Lung Resection in the Postpneumonectomy Patient.

Pulmonary resection after pneumonectomy is a reasonable option in selected patients. Wedge resection for single peripheral metachronous disease has the best outcome with 5-year survival as high as 63%. Current and predicted postoperative cardiopulmonary reserve should be evaluated carefully. Stereotactic body radiotherapy is a promising alternative for inoperable patients.

Benefits of Supplemental Jejunostomy Tube Feeding During Neoadjuvant Therapy in Patients with Locally Advanced, Potentially Resectable Esophageal Cancer.

BACKGROUND: Standard treatment for locally advanced esophageal cancer includes neoadjuvant therapy followed by surgical resection. However, many patients experience a period of decreased oral intake during neoadjuvant treatment and are at risk for malnutrition. We hypothesize that use of jejunostomy tube (j-tube) feedings during neoadjuvant therapy in selected patients may be associated with better perioperative outcomes. METHODS: A prospectively collected database at a single institution was retrospectively analyzed. The study period was from 2005 to 2015. Patients who underwent j-tube placement before neoadjuvant therapy before definitive resection for esophageal cancer were included in the analysis. Perioperative outcomes were compared between patients who adhered to recommended tube feeds during neoadjuvant therapy (users) and patients who did not adhere (nonusers). RESULTS: During the study period, 94/301 patients received a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds regularly during the neoadjuvant phase, while 21 patients did not. The groups did not differ significantly with respect to clinical factors such as dysphagia on presentation, postneoadjuvant therapy performance status, or Charlson Comorbidity Index. Perioperative pneumonia rates were lower in j-tube users compared to nonusers (6.8% [5 of 73] versus 23.8% [5 of 21]), respectively, P = .036); this difference remained significant with adjustment for type of surgery (odds ratio = 0.16, P = .018). CONCLUSIONS: j-Tube users had a significantly lower incidence of pneumonia within 30 days of curative resection when compared to nonusers. j-Tube feedings during neoadjuvant therapy for selected patients with locally advanced esophageal cancer should be encouraged.

Induction Therapy for Locally Advanced, Resectable Esophagogastric Cancer: A Phase I Trial of Vandetanib (ZD6474), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiotherapy Followed by Resection.

OBJECTIVES: Preoperative chemotherapy and radiation for localized esophageal cancer produces cure rates near 30% when combined with surgical resection. Vandetanib, a small molecule receptor tyrosine kinase inhibitor of VEGFR-2, VEGFR-3, RET, and EGFR, demonstrated synergy with radiation and chemotherapy in preclinical models. We conducted a phase I study to assess the safety and tolerability of vandetanib when combined with preoperative chemoradiation in patients with localized esophageal carcinoma who were surgical candidates. METHODS: Patients with stage II-III esophageal and gastroesophageal junction carcinoma without prior therapy were enrolled in a 3+3 phase I design. Patients received once-daily vandetanib (planned dosing levels of 100, 200, and 300 mg) with concomitant daily radiotherapy (1.8 Gy/d, 45 Gy total) and chemotherapy, consisting of infusional 5-FU (225 mg/m/d over 96 h, weekly), paclitaxel (50 mg/m, days 1, 8, 15, 22, 29) and carboplatin (AUC of 5, days 1, 29). RESULTS: A total 9 patients were enrolled with 8 having either distal esophageal or gastroesophageal junction carcinomas. All patients completed the planned preoperative chemoradiation and underwent esophagectomy. Nausea (44%) and anorexia (44%) were the most common acute toxicities of any grade. One grade 4 nonhematologic toxicity was observed (gastrobronchial fistula). One additional patient suffered a late complication, a fatal aortoenteric hemorrhage, not definitively related to the investigational regimen. Five (56%) patients achieved a pathologic complete response. Three (33%) additional patients had only microscopic residual disease. Five (56%) patients remain alive and disease free with a median follow-up of 3.7 years and median overall survival of 3.2 years. The maximum tolerated dose was vandetanib 100 mg/d. CONCLUSIONS: Vandetanib at 100 mg daily is tolerable in combination with preoperative chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy with encouraging efficacy worthy of future study.

Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

OBJECTIVES: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.

PURPOSE: There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. METHODS AND MATERIALS: We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. RESULTS: A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. CONCLUSIONS: Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning.

Minimally Invasive versus Open Thymectomy for Thymic Malignancies: Systematic Review and Meta-Analysis.

Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online databases and identified studies from 1995 to 2014 that compared minimally invasive to open thymectomy for thymic malignancies. Study end points included operative blood loss, operative time, respiratory complications, cardiac complications, length of hospital stay, R0 resection, and recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated ORs for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios for the number of recurrences, accounting for total person-time observed in each study. Of 516 potential reference studies, 30 with a total of 2038 patients met the inclusion criteria. Patients with Masaoka stage I or II thymic malignancy constituted 94.89% of those in the minimally invasive surgery (MIS) group and 78.62% of those in open thymectomy (open) group. Mean tumor size was 4.09 cm (MIS) versus 4.80 (open). Of the 1355 MIS cases, 32 were converted to open cases. Patients in the MIS group had significantly less blood loss; however, no significant differences in operating time, respiratory complications, cardiac complications, or overall complications were identified. Length of stay was shorter for patients in the MIS group. When patients with Masaoka stage I and II thymic malignancy only were analyzed, there was no difference in rate of R0 resection or overall recurrence rate. One postoperative death occurred in the open group. The results of this unadjusted meta-analysis of published reports comparing minimally invasive with open thymectomy suggest that in selected patients with thymic malignancy, minimally invasive thymectomy is safe and can achieve oncologic outcomes similar to those of open thymectomy.

Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion.

INTRODUCTION: Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. CASE REPORT: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo-oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). DISCUSSION: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. CONCLUSION: To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described.

Esophageal and esophagogastric junction cancers, version 1.2015.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer.

BACKGROUND: The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer. METHODS: Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed. RESULTS: Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks. CONCLUSIONS: A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.

Patterns of survival and recurrence after surgical treatment of early stage non-small cell lung carcinoma in the ACOSOG Z0030 (ALLIANCE) trial.

OBJECTIVE: Surgical resection has been the mainstay of curative treatment of early stage lung cancer in selected patients. We evaluated survival and patterns of recurrence after surgical resection for early stage lung cancer from the American College of Surgeons Oncology Group Z0030/Alliance trial. METHODS: One thousand eighteen patients enrolled in the Z0030 trial were analyzed according to clinical T stage. Differences between groups were compared using the 2-sample rank test or χ(2) test. Log rank test and Cox proportional hazards regression were used to compare survival and recurrence. To compare patients who underwent open versus video-assisted thoracoscopic surgery (VATS) resections, propensity-score matched analysis was performed. Seven hundred fifty-two patients (66 undergoing VATS and 686 undergoing open surgery) were classified into 5 equal-sized propensity-score groups. Proportional hazards regression was used to compare these outcomes. RESULTS: There were 578 patients with cT1 tumors and 440 patients with cT2 tumors. Median follow-up was 6.7 years. Median overall survival was 9.1 years (stage T1) and 6.5 years (stage T2). Overall survival at 5 years was 72% (stage T1) and 55% (stage T2). Local recurrence-free survival at 5 years was 95% (stage T1) and 91% (stage T2) (P = .015). Among patients with stage T1 cancer, 4.2% (23 out of 542) had local recurrences, whereas 7.3% (30 out of 409) of those with stage T2 tumors had local failure. There was no difference in the development of new primary tumors between stage T1 and stage T2 groups. In the propensity-score matched analysis of VATS versus open lobectomy patients, there was no difference in overall survival, disease-free survival, and freedom from development of a new primary tumor. CONCLUSIONS: Results of patients with resected early stage non-small cell carcinoma from a large-scale, multicenter trial serve as benchmarks against which to compare nonsurgical therapies for early stage lung cancer. Propensity-score matched analysis shows no difference in survival between patients undergoing VATS and open lobectomy.

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.

Disparities in access to video-assisted thoracic surgical lobectomy for treatment of early-stage lung cancer.

BACKGROUND: Video-assisted thoracic surgical (VATS) lobectomy was originally described in 1992 and has slowly gained increasing acceptance. This study documents current utilization and outcomes for VATS versus open lobectomy in three Mid-Atlantic states. SUBJECTS AND METHODS: Inpatient discharge claims data were queried for all lobectomies performed for cancer in the Mid-Atlantic United States (New Jersey, New York, and Pennsylvania) between October 2007 and December 2008. Associations between sociodemographic factors and likelihood of undergoing VATS were tested with multiple logistic regressions. Outcomes were compared using two-sample t tests. RESULTS: There were 5489 lobectomies included. Forty-seven percent of patients were men, and 62% were ≥65 years old. Thirty-two percent (1741 of 5489) were VATS lobectomies. Men were less likely to undergo VATS (odds ratio 0.86, P=.004); those ≥65 years old were more likely to undergo VATS (odds ratio 1.34, P=.009). Uninsured patients underwent VATS less often (odds ratio 0.46, P=.01). Patients from rural areas were less likely to undergo VATS (odds ratio 0.67, P=.001), although travel distances for both groups were similar. A total of 44% of these hospitals (125 of 284) performed only open lobectomies. Patients without private insurance or Medicare were less likely to undergo a VATS lobectomy (P=0.01). In general, the likelihood of VATS lobectomy increased as hospital lobectomy volume increased. VATS patients had a shorter median length of stay (5 versus 6 days, P<.001) and a higher rate of discharge to home (92.5% versus 89.5%, P<.001). Mean total hospital costs were less for VATS patients ($49,948 versus $56,280, P<.001). In-hospital mortality was less for VATS patients (1.2% versus 2.1%, P=.013). CONCLUSION: For the period studied, patients in rural areas, in low-volume hospitals, who had Medicaid, or with lower median incomes underwent VATS lobectomy less often.

Benign metastasizing leiomyoma: a rare cause of multiple pulmonary nodules.

Benign metastasizing leiomyoma (BML) is a rare cause of pulmonary nodules that occurs when uterine leiomyomas metastasize to the lung. The management of these lesions varies from resection and hysterectomy to nonsurgical treatments such as hormonal therapy. We report a case of a 45-year-old woman with multiple nodules of the right lung identified during preoperative imaging before her hysterectomy for uterine fibroids.

Initial results of minimally invasive Ivor Lewis esophagectomy after induction chemoradiation (50.4 gy) for esophageal cancer.

OBJECTIVE: Esophageal cancer patients receiving induction chemoradiation to 41 Gy randomized to minimally invasive (MIS) esophagectomy have fewer postoperative pulmonary complications compared with those who underwent open procedures. We evaluated the feasibility of MIS Ivor Lewis esophagectomy in patients treated with induction chemoradiation to 50.4 Gy. METHODS: We retrospectively analyzed clinical data from 30 consecutive patients undergoing MIS Ivor Lewis esophagectomy after induction chemoradiation to a mean dose of 50.4 Gy by a single surgeon at a tertiary institution since 2010. Data collected included patient demographics, preoperative risk factors, neoadjuvant treatment modalities, histology, staging, operative factors, and perioperative complications. RESULTS: The mean age of the patients was 61 ± 9.5 years, and 87% were men. The dominant histology was adenocarcinoma (90%), with most tumors (70%) located at the gastroesophageal junction. A total of 22 patients (73%) presented with dysphagia, but only 15 (50%) had associated weight loss (mean 12.2% total body mass). All patients had R0 resections; mean number of resected lymph nodes was 27.1 ± 11.4. Mean operating room time was 535 ± 120 minutes, with the last 10 operations 2 hours shorter than the preceding 20. Four patients (13.3%) had major complications. including 2 (6.7%) anastomotic leaks. There was no operative mortality. CONCLUSIONS: Minimally invasive Ivor Lewis esophagectomy after chemoradiation to 50.4 Gy can be performed with decreased morbidity and mortality compared with historical series of open Ivor Lewis esophagectomy. Oncologic outcomes were acceptable as demonstrated by lymph node retrieval and complete resection rates. Operative time decreased significantly after 20 cases.

A comparison of perioperative outcomes of video-assisted thoracic surgical (VATS) lobectomy with open thoracotomy and lobectomy: results of an analysis using propensity score based weighting.

BACKGROUND: Randomized trials comparing VATS lobectomy to open lobectomy are of small size. We analyzed a case-control series using propensity score-weighting to adjust for important covariates in order to compare the clinical outcomes of the two techniques. METHODS: We compared patients undergoing lobectomy for clinical stage I lung cancer (NSCLC) by either VATS or open (THOR) methods. Inverse probability of treatment weighted estimators, with weights derived from propensity scores, were used to adjust cohorts for determinants of perioperative morbidity and mortality including age, gender, preop FEV1, ASA class, and Charlson Comorbidity Index (CCI). Bootstrap methods provided standard errors. Endpoints were postoperative stay (LOS), chest tube duration, complications, and lymph node retrieval. RESULTS: We analyzed 136 consecutive lobectomy patients. Operative mortality was 1/62 (1.6%) for THOR and 1/74 (1.4%) for VATS, P = 1.00. 5/74 (6.7%) VATS were converted to open procedures. Adjusted median LOS was 7 days (THOR) versus 4 days (VATS), P < 0.0001, HR = 0.33. Adjusted median chest tube duration (days) was 5 (THOR) versus 3 (VATS), P < 0.0001, HR = 0.42. Complication rates were 39% (THOR) versus 34% (VATS), P = 0.61. Adjusted mean number of lymph nodes dissected per patient was 18.1 (THOR) versus 14.8 (VATS), p = 0.17. CONCLUSIONS: After balancing covariates that affect morbidity, mortality and LOS in this case-control series using propensity-weighting, the results confirm that VATS lobectomy is associated with a statistically significant shorter LOS, similar mortality and complication rates and similar rates of lymph node removal in patients with clinical stage I NSCLC.

Video-assisted thoracic surgery versus open lobectomy for lung cancer: a secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial.

OBJECTIVE: Video-assisted thoracoscopic lobectomy remains controversial. We compared outcomes from participants in a randomized study comparing lymph node sampling versus dissection for early-stage lung cancer who underwent either video-assisted thoracoscopic or open lobectomy. METHODS: Data from 964 participants in the American College of Surgeons Oncology Group Z0030 trial were used to construct propensity scores for video-assisted thoracoscopic versus open lobectomy (based on age, gender, histology, performance status, tumor location, and T1 vs T2). Propensity scores were used to estimate the adjusted risks of short-term outcomes of surgery. Patients were classified into 5 equal-sized groups and compared using conditional logistic regression or repeated measures analysis of variance. RESULTS: A total of 752 patients (66 video-assisted and 686 open procedures) were analyzed on the basis of propensity score stratification. Median operative time was shorter for video-assisted thoracoscopic lobectomy (video-assisted thoracoscopy 117.5 minutes vs open 171.5 minutes; P < .001). Median total number of lymph nodes retrieved (dissection group only) was similar (video-assisted thoracoscopy 15 nodes vs open 19 nodes; P = .147), as were instances of R1/R2 resection (video-assisted thoracoscopy 0% vs open 2.3%; P = .368). Patients undergoing video-assisted thoracoscopic lobectomy had less atelectasis requiring bronchoscopy (0% vs 6.3%, P = .035), fewer chest tubes draining greater than 7 days (1.5% vs 10.8%; P = .029), and shorter median length of stay (5 days vs 7 days; P < .001). Operative mortality was similar (video-assisted thoracoscopy 0% vs open 1.6%, P = 1.0). CONCLUSION: Patients undergoing video-assisted lobectomy had fewer respiratory complications and shorter length of stay. These data suggest video-assisted thoracoscopic lobectomy is safe in patients with resectable lung cancer. Longer follow-up is needed to determine the oncologic equivalency of video-assisted versus open lobectomy.