Cushing Syndrome due to a Pancreatic Neuroendocrine Tumor Treated With Radiofrequency Ablation.

Delayed diagnosis of Cushing syndrome (CS) results in advanced disease, treatment delays, and poor outcomes. We present a patient with ectopic ACTH syndrome (EAS) from a pancreatic neuroendocrine tumor (NET) whose care posed diagnostic and therapeutic challenges. A 59-year-old female with classic Cushing stigmata, biochemical evidence of ACTH-dependent hypercortisolism, and a 5-mm pituitary lesion presented for inferior petrosal sinus sampling, which was contraindicated due to non-ST elevation myocardial infarction and acute/subacute strokes. Whole-body computed tomography (CT) scan was unrevealing, but elevations in chromogranin A and proopiomelanocortin (POMC) concentrations suggested EAS. Positron emission tomography-CT with gallium 68-DOTATATE demonstrated a 7-mm pancreatic tail lesion, suspicious for a pancreatic NET. The patient was not a surgical candidate and treatment with ketoconazole was complicated by hepatoxicity. Endoscopic ultrasound-guided biopsy and radiofrequency ablation of the lesion was pursued. Pathology confirmed ACTH immunoreactive low-grade pancreatic NET. Post procedure, sustained normalization of ACTH and cortisol was achieved. This case supports the utility of POMC measurements in the differential diagnosis of CS and the use of advanced nuclear imaging for tumor localization. For patients with functional pancreatic NET who are poor surgical candidates or intolerant of pharmacotherapy, novel endoscopic ablation may offer a low-risk therapeutic option and should be further investigated.

Endoscopic Management of Esophageal Cancer.

Esophageal cancer is the eighth most common malignancy worldwide with more than 600,000 new cases diagnosed annually. Although curative approaches to early-stage esophageal cancer have historically been surgical, advances in endoscopic techniques resulted in the identification of patients who may benefit from minimally invasive endoscopic therapies. In this exposition, we discuss the identification of patients who are candidates for endoscopic resection and detail different aspects of endoscopic curative techniques for esophageal neoplasia. We also discuss therapies directed at the palliation of esophageal cancer sequelae.

Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.

BACKGROUND: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. METHODS: This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). CONCLUSION: Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.

Performance and Predictors of Migration of Partially and Fully Covered Esophageal Self-Expanding Metal Stents for Malignant Dysphagia.

BACKGROUND & AIMS: Self-expanding metal stents (SEMS) are routinely used to palliate malignant dysphagia. However esophageal SEMS can migrate or obstruct due to epithelial hyperplasia. The aim of this study was to evaluate the rates and factors predicting migration and obstruction, and the nutritional outcomes in partially covered (pc) vs. fully covered (fc) SEMS vs. fcSEMS with antimigration fins (AF) placed for malignant dysphagia. METHODS: A retrospective review of consecutive patients undergoing SEMS placement for malignant dysphagia at three academic medical centers. RESULTS: Among 357 patients, there were 55 (15.4%) stent migrations, 45 (12.6%) obstructions from epithelial hyperplasia, and 20 (5.6%) food impactions. Median overall survival was 79 days (IQR 41,199). The percent weight change/change in albumin at 30 and 60 days after SEMS placement were -2.24%/-0.544 g/dL and -2.98%/-0.55 g/dL, respectively. Stent migration occurred significantly more often with fcSEMS than pcSEMS (25.3% vs 10.9%; P < .003), but there was no difference when either group was compared to fcSEMS-AF (19.3%). The overall rate of epithelial hyperplasia resulting in stent obstruction was low (12.6%) and not different between stent types. Factors associated with increased risk of SEMS migration on multivariable logistic regression included stricture traversability with a diagnostic endoscope (OR, 2.37; 95% CI, 1.29-4.35) and use of fcSEMS (OR, 2.56; 1.31-5.00) or fcSEMS-AF (OR, 2.30, 1.03-5.14). CONCLUSIONS: Traversability of a malignant esophageal stenosis predicts SEMS migration. In these patients with a limited overall survival, pcSEMS are associated with lower rates of stent migration and similar rates of obstruction compared to fcSEMS.

Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

Use of a double-lumen cytology brush catheter to allow double-guidewire technique for endoscopic interventions.

BACKGROUND AND AIMS: Serial stent placement may be necessary during endoscopic interventions, but the passage of a guidewire alongside an initial stent can be challenging, time-consuming, and sometimes unsuccessful. We describe a modification of a cytology brush catheter to allow simultaneous placement of 2 guidewires to facilitate serial stent placement and demonstrate its application in different scenarios. METHODS: This is a retrospective series of 3 patients with different conditions (acute cholecystitis, pancreas pseudocyst, and severe biliary stricture) in whom placement of a second guidewire facilitated serial stent placement. A step-by-step demonstration of the technique is provided. RESULTS: Serial stent placement was successful in all patients without adverse events. CONCLUSIONS: A modified cytology brush catheter can be used to deliver 2 guidewires simultaneously during ERCP and EUS procedures. This technique may improve procedural efficiency, maintain a safety track, and augment therapy in certain situations.

Extrabiliary applications of fully covered antimigration biliary metal stents.

BACKGROUND AND AIMS: Endoscopic stent placement in luminal GI strictures is not always feasible with traditional stents. For example, standard luminal stent delivery catheters may not successfully traverse severe strictures, and enteral stents may not be suitable for sites in the GI tract that pose significant adverse events if downstream migration were to occur. We demonstrate extrabiliary applications of specialized, fully covered antimigration biliary metal stents. METHODS: This is a retrospective series of 4 patients with different benign and malignant luminal GI strictures who underwent placement of fully covered antimigration biliary metal stents in different configurations as a bridge or destination therapy. RESULTS: Luminal obstruction resolved without adverse events in all cases. CONCLUSIONS: Although off label, extrabiliary use of these stents can successfully address scenarios of complex luminal pathology. To compensate for the small stent caliber, two stents may be placed side by side in a double-barrel configuration. Strict diet modifications are necessary when applying this therapeutic paradigm.

Advanced endoscopic imaging of indeterminate biliary strictures.

Endoscopic evaluation of indeterminate biliary strictures (IDBSs) has evolved considerably since the development of flexible fiberoptic endoscopes over 50 years ago. Endoscopic retrograde cholangiography pancreatography (ERCP) was introduced nearly a decade later and has since become the mainstay of therapy for relieving obstruction of the biliary tract. However, longstanding methods of ERCP-guided tissue acquisition (i.e., biliary brushings for cytology and intraductal forceps biopsy for histology) have demonstrated disappointing performance characteristics in distinguishing malignant from benign etiologies of IDBSs. The limitations of these methods have thus helped drive the search for novel techniques to enhance the evaluation of IDBSs and thereby improve diagnosis and clinical care. These modalities include, but are not limited to, endoscopic ultrasound, intraductal ultrasound, cholangioscopy, confocal endomicroscopy, and optical coherence tomography. In this review, we discuss established and emerging options in the evaluation of IDBSs.

Endoscopic management of benign biliary strictures.

Endoscopic management of biliary obstruction has evolved tremendously since the introduction of flexible fiberoptic endoscopes over 50 years ago. For the last several decades, endoscopic retrograde cholangiopancreatography (ERCP) has become established as the mainstay for definitively diagnosing and relieving biliary obstruction. In addition, and more recently, endoscopic ultrasonography (EUS) has gained increasing favor as an auxiliary diagnostic and therapeutic modality in facilitating decompression of the biliary tree. Here, we provide a review of the current and continually evolving role of gastrointestinal endoscopy, including both ERCP and EUS, in the management of biliary obstruction with a focus on benign biliary strictures.

Persistent contamination on colonoscopes and gastroscopes detected by biologic cultures and rapid indicators despite reprocessing performed in accordance with guidelines.

BACKGROUND: Pathogens have been transmitted via flexible endoscopes that were reportedly reprocessed in accordance with guidelines. METHODS: Researchers observed reprocessing activities to ensure guideline compliance in a large gastrointestinal endoscopy unit. Contamination was assessed immediately after bedside cleaning, manual cleaning, high-level disinfection, and overnight storage via visual inspection, aerobic cultures, and tests for adenosine triphosphate (ATP), protein, carbohydrate, and hemoglobin. RESULTS: All colonoscopes and gastroscopes were reprocessed in accordance with guidelines during the study. Researchers collected and tested samples during 60 encounters with 15 endoscopes. Viable microbes were recovered from bedside-cleaned (92%), manually cleaned (46%), high-level disinfected (64%), and stored (9%) endoscopes. Rapid indicator tests detected contamination (protein, carbohydrate, hemoglobin, or ATP) above benchmarks on bedside-cleaned (100%), manually cleaned (92%), high-level disinfected (73%), and stored (82%) endoscopes. Visible residue was never observed on endoscopes, but it was often seen on materials used to sample endoscopes. Seven endoscopes underwent additional reprocessing in response to positive rapid indicators. Control endoscope channels were free of biologic residue and viable microbes. CONCLUSION: Despite reprocessing in accordance with US guidelines, viable microbes and biologic debris persisted on clinically used gastrointestinal endoscopes, suggesting current reprocessing guidelines are not sufficient to ensure successful decontamination.

The use of rapid indicators for the detection of organic residues on clinically used gastrointestinal endoscopes with and without visually apparent debris.

BACKGROUND: Outbreaks of multidrug-resistant organisms have been linked to endoscope reprocessing lapses. Meticulous manual cleaning before high-level disinfection (HLD) is essential in reducing residual contamination that can interfere with HLD. Current reprocessing guidelines state that visual inspection is sufficient to confirm adequate cleaning. OBJECTIVE: Our aim was to evaluate contamination of clinically used endoscopes, using visual inspection and rapid indicator tests before and after manual cleaning. A second objective was to determine which rapid indicator instruments and methods could be used for quality improvement initiatives in endoscope reprocessing. DESIGN: Clinical use study of endoscope reprocessing effectiveness. SETTING: Tertiary care teaching hospital with an inpatient endoscopy center. METHODS: Researchers sampled endoscopes used for gastrointestinal procedures before and after manual cleaning. The external surfaces and 1 channel of each endoscope were visually inspected and tested with rapid indicators to measure protein, blood, and adenosine triphosphate (ATP) contamination levels. RESULTS: Multiple components were sampled during 37 encounters with 12 unique endoscopes. All bedside-cleaned endoscopes had high levels of ATP and detectable blood or protein, whether or not any residue was visible. Although there was no visible residue on any endoscopes after manual cleaning, 82% had at least 1 positive rapid indicator test. CONCLUSIONS: Relying solely on visual inspection of endoscopes prior to HLD is insufficient to ensure reprocessing effectiveness. For quality assurance initiatives, tests of different endoscope components using more than 1 indicator may be necessary. Additional research is needed to validate specific monitoring protocols.

Effect of hypercarbia and isoflurane on brain cell death and neurocognitive dysfunction in 7-day-old rats.

BACKGROUND: Millions of neonates undergo anesthesia each year. Certain anesthetic agents cause brain cell death and long-term neurocognitive dysfunction in postnatal day (P)7 rats. Despite its intuitive appeal, a causal link between cell death and neurocognitive decline after anesthesia has not been established. If one existed, the degree of cell death would be expected to correlate with the degree of neurocognitive dysfunction caused by anesthesia. The authors therefore tested if cell death caused by various durations of isoflurane at 1 minimum alveolar concentration causes duration-dependent long-term neurocognitive dysfunction. METHODS: Isoflurane was administered to P7 rats at 1 minimum alveolar concentration for 0, 1, 2, or 4 h. To control for the respiratory depressant effects of anesthesia, a group of rats was treated with 4 h of carbon dioxide. Cell death was assessed by FluoroJade staining 12 h after the end of each intervention, and neurocognitive outcome was assessed 8 weeks later by using fear conditioning, spatial reference memory, and spatial working memory tasks. RESULTS: Widespread brain cell death was caused by 2 h and 4 h of isoflurane and by 4 h of carbon dioxide. The degree and distribution of thalamic cell death was similar in 4 h isoflurane-treated and 4-h carbon dioxide-treated rats. Only 4 h of isoflurane caused a long-term neurocognitive deficit affecting both spatial reference memory and spatial working memory. Working memory was improved in carbon dioxide-treated rats. CONCLUSION: Isoflurane-induced brain cell death may be partly caused by hypercarbia. The inconsistencies between cell death and neurocognitive outcome suggest that additional or alternative mechanisms may mediate anesthesia-induced long-term neurocognitive dysfunction.

Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats.

BACKGROUND: Anesthetic agents cause cell death in the developing rodent brain and long-term, mostly hippocampal-dependent, neurocognitive dysfunction. However, a causal link between these findings has not been shown. Postnatal hippocampal neurogenesis affects hippocampal function into adulthood; therefore, the authors tested the hypothesis that isoflurane affects long-term neurocognitive function via an effect on dentate gyrus neurogenesis. METHODS: The S-phase marker 5-bromodeoxyuridine was administered at various times before, during, and after 4 h of isoflurane given to postnatal day (P)60 and P7 rats to assess dentate gyrus progenitor proliferation, early neuronal lineage selection, and long-term survival of new granule cell neurons. Fear conditioning and spatial reference memory was tested at various intervals from 2 weeks until 8 months after anesthesia. RESULTS: In P60 rats, isoflurane increased early neuronal differentiation as assessed by BrdU/NeuroD costaining, decreased progenitor proliferation for 1 day, and subsequently increased progenitor proliferation 5-10 days after anesthesia. In P7 rats, isoflurane did not induce neuronal lineage selection but decreased progenitor proliferation until at least 5 days after anesthesia. Isoflurane improved spatial reference memory of P60 rats long-term, but it caused a delayed-onset, progressive, persistent hippocampal deficit in P7 rats in fear conditioning and spatial reference memory tasks. CONCLUSION: The authors conclude that isoflurane differentially affects both neurogenesis and long-term neurocognitive function in P60 and P7 rats. Neurogenesis might mediate the long-term neurocognitive outcome after isoflurane at different ages.