergoing resection, and patients without resection were 20, 26 and 11months respectively. Sixteen (23%) of the 69 patients are alive without disease with a median follow-up of 47months (36–60). ConclusionNeoadjuvant chemoXRT can facilitate a margin negative resection in patients with localized PCa.

Mo1752 Does Weight Affect Outcomes Following Total Pancreatectomy With Islet Autotransplantation?

noma at a single institution from 2000 to 2007 were included in this retrospective study. Patients who received neoadjuvant treatment prior to resection and patients with arterial abutment were excluded. Venous involvement was categorized using pre-operative crosssectional imaging as 1) none, 2) portomesenteric vein (PMV) abutment ,180°, 3) PMV abutment ≥180°, and 4) PMV impingement/occlusion. Univariate logistic regression and Cox proportional hazards models were constructed. All four levels of venous involvement were compared to each other; Benjamini-Hochberg method was used to adjust for multiple comparisons. Results: 290 patients (median age 68 years (range 38 90), 58% male) underwent pancreaticoduodenectomy. 30and 90day mortality was 0.7% and 1.7%, respectively. 117 patients (40%) had venous involvement: 73 abutment ,180°, 21 abutment ≥180°, and 23 PMV impingement/occlusion. Margin negative resection was achieved in 83% of patients without venous involvement compared to 73% patients with abutment ,180° (p=0.09), 29% of patients with abutment ≥180° (p,0.01), and 52% of patients with PMV impingement/occlusion (p,0.01). Patients with abutment ,180° were more likely to have margin negative resection than patients with abutment ≥180° (p,0.01). Retroperitoneal margin was positive in 15%, 16%, 48%, and 30% among the patient groups. Patients with abutment ≥180° had more frequent positive retroperitoneal margins than patients without venous involvement or abutment ,180° (both p≤0.01). 58 patients (20%) required PMV resection and reconstruction: 7% of patients without venous involvement compared to 36% with abutment ,180°, 43% with abutment ≥180°, and 48% with PMV impingement/ occlusion (all p,0.01). There were no significant group differences in recurrence-free and overall survival (all p≥0.09). Conclusions: Portomesenteric vein abutment ≥180° is associated with significantly higher risk of margin positive resection. While patients without venous involvement and patients with vein abutment ,180° can be explored for curative resection, patients with PMV abutment ≥180° and impingement/occlusion might benefit from neoadjuvant therapy.

Staging of pancreatic cancer before and after neoadjuvant chemoradiation

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine the utility of staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT. Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT. Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT.