Pancreatic cysts: can surveillance interval for small low-risk lesions be lengthened?

BACKGROUND: Surveillance of pancreatic cysts are necessary due to risk of malignant transformation. However, reported progression rates to advanced neoplasia are variable and the high frequency of surveillance scans may pose a considerable burden on healthcare resources. PURPOSE: To validate the effectiveness of the Fukuoka Guidelines surveillance regime and determine if a longer surveillance interval can be established. MATERIAL AND METHODS: All magnetic resonance imaging (MRI) studies of the pancreas performed at our institution between January 2014 and December 2016 with at least one pancreatic cystic lesion and follow-up MRI or computed tomography (CT) over at least two years were reviewed for size, worrisome feature (WF), and high-risk stigmata (HRS) at diagnosis and follow-up imaging (up to year 6). Reference standards for advanced neoplasia were based on endoscopic ultrasound, fine needle aspiration cytology, or the presence of ≥2 WF or ≥1 HRS on imaging. Comparison of MRI features of progression and outcomes of diagnostic endpoints between lesions <20 mm and ≥20 mm was performed. RESULTS: A total of 270 patients were included (201 cysts <20 mm, 69 cysts ≥20 mm). Compared with cysts <20 mm, cysts ≥20 mm were more likely to be associated with WF or HRS (40.6% vs. 12.4%; P ≤0.00001), demonstrate increase in size of ≥5 mm in two years (20.3% vs. 10.9%; P = 0.049), and develop advanced neoplasia (24.6% vs. 0.5%; P <0.00001). CONCLUSION: Pancreatic cysts <20 mm have a low risk of developing WF and HRS and surveillance interval may be lengthened.

Defining the endoscopic ultrasound features of chronic pancreatitis in Asians: a multicenter validation study.

BACKGROUND: Although endoscopic ultrasound (EUS) features and criteria have been described in chronic pancreatitis, challenges remain with interoperator variability and ease of adoption. The aim of this study was to define and validate the EUS features of chronic pancreatitis in a multicenter prospective study in Asia. METHOD: The study was divided into two parts: the first part was conducted to derive the EUS features of chronic pancreatitis with adequate interoperator agreement; the second was to prospectively evaluate these features in a multicenter cross-sectional study and determine the optimal combination of features for the diagnosis of chronic pancreatitis. Prospectively enrolled cases had standard internationally validated radiologic or histologic features of chronic pancreatitis, and controls were patients without chronic pancreatitis who underwent EUS examination. RESULTS: The top six EUS features that had good interobserver agreement (mean kappa 0.73, range 0.60 - 0.90) were selected to be further evaluated in part II of the study. These included: hyperechoic foci with shadowing, lobularity with honeycombing, cysts, dilated main pancreatic duct, dilated side branches, and calculi in the main pancreatic duct. A total of 284 subjects (132 cases, 152 controls) were enrolled from 12 centers in Asia. All six features had high accuracy ranging from 63.3 % to 89.1 %. Two or more of these six EUS features accurately defined chronic pancreatitis (sensitivity 94.7 %, specificity 98.0 %), with an area under the receiver operating curve of 0.986. CONCLUSION: This multicenter Asian study characterized and defined the EUS features of chronic pancreatitis. This provides a useful tool in clinical practice and further research in pancreatic cancer surveillance.

High-stakes examinations during the COVID-19 pandemic: to proceed or not to proceed, that is the question.

The COVID-19 pandemic has disrupted education-related activities, including the conduct of examinations. We review the literature regarding high-stakes examinations during the pandemic, discuss the decision-making process of whether to proceed with a high-stakes examination and share published experiences in conducting high-stakes examinations during the pandemic. We illustrate our own recent experiences of decision-making and conduct of our high-stakes gastroenterology licencing examinations during the height of the COVID-19 pandemic. It is possible to conduct high-stakes examinations virtually during pandemic situations with fidelity and adherence to the established format and standards.

Deep convolutional neural networks for automatic segmentation of thoracic organs-at-risk in radiation oncology - use of non-domain transfer learning.

PURPOSE: Segmentation of organs-at-risk (OARs) is an essential component of the radiation oncology workflow. Commonly segmented thoracic OARs include the heart, esophagus, spinal cord, and lungs. This study evaluated a convolutional neural network (CNN) for automatic segmentation of these OARs. METHODS: The dataset was created retrospectively from consecutive radiotherapy plans containing all five OARs of interest, including 22,411 CT slices from 168 patients. Patients were divided into training, validation, and test datasets according to a 66%/17%/17% split. We trained a modified U-Net, applying transfer learning from a VGG16 image classification model trained on ImageNet. The Dice coefficient and 95% Hausdorff distance on the test set for each organ was compared to a commercial atlas-based segmentation model using the Wilcoxon signed-rank test. RESULTS: On the test dataset, the median Dice coefficients for the CNN model vs. the multi-atlas model were 71% vs. 67% for the spinal cord, 96% vs. 94% for the right lung, 96%vs. 94% for the left lung, 91% vs. 85% for the heart, and 63% vs. 37% for the esophagus. The median 95% Hausdorff distances were 9.5  mm vs. 25.3 mm, 5.1  mm vs. 8.1 mm, 4.0  mm vs. 8.0 mm, 9.8  mm vs. 15.8 mm, and 9.2 mm vs. 20.0 mm for the respective organs. The results all favored the CNN model (P < 0.05). CONCLUSIONS: A 2D CNN can achieve superior results to commercial atlas-based software for OAR segmentation utilizing non-domain transfer learning, which has potential utility for quality assurance and expediting patient care.

Deep learning for contour quality assurance for RTOG 0933: In-silico evaluation.

PURPOSE: To validate a CT-based deep learning (DL) hippocampal segmentation model trained on a single-institutional dataset and explore its utility for multi-institutional contour quality assurance (QA). METHODS: A DL model was trained to contour hippocampi from a dataset generated by an institutional observer (IO) contouring on brain MRIs from a single-institution cohort. The model was then evaluated on the RTOG 0933 dataset by comparing the treating physician (TP) contours to blinded IO and DL contours using Dice and Haussdorf distance (HD) agreement metrics as well as evaluating differences in dose to hippocampi when TP vs. IO vs. DL contours are used for planning. The specificity and sensitivity of the DL model to capture planning discrepancies was quantified using criteria of HD > 7 mm and Dmax hippocampi > 17 Gy. RESULTS: The DL model showed greater agreement with IO contours compared to TP contours (DL:IO L/R Dice 74%/73%, HD 4.86/4.74; DL:TP L/R Dice 62%/65%, HD 7.23/6.94, all p < 0.001). Thirty percent of contours and 53 % of dose plans failed QA. The DL model achieved an AUC L/R 0.80/0.79 on the contour QA task via Haussdorff comparison and AUC of 0.91 via Dmax comparison. The false negative rate was 17.2%/20.5% (contours) and 5.8% (dose). False negative cases tended to demonstrate a higher DL:IO Dice agreement (L/R p = 0.42/0.03) and better qualitative visual agreement compared with true positive cases. CONCLUSION: Our study demonstrates the feasibility of using a single-institutional DL model to perform contour QA on a multi-institutional trial for the task of hippocampal segmentation.

Current status on the diagnosis and evaluation of pancreatic tumor in Asia with particular emphasis on the role of endoscopic ultrasound.

In Asia, the incidence of pancreatic cancer in some countries has been increasing. Owing to most cases being diagnosed late, prognosis for pancreatic cancer remains dismal. It is clear that the future for pancreatic cancer lies in early detection. While the possible presence of pancreatic masses is often first raised by non-invasive abdominal imaging, such as computerized tomography and magnetic resonance imaging, smaller lesions and locoregional lymph node metastases are often not detectable by these means. Endoscopic ultrasonography (EUS) offers a higher sensitivity (93-100%) for detection of small potentially curable pancreatic masses than other existing imaging modalities. It is also recommended for the evaluation of portal vein confluence, portal vein, celiac axis, and superior mesentric artery origin, and exclusion of resectability. Due to the closer proximity of EUS to the target structure, and lower rate of needle tract seeding, EUS-guided fine-needle aspiration of pancreatic mass is considered the most suitable tissue acquisition technique. Lastly, EUS also enables the performance of endoscopic interventions. Its performance can be further enhanced with newer techniques, including contrast-enhanced ultrasound and elastrography. It is anticipated that in the near future, molecular technologies may make it possible to detect microscopic amounts of cancer in tissue or blood, predict relapse and survival after therapy, as well as determine optimal therapy.

Factors determining diagnostic yield of endoscopic ultrasound guided fine-needle aspiration for pancreatic cystic lesions: a multicentre Asian study.

BACKGROUND AND AIM: The purpose of this study was to determine (1) the diagnostic yield for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in patients with pancreatic cystic lesions, (2) additional value of EUS-FNA over EUS alone in the diagnosis of pancreatic cysts, and (3) diagnostic sensitivity and specificity of EUS and EUS-FNA in the subset of patients where histopathology of surgical specimens were available. METHODS: All patients who underwent EUS examination for the evaluation of pancreatic cystic lesions in six Asian centres were included in the study. RESULTS: Of 298 patients with pancreatic cysts who underwent EUS, 132 (44.3 %) underwent FNA. In the entire cohort, pseudocysts and intraductal papillary mucinous neoplasm (IPMN) were the predominant cystic lesions. The cytologic yield of EUS-FNA was 47 %. On univariate analysis, factors associated with higher cytologic yield included vascular involvement on EUS, presence of solid cystic component, and increased number of needle passes during EUS-FNA. On multivariate analysis, presence of solid cystic components and increased number of needle passes during EUS-FNA were associated with higher diagnostic yield of EUS-FNA. For pancreatic cysts with a solid component, the diagnostic yield of EUS-FNA increased significantly from 44 % with one pass to 78 % with more than one pass (p = 0.016). In the absence of a solid component, the diagnostic yield was 29 % with one pass and was not significantly different from the diagnostic yield of 50 % with more than one pass, p = 0.081. CONCLUSION: The cytologic yield of EUS-FNA was 47 %. When a solid component was present in the cyst, doing more than one pass during EUS-FNA increased its diagnostic yield.

Aortoenteric fistula treated with endovascular aortic stent-graft and bilateral chimney stent-grafts to renal arteries.

We report a patient with secondary aortoenteric fistula (AEF) presenting with a rectal bleeding. The patient had multiple comorbidities, precluding major open vascular surgery. We opted to perform a two-stage procedure, where an endovascular stent-graft was first deployed to exclude the AEF from the systemic circulation. As the AEF was at the proximal anastomosis of the previous Dacron graft and close to the renal artery ostia, chimney stent-grafts were placed in both renal arteries to maintain their patency. The second stage of the procedure involved a laparotomy to repair the defect in the duodenum to prevent further contamination from bowel contents.

Intrapancreatic accessory spleen with an epidermoid cyst: a malignant mimicry.

With the liberal use of CT scan for clinical diagnosis, clinicians are faced with an increasing number of pancreatic incidentalomas. Compared with other incidentalomas, pancreatic incidentalomas have higher chances of future malignant transformation. There are many differential diagnoses, and epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) is extremely rare, with only a handful of reports. Preoperative diagnosis is often complicated, and the final diagnosis is usually only made after surgical resection.We report a 34-year-old man who had an incidentally noted 2.8 cm pancreatic tail cystic lesion on a CT scan done for urinary symptoms. The lesion had a solid nodular component that was worrisome for malignancy, and the patient underwent further evaluation with an MRI scan and endoscopic ultrasound of the pancreas. The differential diagnoses of cystic degeneration of neuroendocrine tumour, branch-duct intraductal papillary mucinous neoplasm with worrisome features or ectopic intrapancreatic spleen were made. A multidisciplinary tumour board recommended surgical resection given risk features of malignancy. The patient subsequently underwent a laparoscopic distal pancreatectomy with splenectomy, and histology confirmed the diagnosis of ECIPAS.Imaging characteristics of ECIPAS are non-specific, and most patients have a diagnosis made only after surgery. Therefore, more evidence is warranted for accurate preoperative imaging diagnosis to avoid unnecessary pancreatic surgery, which is not without its risks.

Clinical guidance on endoscopic management of colonic polyps in Singapore.

Colonoscopy with endoscopic resection of detected colonic adenomas interrupts the adenoma-carcinoma sequence and reduces the incidence of colorectal cancer and cancer-related mortality. In the past decade, there have been significant developments in instruments and techniques for endoscopic polypectomy. Guidelines have been formulated by various professional bodies in Europe, Japan and the United States, but some of the recommendations differ between the various bodies. An expert professional workgroup under the auspices of the Academy of Medicine, Singapore, was set up to provide guidance on the endoscopic management of colonic polyps in Singapore. A total of 23 recommendations addressed the following issues: accurate description and diagnostic evaluation of detected polyps; techniques to reduce the risk of post-polypectomy bleeding and delayed perforation; the role of specific endoscopic resection techniques; the histopathological criteria for defining endoscopic cure; and the role of surveillance colonoscopy following curative resection.

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer: A NCDB analysis.

OBJECTIVES: Occult primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Very limited retrospective data are available in the literature. Its prognosis and response to systemic chemotherapy have not been investigated with large scale data. MATERIALS AND METHODS: Using National Cancer Database (NCDB), cases that had undergone radiation therapy without surgery for N2-3M0 NSCLC were selected. Demographics and survival data were compared between T0 and T1-4 groups. Survival analyses were conducted with Kaplan-Meier and log-rank tests. Cox proportional hazard models were used for univariate and multivariate analyses. RESULTS: Between 2004 and 2016, 84,263 and 458 cases met criteria for unresectable stage III NSCLC with T1-4 and T0 stage, respectively. T0 status was associated with younger age, recent diagnosis (year 2010-2016), adenocarcinoma histology, N3 stage, and use of chemotherapy. Survival analysis demonstrated that those with T0 status had prolonged overall survival as compared to T1-4 counterparts in both overall and chemotherapy groups (p < 0.0001 for each). Five-year overall survival rates for T0 and T1-4 groups were 30.5% and 12.7% in all groups, and 33.6% and 14.6% in chemotherapy groups, respectively. Propensity score matching also demonstrated a statistically significant difference in overall survival (p < 0.0001). These findings are confirmed by independent analysis using Surveillance, Epidemiology, and End Results Program (SEER). CONCLUSION: This large hospital-based study demonstrates the favorable prognosis for T0 status in the setting of unresectable stage III NSCLC. Researchers may consider it as distinct stage (e.g., stage IIC) for future studies.

The Cost-Effectiveness and Value Proposition of Brachytherapy.

Brachytherapy is an effective treatment modality for a wide range of malignancies. However, brachytherapy utilization for both prostate and gynecologic malignancies has significantly declined over the last 20 years in favor of external beam radiation techniques. The cause of this decline is multifactorial, with logistical challenges, lower reimbursement, and inadequate training contributing to the preference of many radiation oncologists to more frequently recommend external beam radiation therapy. While the authors recognize the application of brachytherapy to a wider range of disease presentations among which include breast, skin, head and neck, and connective tissue cancers, in this review, we will review the analyses supporting brachytherapy as a cost-effective component of the management in patients with prostate, cervix, and endometrial cancer.

Outcomes After Salvage Radiation Therapy for Recurrent Endometrial Cancer in Patients With No Prior Adjuvant Therapy: An Institutional Review.

PURPOSE: After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. METHODS AND MATERIALS: Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. RESULTS: The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5-81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. CONCLUSIONS: In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Chapter of Gastroenterologists professional guidance on risk mitigation for gastrointestinal endoscopy during COVID-19 pandemic in Singapore.

In this paper, we aimed to provide professional guidance to practising gastrointestinal (GI) endoscopists for the safe conduct of GI endoscopy procedures during the current coronavirus disease 2019 (COVID-19) pandemic and future outbreaks of similar severe respiratory tract infections in Singapore. It draws on the lessons learnt during the severe acute respiratory syndrome (SARS) epidemic and available published data concerning the COVID-19 pandemic. It addresses measures before, during and after endoscopy that must be considered for both non-infected and infected patients, and provides recommendations for practical implementation.

Chapter of Gastroenterologists professional guidance for management of patients with liver disease in Singapore during the COVID-19 pandemic.

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.

Trends in Medicare Reimbursement and Work Relative Value Unit Production in Radiation Oncology.

PURPOSE: Medicare payments to individual physicians are released annually by the CMS. The purpose of this study is to analyze trends in Medicare reimbursement and work relative value unit (wRVU) production to radiation oncologists. MATERIALS AND METHODS: The Medicare Physician Supplier and Other Provider Public Use File and the CMS Physician Fee Schedule Relative Value Files (to calculate wRVUs) for the calendar years 2012 to 2015 were used in this analysis. Medicare reimbursement was aggregated for each calendar year. Using the CMS Physician Fee Schedule Relative Value Files, the number of Medicare wRVUs was calculated for each radiation oncologist. RESULTS: In 2015, 4,323 radiation oncologists produced 12,895,298 wRVUs compared with 11,352,286 wRVUs produced in 2012. These datasets include only Medicare reimbursements and do not include wRVUs from private insurance or other payers. In 2015, radiation oncologists produced a median of 2,486 wRVUs from Medicare (range 3 to 24,349). Billing to Healthcare Common Procedure Coding System Code 77427 (radiation treatment management, five treatments), a proxy for total radiation treatments, fell from 1,111,670 in 2012 to 1,039,403 in 2015, a decline of 7%. CONCLUSION: The total number of wRVUs produced by radiation oncologists has risen by 14% from 2012 to 2015. However, the number of external beam radiation fractions has declined by approximately 7% over this same period, likely due to a trend toward hypofractionated courses of treatment and use of special treatment modalities such as proton beam therapy or stereotactic body radiation therapy.

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

BACKGROUND: Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. METHODS: The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. RESULTS: A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). CONCLUSIONS: The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

Cost-effectiveness of prostate boost with high-dose-rate brachytherapy versus intensity-modulated radiation therapy in the treatment of intermediate-high risk prostate cancer.

PURPOSE: The recently published ASCENDE-RT randomized clinical trial demonstrated improved biochemical control, albeit with increased toxicity, for a prostate boost with brachytherapy versus external beam radiation therapy alone in patients with intermediate-high risk prostate cancer. In this study, we investigated the cost-effectiveness of these two modalities in the treatment of intermediate-high risk prostate cancer. METHODS AND MATERIALS: A multistate Markov model was created to model a patient with intermediate-high risk prostate cancer. The two treatment options modeled were (1) 23 fractions of intensity-modulated radiation therapy (IMRT) and two fractions of high-dose-rate prostate brachytherapy (brachytherapy boost) and (2) 44 fractions of IMRT (IMRT alone). Each patient received 1 year of hormone therapy, per the ASCENDE-RT protocol. Model assumptions, including clinical outcomes, toxicity, and utilities were derived from the medical literature. Costs of radiation therapy were estimated using Medicare reimbursement data. RESULTS: The estimated expected lifetime cost of brachytherapy boost was $68,696, compared to $114,944 for IMRT alone. Brachytherapy boost significantly lowered expected lifetime treatment costs because it decreased the incidence of metastatic castration-resistant prostate cancer, cutting the use of expensive targeted therapy for metastatic castration-resistant prostate cancer. Brachytherapy boost had an expected quality-adjusted life years of 10.8 years, compared to 9.3 years for IMRT alone. One-way sensitivity analyses of our results found brachytherapy boost to be cost-effective over a wide range of cost, utility, and cancer progression rate assumptions. CONCLUSIONS: IMRT with high-dose-rate brachytherapy boost is a cost-effective treatment for intermediate-high risk prostate cancer compared to IMRT alone.