Topazian, Mark

Background: Thiamin deficiency is a major public health concern in several low- and middle-income countries (LMICs)—current attention to the problem is lacking. Aim: This review discusses prevalence of thiamin insufficiency and thiamin-deficiency disorders (TDDs) in LMICs, outlines programmatic experience with thiamin interventions, and offers recommendations to improve public-health and research attention to thiamin in LMICs. Discussion: Thiamin insufficiency, i.e. low-blood-thiamin status, is endemic among several Southeast Asian countries: Cambodia (70–100% of infants and 27–100% of reproductive-age women); Laos (13% of hospitalized infants); Thailand (16–25% of children and 30% of elderly adults). Thiamin deficiency accounts for up to 45% of under-5 deaths in Cambodia, 34% of infant deaths in Laos, and 17% of infant deaths in Myanmar. Deficiency also exists in Africa, Asia, and the Americas, but these instances have typically been isolated. Exclusively breastfed infants of thiamin-deficient mothers are at highest risk for TDD and related death. Intervention strategies that have been employed to combat thiamin deficiency include food processing, fortification, supplementation, dietary diversification, and dietary behaviors, all of which have shown varying levels of effectiveness. Conclusions: We recommend universal thiamin-fortification of context-specific staple-foods in LMICs as a promising solution, as well as thiamin supplementation, particularly for pregnant and lactating women. Food processing regulations, dietary diversification, and modification of dietary behaviors to increase consumption of thiamin-rich foods may provide benefits in some circumstances, especially in countries without universal fortification programs or in populations dependent on food aid.

BACKGROUND: There is lack of consensus on post-operative surveillance for resected non-invasive intraductal papillary neoplasms (IPMNs). In this study we explored risk factors for subsequent PC in patients with MD-IPMN undergoing partial pancreatectomy. METHODS: We searched the Mayo Clinic surgical pathology database for all cases of resected MD-IPMN between 1997 and 2014. Cases with histologically confirmed main pancreatic duct involvement either isolated or in a mixed pattern with branch-duct involvement were included. Outcomes of PC in the remnant pancreas, and death related to MD-IPMN were assessed with survival analyses (Kaplan–Meier and Cox regression). RESULTS: Among the 179 patients with resected MD-IPMN the incidence of concomitant PC and high-grade dysplasia (HGD) in the resected specimen was 23 and 14%, respectively. The mean duration of follow-up was 4.31 years (range 0.12–13.5 years). Excluding 28 subjects who either underwent initial total pancreatectomy or partial pancreatectomy with surgical margins positive for PC/HGD, the 5-year incidence of subsequent PC was 12%, including 60.6% and 15.6% in those with initial PC and HGD, respectively. The 10-year incidence of PC was 21.2% overall, 60.6% for PC, 38.3% for HGD, and 3.0% for LGD. Risk of subsequent PC was significantly higher for those with initial PC compared with HGD (HR = 4.95, 95% CI: 1.63–15.03, p = 0.005 and for HGD compared with LGD (HR = 11.30, 95% CI: 1.55–82.26, p = 0.017). CONCLUSIONS: Patients with MD-IPMN with PC or HGD undergoing segmental pancreatectomy are at higher risk of subsequent PC and may benefit from post-operative surveillance. The post-operative surveillance intervals in resected MD-IPMNs need to be tailored based on dysplasia grade.

Abstract High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer.

Abstract Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP—controls, suspected CP, and definite CP. In addition to collecting detailed information using structured case report forms and protocol-mandated evaluations at baseline and during follow-up, PROCEED will establish a linked biorepository of blood, urine, saliva, stool, pancreatic fluid, and pancreatic tissue. Enrollment for PROCEED began in June 2017. As of July 1, 2018, nine clinical centers of the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer are enrolling, and 350 subjects have completed baseline evaluation. In conclusion, PROCEED will provide the most accurate and reliable estimates to date on progression of CP. The established cohort and biorepository will facilitate numerous analyses, leading to new strategies for diagnosis, methods to monitor disease progression, and treatment of CP.

Abstract Background and aims Benign gastrointestinal (GI) strictures are often refractory to standard endoscopic interventions. Fully covered coaxial lumen-apposing metal stents (LAMS) have emerged as a novel therapy for these strictures. The aim of this study was to evaluate the safety and efficacy of LAMS for refractory GI strictures. Patients and methods A retrospective analysis was performed for patients who underwent LAMS placement for benign luminal strictures in three US centers between January 2014 and December 2016. The primary outcomes were technical success and initial clinical success of LAMS placement. Secondary outcomes were stent migration, rate of re-intervention, and adverse events. Results A total of 49 patients underwent 56 LAMS placement procedures. Previous treatment had failed in 39 patients (79.6 %), and anastomotic strictures were the indication in 77.6 % (38/49), with the most common site being gastrojejunal (34.7 % [17/49]). Technical success was achieved in all procedures and initial clinical success was achieved in 96.4 % of all procedures (54/56). Patient initial clinical success was 95.9 % (47/49). Stent migration occurred in 17.9 % of procedures, and was more likely to occur at sites in the lower GI tract (P = 0.02). The mean stent dwell time was 100.6 days, and the mean follow-up was 169.8 days. Minor adverse events, not requiring hospitalization, occurred in 33.9 % of procedures, including subsequent stricture progression (10.7 %). In cases where LAMS were removed, mean follow-up time was 102.2 days. The re-intervention rate was 75 % at 300 days follow-up after stent removal. Of the LAMS placed at anastomotic strictures, 36.4 % required re-intervention, with approximately two-thirds of these re-interventions requiring placement of a new stent or surgery. Conclusion LAMS placement was successful for the management of refractory GI strictures, with good technical and initial clinical success rates. However, re-intervention rates after LAMS removal were high, and many strictures were not resolved by an extended period of stenting with these coaxial stents. LAMS placement offers additional therapeutic options and in selected cases might be considered a destination therapy for patients with recalcitrant benign strictures.

Abstract Background: Esophageal cancer is the 6th leading cause of cancer death globally, with geographical high-risk areas in Asia, the Middle East, and eastern and southern Africa. Esophageal squamous cell carcinoma (ESCC) is the more common variant in Africa. In Kenya, its incidence is 2nd in men after prostate cancer and 3rd in women after breast and cervix-uteri cancers. Late presentation is a common occurrence in developing countries and is multifactorial due to challenges in access to health care, low socioeconomic status and delayed or missed diagnosis. A large percentage of these tumors are thus unresectable and are only eligible for palliative care via stenting. Our hospital is a 300-bed referral center in southwestern Kenya, which is a hotspot for ESCC, and we see over 400 cases of ESCC annually. Methods: We have developed a technique for placement of esophageal self-expanding metallic stents (SEMS) without fluoroscopy that is safe and easily reproducible. This is an outpatient procedure, with the majority done under conscious sedation, and routine followup is not necessary. The tumor margins are noted at time of video endoscopy, a guidewire is placed, and dilation done with Savary dilators as required. The SEMS are then loaded on the stent delivery device and deployed into the proper position based on measurements, and placement is subsequently confirmed via endoscopic visualization. Results: A total of 3000 SEMS have been placed to date at our hospital, without using fluoroscopy. The male: female ratio has been 1.5:1, and the average age has been 60.4 years. The distribution of tumor locations was 67% in the middle and distal third. The most common complications were tumor overgrowth with obstruction and stent migration. Procedure related mortality was 0.3%. Post-procedure improvement in dysphagia score was seen in over 80% , and patient satisfaction was high. Initial data puts our post stent survival time around 8 months/ 250 days Conclusions: Placement of SEMS for ESCC, without fluoroscopy, is a safe and reproducible procedure which has a low rate of adverse events. This procedure results in effective palliation of a difficult disease and can easily be done in resource-limited settings which have endoscopy capabilities. Current efforts are ongoing to increase opportunities for training endoscopists in this procedure and for provision of affordable stents in Africa. Citation Format: Michael M. Mwachiro, Robert K. Parker, Stephen Burgert, Justus Lando, Sinkeet Rankeeti, Robert Chepkwony, Emmanuel Kiniga, Sanford Dawsey, Mark Topazian, Russell E. White. Esophageal stenting in resource-limited settings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2766. doi:10.1158/1538-7445.AM2017-2766

Abstract Background and study aims The preferred management of bleeding esophageal varices includes endoscopic band ligation. Endoscopic ligation devices (ELDs) are expensive and designed for single use, limiting their uptake in developing countries. We aimed to assess the efficacy of reprocessing ELDs using terminal microbial cultures and adenosine triphosphate (ATP) testing. Materials and methods ELDs were recovered after clinical use and their components (cap, handle, and cord) were subjected to reprocessing. This included manual cleaning, automated high-level disinfection (HLD), and drying with forced air. Using sterile technique, ELD components were sampled for ATP at three stages: before manual cleaning, after manual cleaning, and after HLD. Components were sent to an external laboratory for culturing. Cultures were interpreted as positive upon identification of Gram-negative bacilli. Results A total of 14 clinically used ELDs were studied, and 189 ATP tests and 41 cultures were evaluated. Overall, 95 % (39/41) of components and 86 % (12/14) of ELDs were culture-negative or did not yield Gram-negative bacilli. Two components (5 %; one handle and one cord) harbored Gram-negative bacilli in quantities of 1 CFU per component. There was no apparent correlation between ATP at any juncture of reprocessing and terminal cultures. Conclusions Reprocessing of ELDs is effective, resulting in infrequent and minimal microbial contamination. Microbial culturing can be used to ensure adequacy of ELD reprocessing if pursued. Until reusable ELDs are commercially available, continued efforts to better define the adequacy and long-term effects of reprocessing ELDs are needed.

Thiamine deficiency and beriberi are prevalent in Cambodia, although most infants with nonspecific clinical symptoms of beriberi, including tachypnea, lack echocardiographic evidence diagnostic of the disease. Camphor activates transient receptor potential vanilloid 3 (TRPV3), a nonselective ion channel expressed in the medial preoptic nucleus of the hypothalamus and thought to be important for thermo-sensitivity. Because camphorated ointments are used commonly among Cambodian infants, we hypothesized that topical camphor modulates thermoregulatory behaviors, causing beriberi-simulating tachypnea, separate from any influence of thiamine deficiency. We assessed 9 tachypneic and 10 healthy infants for Tiger Balm use and for presence of camphor in whole blood. However, no camphor was found in blood from any infants, indicating that camphor is unrelated to tachypneic illness in Cambodian infants.

Objective Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5-year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL-IPMN. Design From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. Results Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8–7.1) years. Among FN cysts, 5-year PC risk was low (2–3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0–2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). Conclusions Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately.