Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack.

Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.

Patient Self-Assessment of Surgical Site Infection is Inaccurate.

BACKGROUND: Availability of surgical site infection (SSI) surveillance rates challenges clinicians, healthcare administrators and leaders and the public. The purpose of this report is to demonstrate the consequences patient self-assessment strategies have on SSI reporting rates. METHODS: We performed SSI surveillance among patients undergoing general surgery procedures, including telephone follow-up 30 days after surgery. Additionally we undertook a separate validation study in which we compared patient self-assessments of SSI with surgeon assessment. Finally, we performed a meta-analysis of similar validation studies of patient self-assessment strategies. RESULTS: There were 22/266 in-hospital SSIs diagnosed (8.3%), and additional 16 cases were detected through the 30-day follow-up. In total, the SSI rate was 16.8% (95% CI 10.1-18.5). In the validation survey, we found patient telephone surveillance to have a sensitivity of 66% (95% CI 40-93%) and a specificity of 90% (95% CI 86-94%). The meta-analysis included five additional studies. The overall sensitivity was 83.3% (95% CI 79-88%), and the overall specificity was 97.4% (95% CI 97-98%). Simulation of the meta-analysis results divulged that when the true infection rate is 1%, reported rates would be 4%; a true rate of 50%, the reported rates would be 43%. CONCLUSION: Patient self-assessment strategies in order to fulfill 30-day SSI surveillance misestimate SSI rates and lead to an erroneous overall appreciation of inter-institutional variation. Self-assessment strategies overestimate SSIs rate of institutions with high-quality performance and underestimate rates of poor performance. We propose such strategies be abandoned. Alternative strategies of patient follow-up strategies should be evaluated in order to provide valid and reliable information regarding institutional performance in preventing patient harm.

Dumping syndrome following nissen fundoplication in an adult patient diagnosed by continuous online 13C/12C monitoring of ¹³C-Octanoic acid breath test "a case report".

BACKGROUND: Nissen Fundoplication is a common surgical procedure performed in treating gastroesophageal reflux disease (GERD). Complications include dysphagia, gastric hypersensitivity, abnormal gastric motility, gas bloat syndrome and GERD relapse. Dumping syndrome may occur when a large volume of gastric content is delivered to the duodenum or jejunum, resulting in both gastrointestinal and vasomotor symptoms. Occasionally, dumping syndrome may be a complication in patients that have undergone nissen Fundoplication, especially in adults. The BreathID® continuous online 13C-Octanoicoctanoic acid breath test detects variations of less than 1/100,000 in the 13CO2/12CO2 ratio in exhaled air. CASE PRESENTATION: We report a case of a 38 year old male who was admitted and diagnosed with dumping syndrome following nissen Fundoplication, who was diagnosed using the BreathID® continuous online 13C-Octanoic acid breath test. CONCLUSIONS: Early performance of a gastric emptying rate breath test in symptomatic patients, following upper GI tract surgery may help in the prediction or diagnosis of nissen Fundoplication complications such as dumping syndrome.

Colon Cancer-Associated Fusobacterium nucleatum May Originate From the Oral Cavity and Reach Colon Tumors via the Circulatory System.

Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.

Intra-arterial thrombolysis and stent placement for traumatic carotid dissection with subsequent stroke: a combined, simultaneous endovascular approach.

Traumatic carotid dissection is a well-known cause of ischemic stroke and although the treatment of the dissection itself has received some attention in recent years, the treatment of the concomitant stroke has been less investigated. We present a 43-year-old patient with blunt traumatic internal carotid artery dissection associated with subocclusive stenosis and major cerebral thromboembolic complication. Combined, simultaneous intra-arterial fibrinolysis and carotid stenting through a bilateral approach was successfully performed allowing the complete clinical recovery of the patient. Contralateral carotid artery approach allowed the beginning of intra-arterial thrombolysis without delay, while stent-assisted angioplasty of the injured carotid was simultaneously performed. This approach was proved to be safe and effective and may deserve further evaluation.

Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc.

Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.

Preoperative lower esophageal sphincter pressure affects outcome of laparoscopic esophageal myotomy for achalasia.

The primary aim of this study was to identify factors that influence outcome of the surgical treatment of achalasia. A secondary aim was to compare outcomes after laparoscopic Heller myotomy and partial fundoplication using either a Dor or Toupet hemifundoplication. Between 1994 and 2002, a total of 78 patients underwent laparoscopic Heller myotomy and partial fundoplication. Preoperative investigations included esophageal manometry, a videoesophogram, and upper gastrointestinal endoscopy with biopsy. In 64 patients (35 males and 29 females), telephone contact was possible at a median 24 months (IQR 14-34). A Dor fundoplication was performed in 41 patients and a Toupet fundoplication in 23. Symptoms were assessed prior to surgery and at follow-up by an independent physician using standardized definitions to grade the severity of dysphagia, regurgitation, and chest pain. To assess outcome, dysphagia was categorized as persistent or resolved. Persistent was defined as dysphagia that occurred on a weekly or daily basis. Resolved was defined as dysphagia that occurred occasionally or not at all. At follow-up, patients were asked to make a personal evaluation of their outcome as to whether (1) their swallowing was improved by the procedure, (2) they were satisfied with the outcome, and (3) they would undergo surgery again under the same circumstances. There was a significant improvement in dysphagia and regurgitation scores after surgery (P<0.05). The scores for chest pain/heartburn remained unchanged. By physician assessment, dysphagia was resolved in 49 patients (77%) and persisted in 15 (33%). By patient assessment, 62 patients (97%) reported an improvement in the symptom of dysphagia, and 60 (94%) stated that they were satisfied with their improvement and would undergo surgery if they had to make the choice again. On univariate analysis, patients who had resolution of their dysphagia had a significantly higher resting lower esophageal sphincter (LES) pressure prior to myotomy (P=0.01) and on multivariate analysis only a high resting LES pressure prior to surgery was a predictor of resolution of dysphagia (P=0.015). Outcome comparison of patients with Dor and Toupet fundoplications showed no significant differences in physician assessment of postoperative symptom scores and resolution of dysphagia, patient assessment of outcome, or postoperative use of proton pump inhibitors. Ninety-four percent of patients are satisfied with their surgical myotomy for achalasia. By physician assessment dysphagia was resolved in 77% of patients. A high LES resting pressure before surgery predicted resolution of dysphagia.

Surgical management of hypertensive lower esophageal sphincter with dysphagia or chest pain.

Hypertensive lower esophageal sphincter (LES) is an uncommon manometric abnormality found in patients with dysphagia and chest pain, and is sometimes associated with gastroesophageal reflux disease (GERD). Preventing reflux by performing a fundoplication raises concerns about inducing or increasing dysphagia. The role of myotomy in isolated hypertensive LES is also unclear. The aim of this study was to determine the outcome of surgical therapy for isolated hypertensive LES and for hypertensive LES associated with GERD. Sixteen patients (5 males and 11 females), ranging in age from 39 to 89 years, with hypertensive LES (>26 mm Hg; i.e., >95th percentile of our control population) who had surgical therapy between 1996 and 1999 were reviewed. Patients with a diagnosis of achalasia and diffuse esophageal spasm were excluded. All patients had dysphagia or chest pain. Eight of 16 patients had symptoms of GERD, four had a type III hiatal hernia, and four had isolated hypertensive LES pain. Patients with hypertensive LES and GERD or type III hiatal hernia had a Nissen fundoplication, and those with isolated hypertensive LES had a myotomy of the LES with partial fundoplication. Outcome was assessed as follows: excellent if the patient was asymptomatic; good if symptoms were present but no treatment was required; fair if symptoms were present and required treatment; and poor if symptoms were unimproved or worsened. All patients were contacted by telephone for symptom assessment at a median of 3.6 years (range 3 to 6.1 years) after surgery. Patients with hypertensive LES and GERD or type III hiatal hernia had significantly lower LES pressure than those with isolated hypertensive LES (29.9 vs. 47.4 mm Hg; P=0.013). Dysphagia and chest pain were relieved in all patients at long-term follow up. Outcome was excellent in 10 of 16, good in 3 of 16, and fair in 3 of 16. All patients but one were satisfied with their outcome. Patients with hypertensive LES are a heterogeneous group in regard to symptoms and etiology. Treatment of patients with hypertensive LES should be individualized. A Nissen fundoplication for hypertensive LES with GERD or type III hiatal hernia relieves dysphagia and chest pain suggesting reflux as an etiology. A myotomy with partial fundoplication for isolated hypertensive LES relieves dysphagia and chest pain suggesting a primary sphincter dysfunction.

Diagnostic and therapeutic approach to obscure gastrointestinal bleeding in a patient with a jejunal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors of the alimentary tract may present with severe bleeding. Localization and treatment of obscure gastrointestinal bleeding is challenging in cases of negative bi-directional endoscopy. CASE PRESENTATION: A previously healthy 64-year-old Caucasian female presented with clinical signs of active gastrointestinal bleeding. Esophagogastroduodenoscopy was normal, and colonoscopy revealed passage of blood from the small bowel. Computerized tomography angiography demonstrated a hypervascular lesion with active extravasation located in the jejunum. Angiography of the superior mesenteric artery revealed a focal hypervascular mass in the jejunum, and super selective distal coil embolization of the feeding vessel was performed. When the patient was taken for laparoscopic exploration, a 2.5 cm tumor arising from the anti-mesenteric border of the proximal jejunum was identified and resected with primary anastomosis. Pathological results demonstrated a gastrointestinal stromal tumor with a low proliferation index of 1%. Small erosions in the adjacent mucosa confirmed the locus of bleeding. CONCLUSIONS: Computerized tomography is a useful tool for initial diagnosis of submucosal alimentary tumors in patients with obscure but clinically overt gastrointestinal bleeding. Selective angiography, following positive computerized tomography findings, is an important modality to allow both localization and hemostasis in actively bleeding small bowel tumors, but the procedure carries the risk of bowel necrosis. Complete surgical resection remains the mainstay for treatment of gastrointestinal stromal tumors.

Suicide bombing injuries: the Jerusalem experience of exceptional tissue damage posing a new challenge for the reconstructive surgeon.

BACKGROUND: Suicide bomb injuries vary in form and magnitude. From the onset of the second Palestinian "intifada" in October of 2000 until January of 2004, 577 victims of suicide bombings were admitted to the Hadassah-Hebrew University Medical Center. A single bomber carrying a handbag or belt containing multiple metal objects and explosives carried out most of the attacks. As a result, many of the victims suffered massive tissue destruction in addition to conventional blast injuries. METHODS: This article describes the management of this trauma-related "syndrome" of combined primary and high-magnitude secondary blast injury. RESULTS: The management of the extensive soft-tissue damage is described and two representative cases presented. CONCLUSION: Suicide bombing-related injuries in their present form are a true challenge for the reconstructive surgeon.