Sustained Complete Response after Biological Downstaging in Patients with Hepatocellular Carcinoma: XXL-Like Prioritization for Liver Transplantation or "Wait and See" Strategy?

The XXL trial represents the first prospective validation of "biological downstaging" in liver transplantation (LT) for hepatocellular carcinoma. The aim of this study was to compare the Padua downstaging protocol to the XXL protocol in terms of downstaging failure rates and patient outcome. A total of 191 patients undergoing aggressive surgical downstaging and potentially eligible for LT from 2012 to 2018 at our center were retrospectively selected according to XXL trial criteria. Unlike the XXL trial, patients with a complete response to downstaging did not receive any prioritization for LT. Downstaging failure was defined as stable progressive disease or post-treatment mortality. The statistical method of "matching-adjusted indirect comparison" was used to match the study group to the XXL population. Downstaging failure rate was considerably lower in the study group than in the XXL trial (12% vs. 32%, d value = |0.683|). The survival curves of our LT group (n = 68) overlapped with those of the LT-XXL group (p = 0.846). Survival curves of non-LT candidates with a sustained complete response (n = 64) were similar to those of transplanted patients (p = 0.281). Our study represents a validation of the current Padua and Italian policies of denying rapid prioritization to patients with complete response to downstaging. Such a policy seems to spare organs without worsening patient outcome.

Early outcome of thoracoscopic and hybrid esophagectomy: Propensity-matched comparative analysis.

BACKGROUND: Transthoracic esophagectomy remains the current therapeutic standard for localized esophageal carcinoma. Minimally invasive surgery has proven at least equivalent to open surgery regarding the early outcomes, but only 1 randomized study has compared the thoracoscopic with the thoracotomy approach. The primary objective of this study was to assess the early outcome of the thoracoscopic prone esophagectomy (TPE) and the hybrid Ivor Lewis (HIL) esophagectomy in 2 concurrent patient cohorts. METHODS: We compared the 1-year outcome of 3-stage TPE and 2-stage HIL done over the same time period in a single center. The propensity score matching method was used to reduce selection bias by creating 2 groups of patients similarly likely to receive a treatment on the basis of measured baseline characteristics. After generating propensity scores using the covariates of age, sex, body mass index, forced expiration volume at 1 second, Charlson comorbidity index, American Society of Anesthesiologists score, histologic tumor type, tumor site, pTNM stage, and neoadjuvant therapy, 93 TPE patients were matched with 197 HIL patients using a 1:1 ratio and the nearest-neighbor score matching. Main outcome measure was the incidence of postoperative complications. RESULTS: Operative time was longer in TPE patients (P < .01). All postoperative outcomes, including morbidity, mortality, nodal harvest, R0 resection rate, and 1-year survival rates were similar in the 2 matched groups. CONCLUSION: Both operative approaches are safe and effective; using 1 or the other depends on the tumor site, surgeon experience and preference, and patient expectations.

Current status of minimally invasive endoscopic management for Zenker diverticulum.

Surgical resection has been the mainstay of treatment of pharyngoesophageal (Zenker) diverticula over the past century. Developments in minimally invasive surgery and new endoscopic devices have led to a paradigm change. The concept of dividing the septum between the esophagus and the pouch rather than resecting the pouch itself has been revisited during the last three decades and new technologies have been investigated to make the transoral operation safe and effective. The internal pharyngoesophageal myotomy accomplished through the transoral stapling approach has been shown to effectively relieve outflow obstruction and restore physiological bolus transit in patients with medium size diverticula. Transoral techniques, either through a rigid device or by flexible endoscopy, are gaining popularity over the open surgical approach due the low morbidity, the fast recovery time and the fact that the procedure can be safely repeated. We provide an analysis of the the current status of minimally invasive endoscopic management of Zenker diverticulum.

Long-term outcome and quality of life after transoral stapling for Zenker diverticulum.

AIM: To investigate long-term results and quality of life after transoral stapling of Zenker diverticulum. METHODS: The data of all patients admitted to our institution for the surgical treatment of Zenker diverticulum were entered into a prospective database. Demographics, symptoms, intraoperative and postoperative data, morbidity, time to oral feeding, and length of hospital stay were recorded. All patients underwent upper gastrointestinal endoscopy and a barium swallow study to measure the length of the diverticulum from the apex of the septum to the bottom of the pouch. Transoral stapling was performed using a Weerda diverticuloscope under general anesthesia. Over time, the technique was modified by applying traction sutures to ease engagement of the common septum inside the stapler jaws. Perioperative variables, symptoms, long-term outcome, and quality of life were analyzed. The operation was considered successful if the patient reported complete remission (grade 1) or marked improvement (grade 2) of dysphagia, regurgitation, and respiratory symptoms. Statistical analysis was performed using Statistical Package for Social Science (SPSS, Version 15, SPSS, Inc., Chicago, IL). RESULTS: Between 2001 and 2013, the transoral approach was successfully completed in 100 patients with a median age of 75 years. Patients with a larger (≥3 cm) diverticulum were older than those with a smaller pouch (P<0.038). Complications occurred in 4% of the patients but there was no mortality. A statistically significant improvement of dysphagia and regurgitation scores (P<0.001) was recorded over a median follow-up of 63 mo. Similarly, a significant decrease in the median number of pneumonia episodes per year (P<0.001) was recorded after surgery. The overall long-term success rate of the procedure was 76%. The success rate of the operation was greater in patients of 70 years of age or older compared to younger individuals (P=0.038). Use of traction sutures on the septum was associated with an improved success rate compared with the standard procedure (P=0.04). All items of the health related quality of life questionnaire were significantly higher compared to baseline (P<0.05). CONCLUSION: Transoral stapling is safe and effective. The operation significantly improves patients' quality of life. It appears that elderly patients with large diverticula significantly benefit from the procedure and that the modified surgical technique including traction sutures can further improve the success rate.

Combination of the c-Met inhibitor tivantinib and zoledronic acid prevents tumor bone engraftment and inhibits progression of established bone metastases in a breast xenograft model.

Bone is the most common metastatic site for breast cancer. There is a significant need to understand the molecular mechanisms controlling the engraftment and growth of tumor cells in bone and to discover novel effective therapeutic strategies. The aim of this study was to assess the effects of tivantinib and Zoledronic Acid (ZA) in combination in a breast xenograft model of bone metastases. Cancer cells were intracardially implanted into immunodeficient mice and the effects of drugs alone or in combination on bone metastasis were evaluated by in vivo non-invasive optical and micro-CT imaging technologies. Drugs were administered either before (preventive regimen) or after (therapeutic regimen) bone metastases were detectable. In the preventive regimen, the combination of tivantinib plus ZA was much more effective than single agents in delaying bone metastatic tumor growth. When administered in the therapeutic schedule, the combination delayed metastatic progression and was effective in improving survival. These effects were not ascribed to a direct cytotoxic effect of the combined therapy on breast cancer cells in vitro. The results of this study provide the rationale for the design of new combinatorial strategies with tivantinib and ZA for the treatment of breast cancer bone metastases.