Borderline Resectable Pancreatic Carcinoma Research Articles

Irreversible electroporation as treatment of locally advanced and as margin accentuation in borderline resectable pancreatic adenocarcinoma.

In recent years, many local ablation technologies based on thermal damage have been used in the treatment of locally advanced pancreatic carcinoma (LAPC) and borderline resectable pancreatic carcinoma (BLRPC). However, they are associated with major complications because of possible vascular and ductal damage. Irreversible electroporation (IRE) is a nonthermal ablation technology that seems safe near vital vascular and ductal structures. IRE could be used as exclusive treatment of LAPC (en situ to IRE) after induction chemotherapy In BLRPC, surgery is not really radical in 6% of patients (microscopic residual) and local recurrences occur in 11-42% of apparent radical resections. IRE could be used as margin accentuation to increase posterior margin during radical surgery in BLRPC. Our outcomes are safety, time to progression. Secondary outcomes are overall survival, pain control and quality of life. We are performing a prospective evaluation of patients undergoing IRE for LAPC or BLRPC since July 2014. We have included patients with non-metastatic LAPC with maximum size ≤4cm (en situ to IRE) and patients with BLRPC (complementary IRE). We have performed induction chemotherapy in both groups. After treatment, patients were evaluated on days 1, 2, 4, 7, 14, 21, 30, 60 and 90 with amylase and lipase serum and abdominal drainage test. Based on Ethics Committee's request, follow-up imaging was performed at the 10thday for safety evaluation, at 30, 60 and 90days for response evaluation and then every 3months. Seven patients (two women and five men) underwent IRE. Two patients had LAPC and received en situ to IRE. In five patients affected by BLRPC we performed IRE and pancreatic head resection. In all patients, intraoperative imaging confirmed that the treatment of the whole tumor volume was complete. All seven patients demonstrated nonclinically relevant elevation of their amylase and lipase, which returned normal at 5days postprocedure. No patient showed evidence of clinical pancreatitis or fistula. No major complications were recorded. Patients with LAPC died of distant metastases 6month after treatment. At 3- and 6-month follow-up, all patients with BLPRC were alive and disease free. Only one patient has already reached 9-month follow-up and is alive and disease free. Our results are only preliminary. However, IRE ablation of LAPC and BLRPC seems a safe and feasible treatment.

Endoscopic ultrasonography complements computed tomography in predicting portal or superior mesenteric vein resection in patients with borderline resectable pancreatic carcinoma

BackgroundCurrent guidelines recommend computed tomographic (CT) scans for vascular staging of patients with pancreatic carcinoma; however, endoscopic ultrasonography (EUS) in these patients is not required and its utility in combination with CT scan is less well-defined. The purpose of this study is to explore the utility of EUS in addition to CT in identifying patients with borderline resectable pancreatic carcinoma (BRPC). MethodsWe reviewed our database of patients with BRPC who went to surgery with curative intent. Inclusion criteria were preoperative staging with CT scan and EUS, completion of neoadjuvant chemotherapy and radiotherapy, and surgical resection. ResultsWe identified 62 patients (average age of 65 ± 9 years, 60% male); 97% of patients underwent R0 resections. We found that 29% of patients were classified as BRPC by EUS alone, 23% by CT alone, and 48% by both modalities. Of 34 patients who required vein resection, EUS alone preoperatively identified 88% of these patients while CT alone identified 67%. EUS identified 11 patients who required vein resection that CT did not identify as BRPC, whereas CT identified 4 patients that EUS did not identify as BRPC. On multivariate analysis, EUS was associated with vein resection (P < 0.02), but CT scan findings, tumor size, and CA19-9 values were not associated (each P > 0.1). ConclusionsEUS complemented CT in identifying BRPC patients requiring vein resection, with nearly one-third of patients identified with EUS alone, supporting EUS use in addition to CT scan for vascular staging of patients with pancreatic carcinoma.

Pancreatectomy with Mesenteric and Portal Vein Resection for Borderline Resectable Pancreatic Cancer: Multicenter Study of 406 Patients.

The role of pancreatectomy with en bloc venous resection and the prognostic impact of pathological venous invasion are still debated. The authors analyzed perioperative, survival results, and prognostic factors of pancreatectomy with en bloc portal (PV) or superior mesenteric vein (SMV) resection for borderline resectable pancreatic carcinoma, focusing on predictive factors of histological venous invasion and its prognostic role. A multicenter database of 406 patients submitted to pancreatectomy with en bloc SMV and/or PV resection for pancreatic adenocarcinoma was analyzed retrospectively. Univariate and multivariate analysis of factors related to histological venous invasion were performed using logistic regression model. Prognostic factors were analyzed with log-rank test and multivariate proportional hazard regression analysis. Complications occurred in 51.9% of patients and postoperative death in 7.1%. Histological invasion of the resected vein was confirmed in 56.7% of specimens. Five-year survival was 24.4% with median survival of 24months. Vein invasion at preoperative computed tomography (CT), N status, number of metastatic lymph nodes, preoperative serum albumin were related to pathological venous invasion at univariate analysis, and vein invasion at CT was independently related to venous invasion at multivariate analysis. Use of preoperative biliary drain was significantly associated with postoperative complications. Multivariate proportional hazard regression analysis demonstrated a significant correlation between overall survival and histological venous invasion and administration of adjuvant therapy. This study identifies predictive factors of pathological venous invasion and prognostic factors for overall survival, including pathological venous invasion, which may help with patients' selection for different treatment protocols.

Knowing Your Boundaries: A Review of the Definitions and Imaging Features of Borderline Resectable Pancreatic Carcinoma

Introduction Pancreatic adenocarcinoma is the fourth leading cause of cancer death in the United States and has the lowest survival rate of any solid malignancy. Additionally, it is one of the few cancers with an increasing incidence over the past decade. Owing to the tumor 's insidious onset and aggressive biology, tumors often present at an advanced stage. Marginnegative tumor resection is the only curative technique, but only 15%-20%of patients have potentially resectable disease at the time of presentation. Although surgical techniques and chemotherapeutic options have become more advanced, the mortality rate has actually slightly increased between 1996 and 2011. Imaging is the primary means for staging pancreatic cancer and therefore carries substantial implications for appropriate patient management. Most commonly, the staging of pancreatic carcinoma follows American Joint Committee on Cancer guidelines. In the absence of metastatic disease, tumors are classified into resectable, borderline resectable, and unresectable locally advanced disease for the purposes of clinical management. Unfortunately, multiple classification definitions have been proposed, making standardization difficult. In this article, we will discuss different imaging strategies used to assess pancreatic adenocarcinoma and review the current, most common definitions of borderline resectable pancreatic carcinoma, including recent updates. We will review and demonstrate the imaging features of borderline resectable tumors. Examples will illustrate how using different definitions can cause the same tumor to be classified differently, as either resectable, borderline resectable, or locally advanced.

Association of decreased peak SUV on PET after neoadjvuant therapy in patients with borderline resectable pancreatic carcinoma with pathologic response.

423 Background: Despite the use of PET scan in metastatic staging, its utility as a biomarker for borderline resectable pancreatic carcinoma (BRPC) is unclear. The peak standardized uptake value (SUVpeak) is the average SUV around the most avid portion of the tumor. We hypothesized that tumor pathologic response (PR) to neoadjuvant therapy will correlate with SUVpeak changes after therapy. Methods: We reviewed our database of patients with BRPC who completed neoadjuvant chemotherapy (GTX) followed by radiation and had pre- and post- neoadjuvant PET scans. Changes in the SUVpeak were calculated by subtracting the post-neoadjuvant/pre-resection PET scan from the pre-neoadjuvant PET scan. PET responders were defined as those patients whose SUVpeak decreased by 4 units (the overall average decrease in SUVpeak) or more. Results: We identified 74 patients- 32 patients developed progressive disease and 42 patients underwent surgery. The average age was 66 ± 9 years; 61% of patients were male. On the final pathologic specimens, 5 patients had a complete PR to therapy while 23 patients had a moderate PR (1-49% viable tumor) and 14 patients had a minimal PR (≥ 50% viable tumor). PR is associated with a decrease in SUVpeak (p = 0.02; Table). The area under the receiver operator characteristic curve for changes in SUVpeakand complete PR was 0.83 ± 0.08. Of the PET responders who underwent surgery, 29% had a complete PR while none of the PET non-responders had a complete PR (p = 0.004). Of the unresected patients, PET responders had a longer overall survival compared to non-responders (18 ± 7 vs. 12 ± 7 months, p &lt; 0.05). Nodal disease was not associated with PR (p &gt; 0.3). Conclusions: PR was significantly associated with a decrease in SUVpeak post-neoadjuvant therapy in patients with BRPC. Even in patients with unresectable disease, SUVpeak provides useful prognostic data. We believe that pre- and post-neoadjuvant therapy PET scans may be used as a prognostic biomarker in patients with BRPC. [Table: see text]

EUS combined with CT in predicting SMV/PV resection in patients with borderline resectable pancreatic carcinoma.

432 Background: Guidelines recommend pancreatic protocol CT scan (CT) for staging vascular involvement in patients with pancreatic cancer (PC). While endoscopic ultrasound (EUS) has been demonstrated to be effective in venous staging of PC, its role when combined with CT is poorly defined. We evaluated the utility of EUS in addition to CT in staging PC. We hypothesized that EUS complements CT in identifying SMV/PV tumor involvement as measured by the requirement for vein resection. Methods: We reviewed our database of patients with borderline resectable PC who went to surgery with curative intent. Inclusion criteria were pre-operative staging with CT scan, EUS, PET scan, and CA 19-9 levels, as well as completion of neoadjuvant chemotherapy and radiation. Results: We identified 62 patients with 74% of tumors in the pancreatic head. 97% of resections were R0. The average age was 65 ± 9 years; 60% were male. Patients were classified as borderline resectable by EUS alone in 29%, CT alone in 23%, and both modalities in 48% of patients, respectively. 34 patients required vein resection; EUS identified 88% of these patients pre-operatively while CT identified 68%. EUS identified 11 patients who required vein resection that CT did not identify while CT identified 4 patients that EUS did not identify. EUS had higher sensitivity and specificity than CT in identifying patients requiring venous resection (Table). On multivariate logistic regression analysis, EUS was predictive of vein resection (P &lt; 0.02) but CT scan findings, PET scan findings, tumor size, and CA19-9 values were not predictive (each P &gt; 0.1). In margin negative resected patients, median survival was longer when both CT and EUS identified borderline status compared to only 1 modality (43 vs 23 months, P &lt; 0.05). Conclusions: EUS complemented CT in identifying patients with borderline resectable PC requiring vein resection- 29% of patients were identified with EUS alone. This observation supports the use of EUS in addition to CT scan for the vascular staging of patients with PC. [Table: see text]

Highlights and difficulties in surgical treatment for pancreatic carcinoma

Pancreatic carcinoma is still a challenging disease, although the resection rate and the operative safety have been improved, the prognosis of the patients is dismal. Now the therapy strategy is changed from surgery firstinto the mode of multidisciplinary team (MDT). Surgical resection is the only curable therapy for pancreatic carcinoma. Recently, the clinical role of extent of lymphadenectomy, combined vascular resection, and total mesopancreas excision was recognized more deeply. If 1 mm ruleis applied to define the resection margin, most pancreatic cancer resections are R1 resections, which benefit the patients. There has been consensus on the definition of perioperative complications. Neoadjuvant therapy is advocated for patients with borderline resectable pancreatic carcinoma. Key words: Pancreatic neoplasms; Surgical therapy; Neoadjuvant therapy

En bloc vascular resection for the treatment of borderline resectable pancreatic head carcinoma.

Borderline resectable (BR) pancreatic head carcinoma (PhC) is an advanced disease, presenting with infiltration of major vessels. Major vascular resection (VR), particularly arterial resection, to achieve microscopic no residual tumor (R0) is a controversial approach, due to the potential complications. In this study, we aimed to clarify the benefit of en bloc R0 resection with VR for PhC by retrospectively evaluating 78 PhC patients who underwent pancreatoduodenectomy at our institute. The patients were divided into 4 groups as follows: R, resectable (n=20); BR-V, BR involving the superior mesenteric vein or portal vein (PV) (n=28); BR-SMA, BR involving the superior mesenteric artery (n=21); and BR-HA, BR involving the hepatic artery (n=9). In total, 65 patients underwent VR, with 63, 21 and 9 patients undergoing PV, SMA and HA resection, respectively. The R0 rates were as follows: R group, 85%; BR-V, 82%; BR-SMA, 71%; and BR-HA, 33%. The median survival time and 5-year survival rate for R0 resection were 31 months and 25% in the R group, 22 months and 28% in the BR-V group, 17 months and 27% in the BR-SMA group and 10 months and 0% in the BR-HA group, respectively. The prognosis was comparable among the BR-V, BR-SMA and R groups, but was significantly poorer in the BR-HA group. In total, 5 patients (6.4%) died perioperatively (4 from postoperative hemorrhage and 1 from suffocation due to failure of expectoration, without pneumonia or asthma). Of the 4 patients who succumbed to hemorrhage, 3 had undergone arterial resection. Therefore, en bloc resection with major VR for R0 may be suitable for BR-V and BR-SMA PhC patients.

Multidisciplinary management of locally advanced–borderline resectable adenocarcinoma of the head of the pancreas

Borderline resectable pancreatic head carcinoma is a challenging disease that requires multidisciplinary approach to obtain maximal benefits from current therapeutical possibilities. We review current knowledge and therapeutic options for the patients from the surgical, medical oncology and radiotherapy views and emphasize the need for a coordinated multidisciplinary approach to obtain optimal results.

Self-Expanding Metal Stents (SEMS) for Preoperative Biliary Decompression in Patients with Resectable and Borderline-Resectable Pancreatic Cancer: Outcomes in 241 Patients

Obstructive jaundice caused by distal biliary obstruction can present in up to 70 % of patients with localized cancer of the head of the pancreas. The aim of this study was to report our experience in using self-expanding metal stents (SEMS) for preoperative biliary decompression in patients with resectable and borderline resectable carcinoma of the pancreatic head. We performed a retrospective study evaluating patients from two tertiary referral centers. Two-hundred and forty-one patients with resectable and borderline resectable pancreatic carcinoma underwent ERCP with metal biliary stent placement between September 2006 and August 2011. We assessed the effectiveness of SEMS to adequately decompress the biliary tree, procedural success, patient survival, stent patency, and stent-related complications. Two-hundred and forty-one patients were evaluated [123 male, mean age (± SD) 67.4 ± 9.8 years; resectable 174, borderline resectable 67]. Patients with borderline-resectable cancer underwent neoadjuvant therapy and restaging before possible curative surgery. Successful placement of a metal biliary stent was achieved in all patients and improved jaundice. Patients were followed for mean duration of 6.3 months. The overall survival was 49 % at 27 months. Fourteen (5.8 %) patients experienced stent occlusion; the mean time to stent occlusion was 6.6 (range 1-20) months. Immediate complications included: post-ERCP pancreatitis (n = 14), stent migration (n = 3), and duodenal perforation (n = 3). Long-term complications included stent migration (n = 9) and hepatic abscess (n = 1). A total of 144/174 patients deemed to have resectable cancer at time of diagnosis underwent curative surgery. Due to disease progression or the discovery of metastasis after neoadjuvant therapy, only 22/67 patients with borderline-resectable cancer underwent curative surgery. SEMS should be considered for patients with obstructive jaundice and resectable or borderline resectable pancreatic cancer, especially if surgery is not planned immediately as a result of preoperative chemoradiation. These stents appear to be safe and effective.

Neoadjuvant chemoradiotherapy has a potential role in pancreatic carcinoma

Pancreatic cancer has an extremely poor prognosis, only a small minority of patients undergo a resection with curative intent. Chemotherapy and/or radiochemotherapy may improve this by prolonging survival or disease-free interval and improving resectability and the proportion of microscopically complete (R0) resections. With regard to prolonging survival, both in the postoperative adjuvant setting and in locally advanced disease, chemotherapy has a positive but limited effect on survival and may be considered standard. The role of postoperative adjuvant radiochemotherapy remains debatable. For improving resectability/proportion of R0 resections, many studies suggest that the proportion of patients undergoing a resection during exploration and the proportion of R0 resections increase after neoadjuvant radiochemotherapy. This may improve the prognosis of patients with a resectable or borderline resectable pancreatic carcinoma. The effect of neoadjuvant radiochemotherapy, if any, is modest. The search for better combinations, including targeted therapy, must continue. The interpretation of single-arm studies is hampered by (selection) biases. The reporting of pathology and study endpoints should be internationally standardized. To avoid biases in studies of patients with (borderline) resectable tumours, prospective parallel registration of all patients referred for surgery would help. Ultimately, randomized controlled phase III trials should establish the role of neoadjuvant radiochemotherapy. Thus, neoadjuvant radiochemotherapy has a potential benefit in resectable and borderline resectable pancreatic cancer, but better combinations are warranted.

Covered Self Expandable Metal Stents in Border-Line Resectable Pancreatic Carcinoma: Prospective Study Concerning Effectiveness and Safety

Aims: Placement of biliary self expandable metal stents (SEMS) in patients with pancreatic carcinoma suitable of surgical treatment has been controversial. Since covered SEMS (SEMSc) became available, the possibility of inserting these stents in potentially surgical patients is safer as they can be removed if necessary in 85-95% of cases. The aim of this study is to assess the effectiveness and safety of SEMSc in patients with malignant jaundice secondary to border-line resectable pancreatic carcinoma. Material and Method: 33 consecutive patients (23 m/10f; age 69.1 yrs) with obstructive jaundice secondary to border-line resectable pancreatic carcinoma (superior mesenteric vein invasion,large tumor, retroperitoneal growth) were included in the study. After biliary drainage with a SEMSc,patients underwent neoadjuvant treatment with gemcitabin and radiotherapy during 8 weeks. Patients were reevaluated after treatment by CT scan and tumors staged as unresectable or potentially resectable. In those patients harbouring potentially resectable tumors surgery was indicated. Effectiveness in jaundice palliation, accomplishment of neoadjuvant therapy and stent removal requirements during presurgical period were assessed. Stent related postsurgical complications were also evaluated. Results: SEMSc could be inserted in all patients although in one case the stent had to be removed 72 hours after placement due to acute cholecystitis (3%). 32 patients completed oncologic treatment with no toxicity related to the stent. After CT reevaluation,21 patients (65.6%) were considered unsuitable for surgery and 11 patients (34.4%) candidates for tumor resection. Bilirubin levels dropped from 15.3 to 1.1 mg/dl (p < 0.01) in surgical patients with no episodes of cholangitis. In 4 of the 11 patients stent removal was indicated prior to surgery to assure bilioenteric anastomosis. It was successfully performed in all patients with a polypectomy snare after a mean post insertion period of 11.5 weeks. At operation,4 patients were not resected due to peritoneal disease and 7 patients finally resected (21.9%). Cholangitis pathological features were present in all surgical specimens but clinical cholangitis or anastomotic fistula were not registered during postoperative follow up in any patient. Conclusions: 1. SEMSc are effective in presurgical jaundice palliation in patients with border-line resectable pancreatic carcinoma. 2. These stents allow neoadjuvant oncologic treatment accomplishment without any added toxicity. 3. The possibility of stent removal when needed is a remarkable advantage in terms of safety. 4. Postoperative complications do not increase in relation to presurgical SEMSc insertion.