Repeated Surgical or Endoscopic Myotomy for Recurrent Dysphagia in Patients After Previous Myotomy for Achalasia

Aim

Surgical myotomy of the lower esophageal sphincter has a 5-year success rate of approximately 91 %. Peroral endoscopic myotomy can provide similar results for controlling dysphagia. Some patients experience either persistent or recurrent dysphagia after myotomy. We present here a retrospective analysis of our experience with redo myotomy for recurrent dysphagia in patients with achalasia.

Methods

From March 1996 to February 2015, 234 myotomies for primary or recurrent achalasia were performed in our center. Fifteen patients (6.4 %) had had a previous myotomy and were undergoing surgical redo myotomy (n?=?9) or endoscopic redo myotomy (n?=?6) for recurrent symptoms.

Results

Patients presented at a median of 10.4 months after previous myotomy. Median preoperative Eckardt score was 6. Among the nine patients undergoing surgical myotomy, three esophageal perforations occurred intraoperatively (all repaired immediately). Surgery lasted 111 and 62 min on average (median) in the surgical and peroral endoscopic myotomy (POEM) groups, respectively. No postoperative complications occurred in either group. Median postoperative stay was 3 and 2.5 days in the surgical and POEM groups, respectively. In the surgical group, Eckardt score was <3 for seven out of nine patients after a mean follow-up of 19 months; it was <3 for all six patients in the POEM group after a mean follow-up of 5 months.

Conclusions

A redo myotomy should be considered in patients who underwent myotomy for achalasia and presenting with recurrent dysphagia. Preliminary results using POEM indicate that the technique can be safely used in patients who have undergone previous surgical myotomy.

     

Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10^?6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10^?10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10^?5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10^?9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.     

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial

Background

Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period.

Methods

Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan–Meier analysis and the log-rank test.

Results

The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively).

Conclusions

SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

     

Channels, carriers, and pumps in the pathogenesis of sodium-sensitive hypertension

Sodium-sensitive hypertension is thought to be dependent on primary alterations in renal tubular sodium reabsorption. The major apical plasma membrane Na(+) transporters include the proximal tubular Na(+)-H(+) exchanger, the thick ascending limb Na(+)-K(+)-2Cl(-) cotransport system, the distal tubular Na(+)-Cl(-) cotransporter, and the collecting duct epithelial sodium channel (ENaC). This article explores the role of each transporter in the pathogenesis of hypertension. Although the contribution of the proximal tubule Na(+)-H(+) exchanger is not yet defined completely, more convincing data have been generated about the importance of the Na(+)-K(+)-2Cl(-). Indeed at least 2 forms of hypertension appear to be related to the up-regulation of the transporter: the so-called programmed hypertension induced by low-protein diet during pregnancy and the early phase of hypertension in the Milan strain of rats. With respect to the Na(+)-Cl(-) cotransporter this may be overactive caused by inactivating mutation of WNK4 as in the Gordon syndrome, although it is the main actor for the maintenance phase of the hypertension found in the Milan strain of rats. Finally, the contribution of the ENaC has been established clearly; indeed, in the Liddle syndrome the mutation of the ENaC gene leads to a longer retention of the channel on the cell surface of collecting duct principal cells, thus inducing stronger sodium reabsorption along this segment. All these examples clearly indicate that renal sodium transporters may be responsible for various types of sodium-sensitive hypertension.     

Early assessment of sub-clinical cardiac involvement in systemic sclerosis (SSc) using delayed enhancement cardiac magnetic resonance (CE-MRI)

Objectives

Systemic sclerosis heart involvement (SHI) is one of systemic sclerosis (SSc) most frequent complications, both in diffuse (dcSSc) and limited (lcSSc) cutaneous forms of disease. Nowadays, SHI is a major factor decreasing SSc survival rate because, when clinically evident, is associated with 70% of mortality at 5 years. SHI shows different forms, primary and/or secondary. Primary myocardial SHI is characterized by fibrosis. Aim of our study is to assess the presence and pattern of fibrosis as detected by cardiac magnetic resonance (CMR) in systemic sclerosis.

Methods

In this study, we used CE-MRI (contrast enhanced-MRI) in 58 female SSc patients. Images were evaluated to obtain functional parameters and to see presence, location and pattern (nodular, linear or diffuse) of myocardial LE, sign of fibrosis. CE-MRI findings were correlated with patients clinical setting.

Results

Myocardial fibrosis was detected in 25 of 58 patients (43%). The main finding observed in 16 of these 25 patients was a late enhancement showing a linear pattern, without coronary distribution and sparing the sub-endocardial myocardial layers. A patchy nodular enhancement pattern was observed in 9 patients (36%). Patients with linear pattern presented dcSSc, on the contrary patients with nodular LE displayed the lcSSc form.

Conclusions

This study shows that CE-MRI is a reliable technique to detect SHI earlier than other methods. SHI increase passive myocardial stiffness, proportional to collagen deposition degree, leading to cardiac remodelling with possible development of heart failure, even with normal ejection fraction. An early treatment of SHI might improve SSc patients outcome.     

Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study

Atheroembolic renal disease (AERD) is part of a multisystemic disease accompanied by high cardiovascular comorbidity and mortality. Interrelationships between traditional risk factors for atherosclerosis, vascular comorbidities, precipitating factors, and markers of clinical severity of the disease in determining outcome remain poorly understood. Patients with AERD presenting to a single center between 1996 and 2002 were followed-up with prospective collection of clinical and biochemical data. The major outcomes included end-stage renal disease (ESRD) and death. Ninety-five patients were identified (81 male). AERD was iatrogenic in 87%. Mean age was 71.4 yr. Twenty-three patients (24%) developed ESRD; 36 patients (37.9%) died. Cox regression analysis showed that significant independent predictors of ESRD were long-standing hypertension (hazard ratio [HR] = 1.1; P < 0.001) and preexisting chronic renal impairment (HR = 2.12; P = 0.02); use of statins was independently associated with decreased risk of ESRD (HR = 0.02; P = 0.003). Age (HR = 1.09; P = 0.009), diabetes (HR = 2.55; P = 0.034), and ESRD (HR = 2.21; P = 0.029) were independent risk factors for patient mortality; male gender was independently associated with decreased risk of death (HR = 0.27; P = 0.007). Cardiovascular comorbidities, precipitating factors, and clinical severity of AERD had no prognostic impact on renal and patient survival. It is concluded that AERD has a strong clinical impact on patient and renal survival. The study clearly shows the importance of preexisting chronic renal impairment in determining both renal and patient outcome, this latter being mediated by the development of ESRD. The protective effect of statins on the development of ESRD should be evaluated in a prospective study.     

Endoscopic endonasal approach to the pterygopalatine fossa: anatomic study

OBJECTIVE: The pterygopalatine fossa is a relatively small anatomic region. Because of its rich vasculonervous contents and its connections with several intracranial and extracranial compartments, it is of particular surgical interest. Because of its deep localization and despite its small size, however, it can require extensive anatomic approaches, especially for invasive cranial base lesions. We performed a cadaveric study through a minimally invasive endoscopic endonasal approach to the pterygopalatine fossa. METHODS: We studied 16 pterygopalatine fossae in eight adult cadaveric heads in which the arteries and veins were injected with latex. For visualization, we used rod-lens endoscopes, 4 mm in diameter and 18 cm in length, with 0-, 30-, 45-, and 70-degree lenses. An endonasal middle meatal transpalatine approach, an endonasal middle meatal transantral approach, and an endonasal inferior turbinectomy transantral approach were used. RESULTS: The middle meatal transpalatine approach allows for medial exposure of the pterygopalatine fossa contents, the middle meatal transantral approach allows a lateral view, and the inferior turbinectomy transantral approach allows the widest view and room for surgical maneuvering in the medial and lateral compartments of the pterygopalatine fossa and the infratemporal fossa. CONCLUSION: Our anatomic study shows that this approach can be considered a valid minimally invasive option to approach pterygopalatine fossa lesions.     

Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse

Healing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes‐related healing defect using an incisional skin‐wound model produced on the back of female diabetic mice (db+/db+) and their normal littermates (db+/+m). Animals were treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 μL 0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, to assay angiogenesis and tissue remodeling through histological evaluation, and to study CD31, Angiopoietin‐1 and Transglutaminase‐II. Furthermore, we measured wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an increased VEGF message (vehicle=1.0±0.2 n‐fold vs. β‐actin; PDRN=1.5±0.09 n‐fold vs. β‐actin) and protein wound content on day 6 (vehicle=0.3±0.07 pg/wound; PDRN=0.9±0.1 pg/wound). PDRN injection improved the impaired wound healing and increased the wound‐breaking strength in diabetic mice. PDRN also caused a marked increase in CD31 immunostaining and induced Transglutaminase‐II and Angiopoietin‐1 expression. Furthermore, the concomitant administration of 3,7‐dimethyl‐1‐propargilxanthine, a selective adenosine A2A receptor antagonist, abolished PDRN positive effects on healing. However, 3,7‐dimethyl‐1‐propargilxanthine alone did not affect wound healing in both diabetic mice and normal littermates. These results suggest that PDRN might be useful in wound disorders associated with diabetes.     

Recurrences, testicular growth and semen parameters after laparoscopic Palomo varicocelectomy

The aim of this study was to evaluate the influence of laparoscopic Palomo varicocelectomy on testicular volume and sperm parameters. Laparoscopic Palomo varicocelectomy was performed on 91 patients for left-sided grade II and grade III varicoceles. Ultrasound-derived testicular volumes, semen volume, sperm concentration, percentage sperm motility and total motile sperm count were compared before and after the procedure. Postoperative complications and recurrence rate were also assessed. There were no surgical complications. Four patients (5%) had a mild hydrocele, but did not need hydrocelectomy. No patients presented signs of testicular atrophy and the left testicular volume increased in the adolescents (p < 0.05), but not in the adults. Our data suggest that laparoscopic high mass ligation of both the testicular artery and vein is a highly effective, reliable method for the treatment of varicocele. It is associated with very low complication and recurrence rates and with an objective improvement in fertility parameters.     

Use of StarClose for brachial artery closure after percutaneous endovascular interventions

The objective of this study was to evaluate a percutaneous extravascular closure device (StarClose, Abbott Vascular, Redwood City, CA) after brachial endovascular approach. From 2004 to 2006, 29 patients received StarClose for brachial closure. Primary endpoints were successful deployment and absence of procedure-related morbidity, secondary endpoints were brachial artery patency on duplex and absence of late (> 30 days) complications. The device was successfully deployed in all patients. In two patients (6.8%) local complications occurred: one patient developed a large hematoma successfully treated with prolonged compression and a second patient presented with brachial artery occlusion requiring operative intervention. After a mean follow-up of 7.5+/-7.2 months, all patients had a palpable brachial/radial pulse; none had signs of infection, distal embolization or neurological deficits. On ultrasound b-mode imaging, the clip was visible as a 4 mm echolucent area at the outer anterior wall of the artery. Based on the peak systolic velocity ratios between the site of StarClose and proximal brachial artery (mean 1.08+/-0.2), none of the studied patients had a significant stenosis at the site of closure. StarClose is safe and effective in providing hemostasis following interventional procedures through the brachial artery; further advantages include patients comfort and early discharge.