Ex vivo comparative study using the Endolifter® as a traction device for enhancing submucosal visualization during endoscopic submucosal dissection

Background

Endoscopic submucosal dissection (ESD) is a technically demanding procedure, and exposure of the submucosa depends on the action of gravity and submucosal injection. The aim of the study was to investigate the effectiveness of the Endolifter^® as a traction device for enhancing submucosal visualization during ESD.

Methods

This was a prospective ex vivo comparative study conducted between September 2010 and March 2011 in the Prince of Wales Hospital. Consecutive ESDs were performed by four experienced endoscopists in an ex vivo ESD model with or without the Endolifter^®. The Endolifter^® allows simultaneous grasping, retracting and lifting of the mucosa during ESD, resulting in exposure of the submucosa. Each of the procedures were recorded and reviewed later by two independent assessors. The outcome measures included the proportion of time that the submucosa was visualized during the procedures (SM ratio), procedural times, perforation rates, amount of submucosal injections, and the difficulty of the procedure.

Results

Forty-eight gastric ESD procedures were performed on the model. The SM ratio was higher in the Endolifter^® group (P = 0.007), particularly for lesions located at the antrum (P < 0.001). The time required for submucosal dissection and the total procedural time were also less in the Endolifter^® group. The endoscopists rated the ESD procedures in the Endolifter^® group as less difficult (P = 0.033).

Conclusions

The Endolifter^® improved submucosal visualization during gastric ESD and reduces the difficulty of performing the procedures. The device may improve the ease of performing ESD in low-volume centers or large mucosal lesions.     

Laparoscopic repair of giant hiatus hernia: prosthesis is not required for successful outcome

Background

Giant hiatus hernia (GHH) are difficult to manage effectively. This study reports a laparoscopic, prosthesis-free technique to repair of GHH.

Methods

Retrospective analysis of a prospectively populated database of a single surgeon’s experience of GHH (>30 % intrathoracic stomach) repair using a novel, uniform technique was performed. Routine postoperative endoscopy, quality of life (QOL), and Visick scoring was conducted.

Results

Surgery was conducted in 100 patients (70F, 30 M). Mean (standard deviation [SD]) age was 69.1 (±11.4), median (interquartile range) ASA was 2 (range, 2–3), and mean (SD) body mass index (BMI) was 29.1 (±4.5). Mean follow-up was 574.1 (±240.5) days. One (1 %) patient was converted to an open procedure due to technical issues. Median stay was 2.5 days (range, 2–4). One postoperative death occurred secondary to respiratory sepsis. Eight (8 %) patients had perioperative complications: 4 major (PE, non-ST elevation MI, postoperative bleed managed conservatively, infected mediastinal fluid collection); and 4 minor (pneumothorax, asymptomatic troponin leak, subacute small bowel obstruction, and urinary retention). Ninety-nine (99 %) patients had objective screening for recurrence at 3–6 months. Two (2 %) patients have had symptomatic recurrence of their hiatus hernia; both involved a recurrent fundal herniation. Another seven (7 %) had small (<2 cm), asymptomatic recurrences diagnosed only on routine follow-up. Seven (7 %) patients have required reintervention for dysphagia with endoscopic dilatation conducted to good effect in all cases. Two (2 %) patients have required revisional surgery: one for a symptomatic recurrence at 3 months and a second for recurrent mediastinal collection. The Visick score fell from a mean (SD) of 3 (±1.1) to 1.7 (±0.8) postoperatively (p < 0.0001). The mean (SD) QOL preoperatively was 87.8 (±24) versus 109.1 (±22.3) postoperatively (p < 0.0001).

Conclusions

GHH can be managed safely and effectively laparoscopically, without the use of a prosthesis.     

Postablation Stimulated Thyroglobulin Level is an Important Predictor of Biochemical Complete Remission after Reoperative Cervical Neck Dissection in Persistent/Recurrent Papillary Thyroid Carcinoma

Background

The efficacy of reoperative cervical neck dissection (RND) in achieving biochemical complete remission (BCR) (or postreoperation stimulated thyroglobulin [sTg] of <0.5 ng/mL) remains unclear in persistent/recurrent papillary thyroid carcinoma (PTC). We hypothesized that lower postablation sTg levels would indicate a higher rate of BCR after RND. Our study examined the association between postablation sTg and BCR after one or more RNDs.

Methods

Of 199 patients who underwent RND, 81 patients were eligible. The postablation sTg levels (≤2 and >2 ng/mL) were correlated with the postreoperation sTg levels after RNDs. Patients’ clinicopathological characteristics, operative findings, and subsequent RNDs were compared between those with BCR after RNDs and those without.

Results

Those with postablation sTg levels of ≤2 ng/mL had significantly higher BCR rate after the first RND (77.8 vs. 5.6 %, p < 0.001), overall BCR after one or more RNDs (77.8 vs. 9.3 %, p < 0.001), and better 5-year recurrence-free survival after the first RND (80.0 vs. 60.1 %, p = 0.049) than those with postablation sTg levels of >2 ng/mL. Overall BCR gradually decreased after each subsequent RND. Postablation sTg significantly correlated with postreoperation sTg (ρ = 0.509, p < 0.001). After adjusting for the number of metastatic lymph nodes excised at first RND and presence of extranodal extension, postablation sTg of ≤ 0.2 ng/mL was the only independent factor for BCR after one or more RNDs (odds ratio 37.0, 95 % confidence interval 5.68–250.0, p = 0.001).

Conclusions

Only a third of patients who underwent one or more RNDs for persistent/recurrent PTC had BCR afterward. Postablation sTg level was an independent factor for BCR. Completeness of the initial operation is important for the subsequent success of RND.     

A Systematic Review and Meta-Analysis Comparing Laparoscopic Versus Open Gastric Resections for Gastrointestinal Stromal Tumors of the Stomach

Background

This study is a systematic review and meta-analysis that compares the short- and long-term outcomes of laparoscopic gastric resection (LR) versus open gastric resection (OR) for gastric gastrointestinal stromal tumors (GISTs).

Methods

Comparative studies reporting the outcomes of LR and OR for GIST were reviewed.

Results

A total of 11 nonrandomized studies reviewed 765 patients: 381 LR and 384 OR. A higher proportion of high-risk tumors and gastrectomies were in the OR compared with LR (odds ratio, 3.348; 95 % CI, 1.248–8.983; p = .016) and (odds ratio, .169; 95 % CI, .090–.315; p < .001), respectively. Intraoperative blood loss was significantly lower in the LR group [weighted mean difference (WMD), ?86.508 ml; 95 % CI, ?141.184 to ?31.831 ml; p < .002]. The LR group was associated with a significantly lower risk of minor complications (odds ratio, .517; 95 % CI, .277–.965; p = .038), a decreased postoperative hospital stay (WMD, ?3.421 days; 95 % CI, ?4.737 to ?2.104 days; p < .001), a shorter time to first flatus (WMD, ?1.395 days; 95 % CI, ?1.655 to ?1.135 days; p < .001), and shorter time for resumption of oral intake (WMD, ?1.887 days; 95 % CI, ?2.785 to ?.989 days; p < .001). There was no statistically significant difference between the two groups with regard to operation time (WMD, 5.731 min; 95 % CI, ?15.354–26.815 min; p = .594), rate of major complications (odds ratio, .631; 95 % CI, .202–1.969; p = .428), margin positivity (odds ratio, .501; 95 % CI, .157–1.603; p = .244), local recurrence rate (odds ratio, .629; 95 % CI, .208–1.903; p = .412), recurrence-free survival (RFS) (odds ratio, 1.28; 95 % CI, .705–2.325; p = .417), and overall survival (OS) (odds ratio, 1.879; 95 % CI, .591–5.979; p = .285).

Conclusions

LR results in superior short-term postoperative outcomes without compromising oncological safety and long-term oncological outcomes compared with OR.     

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.Cardiovascular disease remains the most important cause of death among patients with CKD,¹ and it is associated with a baseline inflammatory status.^2,3 Atherosclerosis is highly prevalent and advances more rapidly in individuals with renal dysfunction compared with the general population.^4–6 A key role in the development of atherosclerosis is played by leukocyte–endothelial interactions.²CKD is characterized by the progressive retention of a host of solutes. A substantial number of these compounds is protein-bound.^7,8 The indole indoxylsulfate (IS) and the phenolic conjugates p-cresylsulfate (pCS) and p-cresylglucuronide (pCG) are prototype members of this group. Observational data associate these solutes with enhanced cardiovascular damage and progression of kidney failure, and in in vitro experiments, several underlying isolated molecular mechanisms support the link with these observational data.^8–12 Although for all three compounds, one of two key mechanisms of vascular damage (i.e., leukocyte activation or endothelial dysfunction) have been shown in separate in vitro models, they were, to the best of our knowledge, never directly assessed by evaluating the complicated crosstalk between endothelium and leukocytes in an in vivo situation. Intravital microscopy permits in vivo visualization of leukocyte recruitment in translucent tissues in real time. This technique was already applied successfully by our group to study harmful effects of peritoneal dialysis solutions on peritoneal membrane physiology.¹³The present study evaluates the effects of an acute peritoneal superfusion of the protein-bound uremic compounds IS, pCS, and pCG and also, continuous intravenous infusion of IS on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using this intravital microscopic method.     

Siah2‐deficient mice show impaired skin wound repair

Hypoxia is associated with the dermal wound healing process and hypoxia signaling is presumed to be crucial for normal wound repair. The Siah2 ubiquitin ligase controls the abundance of hypoxia‐inducible factor‐1 alpha, and loss of Siah2 results in destabilization of hypoxia‐inducible factor‐1 alpha under hypoxia. Utilizing Siah2^?/? mice we demonstrate that cutaneous wound healing is impaired in these mice. Wounds in Siah2^?/? mice heal slower and are associated with delayed induction of myofibroblast infiltration and reduced collagen deposition. This coincides with delayed angiogenesis and reduced macrophage infiltration into the wounds of Siah2^?/? mice. We furthermore demonstrate that primary Siah2^?/? dermal fibroblasts have reduced migratory capacities and produce less collagen than wild‐type fibroblasts. Additionally, Siah2^?/? fibroblasts showed conserved responses to transforming growth factor‐β at the receptor level (pSmad 2C activation) but reduced responses downstream. Together, our data show, for the first time, that Siah2 is involved as a positive regulator in the wound healing response. Understanding the role of hypoxia signaling in tissue repair and fibrosis and interference with the hypoxia signaling pathway via regulation of Siah2 may provide new targets for clinical regulation of fibrosis and scarring.     

Advanced Imaging Modalities in Early Stage Breast Cancer: Preoperative Use in the United States Medicare Population

Background

Guidelines for breast cancer staging exist, but adherence remains unknown. This study evaluates patterns of imaging in early stage breast cancer usually reserved for advanced disease.

Methods

Surveillance Epidemiology, and End Results data linked to Medicare claims from 1992–2005 were reviewed for stage I/II breast cancer patients. Claims were searched for preoperative performance of computed tomography (CT), positron emission tomography (PET), bone scans, and brain magnetic resonance imaging (MRI) (“advanced imaging”).

Results

There were 67,874 stage I/II breast cancer patients; 18.8 % (n = 12,740) had preoperative advanced imaging. The proportion of patients having CT scans, PET scans, and brain MRI increased from 5.7 % to 12.4 % (P < 0.0001), 0.8 % to 3.4 % (P < 0.0001) and 0.2 % to 1.1 % (P = 0.008), respectively, from 1992 to 2005. Bone scans declined from 20.1 % to 10.7 % (P < 0.0001). “Breast cancer” (174.x) was the only diagnosis code associated with 62.1 % of PET scans, 37.7 % of bone scans, 24.2 % of CT, and 5.1 % of brain MRI. One or more symptoms or metastatic site was suggested for 19.6 % of bone scans, 13.0 % of CT, 13.0 % of PET, and 6.2 % of brain MRI. Factors associated (P < 0.05) with use of all modalities were urban setting, breast MRI and ultrasound. Breast MRI was the strongest predictor (P < 0.0001) of bone scan (odds ratio [OR] 1.63, 95 % confidence interval [CI] 1.44–1.86), Brain MRI (OR 1.74, 95 % CI 1.15–2.63), CT (OR 2.42, 95 % CI 2.12–2.76), and PET (OR 5.71, 95 % CI 4.52–7.22).

Conclusions

Aside from bone scans, performance of advanced imaging is increasing in early stage Medicare breast cancer patients, with limited rationale provided by coded diagnoses. In light of existing guidelines and increasing scrutiny about health care costs, greater reinforcement of current indications is warranted.     

Loss of APKC expression independently predicts tumor recurrence in superficial bladder cancers

ObjectivesEpithelial-mesenchymal transition (EMT) is known to play an important role in the development of tumor invasion and progression in tumors of epithelial origin. Our aim was to investigate the role of tight junction proteins, Par3/Par6/atypical protein kinase C (APKC), Discs large (Dlg), and Scribble in human bladder pathogenesis.MethodsWe evaluated levels of APKC, Dlg, and Scribble in 92 superficial bladder tumors using tissue microarrays and immunohistochemistry, and correlated expression with pathologic variables and clinical outcomes.ResultsThere was a slight apparent enrichment in strong vs. weak staining for APKC (54.9% vs. 45.1%), Dlg (65.7% vs. 34.3%), and a marked enrichment for Scribble (75% vs. 25%) in the superficial bladder tumors. Univariate analysis determined that both tumor focality and APKC expression were significantly associated with tumor recurrence (P < 0.05). Multivariate analysis using the Cox's proportional hazards model revealed that only APKC (P = 0.025) as well as tumor focality (P = 0.018) were independent and significant prognostic factors for tumor recurrence in all patients. We found that no immunohistochemical staining of any of the cell polarity proteins significantly predicted for tumor progression on either univariate or multivariate analysis.ConclusionsLoss of APKC expression in superficial bladder tumors is a strong predictor of tumor recurrence.     

Chicken bone perforation of an irreducible inguinal hernia: a case report and review of the literature

Foreign bodies causing perforation of hernias are extremely uncommon with only a few cases reported in the literature. Here, we present a case of a patient with ingestion of a foreign body, which was initially managed expectantly but developed a perforation due to the foreign body impacting and causing perforation of an irreducible inguinal hernia. Management of this condition usually involves resection of the involved loop of bowel with repair of the hernia defect at the time of surgery. Patients with ingested foreign bodies who have irreducible hernias have altered anatomy and should be considered for early surgical intervention to prevent complications.