Colonic-enteric lumen-apposing metal stents: a promising and safe alternative for endoscopic management of small-bowel obstruction.

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) have revolutionized the treatment of various gastroenterologic conditions that previously required surgery. The use of LAMSs for the management of small-bowel obstruction (SBO) involves EUS-guided coloenterostomy (EUS-CE) between the colon and a dilated loop of the small intestine proximal to the point of obstruction. This procedure is potentially beneficial for patients with malignant SBO who are poor surgical candidates. METHODS: A retrospective cohort study was conducted at 2 tertiary care hospitals. Patients who underwent EUS-CE for SBO were identified, and data regarding patient demographics, indication for the procedure, location of the obstruction, procedural details, and adverse events were collected. The primary outcome was technical success of the procedure. Secondary outcomes were clinical success, resolution of symptoms, ability to tolerate enteral nutrition, and adverse events. RESULTS: Twenty-six patients who underwent the EUS-CE procedure were included. Technical success was achieved in all 26 patients, clinical success (resolution of obstructive symptoms) was achieved in 92.3% of patients (24/26), and the ability to resume enteral nutrition in 84.6% (22/26). Adverse events occurred in 4 patients (15.4%) and included bleeding (1/26), diarrhea (2/26), and postprocedure sepsis (1/26). Patients were followed for a mean of 54.8 days (range, 2-190). CONCLUSIONS: This study highlights that EUS-CE with LAMSs can be performed with high technical and clinical success for the management of SBO, particularly in patients with malignant obstructions who are not suitable candidates for surgical interventions. Further research with larger sample sizes will be essential to substantiate its efficacy and safety.

Safety, Efficacy and Clinical Utility of the 5.1mm EndoRotor Powered Debridement Catheter for Treatment of Walled-Off Pancreatic Necrosis.

BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) is a recommended strategy for treatment of walled-off-necrosis (WON). DEN uses a variety of devices including the EndoRotor (Interscope, Inc.) debridement catheter. Recently, a 5.1 mm EndoRotor with increased chamber size and rate of tissue removal was introduced. The aim of this study was to assess the efficacy and safety of this device. METHODS: A multi-center cohort study was conducted at eight institutions including patients who underwent DEN with the 5.1 mm EndoRotor. The primary outcome was the number of DEN sessions needed for WON resolution. Secondary outcomes included the average percent reduction in solid WON debris and decrease in WON area per session, total time spent performing EndoRotor therapy for WON resolution, and adverse events. RESULTS: 64 procedures in 41 patients were included. For patients in which the 5.1 mm EndoRotor catheter was the sole therapeutic modality, an average of 1.6 DEN sessions resulted in WON resolution with an average cumulative time of 85.5 minutes. Of the 21 procedures with data regarding percent of solid debris, the average reduction was 85% +/- 23% per session. Of the 19 procedures with data regarding WON area, the mean area significantly decreased from 97.6 +/- 72.0 cm2 to 27.1 +/- 35.5 cm2 (p<0.001) per session. Adverse events included two intra-procedural LAMS dislodgements managed endoscopically and three perforations none of which were related to EndoRotor. Bleeding was reported in seven cases, none required embolic or surgical therapy and two required blood transfusions. CONCLUSIONS: This is the first multi-center retrospective study to investigate the efficacy and safety of the 5.1 mm EndoRotor catheter for WON. Results from this study showed an average of 1.6 DEN sessions were needed to achieve WON resolution with an 85% single session reduction in solid debris and a 70% single session decrease in WON area with minimal adverse events.

Factors predictive of persistent fistulas in EUS-directed transgastric ERCP: a multicenter matched case-control study.

BACKGROUND AND AIMS: EUS-directed transgastric ERCP (EDGE) is an established method for managing pancreaticobiliary pathology in Roux-en-Y gastric bypass patients, with high rates of technical success and low rates of serious adverse events (AEs). However, widespread adoption of the technique has been limited because of concerns about the development of persistent gastrogastric or jejunogastric fistulas. Gastrogastric and jejunogastric fistulas have been reported in up to 20% of cases in some series, but predictive risk factors and long-term management and outcomes are lacking. Therefore, our aims were to assess factors associated with the development of persistent fistulas and the technical success of endoscopic fistula closure. METHODS: This is a case-control study involving 9 centers (8 USA, 1 Europe) from February 2015 to September 2021. Cases of persistent fistulas were defined as endoscopic or imaging evidence of fistula more than 8 weeks after lumen-apposing metal stent (LAMS) removal. Control subjects were defined as endoscopic or imaging confirmation of no fistula more than 8 weeks after LAMS removal. AEs were defined and graded according to the American Society for Gastrointestinal Endoscopy lexicon. RESULTS: Twenty-five patients identified to have evidence of a persistent fistula on follow-up surveillance (cases) were matched with 50 patients with no evidence of a persistent fistula on follow-up surveillance (control subjects) based on age and sex. Mean LAMS dwell time was 74.7 ± 106.2 days. After LAMS removal, argon plasma coagulation (APC) ablation of the fistula was performed in 46 patients (61.3%). Primary closure of the fistula was performed in 26.7% of patients (20: endoscopic suturing in 17, endoscopic tacking in 2, and over-the-scope clips + endoscopic suturing in 1). When comparing cases with control subjects, there was no difference in baseline demographics, fistula site, LAMS size, or primary closure frequency between the 2 groups (P > .05). However, in the persistent fistula group, the mean LAMS dwell time was significantly longer (127 vs 48 days, P = .02) and more patients had ≥5% total body weight gain (33.3% vs 10.3%, P = .03). LAMS dwell time was a significant predictor of persistent fistula (odds ratio, 4.5 after >40 days in situ, P = .01). The odds of developing a persistent fistula increased by 9.5% for every 7 days the LAMS was left in situ. In patients with a persistent fistula, endoscopic closure was attempted in 19 (76%) with successful resolution in 14 (73.7%). CONCLUSIONS: Longer LAMS dwell time was found to be associated with a higher risk of persistent fistulas in EDGE patients. APC or primary closure of the fistula on LAMS removal was not found to be protective against developing a persistent fistula, which, if present, can be effectively managed through endoscopic closure in most cases.

Novel through-the-scope suture closure of colonic EMR defects (with video).

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.

A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. METHODS: We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a < 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. RESULTS: 82 patients with a median defect size of 30 (interquartile range 25-40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. CONCLUSION: The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.

RHEMITT Score Predicts Rebleed After Capsule Endoscopy: First Validation at a U.S. Tertiary Care Center.

BACKGROUND: Patients with obscure gastrointestinal bleeding undergo small bowel capsule endoscopy (SBCE), but often return for recurrent bleeding or anemia. The RHEMITT score evaluates patients based on 7 variables (heart failure, chronic kidney disease, Saurin P1/P2 lesions, major bleeding, incomplete SBCE, smoking status, and endoscopic treatment) and seeks to predict the risk of rebleeding. AIMS: This study aims to perform an external validation of the RHEMITT score in the United States. METHODS: SBCEs performed to evaluate anemia or GI bleeding from a tertiary-care center's PillCam database between 1/22/2018 and 7/21/2020 were reviewed. Variables based on the RHEMITT score were collected. The primary outcome was rebleeding, defined as (1) melena or hematochezia or (2) hemoglobin drop of 2 g/dL. Patient were categorized into low, intermediate, and high-risk categories based on RHEMITT score. The accuracy of the RHEMITT score for predicting rebleeding was assessed. RESULTS: A total of 361 SBCEs were included in the study. Age, indication for SBCE, endoscopic treatment, antiplatelet use, cirrhosis, heart failure, chronic kidney disease, and major bleeding were significantly associated with risk of rebleed (p < 0.05). Each increasing risk category for the RHEMITT score predicted increased probability of this study's primary outcome, rebleeding (p < 0.001). There was a significant association between RHEMITT risk category and rebleeding-free survival (log-rank p < 0.001). An area under the receiver operating characteristic curve for the RHEMITT score was 0.790 (p < 0.001). CONCLUSION: Our findings validate the RHEMITT score and confirm acceptable performance for predicting rebleeding at a tertiary referral center in the United States.

Prediction and management of bleeding during endoscopic necrosectomy for pancreatic walled-off necrosis: results of a large retrospective cohort at a tertiary referral center.

BACKGROUND AND AIMS: Lumen-apposing metal stents (LAMSs) provide an endoscopic method for management of walled-off necrosis (WON) and a gateway for the performance of endoscopic necrosectomy (EN). However, bleeding may occur in up to 20% of EN procedures. Predictive factors for bleeding in this patient population are unknown, and there is no agreed-on algorithm for the management of bleeding. The aim of this study was to evaluate preprocedural risk factors for bleeding in patients undergoing endoscopic drainage or EN for WON. METHODS: A retrospective cohort of patients undergoing EN for WON was reviewed. Demographics, comorbidities, concurrent medications, and etiology of pancreatitis were recorded. Pre-, peri-, and postprocedural clinical variables were compared using the χ2 test and independent t test. RESULTS: Between June 2014 and October 2020, 536 ENs were performed in 151 patients. Intraprocedural bleeding occurred during 28 procedures (5.2%) in 18 patients (11.9%). Endoscopic hemostasis was attempted in 8 patients (10 procedures). Eight patients (10 procedures) in total were treated by interventional radiology (IR). Thrombocytopenia (P = .006) and cirrhosis (P = .049) were associated with intraprocedural bleeding, although thrombocytopenia was present in only 1 patient. Identification of a vessel within the cavity endoscopically was also associated with bleeding (P < .001). On multivariate analysis, identification of a vessel within the cavity endoscopically remained a strong predictor of bleeding (P < .001), whereas cirrhosis was no longer significant. Patients who required IR for hemostasis were transfused with significantly more blood before the procedure than patients who did not (3.4 units vs .67 units, P = .002). CONCLUSIONS: EN for WON was associated with a 5.2% per-procedure risk of bleeding and an 11.9% per-patient bleeding risk. Identification of a vessel within the cavity during endoscopy is predictive of bleeding during EN. Patients who require more transfusions before endoscopy may require earlier intervention by IR.

EUS-directed transgastric interventions in Roux-en-Y gastric bypass anatomy: a multicenter experience.

BACKGROUND AND AIMS: Placement of a lumen-apposing metal stent (LAMS) between the gastric pouch and the excluded stomach allows for EUS-guided transgastric interventions (EDGIs) in patients with Roux-en-Y gastric bypass (RYGB). Although EUS-guided transgastric ERCP (EDGE) outcomes have been reported, data are scant on other endoscopic interventions. We aimed to evaluate the outcomes and safety of EDGIs. METHODS: This retrospective study involved 9 centers (United States, 8; Europe, 1) and included patients with RYGB who underwent EDGIs between June 2015 and September 2021. The primary outcome was the technical success of EDGIs. Secondary outcomes were adverse events (AEs), length of hospital stay, and fistula follow-up and management. RESULTS: Fifty-four EDGI procedures were performed in 47 patients (mean age, 61 years; 72% women), most commonly for the evaluation of a pancreatic mass (n = 16) and management of pancreatic fluid collections (n = 10). A 20-mm LAMS was used in 26 patients and a 15-mm LAMS in 21, creating a gastrogastrostomy in 37 patients and jejunogastrostomy in 10. Most patients (n = 30, 64%) underwent a dual-session EDGI, with a median interval of 17 days between the 2 procedures. Single-session EDGI was performed in 17 patients, of whom 10 (59%) had anchoring of the LAMS. The most common interventions were diagnostic EUS (with or without FNA or fine-needle biopsy sampling; n = 28) and EUS-guided cystgastrostomy (n = 8). The mean procedural time was 97.6 ± 78.9 minutes. Technical success was achieved in 52 patients (96%). AEs occurred in 5 patients (10.6%), of which only 1 AE (2.1%) was graded as severe. Intraprocedural LAMS migration was the most common AE, occurring in 3 patients (6.4%), whereas delayed spontaneous LAMS migration occurred in 2 (4.3%). Four of the 5 LAMS migration events were managed endoscopically, and 1 required surgical repair. LAMS anchoring was found to be protective against LAMS migration (P = .001). The median duration of hospital stay was 2.1 ± 3.7 days. Of the 17 patients who underwent objective fistula assessment endoscopically or radiologically after LAMS removal, 2 (11.7%) were found to have persistent fistulas. In 1 case the fistula was intentionally left open to assist with weight gain. The other fistula was successfully closed endoscopically. CONCLUSIONS: EDGI is effective and safe for the diagnosis and management of pancreaticobiliary and foregut disorders in RYGB patients. It is associated with high rates of technical success and low rates of severe AEs. LAMS migration is the most common AE with evidence that anchoring can be protective against its occurrence. Persistent fistulas may occur, but endoscopic closure seems to be effective.

Endoscopic full-thickness resection of polyps involving the appendiceal orifice: a multicenter international experience.

BACKGROUND: Endoscopic resection of lesions involving the appendiceal orifice remains a challenge. We aimed to report outcomes with the full-thickness resection device (FTRD) for the resection of appendiceal lesions and identify factors associated with the occurrence of appendicitis. METHODS: This was a retrospective study at 18 tertiary-care centers (USA 12, Canada 1, Europe 5) between November 2016 and August 2020. Consecutive patients who underwent resection of an appendiceal orifice lesion using the FTRD were included. The primary outcome was the rate of R0 resection in neoplastic lesions, defined as negative lateral and deep margins on post-resection histologic evaluation. Secondary outcomes included the rates of: technical success (en bloc resection), clinical success (technical success without need for further surgical intervention), post-resection appendicitis, and polyp recurrence. RESULTS: 66 patients (32 women; mean age 64) underwent resection of colonic lesions involving the appendiceal orifice (mean [standard deviation] size, 14.5 (6.2) mm), with 40 (61 %) being deep, extending into the appendiceal lumen. Technical success was achieved in 59/66 patients (89 %), of which, 56 were found to be neoplastic lesions on post-resection pathology. Clinical success was achieved in 53/66 (80 %). R0 resection was achieved in 52/56 (93 %). Of the 58 patients in whom EFTR was completed who had no prior history of appendectomy, appendicitis was reported in 10 (17 %), with six (60 %) requiring surgical appendectomy. Follow-up colonoscopy was completed in 41 patients, with evidence of recurrence in five (12 %). CONCLUSIONS: The FTRD is a promising non-surgical alternative for resecting appendiceal lesions, but appendicitis occurs in 1/6 cases.

Maximizing success in single-session EUS-directed transgastric ERCP: a retrospective cohort study to identify predictive factors of stent migration.

BACKGROUND AND AIMS: EUS-directed transgastric ERCP (the EDGE procedure) is a simplified method of performing ERCP in Roux-en-Y gastric bypass patients. The EDGE procedure involves placement of a lumen-apposing metal stent (LAMS) into the excluded stomach to serve as a conduit for passage of the duodenoscope for pancreatobiliary intervention. Originally a multistep process, urgent indications for ERCP have led to the development of single-session EDGE (SS-EDGE) with LAMS placement and ERCP performed in the same session. The goal of this study was to identify predictive factors of intraprocedural LAMS migration in SS-EDGE. METHODS: We conducted a multicenter retrospective review that included 9 tertiary medical centers across the United States. Data were collected and analyzed from 128 SS-EDGE procedures. The primary outcome was intraprocedural LAMS migration. Secondary outcomes were other procedural adverse events such as bleeding and perforation. RESULTS: Eleven LAMS migrations were observed in 128 procedures (8.6%). Univariate analysis of clinically relevant variables was performed, as was a binary logistic regression analysis of stent diameter and stent dilation. This revealed that use of a smaller (15 mm) diameter LAMS was an independent predictor of intraprocedural stent migration (odds ratio, 5.36; 95% confidence interval, 1.29-22.24; P = .021). Adverse events included 3 patients who required surgery and 2 who experienced intraprocedural bleeding. CONCLUSIONS: Use of a larger-diameter LAMS is a predictive factor for a nonmigrated stent and improved procedural success in SS-EDGE. Although larger patient cohorts are needed to adequately assess these findings, performance of LAMS dilation and fixation may also decrease risk of intraprocedural LAMS migration and improve procedural success.

Comprehensive analysis of adverse events associated with transmural use of LAMS in patients with liver cirrhosis: International multicenter study.

Background and study aims Endoscopic ultrasound (EUS)-guided transmural (TM) deployment of lumen-apposing metal stents (LAMS) is considered relatively safe in non-cirrhotic patients and is cautiously offered to cirrhotic patients. Patients and methods This was a retrospective, multicenter, international matched case-control study to study the safety of EUS-guided TM deployment of LAMS in cirrhotic patients. Results Forty-three cirrhotic patients with model for end-stage liver disease score 12.5 ± 5, with 23 having ascites and 16 with varices underwent EUS-guided TM LAMS deployment, including 19 for pancreatic fluid collection (PFC) drainage, 13 gallbladder drainage, six for endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP), three for EDGI, one for endoscopic ultrasound-directed transenteric ERCP, and one postsurgical collection drainage. Technical failure occurred in one LAMS for PFC drainage. Clinical failure was encountered in another PFC. Nine adverse events (AEs) occurred. The most common AE was LAMS migration (3), followed by non-bleeding mucosal erosion (2), delayed bleeding (2), sepsis (1), and anesthesia-related complication (pulseless electrical activity) (1). Most AEs were graded as mild (6), followed by severe (2), and moderate (1); the majority were managed conservatively. On univariable comparison, risk of AE was higher when using a 20 × 10 mm LAMS and the absence of through-the-LAMS plastic stent(s). Conditional logistic regression of matched case-control patients did not show any association between potential predicting factors and occurrence of AEs. Conclusions Our study demonstrated that mainly in patients with Child-Pugh scores A and B cirrhosis and despite the presence of mild-to-moderate ascites in over half of cases, the majority of AEs were mild and could be managed conservatively. Further studies are warranted to verify the safety of LAMS in cirrhotic patients.

Gastrointestinal toxicities of immune checkpoint inhibitors: a multicenter retrospective analysis.

BACKGROUND: Immune checkpoint inhibitors are monoclonal antibodies that augment immune cell function and are used to treat malignancy. However, they may cause proinflammatory adverse events. This study investigated gastrointestinal (GI) adverse events associated with specific immune checkpoint inhibitors. METHODS: Charts of patients aged >18 years with a solid tumor who underwent treatment with immune checkpoint inhibitors between 1st April 2011 and 1st August 2019 were reviewed for GI toxicities. Clinical data, including interventions, treatment duration and outcomes, were recorded. RESULTS: One hundred patients were included in the study, of whom 22 experienced a GI adverse event directly attributable to immune checkpoint inhibitors. Transaminitis (9/22; 40.9%) and colitis (8/22; 36.3%) were most prevalent. The majority of events occurred within 4 cycles of treatment onset and were most prevalent with the nivolumab + ipilimumab combination (7/12; 58.3%). In 91% of cases (20/22), patients showed improvement or resolution of the event. Among the colitis cases, there was a significant difference (P=0.004) in recovery time between those who received infliximab and those who did not. Despite symptom resolution, only 7/22 were left on the same or part of the same treatment regimen. CONCLUSIONS: Most patients experienced their GI adverse events within 4 cycles of starting treatment, the most common being transaminitis and colitis. Nivolumab + ipilimumab dual therapy was most strongly associated with colitis. Most adverse events self-resolved, with infliximab being particularly helpful in improving colitis symptoms. However, most patients were unable to tolerate the same immunotherapy regimen and ultimately expired.

Hepatitis B-related hepatocellular carcinoma and stress: untangling the host immune response from clinical outcomes.

Chronic hepatitis B virus (HBV) infection is a major public health challenge on the global scale. Affecting hundreds of millions worldwide, HBV is a leading risk factor for hepatocellular carcinoma (HCC). Clinical outcomes from chronic HBV infection are varied and appear to be influenced by a complex and dysregulated host immune response. In turn, much attention has been given to the immunologic response to HBV in an effort to identify host factors that lead to the development of HCC. However, the role of nonimmunologic host factors, such as chronic stress, in HBV-related HCC is poorly defined. Indeed, a growing appreciation for the effects of stress on chronic liver diseases raises the question of its role in chronic HBV infection. In this light, the present review will untangle the roles of key host factors in HBV-related HCC with an emphasis on chronic stress as a viable contributor. First discussed is the interplay of stress, inflammation and chronic liver disease. The host immune response's role as a driver of HBV-related HCC is then reviewed, allowing for a close exploration of the effects of stress on immune function in chronic hepatitis B and as a potential risk factor for HBV-related HCC.

Syphilis, The Great Mimicker, Presents As a Rare Case of Concurrent Hepatitis and Gastroparesis.

Syphilis has been called "the great mimicker" given its ability to affect a wide variety of organs and subsequently present with a vast array of symptoms. The variability in clinical presentation seen in syphilis can make the diagnosis challenging. We describe a unique presentation of syphilis manifesting as hepatitis and gastroparesis. To our knowledge, this is the first case report with simultaneous hepatic and gastric involvement.

A Quality Improvement Intervention to Improve the Efficiency of Arteriovenous Access Placement for Pre-Dialysis Inpatients.

The authors aimed to improve the rate of pre-dialysis arteriovenous (AV) access placement for hospitalized patients with advanced chronic kidney disease. The authors developed and implemented a protocol for hospitalized adult patients with an estimated glomerular filtration rate <20 mL/min to streamline the workflow for obtaining AV access. The protocol was piloted on 5 inpatient medical services over 3 months at 1 institution. Specific-Measurable-Achievable-Realistic-Timely (SMART) aims, Fishbone diagrams, Plan-Do-Study-Act cycles, and run charts were used to assess the process and outcomes of the intervention. There were 22 patients in the baseline group and 27 patients in the intervention group. Pre-dialysis AV access increased from 23% to 46%. Length of stay did not differ significantly between the baseline group (8.31 days) and the intervention group (8.4 days). Pathways can improve pre-dialysis AV access without significantly increasing length of stay.

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

A Case of Carcinoid Syndrome Due to Malignant Metastatic Carcinoid Tumor with Carcinoid Heart Disease Involving Four Cardiac Valves.

BACKGROUND Carcinoid tumor, benign, low-grade malignant, and high-grade malignant, can be associated with the release of vasoactive substances that cause symptoms including cutaneous flushing, diarrhea, and bronchospasm. In 50-60% of patients with carcinoid syndrome, the vasoactive substances cause fibrosis of the pulmonary and tricuspid heart valves which lead to regurgitation and right-sided heart failure. The right side of the heart is usually affected because monoamine oxidases in the lungs usually inactivate the vasoactive substances. CASE REPORT A 62-year-old woman presented with a four-month history of diarrhea and abdominal discomfort. The patient had bilateral pelvic masses and elevated serum CA125 and an elevated urinary 5-hydroxyindoleacetic acid (5-HIAA). Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) identified a primary appendiceal carcinoid tumor with bilateral ovarian metastases. Post-operatively, a computed tomography (CT) scan showed cardiomegaly. Transthoracic echocardiography showed morphologic changes that affected all four heart valves, consistent with carcinoid heart disease but without a patent foramen ovale (PFO). The patient was evaluated for valve replacement surgery, but surgery was not performed due to the degree of heart failure. CONCLUSIONS This report describes a rare case of carcinoid heart disease with involvement of all four cardiac valves, but without the presence of a PFO, possibly due to a large amount of vasoactive substances in the patient's circulation, as supported by the patient's elevated urinary 5-HIAA. This rare presentation highlights the importance of early diagnosis and treatment with tumor resection and, if possible, Cardiac valve replacement to prevent irreversible heart failure.

Unilateral testicular metastasis of low PSA level prostatic adenocarcinoma.

A 71-year-old man presented with a firm left testicle 15 years after being diagnosed with prostatic adenocarcinoma. After the initial diagnosis, the patient underwent a radical prostatectomy. He received radiation therapy 5 years after surgery for a slightly elevated prostate-specific antigen (PSA) level and a negative metastatic workup. Eight years later, the patient's PSA rose to 3.38 ng/mL and he was started on intermittent Lupron therapy. It was then 3 years later when the patient discovered the testicular mass. At that time, his PSA level was 2.98 ng/mL. He underwent a left orchiectomy which demonstrated metastatic prostatic adenocarcinoma. Currently, the patient is doing well 3 months postorchiectomy and is now receiving continuous testosterone suppression therapy. This case report discusses the unique modes of spread from the prostate to the testicle as well as the importance of follow-up care in patients with prostate cancer, especially in the setting of low PSA levels.