Parag Tolat

Survival of patients with resectable pancreatic cancer who received neoadjuvant therapy

BACKGROUND Enthusiasm for neoadjuvant therapy is growing from the emerging consensus that pancreatic cancer is a systemic disease at the time of diagnosis. Those who remain in favor of upfront surgery often cite the lack of reported data to support alternative treatment sequencing. We therefore report the results of all patients treated outside of a clinical trial under the direction of a multidisciplinary pancreatic cancer working group. METHODS We reviewed all patients with resectable pancreatic cancer treated with neoadjuvant therapy (NeoTx) from 2009 to 2013; we excluded those patients treated on prospective clinical trials as they will be the subject of subsequent reports. Data regarding demographics, NeoTx, operative outcomes, pathology, and survival data were abstracted from a prospective database. RESULTS NeoTx was initiated in 69 patients; median age was 65 years (interquartile range [IQR]: 11) and median carbohydrate antigen 19-9 at diagnosis was 96.5 (IQR 210). NeoTx consisted of chemotherapy alone (n = 10, 14%), chemotherapy and radiation (chemoradiation, n = 53, 77%), or both (n = 6, 9%). Median carbohydrate antigen 19-9 after NeoTx was 39 (IQR 104) corresponding to a median decrease of 60%. Operative resection was completed in 60 (87%) of the 69 patients. At restaging after NeoTx, 5 (7%) of 69 patients were not considered candidates for surgery because of the development of metastatic disease (n = 4) or an inadequate performance status (n = 1). At the time of surgery, 4 (6%) of 64 patients had metastatic disease found at laparoscopy. Of the 60 patients who underwent surgical resection, a complete pathologic response was observed in 2 (3%) patients; 20 (33%) had positive lymph nodes, and the median number of positive lymph nodes was 2 (IQR 3). R0 resections were achieved in 58 (97%) of the 60 patients. Additional postoperative adjuvant therapy was administered to 37 (62%) of the 60 patients. Median survival of all 69 patients was 31.5 months; 44.9 months for the 60 patients who completed all NeoTx and resection compared with 8.1 months for the 9 patients who were not resected (log rank P < .001). CONCLUSION NeoTx for resectable pancreatic cancer was associated with a median overall survival of 32 months; something not reported for patients treated with surgery first if based on intent-to-treat analysis. Treatment sequencing may provide an oncologic benefit beyond that of the selection bias afforded surgery after a period of induction therapy.

Current staging systems for pancreatic cancer.

Accurate pretreatment staging of pancreatic cancer is a crucial initial step in the development of a stage-specific treatment plan, either on- or off-protocol for any patient with pancreatic cancer. Importantly, current American Joint Committee on Cancer staging utilizes the maximal information available; if surgery has been performed, then pathological information from the resected specimen will provide additional information for both T and N staging. If surgery has not been performed, then staging is based on information from available cross-sectional imaging studies. Although American Joint Committee on Cancer staging was modified in the sixth edition to reflect the survival difference between patients with operable/resectable versus nonoperable/unresectable disease, the precise definitions of resectability continue to evolve. It is essential for clinicians of different specialties to understand the definitions of resectability to facilitate optimal patient care and to allow for accurate interpretation of the literature. This review focuses on important aspects of the pretreatment assessment of patients with particular attention to definitions of resectability. Computed tomography has become the optimal imaging modality for pancreatic cancer staging, but other adjunct studies, including endoscopic ultrasound and laparoscopy, may provide additional staging information especially in circumstances where computed tomography technology is limited. In addition, the process of a standardized pathological review is summarized, with emphasis on assessment of the superior mesenteric artery margin and the definitions of R0, R1, and R2. Finally, the prognostic importance of key components of the pathological report such as lymph node status, lymph node ratio, and treatment effect is reviewed.

Arterial resection at the time of pancreatectomy for cancer

BACKGROUND Tumor-induced arterial abutment/encasement has been traditionally a contraindication to surgery in patients with localized pancreatic cancer (PC). One recent meta-analysis reported greater mortality rates in this setting. We report herein a series of planned arterial resections in carefully selected patients who responded favorably to combined modality therapy for localized PC. METHODS We reviewed all patients with PC and arterial encasement treated between May 2011 and September 2013; all patients received an extensive course of neoadjuvant therapy before surgery. RESULTS Of 15 patients taken to surgery, 2 had peritoneal disease at laparoscopy, and therefore, laparotomy was not performed. Pancreatectomy (pancreaticoduodenectomy, 3; distal, 8; central pancreatectomy, 1; total, 1) was performed in the remaining 13, 10 of whom required arterial resection. The most common operation was an Appleby procedure. Of 10 patients who underwent combined pancreatectomy and arterial resection, their median age was 62 years (range, 33-75), median operative time was 7.5 hours, and median blood loss was 725 mL. Complications occurred in 3 of 15 patients with no perioperative mortality. Median duration of hospital stay was 9 days (range, 5-19). An R0 resection was achieved in 11 (85%) of 13 patients. At a median follow-up of 21 months, 8 of these 13 resected patients (62%) are alive without disease. CONCLUSION Planned arterial resection at the time of pancreatectomy can be performed with acceptable morbidity and mortality; patient selection and induction therapy are likely critically important variables that seem to impact patient outcome. Those patients with stable or responding disease after induction therapy represent the subset of patients with potentially favorable tumor biology in whom extended resections may enhance survival duration.

Minimal aortic injury after blunt trauma: Selective nonoperative management is safe

BACKGROUND An increasing number of minimal aortic injuries (MAIs) are being identified with modern computed tomography (CT) imaging techniques. The optimal management and natural history of these injuries are unknown. We have adopted a policy of selective multidisciplinary nonoperative management of MAI. This study examines our experience with these patients from July 2004 to June 2009. METHODS Retrospective chart review of all blunt trauma patients who underwent chest CT angiography to evaluate for blunt aortic injury (BAI) was undertaken. All patients deemed to have a MAI were managed nonoperatively, and those with a severe aortic injury underwent repair. Data collected included age, mechanism of injury, Injury Severity Score, type and location of aortic injury, intensive care unit length of stay (LOS), overall LOS, ventilator days, disposition, and mortality. In addition, all BAIs were graded according to the Presley Trauma Center CT Grading System of Aortic Injury. RESULTS Forty-seven patients with BAI were identified. Thirty-two were classified as severe injuries, and 15 were considered MAI (32%). Nineteen underwent operative repair, 13 underwent endovascular stent graft repair, and 15 were managed nonoperatively. The average Injury Severity Score was 31 ± 10, and the average age was 44 ± 20 with no significant difference across treatment groups. There was no difference in overall or intensive care unit LOS. The nonoperative group had a shorter duration of ventilator days (1.1 vs. 4.28, p = 0.02). There were five deaths, none in the nonoperative group. None of these patients required subsequent intervention. All nonoperative patients had follow-up imaging at median of 4 days; on CT chest angiography, five injuries had resolved, eight had stable intimal flaps or pseudoaneurysm, and two had no detectable injury on subsequent aortogram. CONCLUSION Almost one-third of our BAI were safely managed nonoperatively. Patients with MAI should be considered for selective nonoperative management in a multidisciplinary approach with close radiographic follow-up. We recommend that patients with MAIs should be considered for selective nonoperative management.

Critical steps for pancreaticoduodenectomy in the setting of pancreatic adenocarcinoma

Pancreatic resection is one part of a multimodal, multidisciplinary approach to current treatment of pancreatic adenocarcinoma. The operation herein has been divided into six discreet steps followed by methods of reconstruction. Management of portal venous and arterial involvement is discussed in detail. The key steps to safe pancreatic surgery are emphasized as one part of present and future pancreatic cancer care. J. Surg. Oncol. 2013;107:33–38.

Optimal Management of the Splenic Vein at the Time of Venous Resection for Pancreatic Cancer: Importance of the Inferior Mesenteric Vein

BackgroundResection of the superior mesenteric vein (SMV)-portal vein (PV)-splenic vein (SV) confluence during pancreatectomy for pancreatic cancer requires management of the SV.DiscussionSimple SV ligation can result in sinistral portal hypertension if the inferior mesenteric vein (IMV) enters the confluence and is thereby resected, or if the IMV is insufficient to drain the SV. We describe herein three patients whose clinical course confirms the importance of the IMV decompressing the SV to avoid sinistral hypertension.

Neoadjuvant therapy for localized pancreatic cancer: guiding principles

The management of localized pancreatic cancer (PC) remains controversial. Historically, patients with localized disease have been treated with surgery followed by adjuvant therapy (surgery-first approach) under the assumption that surgical resection is necessary, even if not sufficient for cure. However, a surgery-first approach is associated with a median overall survival of only 22-24 months, suggesting that a large proportion of patients with localized PC have clinically occult metastatic disease. As a result, adjuvant therapy has been recommended for all patients with localized PC, but in actuality, it is often not received due to the high rates of perioperative complications associated with pancreatic resections. Recognizing that surgery may be necessary but usually not sufficient for cure, there has been growing interest in neoadjuvant treatment sequencing, which benefits patients with both localized and metastatic PC by ensuring the delivery of oncologic therapies which are commensurate with the stage of disease. For patients who have clinically occult metastatic disease, neoadjuvant therapy allows for the early delivery of systemic therapy and avoids the morbidity and mortality of a surgical resection which would provide no oncologic benefit. For patients with truly localized disease, neoadjuvant therapy ensures the delivery of all components of the multimodality treatment. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable (BLR) disease.

Staging chest computed tomography and positron emission tomography in patients with pancreatic adenocarcinoma: utility or futility?

OBJECTIVES This study was conducted to determine if routine staging chest computed tomography (CT) or positron emission tomography (PET) scanning alters the clinical management of patients with newly diagnosed pancreatic adenocarcinoma. METHODS All new pancreas cancers seen in medical oncology, radiation oncology and surgery from 1 June 2008 to 20 June 2010 were retrospectively reviewed. Patients with metastatic disease on chest CT or PET, that had been unsuspected on initial imaging, were identified. RESULTS Pancreatic adenocarcinoma was present in 247 consecutive patients. Abdominal CT demonstrated metastases in 108 (44%) and localized disease in 139 (56%) patients. Chest CT and PET were not performed in 15 (11%) of these 139 patients. In the remaining 124 patients, CT imaging suggested resectable disease in 46, borderline resectable disease in 52 and locally advanced disease in 26 patients. Chest CT demonstrated an unsuspected lymphoma in one patient with borderline resectable disease and PET identified extrapancreatic disease in two patients with locally advanced disease. Chest CT and PET added no information in 121 (98%) of the 124 patients. CONCLUSIONS The addition of chest CT and PET to high-quality abdominal CT is of little clinical utility; additional sites of metastasis are rarely found. As the quality of abdominal imaging declines, the yield from other imaging modalities will increase. Dedicated pancreas-specific abdominal CT remains the cornerstone of initial staging in suspected or biopsy-proven pancreatic cancer.

Evolution of the Management of Resectable Pancreatic Cancer

In pancreatic cancer, as with many other solid tumors, a commonly held surgical adage-a chance to cut is a chance to cure-has been promulgated throughout the years. Following such reasoning, surgical extirpation of a localized tumor would prevent tumor dissemination and metastatic tumor progression. However, decades of surgical experience have demonstrated that surgical resection alone provides a limited median survival benefit. Despite the optimization of surgical technique and perioperative management over the past three decades, little progress has been made to improve the limited survival of patients with localized pancreatic cancer who receive surgery. In this article, we discuss the rationale for a novel management strategy for patients with resectable pancreatic cancer, which may improve patient selection and the delivery of multimodality therapy.

Pancreas Transplant Imaging: How I Do It

Pancreas transplantation aims to restore physiologic normoglycemia in diabetic patients with glomerulopathy and avoid or delay the onset of diabetic retinopathy and arteriopathy. Simultaneous pancreas-kidney transplant is the most common approach, using a cadaveric pancreas donation in conjunction with either cadaveric or live donor renal transplant. Alternative techniques include pancreas after kidney transplant, in which the pancreas transplant is performed some years after renal transplant. Pancreas transplant alone is utilized rarely in diabetic patients with compensated renal function. Pancreas grafts have vascular and enteric connections that vary in their anatomic approach, and understanding of this is critical for imaging with ultrasonography, computed tomography, or magnetic resonance imaging. Imaging techniques are directed to display the pancreatic transplant arterial and venous vasculature, parenchyma, and intestinal drainage pathway. Critical vascular information includes venous thrombosis (partial or complete), arterial occlusion, or aneurysm. Parenchymal abnormalities are nonspecific and occur in pancreatitis, graft rejection, and subsequent graft ischemia. Peripancreatic fluid collections include hematoma/seroma, pseudocyst, and abscess. The latter two are related to pancreatitis, duct disruption, or leak from the duodenojejunostomy. An understanding of transplant anatomy and complications will lead to appropriate use of imaging techniques to diagnose or exclude important complications.