Comparison of imaging modalities for measuring the diameter of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are pre-malignant pancreatic cysts detected by imaging. Cyst size is one of many features evaluated on computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic ultrasonography (EUS) to help guide IPMN management. Our objective was to determine which imaging modality best predicts pathological cyst size. METHODS: We analyzed records for 57 IPMN cases surgically treated at Moffitt Cancer Center from 2008 to 2016 for whom pre-operative CT, MRI, and EUS IPMN cyst size and post-operative pathological cyst size values were available. Long axis cyst diameter measurements were compared to each other and corresponding pathological cyst measurements using within-subjects ANOVA, Bland-Altman analysis, and linear regression. Consensus measurements were also performed on CT and MRI images. RESULTS: Cyst size measured via CT and MRI overestimated pathological size by 0.33 cm and 0.27 cm, respectively, whereas EUS underestimated pathological size by 0.05 cm and had the narrowest 95% limit of agreement (LOA). Among pathologically-confirmed cysts <3 cm, MRI overestimated pathological size by 0.30 cm (P = 0.049) and had the widest LOA, followed by EUS and CT. Among cysts ≥3 cm, EUS underestimated pathological size by 0.35 cm (P = 0.059) and MRI and CT overestimated pathological size by 0.23 cm and 0.51 cm, respectively. CONCLUSIONS: In this small retrospective study, EUS cyst size measurements correlated best with pathologic specimens compared to CT and MRI, especially for cysts < 3 cm. Larger prospective studies are needed to determine which imaging modalities are best to risk-stratify IPMNs and guide surgical versus. Non-surgical management.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 2.2019.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018.

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.

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

BACKGROUND: Current 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). METHODS: We 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. RESULTS: We 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). CONCLUSIONS: EUS 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.

Endoscopic ultrasound-guided biliary access versus precut papillotomy in patients with failed biliary cannulation: a retrospective study.

Background and aims Precut papillotomy is widely used after failed biliary cannulation. Endoscopic ultrasound (EUS)-guided biliary access techniques are newer methods to facilitate access and therapy in failed cannulation. We evaluated the impact of EUS-guided biliary access on endoscopic retrograde cholangiopancreatography (ERCP) success and compared these techniques to precut papillotomy. Patients and methods We retrospectively compared two ERCP cohorts. One cohort consisted of biliary ERCPs (n = 1053) attempted in patients with native papillae and surgically unaltered anatomy in whom precut papillotomy and/or EUS-guided biliary access were routinely performed immediately after failed cannulation. This cohort was compared with a similar ERCP cohort (n = 1062) in which only precut papillotomy was available for failed cannulation. The following outcomes were compared: conventional cannulation success, rates of attempted advanced access techniques (precut or EUS), precut success, EUS-guided biliary access success, and ERCP failure rates. Results Although conventional cannulation success, rates of attempted advanced access technique (precut or EUS), and precut success were similar, the ERCP failure rate was lower when both EUS-guided biliary access and precut were available (1.0 % [95 % confidence interval (CI) 0.4 - 1.6]), compared with when only precut was possible for failed access (3.6 % [95 %CI 2.5 - 4.7]; P < 0.001). Success for EUS-guided biliary access (95.1 % [95 %CI 89.7 - 100]) was significantly higher than for precut (75.3 % [95 %CI 68.2 - 82.4]; P < 0.001), and mainly due to superiority in malignant obstruction (93.5 % vs. 64 %; P < 0.001). Conclusions EUS-guided biliary access decreases the rate of therapeutic biliary ERCP failure. Our results support the use of EUS-guided biliary access to optimize single-session ERCP success. In experienced hands, these techniques appear as effective, if not more so, than precut papillotomy.

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.

Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other cancers, including of the stomach and ovary. As of 2016, the panel recommends screening all patients with colorectal cancer for Lynch syndrome and provides recommendations for surveillance for early detection and prevention of Lynch syndrome-associated cancers.

Plastic biliary stent patency in patients with locally advanced pancreatic adenocarcinoma receiving downstaging chemotherapy.

BACKGROUND: Plastic stents in patients with biliary obstruction caused by pancreatic adenocarcinoma are typically exchanged at 3-month intervals. Plastic stents may have reduced durability in patients receiving chemotherapy. OBJECTIVE: To determine the duration of plastic biliary stent patency in patients undergoing chemotherapy for pancreatic adenocarcinoma. DESIGN: Retrospective, multicenter cohort study. SETTING: Three tertiary academic referral centers. PATIENTS: A total of 173 patients receiving downstaging chemotherapy for locally advanced or borderline resectable pancreatic adenocarcinoma from 1996 to 2013. INTERVENTIONS: Placement of 10F or larger plastic biliary stents. MAIN OUTCOME MEASUREMENTS: Primary outcome was overall duration of stent patency. Secondary outcomes included the incidence of premature stent exchange (because of cholangitis or jaundice) and hospitalization rates. RESULTS: A total of 233 plastic stents were placed, and the overall median duration of stent patency was 53 days (interquartile range [IQR] 25-99 days). Eighty-seven stents were removed at the time of surgical resection, and 63 stents were exchanged routinely per protocol. The remaining 83 stent exchanges were performed for worsening liver function test results, jaundice, or cholangitis, representing a 35.6% rate of premature stent exchange. The median stent patency duration in the premature stent exchange group was 49 days (IQR 25-91 days) with a 44.6% hospitalization rate. The overall rate of cholangitis was 15.0% of stent exchanges, occurring a median of 56 days after stent placement (IQR 26-89 days). LIMITATIONS: Retrospective study. CONCLUSIONS: Plastic biliary stents placed during chemotherapy/chemoradiation for pancreatic adenocarcinoma have a shorter-than-expected patency duration, and a substantial number of patients will require premature stent exchange. Consideration should be given to shortening the interval for plastic biliary stent exchange.

Colorectal Cancer Screening, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colorectal Cancer Screening provide recommendations for selecting individuals for colorectal cancer screening, and for evaluation and follow-up of colon polyps. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Colorectal Cancer Screening panel meeting. Major discussion topics this year were the state of evidence for CT colonography and stool DNA testing, bowel preparation procedures for colonoscopy, and guidelines for patients with a positive family history of colorectal cancer.

Comparative long-term outcomes of upfront resected pancreatic cancer after preoperative biliary drainage.

BACKGROUND: We evaluated whether preoperative biliary drainage was predictive of recurrence and survival among patients with resectable pancreatic cancer. METHODS: Patients with pancreatic cancer who were treated with upfront surgery between 2000 and 2012 were identified and stratified by preoperative percutaneous transhepatic cholangiogram-guided drainage (PTBD), placement of endoscopic stents (ERCP), or no biliary drainage (NBD). The primary endpoint was overall survival. RESULTS: We identified 193 patients with resectable pancreatic head cancer (33 PTBD; 96 ERCP; and 64 NBD). Key differences between the three groups were more patients who underwent >1 preoperative biliary procedures (p = 0.004) in the PTBD cohort. PTBD patients had a significant increase in hepatic recurrence rate compared with patients who did not undergo PTBD (44.8 vs. 23.3 %, p = 0.02). PTBD patients also had worse overall survival. Median and 5-year survival for PTBD, ERCP, and NBD patients were 17.5 months and 3 %, 22.4 months and 24 %, and 28.9 months and 32 %, respectively (p = 0.002). MVA revealed that percutaneous drainage was an independent predictor of worse overall survival [HR 1.76, 95 % CI (1.05-2.99), p = 0.03]. CONCLUSIONS: Patients with resectable pancreatic cancer who receive PTBD have more advanced disease, higher hepatic recurrence, and worse survival.

Minimally invasive mediastinal staging of non-small-cell lung cancer: emphasis on ultrasonography-guided fine-needle aspiration.

BACKGROUND: Mediastinal staging in patients with non-small-cell lung cancer (NSCLC) is crucial in dictating surgical vs nonsurgical treatment. Cervical mediastinoscopy is the "gold standard" in mediastinal staging but is invasive and limited in assessing the posterior subcarinal, lower mediastinal, and hilar lymph nodes. Less invasive approaches to NSCLC staging have become more widely available. METHODS: This article reviews several of these techniques, including noninvasive mediastinal staging of NSCLC, endobronchial ultrasound (EBUS) and fine-needle aspiration (FNA), endoscopic ultrasound (EUS) and FNA, and the combination of EBUS/EUS. RESULTS: Noninvasive mediastinal staging with computed tomography and positron-emission tomography scans has significant false-negative and false-positive rates and requires lymph node tissue confirmation. FNA techniques, with guidance by EBUS and EUS, have become more widely available. The combination of EBUS-FNA and EUS-FNA of mediastinal lymph nodes can be a viable alternative to surgical mediastinal staging. Current barriers to the dissemination of these techniques include initial cost of equipment, lack of access to rapid on-site cytology, and the time required to obtain sufficient skills to duplicate published results. CONCLUSIONS: Within the last decade, these approaches to NSCLC staging have become more widely available. Continued study into these noninvasive techniques is warranted.

Colorectal cancer screening.

Mortality from colorectal cancer can be reduced by early diagnosis and by cancer prevention through polypectomy. These NCCN Guidelines for Colorectal Cancer Screening describe various colorectal screening modalities and recommended screening schedules for patients at average or increased risk of developing colorectal cancer. In addition, the guidelines provide recommendations for the management of patients with high-risk colorectal cancer syndromes, including Lynch syndrome. Screening approaches for Lynch syndrome are also described.

The Role of Endoscopic Ultrasonography in the Diagnosis and Staging of Pancreatic Cancer.

Pancreatic cancer is the fourth leading cause of cancer-related death and the second gastrointestinal cancer-related death in the United States. Early detection and accurate diagnosis and staging of pancreatic cancer are paramount in guiding treatment plans, as surgical resection can provide the only potential cure for this disease. The overall prognosis of pancreatic cancer is poor even in patients with resectable disease. The 5-year survival after surgical resection is ~10% in node-positive disease compared to ~30% in node-negative disease. The advancement of imaging studies and the multidisciplinary approach involving radiologists, gastroenterologists, advanced endoscopists, medical, radiation, and surgical oncologists have a major impact on the management of pancreatic cancer. Endoscopic ultrasonography is essential in the diagnosis by obtaining tissue (FNA or FNB) and in the loco-regional staging of the disease. The advancement in EUS techniques has made this modality a critical adjunct in the management process of pancreatic cancer. In this review article, we provide an overall description of the role of endoscopic ultrasonography in the diagnosis and staging of pancreatic cancer.

An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advanced pancreatic cancer (OncoPaC-1): Technical details and study protocol.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed. Currently, there is no brachytherapy device approved for pancreatic cancer treatment. Hereby, we present the protocol of a prospective, multicenter, interventional, open-label, single-arm pilot study (OncoPac-1, Clinicaltrial.gov-NCT03076216) aiming to determine the safety and efficacy of Phosphorus-32 when implanted directly into pancreatic tumors using EUS guidance, for patients with unresectable LAPC undergoing chemotherapy (gemcitabine ± nab-paclitaxel).

Interdisciplinary management of an intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is less common than classic invasive ductal adenocarcinoma of the pancreas but is being diagnosed with greater frequency since its clinicopathologic features are now clearly defined. Often multifocal in its existence along the pancreatic duct, IPMN is associated with a significant risk for recurrence and warrants vigilant surveillance, even after a margin-negative resection. METHODS: The authors present a case highlighting important features in the diagnosis, workup, and management of IPMN. They also review existing literature highlighting epidemiology, findings of molecular studies, and current treatment recommendations. RESULTS: Physicians and patients must carefully weigh the risks and benefits associated with treatment options. Limited resection in a patient with a high likelihood of multifocal disease preserves pancreatic parenchyma and reduces the risk of developing pancreatic endocrine and exocrine insufficiency. Though the risk of developing invasive cancer in the remnant is small, the prognosis is worse if it does develop. Conversely, total pancreatectomy eliminates the risk of future malignancy but involves life-long insulin and exogenous pancreatic enzyme dependence and significant associated morbidity. CONCLUSIONS: Decision making for effective treatment of IPMN is complex and requires attention to detail by an interdisciplinary team with experience in the diagnosis and management of these tumors. Treatment must be individualized based on patient life expectancy in terms of remaining years and overall quality. Molecular profiling of these lesions may allow for more precise tailoring of treatment in the future.

Endoscopic Palliation of Pancreatic Cancer.

OPINION STATEMENT: Pancreas cancer is a fourth-leading cause of cancer death in the USA and its incidence is rising as the population is aging. The majority of patients present at an advanced stage due to the silent nature of the disease and treatment have focused more on palliation than curative intent. Gastroenterologists have become integral in the multidisciplinary care of these patients with a focus on providing endoscopic palliation of pancreas cancer. The three most common areas that gastroenterologists palliate endoscopically are biliary obstruction, cancer-related pain, and gastric outlet obstruction. To palliate biliary obstruction, the procedure of choice is to perform endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement. We tend to place covered self-expandable metal stents (SEMS) due to their longer patency and removability unless the patient has resectable disease. Pancreas cancer pain is a result of tumor infiltration of the celiac plexus and can be severe and poorly responsive to narcotics. To improve pain control, neurolysis of the celiac plexus has been performed for decades. Since 1996, neurolysis of the celiac area has been performed endoscopically by Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis. This has proven to be as safe and effective as traditional non-endoscopic methods and has allowed the patients to decrease their narcotic use and improve their pain control. This should be done early on in the course of the disease to have maximal effect. Gastric outlet obstruction (GOO) occurs in approximately 15-20% of patients with pancreas cancer. Endoscopic palliation of GOO can be performed by placing uncovered metal enteral stents across the obstruction. This procedure has proven to be very effective in patients who have a short life expectancy (less than two to 6 months) while surgical bypass should be considered for patients with longer life expectancies because it offers better long-term symptom relief. This chapter will review the current literature, latest advancements, and optimal techniques for endoscopic palliation of pancreatic cancer.

Endoscopic ultrasound-guided fiducial marker placement for image-guided radiation therapy without fluoroscopy: safety and technical feasibility.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS)-guided fiducial marker placement for image-guided radiation treatment (IGRT) is becoming more widespread. Most case series report the procedure performed using fluoroscopy for spatial geometry although the benefits of this are unclear. The aim of our study is to report the technical feasibility, safety, and migration rate of fiducial marker placement in a large cohort of patients with gastrointestinal malignancies who underwent EUS-guided fiducial marker placement for IGRT without fluoroscopy. PATIENTS AND METHODS: A retrospective chart review was performed on all patients referred for EUS-guided fiducial marker placement from 08/1/07 to 7/31/14 at Moffitt Cancer Center. RESULTS: During the study period, 514 patients underwent placement of 1093 gold fiducial markers under EUS-guidance. Two hundred and forty patients with esophageal/gastro-esophageal junction cancer had 405 fiducials placed. In 188 patients with pancreatic ancer, 510 fiducials were placed. In 54 patients with rectal cancer, 103 fiducials were placed and 32 patients had 75 fiducials placed into other gastrointestinal tract lesions. Minor bleeding, which resolved spontaneously, occurred in two patients. Technical difficulty in placing fiducials was noted in 18 patients. Intraprocedural fiducial migration was noted in two patients and only 2/1093 fiducials (.002%) in two esophageal patients migrated as noted on simulation computed tomography scan. CONCLUSIONS: EUS-guided fiducial marker placement without fluoroscopy is technically feasible and safe. There were minimal intraprocedure/post-procedure complications. Imaging at the time of simulation also revealed the migration rate to be extremely low. These results may allow for more widespread adoption of EUS-guided fiducial marker placement.

A randomized controlled cross-over trial and cost analysis comparing endoscopic ultrasound fine needle aspiration and fine needle biopsy.

BACKGROUND AND STUDY AIMS: Techniques to optimize endoscopic ultrasound-guided tissue acquisition (EUS-TA) in a variety of lesion types have not yet been established. The primary aim of this study was to compare the diagnostic yield (DY) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for pancreatic and non-pancreatic masses. PATIENTS AND METHODS: Consecutive patients referred for EUS-TA underwent randomization to EUS-FNA or EUS-FNB at four tertiary-care medical centers. A maximum of three passes were allowed for the initial method of EUS-TA and patients were crossed over to the other arm based on on-site specimen adequacy. RESULTS: A total of 140 patients were enrolled. The overall DY was significantly higher with specimens obtained by EUS-FNB compared to EUS-FNA (90.0 % vs. 67.1 %, P = 0.002). While there was no difference in the DY between the two groups for pancreatic masses (FNB: 91.7 % vs. FNA: 78.4 %, P = 0.19), the DY of EUS-FNB was higher than the EUS-FNA for non-pancreatic lesions (88.2 % vs. 54.5 %, P = 0.006). Specimen adequacy was higher for EUS-FNB compared to EUS-FNA for all lesions (P = 0.006). There was a significant rescue effect of crossover from failed FNA to FNB in 27 out of 28 cases (96.5 %, P = 0.0003). Decision analysis showed that the strategy of EUS-FNB was cost saving compared to EUS-FNA over a wide range of cost and outcome probabilities. CONCLUSIONS: RESULTS of this RCT and decision analysis demonstrate superior DY and specimen adequacy for solid mass lesions sampled by EUS-FNB.

Endoscopic ultrasound-guided fine-needle injection.

With the development of linear array echoendoscopes and the ability to perform endoscopic ultrasound (EUS)-guided fine-needle aspiration, the delivery of therapeutic agents with fine-needle injection (FNI) emerged. EUS-guided FNI is an attractive delivery system because of its minimal invasiveness and low complication rate. This approach is effective in performing celiac plexus neurolysis for pain relief in patients with pancreatic cancer. The most exciting area of interest involves the delivery of antitumor agents in patients with locally advanced cancer, such as cancer of the pancreas or esophagus. The involvement of EUS-guided FNI in tumor therapy adds a host of potential new applications that continue to swing the pendulum of EUS from a diagnostic to a therapeutic modality.

A lupus-like syndrome associated with infliximab therapy.

Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.