Siva P. Raman

Phase 2 multi‐institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma

This phase 2 multi‐institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single‐fraction SBRT in patients with locally advanced pancreatic cancer (LAPC).

A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

BACKGROUND & AIMS The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. METHODS We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers. RESULTS We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%. CONCLUSIONS We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.

A Systematic Review of Solid-Pseudopapillary Neoplasms: Are these rare lesions?

Objective The aim of the study was to determine if there had been any change in the number of solid-pseudopapillary neoplasm (SPN) cases detected and their evaluation or management over time. Methods A systematic review of SPN was performed of all articles published in English in PubMed and Scopus. Results A total of 2744 patients with SPN were identified in 484 studies published between 1961 and 2012; 87.8% of the cases were reported between 2000 and 2012. A total of 2408 (87.8%) were females, and the mean age was 28.5 (SD, 13.7) years. The most common symptom was abdominal pain in 63.6% of the cases and incidentally detected in 38.1% of the cases. There were 2285 patients who underwent pancreatic resection. The mean tumor size was 8.6 (SD, 4.3) cm. Follow-up was reported for 1952 (90.5%) patients, with a mean follow-up of 36.1 (SD, 32.8) months. Disease-free survival was documented in 1866 (95.6%) patients with recurrence in 86 (4.4%) patients; the median time to recurrence was 50.5 months. Conclusions The number of SPNs reported in the literature has seen a 7-fold increase in the number of cases reported since 2000 compared with before. Solid-pseudopapillary neoplasms continue to be primarily found in young women and present with nonspecific symptoms. Surgery remains the mainstay of treatment with an excellent long-term prognosis.

Pancreatic Imaging Mimics: Part 2, Pancreatic Neuroendocrine Tumors and Their Mimics

OBJECTIVE This pictorial essay reviews the imaging appearance of pancreatic neuroendocrine tumors, as well as a number of mimics on CT. CONCLUSION Pancreatic neuroendocrine tumors have a distinct appearance, typically characterized by a well-defined hypervascular mass best visualized on arterial phase images. However, a number of other lesions can mimic the CT appearance of pancreatic neuroendocrine tumors, including pancreatic metastases, acinar cell carcinoma, pancreatoblastoma, solitary fibrous tumor, pancreatic hamartoma, serous adenoma, intrapancreatic splenules, exophytic gastrointestinal stromal tumors, and peripancreatic paragangliomas.

Multimodality imaging of pancreatic cancer-computed tomography, magnetic resonance imaging, and positron emission tomography.

Abstract Pancreatic adenocarcinoma continues to have a dismal prognosis, with curative surgery (resection with negative margins) possible in only a small percentage of patients. Not only does radiological imaging play a major role in diagnosing the primary lesion at presentation, but it is also crucial for staging of locoregional disease and distant metastases, both of which are critical for selecting appropriate candidates for surgery. Over the last 2 decades, computed tomography has become the dominant imaging modality for both the diagnosis and staging of pancreatic cancer, with advances in multidetector computed tomography technology improving the ability to identify small tumors and demonstrate subtle degrees of vascular involvement by tumor. However, magnetic resonance imaging and positron emission tomography are now playing an increasing role in pancreatic cancer imaging. These 3 imaging modalities each have specific strengths and benefits and should be used in a complementary fashion.

Baseline Metabolic Tumor Volume and Total Lesion Glycolysis Are Associated With Survival Outcomes in Patients With Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy

PURPOSE Although previous studies have demonstrated the prognostic value of positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer has yet to be well established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS Thirty-two patients with LAPC in a prospective clinical trial received up to 3 doses of gemcitabine, followed by 33 Gy in 5 fractions of 6.6 Gy, using SBRT. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using custom-designed software. Disease was measured at a threshold based on the liver SUV, using the equation Livermean + [2 × Liversd]. Median values of PET parameters were used as cutoffs when assessing their prognostic potential through Cox regression analyses. RESULTS Of the 32 patients, the majority were male (n=19, 59%), 65 years or older (n=21, 66%), and had tumors located in the pancreatic head (n=27, 84%). Twenty-seven patients (84%) received induction gemcitabine prior to SBRT. Median overall survival for the entire cohort was 18.8 months (95% confidence interval [CI], 15.7-22.0). An MTV of 26.8 cm(3) or greater (hazard ratio [HR] 4.46, 95% CI 1.64-5.88, P<.003) and TLG of 70.9 or greater (HR 3.08, 95% CI 1.18-8.02, P<.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19-22.21, P=.029) and TLG (HR 3.34, 95% CI 1.07-10.48, P=.038) remained independently associated with overall survival in separate multivariate analyses. CONCLUSIONS Pre-SBRT MTV and TLG are potential predictive factors for overall survival in patients with LAPC and may assist in tailoring therapy.

Institutional experience with solid pseudopapillary neoplasms: focus on computed tomography, magnetic resonance imaging, conventional ultrasound, endoscopic ultrasound, and predictors of aggressive histology.

Objective Solid pseudopapillary neoplasms (SPNs) are low-grade malignancies with an excellent prognosis, albeit with the potential for metastatic disease. This study details our institution’s experience with the diagnosis and treatment of SPN, including clinical presentation, multimodality imaging findings, and potential predictors of aggressive tumor behavior. Materials and Methods The institutional pathology database was searched through for all cases of SPN since 1988, yielding 51 patients. The electronic medical record was searched for clinical and demographic information regarding these patients, including age, sex, presenting symptoms, type of surgery, postoperative length of stay, tumor markers, and postsurgical follow-up. All available imaging data were reviewed, including those of 30 patients who underwent multidetector computed tomography, those of 9 patients who underwent magnetic resonance imaging (MRI), those of 3 patients who underwent conventional ultrasound, and those of 11 patients who underwent endoscopic ultrasound. Results A total of 84% of patients were females, with a mean age of only 33 years. Prognosis was excellent, with a mean follow-up of 3 years without recurrence. Only 1 of the 51 patients developed metastatic disease to the liver 8 years after the surgery. On computed tomography, lesions tended to be large (5.3 cm), well circumscribed (29/30), round/oval (20/30), and encapsulated (23/30). The lesions often demonstrated calcification (14/30) and typically resulted in no biliary or pancreatic ductal dilatation. The lesions ranged from completely cystic to completely solid. On MRI, the lesions often demonstrated a T2 hypointense or enhancing capsule (6/9) and demonstrated internal blood products (5/9). The lesions tended to be devoid of vascularity on conventional ultrasound. Ten patients were found to have “aggressive” histology at presentation (T3 tumor, nodal involvement, perineural invasion, or vascular invasion). No demographic, clinical, or multidetector computed tomographic imaging features were found to correlate with aggressive histology. Conclusions Certain imaging features (eg, well-circumscribed mass with calcification, peripheral capsule, internal blood products, and lack of biliary/pancreatic ductal obstruction) on computed tomography and MRI are highly suggestive of the diagnosis of SPN, particularly when visualized in young female patients. However, it is not possible to predict aggressive histology on the basis of imaging findings, clinical presentation, or patient demographic features.

CT After Pancreaticoduodenectomy: Spectrum of Normal Findings and Complications

OBJECTIVE The purpose of this article is to discuss the normal findings and complications after pancreaticoduodenectomy. The Whipple procedure is associated with a set of common complications, including pancreatic fistula, postsurgical hemorrhage, postoperative pancreatitis, portomesenteric venous thrombosis, hepatic infarction, delayed gastric emptying, and anastomotic strictures. CONCLUSION Appropriate diagnosis of these complications is contingent on an understanding of the surgical anatomy, normal postoperative imaging appearance in both the immediate postoperative and chronic settings, and typical CT appearance of each of these complications.

Mapping Patterns of Local Recurrence After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma: A New Approach to Adjuvant Radiation Field Design

PURPOSE To generate a map of local recurrences after pancreaticoduodenectomy (PD) for patients with resectable pancreatic ductal adenocarcinoma (PDA) and to model an adjuvant radiation therapy planning treatment volume (PTV) that encompasses a majority of local recurrences. METHODS AND MATERIALS Consecutive patients with resectable PDA undergoing PD and 1 or more computed tomography (CT) scans more than 60 days after PD at our institution were reviewed. Patients were divided into 3 groups: no adjuvant treatment (NA), chemotherapy alone (CTA), or chemoradiation (CRT). Cross-sectional scans were centrally reviewed, and local recurrences were plotted to scale with respect to the celiac axis (CA), superior mesenteric artery (SMA), and renal veins on 1 CT scan of a template post-PD patient. An adjuvant clinical treatment volume comprising 90% of local failures based on standard expansions of the CA and SMA was created and simulated on 3 post-PD CT scans to assess the feasibility of this planning approach. RESULTS Of the 202 patients in the study, 40 (20%), 34 (17%), and 128 (63%) received NA, CTA, and CRT adjuvant therapy, respectively. The rate of margin-positive resections was greater in CRT patients than in CTA patients (28% vs 9%, P=.023). Local recurrence occurred in 90 of the 202 patients overall (45%) and in 19 (48%), 22 (65%), and 49 (38%) in the NA, CTA, and CRT groups, respectively. Ninety percent of recurrences were within a 3.0-cm right-lateral, 2.0-cm left-lateral, 1.5-cm anterior, 1.0-cm posterior, 1.0-cm superior, and 2.0-cm inferior expansion of the combined CA and SMA contours. Three simulated radiation treatment plans using these expansions with adjustments to avoid nearby structures were created to demonstrate the use of this treatment volume. CONCLUSIONS Modified PTVs targeting high-risk areas may improve local control while minimizing toxicities, allowing dose escalation with intensity-modulated or stereotactic body radiation therapy.

Superior mesenteric artery syndrome: spectrum of CT findings with multiplanar reconstructions and 3-D imaging

ObjectiveThis article reviews the causes, clinical presentation, and CT diagnosis of superior mesenteric artery (SMA) syndrome.ConclusionIn conjunction with an appropriate clinical history, several CT findings can suggest the diagnosis of SMA syndrome. These findings include narrowing of the aortomesenteric angle and distance, distension of the stomach and duodenum, and dilatation of the left renal vein with left-sided venous collaterals.