Preoperative Patient Expectations of Postoperative Pain Are Associated with Moderate to Severe Acute Pain After VATS.

OBJECTIVE: The goal of this post hoc analysis of subjects from a prospective observational study was to identify the predictors of patients developing moderate to severe acute pain (mean numerical rating scale [NRS] ≥4, 0-10) during the first three days after video-assisted thoracoscopic surgery (VATS) from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Results from 82 patients who were enrolled one week before VATS and evaluated during the first three postoperative days are presented. The primary outcome variable of the current study was the presence of moderate to severe acute pain after VATS. RESULTS: Fifty-nine percent (95% confidence interval, 47-69%) of study subjects developed moderate to severe acute pain after VATS. Factors univariately associated with the presence of moderate to severe acute pain were greater average expected postoperative pain, greater pain to a suprathreshold cold stimulus, and longer durations of surgery and hospital stay (P < 0.05). When considered in the multiple logistic regression models, the patients' preoperative average intensity of expected postoperative pain (NRS, 0-10) was the only measure associated with the moderate to severe acute pain. Average intensity of postoperative pain expected by patients when questioned preoperatively mediated the effect of reported intensity of pain to the suprathreshold cold stimulus for moderate to severe acute pain levels. Preoperative patient expectations had greater predictive value than other assessed variables including psychosocial factors such as catastrophizing or anxiety assessed one week before surgery. CONCLUSIONS: None of the preoperative psychosocial measures were associated with the moderate to severe acute pain after VATS. Average expected postoperative pain was the only measure associated with the development of moderate to severe acute pain after VATS.

Per oral endoscopic myotomy: early experience and safety of a multispecialty approach.

BACKGROUND: Per oral endoscopic myotomy (POEM) has gained increasing popularity for treating achalasia. A multidisciplinary approach may allow safe and early adoption of POEM into clinical practice. MATERIALS AND METHODS: We performed a retrospective review of our initial POEM cases. All procedures were performed by a team of interventional gastroenterologist and thoracic surgeon. We analyzed demographics, comorbidities, achalasia subtypes, length of hospital stay, duration of surgery, morbidity, mortality, length of myotomy, preoperative and postoperative Eckardt scores. RESULTS: Thirty-one consecutive patients underwent POEM during the 24-month period from January 2014 to December 2015. Eighteen patients (58%) had prior non-operative interventions. Average duration of follow-up was 9.6 months. Seventeen patients (66.8%) had follow-up of 12 months and longer. Average preoperative Eckardt score was 6.3 (3-10), median 6. Average postoperative Eckardt score was 1.4 (0-8), median 1, in 1 month and an average 2.2, median 1, in 1 year. Patients with type III achalasia were most refractory to treatment, while patients with type II had the best results. Average LOS was 1.3 days (1-5), median 1 day. Average DOS was 106 min (60-148), median 106. Average LOM was 13 cm (10-15), with median of 13 cm. We had one 30-day mortality secondary to coronary artery disease. Four patients had prior Heller myotomies and underwent a posterior myotomy during POEM, with outcomes similar to patients with no prior myotomy. CONCLUSIONS: We demonstrated safety and efficiency of a multispecialty approach for achalasia with POEM with a low rate of complications.

A Prospective Study of Chronic Pain after Thoracic Surgery.

BACKGROUND: The goal of this study was to detect the predictors of chronic pain at 6 months after thoracic surgery from a comprehensive evaluation of demographic, psychosocial, and surgical factors. METHODS: Thoracic surgery patients were enrolled 1 week before surgery and followed up 6 months postsurgery in this prospective, observational study. Comprehensive psychosocial measurements were assessed before surgery. The presence and severity of pain were assessed at 3 and 6 months after surgery. One hundred seven patients were assessed during the first 3 days after surgery, and 99 (30 thoracotomy and 69 video-assisted thoracoscopic surgery, thoracoscopy) patients completed the 6-month follow-up. Patients with versus without chronic pain related to thoracic surgery at 6 months were compared. RESULTS: Both incidence (P = 0.37) and severity (P = 0.97) of surgery-related chronic pain at 6 months were similar after thoracotomy (33%; 95% CI, 17 to 53%; 3.3 ± 2.1) and thoracoscopy (25%; 95% CI, 15 to 36%; 3.3 ± 1.7). Both frequentist and Bayesian multivariate models revealed that the severity of acute pain (numerical rating scale, 0 to 10) is the measure associated with chronic pain related to thoracic surgery. Psychosocial factors and quantitative sensory testing were not predictive. CONCLUSIONS: There was no difference in the incidence and severity of chronic pain at 6 months in patients undergoing thoracotomy versus thoracoscopy. Unlike other postsurgical pain conditions, none of the preoperative psychosocial measurements were associated with chronic pain after thoracic surgery.

A Matched Survival Analysis of Lung Transplant Recipients With Coronavirus Disease 2019-Related Respiratory Failure.

BACKGROUND: Lung transplantation is an acceptable and potentially life-saving treatment option for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome and pulmonary fibrosis. This study was conducted to determine whether recipients of lung transplantation (LT) for COVID-19-related lung disease have comparable outcomes to other recipients with a similar level of lung dysfunction. METHODS: The Organ Procurement and Transplant Network database was queried for adult LT candidates between 2006 and 2021. Recipients with COVID-19-related respiratory failure were matched 1:2 using a nearest-neighbor algorithm. Kaplan-Meier methods with log-rank tests were used to compare long-term survival. A proportional hazards model was used to calculate risk of death. RESULTS: A total of 37,333 LT candidates from all causes were compared with 334 candidates from COVID-19-related respiratory failure. COVID-19 recipients were more likely to be younger (50 vs 57 years, P < .001), male (79% vs 60%, P < .001), require extracorporeal membrane oxygenation (56.3% vs 4.0%, P < .001), and have worse lung function (lung allocation score, 82.4 vs 47.8; P < .001) at transplantation. Subsequently, 227 COVID-19 recipients were matched with 454 controls. Patients who received a transplant for COVID-19 had similar rates of mechanical ventilation, extracorporeal membrane oxygenation, postoperative complications, and functional status at discharge compared with controls. There was no difference in overall survival or risk of death from COVID-19 (hazard ratio, 0.82; 95% CI, 0.45-1.53; P = .54). CONCLUSIONS: Six-month survival for recipients of LT for COVID-19-related respiratory failure was comparable to that of other LT recipients.

Interprofessional veno-veno bypass simulation improved team confidence.

BACKGROUND: Rarely performed procedures can cause stress and communication challenges in emergency situations. A simulation was developed to practice and improve team performance and procedural workflow when it has been determined that a liver transplant patient will need veno-veno bypass. The scenario involved a patient predetermined to need veno-veno bypass to allow team members to practice procedural workflow and communication. The simulation used a checklist outlining steps of the procedure and expected communication needed among surgeon, anesthesiologist, nurses, and perfusion team members. Perfusion and nursing supplied equipment to simulate the veno-veno bypass. Debriefing and a brief survey followed the simulation. RESULTS: During the simulation participants performed steps outlined in the checklist. During debriefing, discussion occurred regarding equipment usage, step order, time documentation, and medication use. Additional discussions occurred regarding modifying perfusion tubing and supplies. Participants rated their confidence in understanding communication (4.2), ability to work with others (4.6), knowledge of supplies (4.4), and use of closed-loop communication (4.4) on a scale of 1 (not at all confident) to 5 (extremely confident) (n = 5). CONCLUSION: Participants concluded going through veno-veno bypass steps was a positive experience. Surgeons acknowledged there were multiple ways to perform this procedure and agreed it should be done the same way each time for standardization. Nursing staff commented they liked reviewing equipment in a nonemergency situation. The checklist will be turned into a resource for future operating room procedures. The perfusion team made modifications to their equipment based on surgeon recommendations. Future training is planned when new members join the team.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. Design, Setting, and Participants: This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Exposures: Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. Main Outcomes and Measures: MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Results: Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Conclusions and Relevance: Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Impact of paravertebral blocks on analgesic and non-analgesic outcomes after video-assisted thoracoscopic surgery: A propensity matched cohort study.

BACKGROUND: Regional analgesic techniques such as paravertebral blocks (PVBs) have been popularized for analgesia following video-assisted thoracoscopic surgery (VATS). In this single center retrospective propensity matched cohort of subjects, we investigate the impact of paravertebral blocks on the analgesic and non-analgesic outcomes. METHODS: Institutional database was queried to identify all patients undergoing VATS between January 2013 and July 2019 and these patients were divided into those who received paravertebral blocks in combination with general anesthesia (GA) [PVB group] and those who received GA without paravertebral blocks [GA group]. Propensity score matching based on common patient confounders were used to identify patients in each group. Primary outcomes of the study were average pain scores and opioid consumption in the first 24 hours. Secondary analgesic outcomes included pain scores and opioid requirements at other timepoints over the first 48 hours. Non analgesic outcomes were obtained from STS General Thoracic Surgery Database and included length of hospital stay, need for ICU admission, composite outcome of any complication during the hospital course and 30-day mortality. Exploratory analyses were conducted to investigate the impact of PVB on analgesia following different types of surgery and as to whether any other covariates had a greater influence on the included patient centered outcomes. MAIN RESULTS: After propensity score matching, a total of 520 patients (260 per group) were selected for the study out of 1095 patients. The opioid consumption in terms of oral morphine milligram equivalent (MME) [Median (IQR)] for the first 24 hours was significantly lower with the use of PVB [PVB group- 78.5 (96.75); GA group-127.0 (111.5); p<0.001] while the average pain scores in the first 24 hours did not differ significantly [PVB group-4.71 (2.28); GA group-4.85 (2.30); p = 0.70]. The length of hospital stay, opioid requirements at other timepoints, need for ICU admission in the immediate post-operative period and the composite outcome-'any complication' (35% vs 48%) were significantly lower with the use of PVB. Subgroup analysis showed a longer duration of benefit following major lung surgeries compared to others. CONCLUSION: Paravertebral blocks reduced the length of stay and opioid consumption up to 48 hours after VATS without significantly impacting pain scores.

Multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine in patients with post-resection melanoma at high risk of recurrence.

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here. METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For an hypothesized HR of 0.625, one-sided alpha of 0.10, and power 80%, target enrollment was 325 patients. RESULTS: For randomized patients (n=347), arms were well-balanced, and treatment-emergent adverse events were similar for seviprotimut-L and placebo. For the primary intent-to-treat endpoint of RFS, the estimated HR was 0.881 (95% CI: 0.629 to 1.233), with stratified logrank p=0.46. However, estimated HRs were not uniform over the stage randomized strata, with HRs (95% CIs) for stages IIB/IIC, IIIA, IIIB/IIIC of 0.67 (95% CI: 0.37 to 1.19), 0.72 (95% CI: 0.35 to 1.50), and 1.19 (95% CI: 0.72 to 1.97), respectively. In the stage IIB/IIC stratum, the effect on RFS was greatest for patients <60 years old (HR=0.324 (95% CI: 0.121 to 0.864)) and those with ulcerated primary melanomas (HR=0.493 (95% CI: 0.255 to 0.952)). CONCLUSIONS: Seviprotimut-L is very well tolerated. Exploratory efficacy model estimation supports further study in stage IIB/IIC patients, especially younger patients and those with ulcerated melanomas. TRIAL REGISTRATION NUMBER: NCT01546571.

Illuminated Transhiatal Retractor for Mediastinal Dissection During Transhiatal Esophagectomy.

Esophagectomy following preoperative chemoradiation provides the best outcomes in the treatment of early stage esophageal carcinoma. The exposure of the mediastinum during transhiatal esophagectomy is limited. We describe our technique of mediastinal dissection during the transhiatal esophagectomy using a newly developed transhiatal retractor.

Experience with Peroral Endoscopic Myotomy for Achalasia and Spastic Esophageal Motility Disorders at a Tertiary U.S. Center.

BACKGROUND/AIMS: Peroral endoscopic myotomy (POEM) is a novel procedure for the treatment of achalasia and spastic esophageal disorders. Experience with POEM is limited, but its reported outcomes are excellent. It is deemed safe even for patients with prior interventions. METHODS: This retrospective review included patients who underwent POEM at a tertiary US center. POEM was performed in a multidisciplinary approach by advanced endoscopists and foregut surgeons. Clinical success was defined as a post-POEM Eckardt score ≤3. RESULTS: A total of 125 patients were included. Median follow-up period was 18 months (interquartile range, 10-22 months). Clinical success was achieved in 92% of patients and persisted at 12 months in 88% of patients. Mucosal barrier failure (MBF) occurred in 7 patients, 2 of whom required surgical intervention. MBF was more common in patients with prior laparoscopic Heller myotomy (19% vs. 3%, p=0.015). MBF requiring surgical intervention occurred early in the learning curve. CONCLUSION: POEM is safe and effective in the treatment of achalasia and spastic esophageal disorders even after failed prior interventions.

Safety and Efficacy of Stereotactic Body Radiation Therapy for Locoregional Recurrences After Prior Chemoradiation for Advanced Esophageal Carcinoma.

Purpose: This study aimed to investigate the feasibility of stereotactic body radiation therapy (SBRT) as salvage therapy for locally recurrent esophageal cancer. We hypothesized that SBRT would provide durable treated tumor control with minimal associated toxicity in patients with progressive disease after definitive radiation, chemotherapy, and surgical resection. Methods: This single-institution retrospective study assessed outcomes in patients who received SBRT for locoregional failure of esophageal cancer after initial curative-intent treatment. Only patients who had received neoadjuvant chemoradiation (≥41.4 Gy) for esophageal cancer were selected. Subsequent surgical resection was optional but institutional follow-up by an oncologist was required. The primary endpoints of this study were gastrointestinal and constitutional toxicity, scored with the Common Terminology Criteria for Adverse Events v5.0. A secondary outcome, treated-tumor control, was assessed with RECIST v1.1. Results: Nine patients (11 locoregional recurrences) treated with SBRT were reviewed, with a median follow-up time of 10.5 months. Most patients initially presented with T3 (88.9%), N1 (55.6%), moderately differentiated (66.7%) adenocarcinoma (88.9%), and had received a median 50.4 Gy delivered over 28 fractions with concurrent carboplatin/paclitaxel chemotherapy followed by surgical resection. Median time to recurrence was 16.3 months. Median total dose delivered by SBRT was 27.5 Gy (delivered in five fractions). Two patients experienced acute grade 1 fatigue and vomiting. No patient experienced grade 3 or higher toxicity. One patient experienced failure in the SBRT treatment field at 5.8 months after treatment and six patients developed distant failure. The median progression-free survival time for SBRT-treated tumors was 5.0 months, and median overall survival time was 12.9 months. Conclusions: This single-institution study demonstrated the feasibility of SBRT for locoregional recurrence of esophageal cancer with minimal treatment-related toxicity and high rates of treated tumor control. Prospective studies identifying ideal salvage SBRT candidates for locoregional failure as well as validating its safety are needed.

The Effect of Improving Basic Preventive Measures in the Perioperative Arena on Staphylococcus aureus Transmission and Surgical Site Infections: A Randomized Clinical Trial.

Importance: Surgical site infections increase patient morbidity and health care costs. The Centers for Disease Control and Prevention emphasize improved basic preventive measures to reduce bacterial transmission and infections among patients undergoing surgery. Objective: To assess whether improved basic preventive measures can reduce perioperative Staphylococcus aureus transmission and surgical site infections. Design, Setting, and Participants: This randomized clinical trial was conducted from September 20, 2018, to September 20, 2019, among 19 surgeons and their 236 associated patients at a major academic medical center with a 60-day follow-up period. Participants were a random sample of adult patients undergoing orthopedic total joint, orthopedic spine, oncologic gynecological, thoracic, general, colorectal, open vascular, plastic, or open urological surgery requiring general or regional anesthesia. Surgeons and their associated patients were randomized 1:1 via a random number generator to treatment group or to usual care. Observers were masked to patient groupings during assessment of outcome measures. Interventions: Sustained improvements in perioperative hand hygiene, vascular care, environmental cleaning, and patient decolonization efforts. Main Outcomes and Measures: Perioperative S aureus transmission assessed by the number of isolates transmitted and the incidence of transmission among patient care units (primary) and the incidence of surgical site infections (secondary). Results: Of 236 patients (156 [66.1%] women; mean [SD] age, 57 [15] years), 106 (44.9%) and 130 (55.1%) were allocated to the treatment and control groups, respectively, received the intended treatment, and were analyzed for the primary outcome. Compared with the control group, the treatment group had a reduced mean (SD) number of transmitted perioperative S aureus isolates (1.25 [2.11] vs 0.47 [1.13]; P = .002). Treatment reduced the incidence of S aureus transmission (incidence risk ratio; 0.56; 95% CI, 0.37-0.86; P = .008; with robust variance clustering by surgeon: 95% CI, 0.42-0.76; P < .001). Overall, 11 patients (4.7%) experienced surgical site infections, 10 (7.7%) in the control group and 1 (0.9%) in the treatment group. Transmission was associated with an increased risk of surgical site infection (8 of 73 patients [11.0%] with transmission vs 3 of 163 [1.8%] without; risk ratio, 5.95; 95% CI, 1.62-21.86; P = .007). Treatment reduced the risk of surgical site infection (hazard ratio, 0.12; 95% CI, 0.02-0.92; P = .04; with clustering by surgeon: 95% CI, 0.03-0.51; P = .004). Conclusions and Relevance: Improved basic preventive measures in the perioperative arena can reduce S aureus transmission and surgical site infections. Trial Registration: ClinicalTrials.gov Identifier: NCT03638947.

Peroral Endoscopic Myotomy Is Feasible and Safe in a Gastric Bypass Population.

BACKGROUND: Obesity is public health problem of epidemic proportions. Esophageal dysmotility including achalasia is more commonly seen in an obese population. Standard therapy for achalasia can be complicated by hepatomegaly and a post-surgical anatomy in a pre- and post-bariatric population. Peroral endoscopic myotomy (POEM) has not been adequately studied in this population. METHODS: A retrospective review of a prospectively collected database was completed. Patients who had undergone a Roux-en-y gastric bypass (RYGB) prior to or following a POEM were enrolled. Patient demographics, operative information and post-operative course data was collected. RESULTS: Six patients underwent POEM prior to or after RYGB. There were no peri-operative complications with an average length of stay of 1.2 days. Five patients experienced a clinical success with excellent symptom resolution. The one failure was in the setting of type III achalasia, but did have objective evidence of lower esophageal sphincter (LES) relaxation post-operatively. CONCLUSION: POEM in the setting of bariatric surgery is safe and feasible. The potential increase in GERD following POEM is obviated by RYGB anatomy. In an obese individual, a staged POEM prior to or following a RYGB is an appropriate treatment algorithm for obese and achalasia.

Timing of Esophagectomy after Neoadjuvant Chemoradiation Therapy Affects the Incidence of Anastomotic Leaks.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) has become the standard of care for esophageal cancer patients prior to esophagectomy. However, the optimal timing for surgery after completion of nCRT remains unclear. METHODS: A retrospective review was performed of patients who underwent esophagectomy with cervical anastomosis for esophageal cancer at a single institution between January 2000 and June 2015. Patients were categorized into 3 cohorts: those who did not receive nCRT prior to esophagectomy (no nCRT), those who underwent esophagectomy within 35 days after nCRT (≤35d), and those who underwent esophagectomy more than 35 days after nCRT (>35d). RESULTS: A total of 366 esophagectomies were performed during the study period, and 348 patients met the inclusion criteria. Anastomotic leaks occurred in 11.8% of all patients included in the study (41 of 348). Within each cohort, anastomotic leaks were detected in 14.7% of patients (17 of 116) in the no nCRT cohort, 7.3% (13 of 177) in the ≤35d cohort, and 20.0% (11 of 55) in the >35d cohort (p=0.020). Significant differences in the occurrence of anastomotic leaks were observed between the no nCRT and ≤35d cohorts (p=0.044), and between the ≤35d and >35d cohorts (p=0.007). CONCLUSION: Esophagectomy with cervical anastomosis within 35 days of nCRT resulted in a lower percentage of anastomotic leaks.

Pioneers of Breast Implant-Associated Anaplastic Large Cell Lymphoma: History from Case Report to Global Recognition.

The first case of breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) was described by John Keech and the late Brevator Creech in 1997. In the following 2 decades, much research has led to acceptance of breast implant ALCL as a specific clinicopathologic entity, a process that we bring up to life through the memories of 6 persons who were involved in this progress, although we acknowledge that many others also have contributed to the current state of the art of this disease. Dr. Keech recalls the events that led him and Creech to first report the disease. Ahmet Dogan and colleagues at the Mayo Clinic described a series of 4 patients with breast implant ALCL, and led to increased awareness of breast implant ALCL in the pathology community. Daphne de Jong and colleagues in the Netherlands were the first to provide epidemiologic evidence to support the association between breast implants and ALCL. Garry Brody was one of the first investigators to collect a large number of patients with the disease, present the spectrum of clinical findings, and alert the community of plastic surgeons. Roberto Miranda and L. Jeffrey Medeiros and colleagues studied the pathologic findings of a large number of cases of breast implant ALCL, and published the findings in 2 impactful studies in the medical oncology literature. The recognition and acceptance of this disease by surgeons, epidemiologists, and medical oncologists, working together, has led to subsequent studies on the pathogenesis and optimal therapy of this disease.

Screening Patients with Esophageal Cancer to Determine Eligibility for Adjuvant Treatment Trials.

BACKGROUND: The tolerability of adjuvant chemotherapy in esophageal cancer is unclear. PATIENTS AND METHODS: This was a phase II trial of adjuvant paclitaxel in patients with esophageal cancer after trimodality treatment. Patients with residual viable tumor after resection were eligible for study inclusion. Treatment was 80 mg/m2 paclitaxel intravenously on days 1, 8, and 15 every 28 days for total of two cycles. The primary objective was to determine whether 75% or more of the patients would tolerate 240 mg/m2 or more of paclitaxel, which corresponded to 50% or more of the total planned dose. RESULTS: Eleven out of the 12 enrolled patients (92%, 95% confidence interval (CI)=62-100%) were able to complete at least 50% of the planned paclitaxel dose. Median progression-free survival was 7 months (95% CI=2-28 months). Median overall survival was 28 months (95% CI=12-36 months). Only one patient experienced a grade 4 adverse event. CONCLUSION: Screening patients with esophageal cancer after trimodality treatment might improve completion of adjuvant trials.

Lobar versus sub-lobar surgery for pulmonary typical carcinoid, a population-based analysis.

BACKGROUND: The optimal surgery for resectable pulmonary typical carcinoid (TC), e.g., lobar resection (L-R) vs. sub-lobar resection (SL-R), is controversial. This is further explored in this population-based study. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to select patients ≥66 years old, and diagnosed between 2000 and 2012 with pulmonary TC. A similar cohort was developed using the SEER-Medicare database (diagnosed from 2000-2007) to identify chemotherapy (CTX) use and co-morbidity. Five-year survival was calculated using univariate and multivariate analysis. RESULTS: A total of 1,506 and 512 patients were identified from SEER and SEER-Medicare, respectively. In the SEER cohort, 49%, 29% and 21% received L-R, SL-R, and no surgery (NS), respectively. Those who received NS were older (P<0.001), had a higher stage (P<0.001), greater comorbidity (P<0.001), and were more likely to receive radiotherapy (XRT) (P<0.001) and CTX (P<0.001). Relative survival was nearly 100% for those who received L-R or SL-R as opposed to 72% for those who received NS (P<0.001). Cox models showed no survival difference for L-R vs. SL-R (HR 1.1, P=0.663), but worse survival for those who received NS vs. L-R or SL-R (HR 3.6, P<0.001). XRT in NS cohort was associated with increased risk of death (HR 2.3, P=0.017). CONCLUSIONS: SL-R was better than NS, and similar to L-R in terms of survival. SL-R should be considered over NS if L-R is unfeasible. Role of adjuvant CTX and XRT is unclear as these did not improve survival in this study.

Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring an STK11 variant.

Metastatic triple-negative breast cancer comprises 12%-17% of breast cancers and carries a poor prognosis relative to other breast cancer subtypes. Treatment options in this disease are largely limited to systemic chemotherapy. A majority of clinical studies assessing efficacy of targeted therapeutics (e.g., the mammalian target of rapamycin [mTOR] inhibitor everolimus) in advanced breast cancer patients have not utilized predictive genomic biomarker-based selection and have reported only modest improvement in the clinical outcome relative to standard of care. However, recent reports have highlighted significant clinical responses of breast malignancies harboring alterations in genes involved in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway to mTOR-inhibitor-involving regimens, underscoring the potential clinical benefit of treating subsets of breast cancer patients with molecularly matched targeted therapies. As the paradigm of cancer treatment shifts from chemotherapeutic regimens to more personalized approaches, the identification of additional reliable biomarkers is essential for identifying patients likely to derive maximum benefit from targeted therapies. Herein, we report a near-complete and ongoing 14-mo response to everolimus therapy of a heavily pretreated patient with biphenotypic, metastatic breast cancer. Genomic profiling of the metastatic triple-negative liver specimen identified a single reportable point mutation, STK11 F354L, that appears to have undergone loss of heterozygosity. No other alterations within the PI3K/mTOR pathway were observed. Published functional biochemical data on this variant are conflicting, and germline data, albeit with unclear zygosity status, are suggestive of a benign polymorphism role. Together with the preclinical data, this case suggests further investigation of this variant is warranted to better understand its role as a potential biomarker for mTOR inhibitor sensitivity in the appropriate clinical context.

A Single-Institution Analysis of Thymic Carcinoma Treated with Multi-Modality Therapy.

PURPOSE: Review of our experience in treating thymic carcinoma patients using a combination of surgery, chemotherapy and radiation therapy. METHODS: An institutional review of thymic carcinoma patients treated between 2007 and 2014 was performed analyzing clinical characteristics, treatment intent, surgical margin status, and radiation treatment dose. Survival curves were generated using the Kaplan-Meier method. RESULTS: Nine individuals were treated for newly diagnosed thymic carcinoma. Three patients had unresectable disease at presentation; two of these were treated with definitive chemoradiation therapy while another received neoadjuvant chemotherapy. Seven subjects underwent surgical resection (one after neoadjuvant chemotherapy) with pathological staging ranging from IIa - IVb disease. Patients were planned for adjuvant radiotherapy followed by chemotherapy; however, one developed liver metastases prior to initiating radiotherapy and was therefore treated with palliative chemotherapy alone. A second patient was non-compliant with radiation treatments and was considered as treated with palliative chemotherapy alone. Of the seven patients who completed definitive treatment, median time to progression and overall survival has yet to be reached. Only one of these patients developed progressive disease 10 months after completing treatment and eventually succumbed to disease 41 months after completing definitive therapy. With a median follow up of 30 months, two year overall survival is 67% for all patients. CONCLUSION: Resection with an emphasis on best possible oncologic margins, followed by radiation and chemotherapy remains an effective treatment strategy for advanced stage thymic carcinoma. In patients who present with unresectable tumors, neoadjuvant chemotherapy or definitive chemoradiation therapy may also be considered as viable treatment strategies.