Biliary Adverse Events During Neoadjuvant Therapy for Pancreatic Cancer.

OBJECTIVE: To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. BACKGROUND: Patients with PC presenting with biliary obstruction require durable decompression before NAT. METHODS: Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. RESULTS: Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE ( P =0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE ( P =0.02). CONCLUSIONS: During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.

The incidence of new mental health disorders after acute pancreatitis: A large, propensity-matched, observational study.

INTRODUCTION: The prevalence of acute pancreatitis (AP) and mental health disorders (MHDs) are rising. While the association between chronic pancreatitis (CP) and MHDs is established, it is unknown whether there is a risk of MHDs after an index episode of AP. The aim of this study was to evaluate the incidence of MHDs and pharmacotherapy use after an episode of AP. METHODS: This was a large observational study using the TriNetX research network, an electronic health record dataset containing inpatient and outpatient data from more than 50 healthcare organizations. Patients with AP from 2015-2020 were identified. Four cohorts were created: acute necrotizing pancreatitis (ANP), acute pancreatitis without necrosis (AP-WON), acute appendicitis, and healthy controls without pancreatitis. The cohorts were matched by age, sex, race, ethnicity, and nicotine and alcohol use. The primary outcome was new composite MHDs at one-year. Secondary outcomes included stratified MHDs, psychiatric medication use, opioid analgesic use, and all-cause mortality. RESULTS: The ANP, AP-WON, appendicitis, and healthy control cohorts contained 11,806, 177,266, 27,187, and 561,833 patients, respectively. Patients with AP-WON had significantly higher rates of composite MHDs compared with those hospitalized for appendicitis (9.7% vs 4.7%, HR 1.9, 95% CI 1.7-1.9). This association was augmented when comparing ANP to appendicitis (12.8% vs 5.2%, HR 2.4, 95% CI 2.1-2.7). All secondary outcomes were observed at significantly higher rates in the AP-WON cohort when compared to appendicitis. Again, these associations were augmented comparing ANP to appendicitis. CONCLUSION: Compared with controls, patients with AP had significantly higher rates of new MHDs and their associated pharmacotherapies at one-year, suggesting that a single episode of AP may independently place patients at risk for developing MHDs irrespective of whether they go on to develop CP.

Systematic review of cholangiocarcinoma in Africa: epidemiology, management, and clinical outcomes.

BACKGROUND: The prevalence, management, and clinical outcomes of cholangiocarcinoma in Africa are unknown. The aim is to conduct a comprehensive systematic review on the epidemiology, management, and outcomes of cholangiocarcinoma in Africa. METHODS: We searched PubMed, EMBASE, Web of Science and CINHAL from inception up to November 2019 for studies on cholangiocarcinoma in Africa. The results reported follow PRISMA guidelines. Quality of studies and risk of bias were adapted from a standard quality assessment tool. Descriptive data were expressed as numbers with proportions and Chi-squared test was used to compare proportions. P values < 0.05 were considered significant. RESULTS: A total of 201 citations were identified from the four databases. After excluding duplicates, 133 full texts were reviewed for eligibility, and 11 studies were included. The 11 studies are reported from 4 countries only: 8 are from North Africa (Egypt 6 and Tunisia 2), and 3 in Sub-Saharan Africa (2 in South Africa, 1 in Nigeria). Ten studies reported management and outcomes, while one study reported epidemiology and risk factors. Median age for cholangiocarcinoma ranged between 52 and 61 years. Despite the proportion with cholangiocarcinoma being higher among males than females in Egypt, this gender disparity could not be demonstrated in other African countries. Chemotherapy is mainly used for palliative care. Surgical interventions are curative and prevent cancer progression. Statistical analyses were performed with Stata 15.1. CONCLUSION: The known global major risk factors such as primary sclerosing cholangitis, Clonorchis sinensis and Opisthorchis viverrini infestation are rare. Chemotherapy treatment was mainly used for palliative treatment and was reported in three studies. Surgical intervention was described in at least 6 studies as a curative modality of treatment. Diagnostic capabilities such as radiographic imaging and endoscopic are lacking across the continent which most likely plays a role in accurate diagnosis.

Updates and new directions in the use of radiation therapy for the treatment of pancreatic adenocarcinoma: dose, sensitization, and novel technology.

Panc reatic ductal adenocarcinoma (PDAC) is a devastating malignancy. There have been few advances that have substantially improved overall survival in the past several years. On its current trajectory, the deaths from PDAC are expected to cross that from all gastrointestinal cancers combined by 2030. Radiation therapy is a technically very complex modality that bridges multiple different treatment strategies. It represents a hybrid among advanced diagnostic imaging, local (often ablative) intervention, and heterogeneous biological mechanisms contributing to normal and oncologic cell kill. In this article, we bring an overview of the several promising strategies that are currently being investigated to improve outcomes using radiation therapy for patients with PDAC.

Endoscopic management and clinical outcomes of obstructive jaundice.

BACKGROUND: This study aimed at evaluating the endoscopic management and clinical outcomes in patients with obstructive jaundice undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP) within a newly established apprenticeship teaching model at an academic centre in a resource-limited setting. MATERIALS AND METHODS: We employed an apprenticeship-style model of ERCP training with graded responsibility, multidisciplinary group feedback and short-interval repetition. We collected sociodemographic and clinicopathologic data on consecutive patients who underwent ERCP from March 2018 to February 2020. RESULTS: A total of 177 patients were referred, of which 146 patients had an ERCP performed for obstructive jaundice and 31 excluded during the study period. The median age was 55 years, age range from 8 to 83 years. The most common referral diagnosis was pancreatic head cancer 56/146 (38.1%), followed by choledocholithiasis 29/146 (19.7%), cholangiocarcinoma 22/146 (15.0%) and gall bladder cancer 11/146 (7.5%). In all, 102 patients had a malignant indication for ERCP. The cannulation rate was 92%. The most common site for malignant biliary obstruction was proximal bile stricture in 31/102 (30.4%), followed by distal bile strictures in 30/102 (28.4%), periampullary cancer 20/102 (19.6%) and mid bile duct stricture in 9/102 (8.8%). The common benign obstructive etiology includes choledocholithiasis in 33/44 (75%) and mid duct obstruction from post-cholecystectomy bile duct injury in 3/44 (2.9%) while 2/44 (2.0%) patients had choledochal cyst. Overall complications were post-ERCP pancreatitis (8/146 patients), cholangitis (3/146 patients), stent migration and post-sphincterotomy bleeding (one patient each). Peri-procedural mortality was 5/146 (3.4%). CONCLUSION: ERCP is an effective and safe method of treatment of patients with benign and malignant biliary obstruction. The low morbidity and mortality and its immediate therapeutic benefits, together with the short duration of hospitalization, indicate that this procedure is an important asset in the management of such patients.

Covered and uncovered biliary metal stents provide similar relief of biliary obstruction during neoadjuvant therapy in pancreatic cancer: a randomized trial.

BACKGROUND AND AIMS: Preoperative biliary drainage with self-expanding metal stents (SEMSs) brings liver function within an acceptable range in preparation for neoadjuvant therapy (NATx) and provides relief of obstructive symptoms in patients with pancreatic cancer. We compared fully-covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs) for sustained biliary drainage before and during NATx. METHODS: Patients with pancreatic cancer and planned NATx who need treatment of jaundice and/or cholestasis before pancreaticoduodenectomy were randomized to FCSEMSs versus UCSEMSs. The primary endpoint was sustained biliary drainage, defined as the absence of reinterventions for biliary obstructive symptoms, and was assessed from SEMS placement until curative intent surgery or at 1 year. RESULTS: The intention-to-treat population included 119 patients (59 FCSEMSs, 60 UCSEMSs). Sustained biliary drainage was equally successful with FCSEMSs and UCSEMSs (72.2% vs 72.9%, noninferiority P = .01). Reasons for FCSEMS and UCSEMS failure differed significantly between the groups and included tumor ingrowth in 0% versus 16.7% (P < .01), and stent migration in 6.8% versus 0% (P = .03), respectively. Serious adverse event rates related to stent placement were not significantly different in both groups (23.7% [14/59] vs 20.0% [12/60], P = .66), as were acute cholecystitis rates when the gallbladder was in situ (9.3% [4/43] vs 4.8% [2/42], P = .68) for FCSEMSs and UCSEMSs, respectively. In our study, independent of stent type, predictors of reinterventions were 4-cm stent length and presence of the gallbladder. CONCLUSION: FCSEMSs and UCSEMSs provide similar preoperative management of biliary obstruction in patients with pancreatic cancer receiving NATx, but mechanisms of stent dysfunction depend on stent type, stent length, and presence of the gallbladder. (Clinical trial registration number: NCT02238847.).

A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video).

BACKGROUND AND AIMS: Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent. METHODS: A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks. RESULTS: Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [-17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group. CONCLUSIONS: The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.).

In-vivo oesophageal regeneration in a human being by use of a non-biological scaffold and extracellular matrix.

BACKGROUND: Tissue-engineered extracellular matrix populated with autologous pluripotent cells can result in de-novo organogenesis, but the technique is complex, not widely available, and has not yet been used to repair large oesophageal defects in human beings. We aimed to use readily available stents and extracellular matrix to regenerate the oesophagus in vivo in a human being to re-establish swallowing function. METHODS: In a patient aged 24 years, we endoscopically placed a readily available, fully covered, self-expanding, metal stent (diameter 18 mm, length 120 mm) to bridge a 5 cm full-thickness oesophageal segment destroyed by a mediastinal abscess and leading to direct communication between the hypopharynx and the mediastinum. A commercially available extracellular matrix was used to cover the stent and was sprayed with autologous platelet-rich plasma adhesive gel. The sternocleidomastoid muscle was placed over the matrix. After 4 weeks, stent removal was needed due to stent migration, and was replaced with three stents telescopically aligned to improve anchoring. The stents were removed after 3·5 years and the oesophagus was assessed by endoscopy, biopsy, endoscopic ultrasonography, and high-resolution impedance manometry. FINDINGS: After stent removal we saw full-thickness regeneration of the oesophagus with stratified squamous epithelium, a normal five-layer wall, and peristaltic motility with bolus transit. 4 years after stent removal, the patient was eating a normal diet and maintaining a steady weight. INTERPRETATION: Maintenance of the structural morphology of the oesophagus with off-the-shelf non-biological scaffold and stimulation of regeneration with commercially available extracellular matrix led to de-novo structural and functional regeneration of the oesophagus. FUNDING: None.

Self-Expanding Metal Stents Improve Swallowing and Maintain Nutrition During Neoadjuvant Therapy for Esophageal Cancer.

BACKGROUND: Patients with locally advanced esophageal cancer can have significant dysphagia. Nutritional support during neoadjuvant therapy is often delivered via nasoenteric or percutaneous feeding tubes. These approaches do not allow for per-oral feeding. AIMS: Evaluate the safety and efficacy of fully covered self-expanding metal esophageal stents for nutritional support during neoadjuvant therapy. METHODS: This was a pilot, prospective study at a single tertiary center. From March 2012 to May 2013, consecutive patients with esophageal cancer eligible for neoadjuvant therapy were enrolled. Metal stents were placed prior to starting neoadjuvant therapy. Data were collected at baseline and predetermined intervals until an endpoint (surgery or disease progression). Outcomes included dysphagia grade, satisfaction of swallowing score, nutritional status (weight, serum albumin), impact on surgery, and adverse events. RESULTS: Fourteen stents were placed in 12 patients (59.1 ± 9.5 years, 11 men, 1 woman). Dysphagia grade (pre 3.4 ± 0.5 vs post 0.2 ± 0.4, p < 0.0001) and swallowing scores (20.2 ± 5.9 vs 6.3 ± 4.7, p < 0.0001) significantly improved after stent placement. Improvements were sustained throughout neoadjuvant therapy. Body weight and serum albumin levels remained stable. Adverse events included severe chest pain (2), food impaction (1), and delayed stent migration (2). Five patients underwent surgical resection. No significant chemoradiation or operative adverse events occurred due to the presence of a stent. CONCLUSIONS: During neoadjuvant therapy for esophageal cancer, self-expanding metal stents are safe and effective in relieving dysphagia and maintaining nutrition. They allow patients to eat orally, thereby improving patient satisfaction. The presence of an in situ stent did not interfere with surgery.

A Novel Protocol Obviates Endoscope Sampling for Carbapenem-Resistant Enterobacteriaceae: Experience of a Center with a Prior Outbreak.

BACKGROUND: Numerous published outbreaks, including one from our institution, have described endoscope-associated transmission of multidrug-resistant organisms (MDROs). Individual centers have adopted their own protocols to address this issue, including endoscope culture and sequestration. Endoscope culturing has drawbacks and may allow residual bacteria, including MDROs, to go undetected after high-level disinfection. AIM: To report the outcome of our novel protocol, which does not utilize endoscope culturing, to address our outbreak. METHODS: All patients undergoing procedures with elevator-containing endoscopes were asked to permit performance of a rectal swab. All endoscopes underwent high-level disinfection according to updated manufacturer's guidance. Additionally, ethylene oxide (EtO) sterilization was done in the high-risk settings of (1) positive response to a pre-procedure risk stratification questionnaire, (2) positive or indeterminate CRE polymerase chain reaction (PCR) from rectal swab, (3) refusal to consent for PCR or questionnaire, (4) purulent cholangitis or infected pancreatic fluid collections. Two endoscopes per weekend were sterilized on a rotational basis. RESULTS: From September 1, 2015 to April 30, 2016, 556 endoscopy sessions were performed using elevator-containing endoscopes. Prompted EtO sterilization was done on 46 (8.3%) instances, 3 from positive/indeterminate PCR tests out of 530 samples (0.6%). No CRE transmission was observed during the study period. Damage or altered performance of endoscopes related to EtO was not observed. CONCLUSION: In this pilot study, prompted EtO sterilization in high-risk patients has thus far eliminated endoscope-associated MDRO transmission, although no CRE infections were noted throughout the institution during the study period. Further studies and a larger patient sample will be required to validate these findings.

History of the Use of Esophageal Stent in Management of Dysphagia and Its Improvement Over the Years.

The art and science of using stents to treat dysphagia and seal fistula, leaks and perforations has been evolving. Lessons learnt from the deficiencies of previous models led to several improvements making stent deployment easier, and with some designs, it was also possible to remove the stents if needed. With these improvements, besides malignant dysphagia, newer indications for using stents emerged. Unfortunately, despite several decades of evolution, as yet, there is no perfect stent that "fits all." This article is an overview of how this evolution process happened and where we are currently with using stents to manage patients with dysphagia and with other esophageal disorders.

Eliminating the Residual Negative Pressure in the Endoscopic Ultrasound Aspirating Needle Enhances Cytology Yield of Pancreas Masses.

BACKGROUND: Prior to withdrawing the EUS-FNA needle from the lesion, the stopcock of the suction syringe is closed to reduce contamination. Residual negative pressure (RNP) may persist in the needle despite closing the stopcock. AIMS: To determine whether neutralizing RNP before withdrawing the needle will improve the cytology yield. METHODS: Bench-top testing was done to confirm the presence of RNP followed by a prospective, randomized, cross-over study on patients with pancreas mass. Ten milliliters of suction was applied to the FNA needle. Before withdrawing the needle from the lesion, the stopcock was closed. Based on randomization, the first pass was done with the stopcock either attached to the needle (S+) or disconnected (S-) to allow air to enter and neutralize RNP and accordingly the second pass was crossed over to S+ or S-. On-site cytopathologist was blinded to S+/S-. RESULTS: Bench tests confirmed the presence of RNP which was successfully neutralized by disconnecting the syringe (S-) from the needle. Sixty patients were enrolled, 120 samples analyzed. S+ samples showed significantly greater GI tract contamination compared to S- samples (16.7 vs. 6.7%, p = 0.03). Of the 53 patients confirmed to have pancreas adenocarcinoma, FNA using S- approach was positive in 49 (93%) compared to 40 using the S+ approach (76%, p = 0.02). CONCLUSIONS: Despite closing the stopcock of the suction syringe, RNP is present in the FNA needle. Neutralizing RNP prior to withdrawing the needle from the target lesion significantly decreased GI tract contamination of the sample thereby improving the FNA cytology yield. CLINICAL TRIALS REGISTRATION NUMBER: NCT01995474.

Efficacy and safety of a new fully covered self-expandable non-foreshortening metal esophageal stent.

BACKGROUND: Fully covered esophageal self-expandable metal stents (SEMSs) are potentially removable but can be associated with high migration rates. For precise positioning, non-foreshortening SEMSs are preferred. Recently, a new fully covered non-foreshortening SEMS with anti-migration features was introduced. OBJECTIVE: To evaluate the efficacy and safety of this new esophageal SEMS. DESIGN: Retrospective study. SETTING: Single, tertiary-care center. PATIENTS: Consecutive patients with malignant and benign strictures with dysphagia grade of ≥3 and patients with fistulas/leaks were studied. INTERVENTIONS: Stent placement and removal. MAIN OUTCOME MEASUREMENTS: Technical success in stent deployment/removal, efficacy in relieving dysphagia and sealing fistulas/leaks, and adverse events. RESULTS: Forty-three stents were placed in 35 patients (mean [± standard deviation] age 65 ± 11 years; 31 male), 24 for malignant and 11 for benign (5 strictures, 6 leaks) indications. Technical success in precise SEMS placement was 100%. The after-stent dysphagia grade improved significantly (at 1 week: 1.5 ± 0.7; at 4 weeks: 1.2 ± 0.4; baseline: 3.8 ± 0.4; P < .0001). Twenty stents were removed for clinical indications, with technical success of 100%. All leaks sealed after SEMS placement and did not recur after stent removal. All benign strictures recurred after stent removal. Adverse events included migration (14%), chest pain (11%), and dysphagia from tissue hyperplasia (6%). There was no stent-related mortality. LIMITATIONS: Nonrandomized, single-center study. CONCLUSION: The new esophageal SEMS was effective in relieving malignant dysphagia, allowed for precise placement, and was easily removable. It was effective in treating benign esophageal fistulas and leaks. Stent-related adverse events were acceptable.

Long-term outcomes of endoscopic submucosal dissection for undifferentiated type early gastric cancer over 2 cm with R0 resection.

BACKGROUND: Endoscopic submucosal dissection (ESD) for over 2 cm in size undifferentiated type (UD type) early gastric cancer (EGC) confined to the mucosa is not only challenging, but also long-term outcomes are not well known. AIM: To evaluate the long-term outcomes of ESD done for UD type EGCs confined to the mucosa over 2 cm in size and compare the results with those where the lesions were less than 2 cm. METHODS: 143 patients with UD type EGC confirmed on histology after ESD at a tertiary hospital were reviewed. Cases with synchronous and metachronous lesions and a case with emergency surgery after ESD were excluded. A total of 137 cases were enrolled. 79 cases who underwent R0 resection were divided into 2 cm or less (group A) and over 2 cm (group B) in size. RESULTS: Among 79 patients who underwent R0 resection, the number in group A and B were 51 and 28, respectively. The mean follow-up period (SD) was 79.71 ± 45.42 months. There was a local recurrence in group A (1/51, 2%) and group B (1/28, 3.6%) respectively. This patient in group A underwent surgery while the patient in group B underwent repeated ESD with no further recurrences in both patients. There was no regional lymph node metastasis, distant metastasis, and deaths in both groups. With R0 resection strategy for ESD on lesions over 2 cm, 20.4% (28/137) of patients were able to avoid surgery compared with expanded indication. CONCLUSION: If R0 resection is achieved by ESD, UD type EGCs over 2 cm also showed good and similar clinical outcomes as compared to lesions less than 2 cm when followed for over 5 years. With R0 resection strategy, several patients can avoid surgery.

Characterization of an oligometastatic state in patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy.

PURPOSE/OBJECTIVES: Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. MATERIALS/METHODS: Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine-based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan-Meier method and compared between groups via the log-rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. RESULTS: 121 patients were included with a median age of 62 years (37-86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19-9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19-9 (p = 0.03). In those patients that normalized their CA 19-9, median overall survival was 16 months. CONCLUSIONS: In this exploratory analysis normalization of CA-19-9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non-metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor-directed interventions.

Fully covered self-expandable metal stents (SEMS), partially covered SEMS and self-expandable plastic stents for the treatment of benign esophageal ruptures and anastomotic leaks.

BACKGROUND: Benign esophageal ruptures and anastomotic leaks are life-threatening conditions that are often treated surgically. Recently, placement of partially and fully covered metal or plastic stents has emerged as a minimally invasive treatment option. We aimed to determine the clinical effectiveness of covered stent placement for the treatment of esophageal ruptures and anastomotic leaks with special emphasis on different stent designs. METHODS: Consecutive patients who underwent placement of a fully covered self-expandable metal stent (FSEMS), a partially covered SEMS (PSEMS) or a self-expanding plastic stent (SEPS) for a benign esophageal rupture or anastomotic leak after upper gastrointestinal surgery in the period 2007-2010 were included. Data on patient demographics, type of lesion, stent placement and removal, clinical success and complications were collected RESULTS: A total of 52 patients received 83 esophageal stents (61 PSEMS, 15 FSEMS, 7 SEPS) for an anastomotic leak (n=32), iatrogenic rupture (n=13), Boerhaave's syndrome (n=4) or other cause (n=3). Endoscopic stent removal was successful in all but eight patients treated with a PSEMS due to tissue ingrowth. Clinical success was achieved in 34 (76%, intention-to-treat: 65%) patients (PSEMS: 73%, FSEMS: 83%, SEPS: 83%) after a median of 1 (range 1-5) stent and a median stenting time of 39 (range 7-120) days. In total, 33 complications in 24 (46%) patients occurred (tissue in- or overgrowth (n=8), stent migration (n=10), ruptured stent cover (all Ultraflex; n=6), food obstruction (n=3), severe pain (n=2), esophageal rupture (n=2), hemorrhage (n=2)). One (2%) patient died of a stent-related cause. CONCLUSIONS: Covered stents placed for a period of 5-6 weeks may well be an alternative to surgery for treating benign esophageal ruptures or anastomotic leaks. As efficacy between PSEMS, FSEMS and SEPS is not different, stent choice should depend on expected risks of stent migration (SEPS and FSEMS) and tissue in- or overgrowth (PSEMS).