Shirley Y. Liu

Peroral endoscopic myotomy for treatment of achalasia: from bench to bedside (with video).

BACKGROUND Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. OBJECTIVE This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. DESIGN Preclinical animal study and prospective clinical study. PATIENTS Consecutive patients diagnosed with achalasia with high-resolution manometry. INTERVENTIONS POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. MAIN OUTCOME MEASUREMENTS Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. RESULTS Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. LIMITATION Small sample size. CONCLUSIONS POEM is a feasible, safe, and effective treatment for achalasia.

Functional performance and quality of life in patients with squamous esophageal carcinoma receiving surgery or chemoradiation: Results from a randomized trial

Objective:The aim of this study was to compare the 2-year functional performance and quality of life in patients with operable squamous cell carcinoma of the esophagus, who have received either surgery or definitive chemoradiation (CRT). Summary Background Data:The functional outcomes and quality of life in patients receiving esophagectomy or definitive CRT is uncertain. Methods:Data were extracted from the database of a prospective randomized controlled trial that included patients with resectable mid or lower thoracic esophageal cancers. The patients were randomized to either standard esophagectomy or definitive CRT. Quality of life assessments were performed using the EORTC QLQ-C30 and QLQ-OES24 modules. Other functional assessments included pulmonary and eating functions. Results:From July 2000 to December 2004, a total of 81 patients were enrolled into the study. No significant longitudinal changes were detected in the global health status in both groups upon available follow-up. Surgery was associated with worsened physical functioning and fatigue symptoms up to 6 months after treatment (P < 0.001 and P = 0.021, respectively) and these scales improved at 2 years. In terms of pulmonary function, dyspnoic and coughing symptoms were significantly worsened 3 months after surgery (P = 0.024 and P = 0.036, respectively) whereas symptoms in the CRT group progressively deteriorated over time. Concerning the eating function, both groups had improvements in dysphagia but there were frequent need for endoscopic intervention. This study has been registered with clinicaltrials.gov and the clinicaltrials.gov ID number is NCT01032967. Conclusion:Neither surgery nor definitive CRT significantly impaired the global health status of patients. Surgery was associated with a short-term negative impact in some aspects of health related quality of life assessments but these changes became insignificant 2 years after treatment. However, CRT was associated with progressive deteriorations in pulmonary function in the longer term.

Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial

BACKGROUND The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. PATIENTS AND METHODS Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. RESULTS Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. CONCLUSIONS Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.

Radiofrequency Ablation for Benign Aldosterone-Producing Adenoma: A Scarless Technique to an Old Disease

Objective: To evaluate the safety and efficacy of radiofrequency ablation (RFA) in treating primary aldosteronism (PA) due to aldosterone-producing adenoma (APA). Background: Radiofrequency ablation is an established technique for treating malignant solid organ neoplasm. Its application on benign functional adrenal adenoma has never been prospectively described. Methods: We prospectively evaluated a patient cohort with computed tomography (CT)-guided percutaneous RFA performed on functional APA of size 4 cm or less. Treatment success was defined as complete tumor ablation on follow-up CT scan plus normalization of serum aldosterone-to-renin ratio (ARR) at 3 to 6 months after RFA. Salvage laparoscopic adrenalectomy was offered to patients who had failed RFA and remained hypertensive. Results: Between August 2004 and August 2008, 28 patients were referred for the procedure. Radiofrequency ablation was not performed on 4 APA because of their close proximity to major vascular structures. Twenty-four patients (11 men and 13 women) with a median age of 51.5 (range = 34–63) years underwent RFA for 11 right and 13 left APA. The median tumor diameter was 16.0 (range = 4.0–25.0) mm. There was no periprocedure hypertensive crisis or major morbidity or mortality. Minor complications occurred in 4 patients (16.7%), including 1 small pneumothorax and 3 retroperitoneal hematomas (<3 cm), which all resolved on conservative treatment. At 3 to 6 months of follow-up, CT scan showed complete tumor ablation in all patients (100%). Primary aldosteronism was biochemically resolved in 23 patients (95.8%). Salvage adrenalectomy was not performed in the single failed patient, as she remained normotensive on repeated follow-up. The overall success rate of RFA was 95.8%. Conclusions: Computed tomography–guided percutaneous RFA is a safe and efficacious alternative to laparoscopic adrenalectomy in treating patients with PA due to small APA.

The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer

Estrogen receptor (ER) and peroxisome proliferator‐activated receptor gamma (PPARγ) are associated with thyroid tumorigenesis and treatment. However, the interaction between them has not been studied.

Estrogen Receptor α Induces Prosurvival Autophagy in Papillary Thyroid Cancer via Stimulating Reactive Oxygen Species and Extracellular Signal Regulated Kinases

CONTEXT The incidence of papillary thyroid cancer (PTC) shows a predominance in females, with a male:female ratio of 1:3, and none of the known risk factors are associated with gender difference. Increasing evidence indicates a role of estrogen in thyroid tumorigenesis, but the mechanism involved remains largely unknown. OBJECTIVE This study aimed to assess the contribution of autophagy to estrogen receptor α (ERα)-mediated growth of PTC. DESIGN The expression of ERα in thyroid tissue of patients with PTC tissues was analyzed. Cell viability, proliferation, and apoptosis were evaluated after chemical and genetic inhibition of autophagy. Autophagy in PTC cell lines BCPAP and BCPAP-ERα was assessed. RESULTS ERα expression was increased in PTC tissues compared with the adjacent nontumor tissues. Estrogen induced autophagy in an ERα-dependent manner. Autophagy induced by estrogen/ERα is associated with generation of reactive oxygen species, activation of ERK1/2, and the survival/growth of PTC cells. Chemical and genetic inhibition of autophagy dramatically decreased tumor cell survival and promoted apoptosis, confirming the positive role of autophagy in the growth of PTC. CONCLUSIONS ERα contributes to the growth of PTC by enhancing an important prosurvival catabolic process, autophagy, in PTC cells. The inhibition of autophagy promotes apoptosis, implicating a novel strategy for the treatment of ERα-positive PTC.

Inhibition of Foxp3 in cancer cells induces apoptosis of thyroid cancer cells

Foxp3+ regulatory T cells (Tregs) in lymphocytes facilitate the thyroid tumor growth and invasion. Very limited information is available on Foxp3 expression in thyroid cancer cells and its function is totally unknown. This study demonstrated that Foxp3 expression was increased in thyroid cancer cells. Inhibition of Foxp3 decreased cell proliferation and migration, but increased apoptosis, suggesting a positive role of Foxp3 in cancer growth. Interestingly, Foxp3 inhibition enhanced PPARγ expression and activity. In addition, Foxp3 inhibition downregulated NF-κB subunit p65 and cyclin D1 but upregulated caspase-3 levels. These molecular changes are in line with Foxp3 shRNA-mediated alteration of cell functions. Collectively, our study demonstrates that thyroid cancer cells express a high level of functional Foxp3 and that the inhibition of the Foxp3 suppresses the proliferation and migration but promotes apoptosis, suggesting that targeting Foxp3 in thyroid cancer cells may offer a novel therapeutic option for thyroid cancer.

Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review

While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival.

Giant Meckel's diverticulitis: a rare condition complicating pregnancy.

A 33-year-old pregnant woman presented with peritonitis at the right iliac fossa. Preoperative ultrasonography identified an 8-cm tubular structure at the tender point that was mistaken as appendicitis. Emergency operation finally confirmed a 12-cm giant Meckels diverticulum with genuine inflammation and imminent perforation. The patient made an uneventful recovery after Meckels diverticulectomy.

Radiofrequency ablation compared with laparoscopic adrenalectomy for aldosterone-producing adenoma

Radiofrequency ablation (RFA) is an emerging treatment for primary aldosteronism owing to aldosterone‐producing adenoma. Whether RFA could be an alternative treatment to laparoscopic adrenalectomy is unknown.