Ivor Lewis Esophagectomy and the Care of Humphrey Bogart's Midesophageal Cancer.

In 1945, the Welsh surgeon Ivor Lewis first reported performing the resection of a midesophageal tumor through a combined approach involving the abdomen and right chest. Although his technique was initially rebuffed by the preeminent esophageal surgeons of the time, it quickly became the standard approach for cancers of the midesophagus. Here we review the development and early dissemination of Lewis' operation using the case of the American actor Humphrey Bogart, who underwent an Ivor Lewis esophagectomy for esophageal cancer in 1956.

Necroptosis Stimulates Interferon-Mediated Protective Anti-Tumor Immunity.

Necroptosis is an inflammatory form of cell suicide that critically depends on the kinase activity of Receptor Interacting Protein Kinase 3 (RIPK3). Previous studies showed that immunization with necroptotic cells conferred protection against subsequent tumor challenge. Since RIPK3 can also promote apoptosis and NF-κB-dependent inflammation, it remains difficult to determine the contribution of necroptosis-associated release of damage-associated molecular patterns (DAMPs) in anti-tumor immunity. Here, we describe a system that allows us to selectively induce RIPK3-dependent necroptosis or apoptosis with minimal NF-κB-dependent inflammatory cytokine expression. In a syngeneic tumor challenge model, immunization with necroptotic cells conferred superior protection against subsequent tumor challenge. Surprisingly, this protective effect required CD4+ T cells rather than CD8+ T cells and is dependent on host type I interferon signaling. Our results provide evidence that death-dependent type I interferon production following necroptosis is sufficient to elicit protective anti-tumor immunity.

The extent of mediastinal lymph node dissection correlates with survival of small cell lung cancer patients after resection: a propensity score-matched cohort study analysis.

Background: Evidence on the importance of lymph node (LN) dissection during resection for small cell lung cancer (SCLC) is scarce. This study sought to investigate the clinical impact of the extent of lymphadenectomy on the survival of patients with SCLC. Methods: Patients who underwent resection for primary SCLC between 2000 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The patients were stratified based on the number of LNs dissected (0, 1-3, 4-11, and ≥12) via an X-Tile software analysis, and lung cancer-specific survival (LCSS) and overall survival (OS) were compared between these stratified groups using Kaplan-Meier curves. A propensity score-matched analysis and a Cox regression model were used to adjust for potential confounders. Results: A total of 1,883 patients with SCLC met our criteria and were enrolled in the study. The LCSS and OS analyses revealed that patients who underwent LN dissection during surgery had longer survival times significantly than patients who did not. Similarly, patients who underwent more extensive LN dissection (≥4 LNs) had longer survival times than those who underwent less extensive LN dissection (1-3 LNs). However, no significant increase in survival time was found for patients who underwent the dissection of ≥12 LNs compared to those who underwent the dissection of 4-11 LNs. These results were confirmed in our propensity-matched and Cox regression analyses. Conclusions: Our study revealed that patient survival after surgical resection for SCLC is associated with the number of dissected LNs, and the number of LNs for dissection ranges from 4 to 11 achieve the best survival outcome.

Clinical features and prognosis of resectable pulmonary primary invasive mucinous adenocarcinoma.

Background: According to the latest the World Health Organization (WHO) classification in 2015, invasive mucinous adenocarcinoma (IMA) is defined as a new pathological subtype of lung adenocarcinoma (LUAD). However, whether this rare subtype of lung pathology has any difference in prognosis than conventional LUAD is debatable. Our study attempted to compare clinical characteristics and prognosis of IMA vs. noninvasive mucinous adenocarcinomas (NMA). Methods: A total of 1,857 patients with LUAD who underwent radical resection were screened from 2010 to 2015 at Zhejiang Cancer Hospital. Patients with pulmonary IMA were matched 1:1 by using propensity scores with LUAD adjusted for clinicopathological characteristics. After follow-up, overall survival (OS) and disease-free survival (DFS) were explored by Kaplan-Meier and Cox regression analyses. Forest plots were used for subgroup analyses. Results: Following screening, 499 patients with LUAD were enrolled, with 97 IMA and 402 NMA. Compared to NMA of the lung, IMA was proportionately lower in women (50.5% vs. 63.4%; P=0.026) and nonsmokers (P<0.001). IMA was also associated with earlier tumor stage I (68.0% vs. 55.5%; P=0.033) and lower frequency of upper lobe tumors compared to NMA (P=0.007). Following propensity score matching, 97 pairs were selected, among which we found that patients with pulmonary IMA had a longer OS than those with NMA (P=0.014). According to the subgroup analysis, improved OS in the IMA cohort versus the NMA cohort was observed across various factors, including the absence of lymphovascular invasion or perineural invasion. Conclusions: In this study, we found that resectable IMA patients had a better OS than NMA patients. This study contributes to the understanding of IMA in depth, but it needs to be validated through additional multicenter studies.

Tumor-intrinsic and immune modulatory roles of receptor-interacting protein kinases.

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are signaling adaptors that critically regulate cell death and inflammation. Tumors have adapted to subvert RIPK-dependent cell death, suggesting that these processes have key roles in tumor regulation. Moreover, RIPK-driven cancer cell death might bolster durable antitumor immunity. By contrast, there are examples in which RIPKs induce inflammation and aid tumor progression. Furthermore, the RIPKs can exert their effects on tumor growth through regulating the activity of immune effectors in the tumor microenvironment, thus highlighting the context-dependent roles of RIPKs. Here, we review recent advances in the regulation of RIPK activity in tumors and immune cells and how these processes coordinate with each other to control tumorigenesis.

The Impact of Adjuvant Therapy on Survival After Esophagectomy for Node-negative Esophageal Adenocarcinoma.

OBJECTIVE: Determine whether adjuvant chemotherapy is associated with a survival benefit in high risk T2-4a, pathologically node-negative distal esophageal adenocarcinoma. SUMMARY OF BACKGROUND DATA: There is minimal literature to substantiate the NCCN guidelines recommending adjuvant therapy for patients with distal esophageal adenocarcinoma and no pathologic evidence of nodal disease. METHODS: The National Cancer Database was used to identify adult patients with pT2-4aN0M0 esophageal adenocarcinoma who underwent definitive surgery (2004-2015) and had characteristics considered high risk by the NCCN. Patients were stratified by receipt of adjuvant chemotherapy with or without radiation. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox Proportional Hazards models. A 1:1 propensity score-matched analysis was also performed to compare survival between the groups. RESULTS: Four hundred three patients met study criteria: 313 (78%) without adjuvant therapy and 90 who received adjuvant chemotherapy with or without radiation (22%). In both unadjusted and multivariable analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit compared to no adjuvant therapy. In a subgroup analysis of 335 patients without high risk features by NCCN criteria, adjuvant chemotherapy was not independently associated with a survival benefit. CONCLUSION: In this analysis, adjuvant chemotherapy with or without radiation was not associated with a significant survival benefit in completely resected, pathologically node-negative distal esophageal adenocarcinoma, independent of presence of high risk characteristics. The risks and benefits of adjuvant therapy should be weighed before offering it to patients with completely resected pT2-4aN0M0 esophageal adenocarcinoma.

The Assassination of Medgar Evers.

In 1995, Dr Martin Dalton published a recounting of his involvement with the first human lung transplant in the Annals of Thoracic Surgery. As recalled in that account, the first lung transplant took place in the summer of 1963 in the context of another historical event, the assassination of Medgar Evers. This article is written in follow-up to Dalton's report in hopes of providing more insight into the events surrounding the assassination. This review will discuss the details of the assassination, attempted resuscitation, and the medical evidence presented in the trial of his assassin.

Impact of Time to Endoscopic Resection on Outcomes for Stage I Esophageal Adenocarcinoma.

BACKGROUND: Endoscopic resection (ER) is the preferred treatment for superficial esophageal cancer; however, a safe time frame for performing ER has not been established. This study evaluated the period in which ER can be performed for patients with stage I esophageal adenocarcinoma without compromising outcomes. METHODS: The 2004-2015 National Cancer Database was used to identify patients with cT1 N0 M0 esophageal adenocarcinoma who underwent upfront ER. The primary outcome was overall survival, which was evaluated using Kaplan-Meier and multivariable Cox proportional hazards methods. The secondary outcome was rate of margin-positive resection, which was evaluated using a multivariable logistic regression. RESULTS: A total of 983 patients met study criteria. The median time from diagnosis to ER was 34 days (interquartile range, 5-70 days). Patients in the highest quartile of time to ER were more likely to be treated at a high-volume center and at a center different from that of diagnosis compared with those in the lowest quartile. Increasing time to ER was not independently associated with survival (adjusted hazard ratio per 10 days, 1.02; 95% confidence interval, 0.98-1.05; P = .32) or margin-positive resection (odds ratio per 10 days 1.01; 95% confidence interval, 0.96-1.06; P = .60). CONCLUSIONS: In this National Cancer Database analysis, increasing time to endoscopic resection, up to 180 days from diagnosis, was not associated with worsened survival or increased odds of margin-positive resection in patients with cT1 N0 M0 esophageal adenocarcinoma. Given these findings, patients may be afforded time to be seen in specialty centers without risk of tumor progression.

Lung retransplantation in the modern era.

Chronic lung allograft dysfunction remains the leading cause of long-term morbidity and mortality for lung transplant recipients. Lung retransplantation currently represents the only therapeutic option for patients for refractory allograft dysfunction. However, debate remains regarding both the efficacy and ethicality of lung retransplantation in light of the shortage of lung allografts. The aim of this review is to discuss the available literature on lung retransplantation in the current era. Through this we hope to provide insight into ideal patient selection, donor organ selection, surgical approaches, and future considerations within the field in order to improve outcomes and best address organ utilization while a waitlist continues to exist. Lung retransplantation in select patients can offer comparable survival outcomes to primary lung transplantation. However, several risk factors including retransplantation with the first year of primary transplantation, older age, poor functional status, and ICU level requirements prior to transplantation are associated with worsened outcomes. Donor organ selection considerations are comparable to those in primary lung transplantation. However, surgical approach is often impacted by dense pleural and mediastinal adhesions in the recipient which increase the complexity of the hilar dissection. The postoperative course is often more complex for patients undergoing retransplantation compared to those undergoing primary lung transplant as well. However, pending more data on long term outcomes in lung retransplantation and the potential impact of retransplant recipients on waitlist mortality, lung retransplantation should remain in use primarily for the treatment of chronic graft dysfunction in carefully selected patients.

Effect of Lymph Node Assessment on Outcomes in Surgery for Limited Stage Small Cell Lung Cancer.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend surgery for limited stage small cell lung cancer (SCLC). However, there is no literature on minimum acceptable lymph node retrieval in surgery for SCLC. METHODS: The National Cancer Database was queried for adult patients undergoing lobectomy for limited stage (cT1-2N0M0) SCLC from 2004 to 2015. Patients with unknown survival, staging, or nodal assessment, and patients who received neoadjuvant therapy were excluded. The number of lymph nodes assessed was studied both as a continuous variable and as a categoric variable stratified into distribution quartiles. The primary outcome was overall survival and the secondary outcome was pathologic nodal upstaging. RESULTS: A total of 1051 patients met study criteria. In multivariable analysis, only a retrieval of eight to 12 nodes was associated with a significant survival benefit (hazard ratio 0.73; 95% confidence interval, 0.56 to 0.98). However, when modeled as a continuous variable, there was no association between number of nodes assessed and survival (hazard ratio 1.00; 95% confidence interval, 0.98 to 1.02). The overall rate of pathologic nodal upstaging was 19%. Modeled as a continuous variable, more than seven lymph nodes assessed at time of resection was significantly associated with nodal upstaging in multivariable regression (odds ratio 1.03; 95% confidence interval, 1.01 to 1.06). CONCLUSIONS: In this study, there was no clear difference in survival based on increasing the number of lymph nodes assessed during lobectomy for limited stage SCLC. However, the number of retrieved lymph nodes was associated with pathologic nodal upstaging. Therefore, patients may benefit from retrieval of more than seven lymph nodes during lobectomy for SCLC.

The immunotherapeutic landscape in non-small cell lung cancer and its surgical horizons.

Lung cancer continues to be a leading cause of cancer-related death worldwide. Despite tremendous advances in surgical technique, chemotherapy regimens, radiation, and targeted therapies, survival is <50% at 5 years. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), demonstrates promise as a solution to this clinical problem. Several agents have been Food and Drug Administration-approved for locally advanced and metastatic non-small cell lung cancer (NSCLC). Further studies are now exploring the use of these agents in the neoadjuvant and adjuvant settings. Although ICIs have demonstrated meaningful efficacy in NSCLC and other advanced malignancies, they are not without adverse toxicities. Furthermore, there are minimal data on their use in the perioperative period. Here we discuss the current domain of ICIs and their surgical implications in NSCLC.

Simultaneous Versus Sequential Heart-liver Transplantation: Ideal Strategies for Organ Allocation.

BACKGROUND: Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research file was queried for adult recipients waitlisted for both heart and liver transplantation. The United Network for Organ Sharing thoracic and liver databases were linked to facilitate examination of waitlist and transplant characteristics for simultaneously listed patients. Univariate survival analysis was used to determine overall survival. RESULTS: Of the 236 patients meeting inclusion criteria, 200 underwent SHL, 7 sequentially underwent LAH, and 29 received heart transplantation only (isolated orthotopic heart transplantation [iOHT]). Recipients of SHL were less likely to have an episode of acute rejection before discharge (LAH, 14.2%; SHL, 2.4%; iOHT, 3.6%; P = .019) or be treated for acute rejection within 1 year after transplantation (LAH, 14.3%; SHL, 2.5%; iOHT, 13.8%; P = .007). Otherwise, postoperative hospital length of stay, stroke, need for dialysis, and need for pacemaker placement were comparable across groups. Ten-year survival similarly favored both LAH and SHL over iOHT (LAH: 100%, 71.4%, 53.6%; SHL: 87.1%, 80.4%, 52.1%, iOHT: 70.1%, 51.6%, 27.5% for 1-, 5-, and 10-year survivals, respectively, P = .003). However, median time between heart and liver transplant was 302 days in patients undergoing sequential transplantation. CONCLUSIONS: Although transplantation in a simultaneous or sequential fashion yields equivalent outcomes, a high fraction of patients undergoing initial heart transplant alone fail to proceed to subsequent liver transplantation. Therefore, in patients with combined heart and liver failure with a projected need for 2 allografts, simultaneous transplantation is associated with maximum benefit.

Salt, Hypertension, and Immunity.

The link between inappropriate salt retention in the kidney and hypertension is well recognized. However, growing evidence suggests that the immune system can play surprising roles in sodium homeostasis, such that the study of inflammatory cells and their secreted effectors has provided important insights into salt sensitivity. As part of the innate immune system, myeloid cells have diverse roles in blood pressure regulation, ranging from prohypertensive actions in the kidney, vasculature, and brain, to effects in the skin that attenuate blood pressure elevation. In parallel, T lymphocyte subsets, as key constituents of the adaptive immune compartment, have variable effects on renal sodium handling and the hypertensive response, accruing from the functions of the cytokines that they produce. Conversely, salt can directly modulate the phenotypes of myeloid and T cells, illustrating bidirectional regulatory mechanisms through which sodium and the immune system coordinately impact blood pressure. This review details the complex interplay between myeloid cells, T cells, and salt in the pathogenesis of essential hypertension.

A Qualitative Study of Smoking Behaviors among Newly Released Justice-Involved Men and Women in New York City.

Long-term effects of cigarette smoking result in an estimated 443,000 deaths each year, including approximately 49,400 deaths due to exposure to secondhand smoke. Tobacco is a major risk factor for a variety of chronic health problems, including certain cancers and heart disease. In this article, authors present qualitative findings derived from individual interviews with men and women who were incarcerated in New York state and New York City. Participants were 60 racially and ethnically diverse men and women ages 21 through 60 (M = 46.42, SD = 6.88). Of the participants interviewed, 91.7 percent released from a smoke-free correctional facility resumed cigarette smoking and 8.3 percent remained abstinent. Daily consumption ranged from smoking four cigarettes to 60 cigarettes. The four themes that emerged from the study were (1) lifetime exposure to cigarette smoking influences smoking behavior; (2) cigarettes help relieve stress and are pleasurable; (3) there is a relationship between access, availability, and relapse; and (4) smoking cessation strategies are available. Negative influences from participants' families and peers, stressful housing situations, and mandated programs emerged from this study as key challenges to abstaining from smoking cigarettes. Involving family members and partners in smoking cessation interventions could influence newly released justice-involved men and women not to resume cigarette smoking and possibly maintain long-term abstinence.