Controversies in preoperative therapy in esophageal cancer: Current evidence and ongoing research

Abstract Esophageal cancer incidence is growing worldwide, especially adenocarcinomas in the western world. Outcomes overall are universally poor, with the best survival seen in earlier stages of the disease, where surgery is the mainstay of treatment. Although squamous cell cancers and adenocarcinomas of the esophagus have different etiology, clinical features, biological behavior and prognosis, earlier research studies have frequently combined the two histologies. Several trials in the past three decades have been carried out in the neoadjuvant, adjuvant and perioperative settings in attempts to improve survival further. Most of the initial studies were small and underpowered, and showed no benefit with neoadjuvant or adjuvant treatment over surgery alone. More recent well‐designed trials have now established that the neoadjuvant (in squamous and adenocarcinomas) and the perioperative (in adenocarcinomas) strategies result in superior outcomes compared to surgery alone. However, the optimum neoadjuvant strategy has still not been identified, with both neoadjuvant chemotherapy and chemoradiotherapy (both followed by surgery) showing superior outcomes over surgery alone. Direct comparisons of these two neoadjuvant protocols have not shown a clear benefit of one over the other, although more trials are ongoing and may settle this debate. Future studies using personalized medicine and immunotherapy are required to evaluate their role in the management of esophageal cancers

Clinical studies with Cannabis in India – A need for guidelines for the investigators and ethics committees

Cannabis is one of the world's oldest cultivated plants and the most commonly used recreational drug worldwide. The plant relevant for medicinal use is Cannabis sativa that has two pharmacologically active ingredients – delta-9-tetrahydrocannabinol that is psychoactive and cannabidiol that does not have psychotropic activity. The policy tapestry of Cannabis has undergone a significant change in the past few decades worldwide. Different countries have diverse policies, ranging from classifying use of Cannabis as illicit, to legalization of its use, both for medicinal and recreational purposes. Cannabis products are approved for use, for instance, in multiple sclerosis and Dravet syndrome (US Food Drug and Administration). Against this backdrop, we find that the knowledge foundations for use of Cannabis in clinical trials in India are still evolving. Conducting ethical research within a clinical trials framework is essential to understand dosing, formulation, shelf life, drug–drug interaction, tolerability, and safety before establishing its utility for various indications. In the absence of guidelines or a regulatory framework for conduct of these studies, the various Institutional Ethics Committees (IECs), which are responsible for reviewing projects related to Cannabis, face unique challenges with respect to the basic requirements. The principal investigators (PIs) are equally strained to find local guidance, recommendations, and literature in support of their application to the respective IEC, thus leading to an impasse and delay in initiating the proposed clinical studies with Cannabis. The present article addresses considerations, questions, and issues that affect the conduct of these clinical studies and recommends mandatory documents and some suggested guidelines for use by both PIs and IECs to take studies with Cannabis forward until such time that an interdisciplinary regulatory framework is firmed up by regulatory authority

Incidence of acute kidney injury and its associated risk factors in patients undergoing elective oesophagectomy surgeries at a tertiary care cancer institute – A pilot prospective observational study

Background and Aims: Acute kidney injury (AKI) is a significant postoperative complication. Multiple perioperative factors are implicated in the causation of AKI in the postoperative period in patients with oesophageal cancer. The study aimed to find out the incidence, causes and effects of AKI following oesophagectomy surgery. Methods: A prospective observational study was conducted in consecutive adult patients undergoing elective oesophagectomy at a tertiary cancer care hospital. Patients with preoperative chronic renal insufficiency (serum creatinine >1.5 mg/dl), AKI in the past and a history of renal replacement therapy were excluded. Serum creatinine values were measured on postoperative days 1, 3, 5, the day of discharge or day 15 and on the day of first follow-up or day 28, following oesophagectomy surgery. The incidence of AKI was measured using the ‘Kidney Disease Improving Global Outcome’ (KDIGO) criteria. Results: The incidence of AKI was 14.7% [95% confidence interval (CI) 9.9%, 20.7%] (i.e., 27/183) in patients who underwent elective oesophagectomy. AKI was associated with prolonged hospital stay [median- 13 days (interquartile range {IQR} 11–21.5) versus 9 days (IQR 8–12), P < 0.001] and increased in-hospital mortality (14.8% versus 1.3%, P 0.004, odds ratio = 13.2, 95% CI 2.3, 77.3). After multivariate analysis, age, anastomotic leak and use of vasopressors in the postoperative period were independent predictors of AKI. Conclusion: The incidence of AKI was 14.7% after elective oesophagectomy. AKI was associated with prolonged hospital stay and in-hospital mortality. Higher age, anastomotic leak and use of vasopressors in the postoperative period were independent predictors of AKI

Management of locally advanced primary mediastinal synovial sarcoma

Primary mediastinal synovial sarcoma (PMSS) is a relatively rare disease, and patients are treated predominantly with surgery for resectable disease. Management of locally advanced borderline resectable and unresectable PMSS is not only challenging but also lacks standard guidelines. We present three patients with PMSS, who were unresectable or borderline resectable at presentation and were treated with neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy

Intraoperative Nerve Monitoring during Minimally Invasive Esophagectomy and 3-Field Lymphadenectomy: Safety, Efficacy, and Feasibility

Background: The objective of this study was to demonstrate the safety, efficacy, and feasibility of intraoperative monitoring of the recurrent laryngeal nerves during thoracoscopic and robotic 3-field esophagectomy. Methods: This retrospective analysis details our initial experience using intraoperative nerve monitoring (IONM) during minimally invasive 3-field esophagectomy. Data were obtained from a prospectively maintained database and electronic medical records. The study included all patients who underwent minimally invasive (video-assisted thoracic surgery/robotic) transthoracic esophagectomy with neck anastomosis. The patients were divided into those who underwent IONM during the study period and a historical cohort who underwent 3-field esophagectomy without IONM at the same institution. Appropriate statistical tests were used to compare the 2 groups. Results: Twenty-four patients underwent nerve monitoring during minimally invasive 3-field esophagectomy. Of these, 15 patients underwent thoraco-laparoscopic operation, while 9 received a robot-assisted procedure. In the immediate postoperative period, 8 of 24 patients (33.3%) experienced vocal cord paralysis. Relative to a historical cohort from the same institution, who were treated with surgery without nerve monitoring in the preceding 5 years, a 26% reduction was observed in the nerve paralysis rate (p=0.08). On follow-up, 6 of the 8 patients with vocal cord paralysis reported a return to normal vocal function. Additionally, patients who underwent IONM exhibited a higher nodal yield and a decreased frequency of tracheostomy and bronchoscopy. Conclusion: The use of IONM during minimally invasive 3-field esophagectomy is safe and feasible. This technique has the potential to decrease the incidence of recurrent nerve palsy and increase nodal yield

A randomized trial to assess the utility of preintubation adult fiberoptic bronchoscope assessment in patients for thoracic surgery requiring one - lung ventilation

Background: Confirmation of placement of Double lumen endobronchial tubes (DLETT) and bronchial blockers (BBs) with the pediatric fiberoptic bronchoscope (FOB) is the most preferred practice worldwide. Most centers possess standard adult FOBs, some, particularly in developing countries might not have access to the pediatric-sized devices. We have evaluated the role of preintubation airway assessment using the former, measuring the distance from the incisors to the carina and from carina to the left and right upper lobe bronchus in deciding the depth of insertion of the lung isolation device. Methods: The study was a randomized, controlled, double-blind trial consisting of 84 patients (all >18 years) undergoing thoracic surgery over a 12-month period. In the study group (n = 38), measurements obtained during FOB with the adult bronchoscope decided the depth of insertion of the lung isolation device. In the control group (n = 46), DLETTs and BBs were placed blindly followed by clinical confirmation by auscultation. Selection of the type and size of the lung isolation device was at the discretion of the anesthesiologist conducting the case. In all cases, pediatric FOB was used to confirm accurate placement of devices. Results: Of 84 patients (DLETT used in 76 patients; BB used in 8 patients), preintubation airway measurements significantly improved the success rate of optimal placement of lung isolation device from 25% (11/44) to 50% (18/36) (P = 0.04). Our incidence of failed device placement at initial insertion was 4.7% (4/84). Incidence of malposition was 10% (8/80) with 4 cases in each group. The incidence of suboptimal placement was lower in the study group at 38.9% (14/36) versus 65.9% (29/44). Conclusions: Preintubation airway measurements with the adult FOB reduces airway manipulations and improves the success rate of optimal placement of DLETT and BB

Anaplastic large cell lymphoma presenting as bilateral endobronchial tumor in a young boy

A 15-year-old boy presented to us with a 4-month history of fever with worsening dyspnea since 1 month. His contrast-enhanced computed tomography scan of the thorax showed bilateral endobronchial lesions with complete collapse-consolidation of the left lung and partial collapse of the right lower lobe. His fiberoptic bronchoscopy guided biopsy had been reported in outside hospital as a neuroendocrine tumor. Due to worsening breathlessness, he had to be intubated. We repeated the endobronchial biopsy and combined with outside slides and blocks, was diagnosed to have an anaplastic lymphoma kinase-1 positive anaplastic large cell lymphoma (ALCL). We started the patient on chemotherapy to which he had a dramatic response radiologically and clinically. ALCL presenting as endobronchial mass is an extremely rare occurrence and it presenting with bilateral endobronchial masses has not been reported yet in literature. Pathologists and clinicians should be aware of this presentation as prompt diagnosis and treatment give promising results

Trimodality treatment in malignant pleural mesothelioma – Ordeal or real deal?

BackgroundManagement of MPM is complex and controversial as there is a paucity of good quality evidence. We report the toxicity and outcomes in patients who received trimodality treatment for non-metastatic MPM at our institution.Methods & materialsWe reviewed the electronic medical records of surgically managed MPM patients at our institution in the last decade. Dosimetric parameters of target volume and organs at risk were documented by the treatment planning workstation. SPSS was used for statistical analysis.ResultsBetween January 2008 and October 2018, 21 patients underwent surgery for MPM – all but 2 patients underwent extra-pleural pneumonectomy (EPP); epithelioid MPM was the most common histology. All patients, except 2, received neoadjuvant Pemetrexed/platinum doublet chemotherapy. Fourteen patients received adjuvant hemithoracic RT; ten patients were treated with a conformal technique at our institute and dosimetric data was available for analysis. Average time to start RT after surgery was 51 days (range 32–82 days). All patients were treated with a conformal technique using IMRT/VMAT to a dose of 45Gy in 25 fractions. Mean overall RT duration was 35 days (range 30–42 days). Grade I/II Pneumonitis was seen in 4 patients. One patient developed grade III acute lung toxicity unrelated to RT. At a median follow up of 25 months, 8 patients had died, of whom six died due to the disease and two died in the immediate post op period. Two-year DFS and OS were 58% and 73%, respectively.ConclusionIn spite of the extensive surgery and complex hemithoracic RT, we demonstrated excellent dosimetry, toxicity profile and favorable outcomes in non-metastatic MPM