PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm.

Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.

Use of esophageal stents to relieve dysphagia during neoadjuvant therapy prior to esophageal resection: a systematic review.

Esophageal cancer stenting offers symptomatic relief for patients suffering from dysphagia. There are limited data to support their use to relieve dysphagia and improve nutrition during neoadjuvant therapy with some concern that they may negatively impact oncological outcomes. The aim of this systematic review was to quantify the impact of esophageal stents on outcomes prior to resection with curative intent. A literature search was performed using Embase, Medline, PubMed, PubMed Central, the Cochrane library for articles pertaining to esophageal stent use prior to or during neoadjuvant chemotherapy or chemoradiotherapy in patients planned for curative esophagectomy. Data extracted included basic demographics, clinical, nutritional and oncologic outcomes. A total of 9 studies involving 465 patients were included. Esophageal stent use resulted in a significant improvement in mean dysphagia scores in the immediate post stent period but failed to demonstrate any positive changes in weight, body mass index (BMI) or albumin. Only 33% of stented patients ultimately progressed to potential curative surgical resection and stents were associated with reduced R0 resection rates and lower overall survival. This systematic review shows that, although esophageal stenting is associated with improvements in dysphagia during neoadjuvant therapy, their effect on improving patient nutritional status is less clear and they may be associated with poorer long-term oncological outcomes. Stents should be used with caution in patients who are being considered for potentially curative resection of esophageal malignancies and other strategies of nutritional supplementation should be considered.

Patterns of recurrence in early-stage oesophageal cancer after chemoradiotherapy and surgery compared with surgery alone.

BACKGROUND: Patterns of disease recurrence in patients with oesophageal cancer following treatment with neoadjuvant chemoradiotherapy and surgery (nCRTS) or surgery alone are poorly reported. An understanding of patterns of disease recurrence is important for subsequent treatment planning. METHODS: An analysis was undertaken of patterns of disease recurrence from a phase III multicentre randomized trial (FFCD9901) comparing nCRTS with surgery alone in patients with stage I and II oesophageal cancer. RESULTS: Some 170 patients undergoing surgical resection were included in the study. R0 resection rates were similar in the two groups: 94 per cent following nCRTS versus 92 per cent after surgery alone (P = 0·749). After a median follow-up of 94·2 months, recurrent disease was found in 39·4 per cent of the overall cohort (31 per cent after nCRTS versus 47 per cent following surgery alone; P = 0·030). Locoregional recurrence was diagnosed in 41 patients (17 versus 30 per cent respectively; P = 0·047) and distant metastatic recurrence in 47 (23 versus 31 per cent respectively; P = 0·244). Metastatic recurrence was more frequent in patients with adenocarcinoma than in those with squamous cell cancer (40 versus 23·1 per cent respectively; P = 0·032). ypT0 N0 category was associated with prolonged time to mixed locoregional and metastatic recurrence (P = 0·009), and time to locoregional (P = 0·044) and metastatic (P = 0·055) recurrence. In multivariable analysis, node-positive disease predicted both locoregional (P = 0·001) and metastatic (P < 0·001) recurrence. CONCLUSION: Locoregional disease control following nCRTS indicated a local field effect not related solely to completeness of resection. pN+ disease was strongly predictive of time to locoregional and metastatic disease recurrence.

Esophageal gastrointestinal stromal tumor: is tumoral enucleation a viable therapeutic option?

OBJECTIVE: The primary objective was to evaluate the feasibility of surgical enucleation of esophageal gastrointestinal stromal tumors (E-GISTs). Secondary objectives evaluated (i) the impact of tumor enucleation on oncological outcomes, (ii) the effect of pretherapeutic biopsy on the feasibility of E-GIST enucleation, and (iii) the impact of mucosal ulceration on outcome. BACKGROUND: E-GISTs are very rare tumors and esophageal resection has been the recommended approach. The feasibility and impact on outcomes of tumor enucleation are unknown. METHODS: Through a large national multicenter retrospective study, 19 patients with E-GISTs were identified between 2001 and 2010. Patients who underwent either enucleation or esophagectomy were compared. RESULTS: Of over 19 patients identified with E-GISTs, curative treatment was surgical for 16 patients, with enucleation in 8 and esophagectomy in 8. In the enucleation group, median tumoral diameter was 40 mm (18-65 mm), without any mucosal ulceration, preoperative capsular ruptures, or incomplete resections. In the esophagectomy group, the median tumoral diameter was 85 mm (55-250 mm), with mucosal ulceration in 4 patients, preoperative capsular rupture in 1, and no incomplete resections. Severe postoperative complication rates were 50% and 25% in the esophagectomy and enucleation groups, respectively, with 2 postoperative deaths after esophagectomy. After a median follow-up of 6.4 years, 2 recurrences were observed after esophagectomy versus 0 after enucleation. Endoscopic biopsies did not expose patients to complications or local recurrence after enucleation. Endoscopic mucosal ulceration was associated with more aggressive tumors. CONCLUSIONS: E-GIST enucleation seems safe for tumors of less than 65 mm in diameter.

Taurine attenuates radiation-induced lung fibrosis in C57/Bl6 fibrosis prone mice.

INTRODUCTION: The amino acid taurine has an established role in attenuating lung fibrosis secondary to bleomycin-induced injury. This study evaluates taurine's effect on TGF-beta1 expression and the development of lung fibrosis after single-dose thoracic radiotherapy. METHODS: Four groups of C57/Bl6 mice received 14 Gy thoracic radiation. Mice were treated with taurine or saline supplementation by gavage. After 10 days and 14 weeks of treatment, TGF-beta1 levels were measured in serum and bronchoalveolar lavage fluid (BALF). Lung collagen content was determined using hydroxyproline analysis. RESULTS: Ten days post radiotherapy, serum TGF-beta1 levels were significantly lower after gavage with taurine rather than saline (P = 0.033). BALF TGF-beta1 at 10 days was also significantly lower in mice treated with taurine (P = 0.031). Hydroxyproline content was also significantly lower at 14 weeks in mice treated with taurine (P = 0.020). CONCLUSION: This study presents novel findings of taurine's role in protecting from TGF-beta1-associated development of lung fibrosis after thoracic radiation.

Student-selected components in surgery: providing practical experience and increasing student confidence.

INTRODUCTION: Reviews of the medical school curriculum in the UK and Ireland have recommended the introduction of student-selected components (SSCs). The Department of Surgery in The Royal College of Surgeons in Ireland (RCSI) has introduced a 6-week surgical SSC, which aims to develop practical clinical skills, provide mentorship and prepare students for internship. METHODS: Emphasis was placed on exposure to surgical specialities, teaching practical skills and student integration into surgical teams. Students completed an online survey pre- and post-SSC, assessing attitudes towards the course and confidence in performing ward-based and surgical skills. RESULTS: The mean Likert scale scores increased for all the skills assessed. Students felt that the SSC prepared them for their first day of work and strengthened their desire to pursue surgical careers. CONCLUSION: A surgical SSC has been successful in increasing student confidence in performing practical skills required for commencing work as a doctor. Provision of dedicated SSCs is likely to influence the career choice of students.

Preparing students to be doctors: introduction of a sub-internship program.

Preparing graduates for the transformation from medical student to doctor provides medical schools with a real challenge. Medical educators advocate a process of graduated delegation of responsibility in the clinical years of medical school. This is best exemplified in the North American system of sub-internship programmes; an educational approach which European medical schools have been slow to adopt. This study reports on the introduction of an intensive two-week surgical sub-internship for final medical year students. "Sub-interns" were asked to complete pre and post sub-internship online questionnaires assessing their readiness to perform clinical and practical skills, attitudes towards the program, and how well it prepared students for internship. Forty-nine students completed a questionnaire pre sub-internship and 47 completed the post-questionnaire. Student confidence towards practical and clinical skills and their first day at work increased over the two weeks. Mean Iikert scores for all 6 practical and clinical skills improved post sub-internship. The introduction of a surgical sub-internship is timely and welcomed by medical students. Its development helps bridge the gap in responsibilities between medical student and doctor.

Neoadjuvant treatment of oesophageal adenocarcinoma.

Oesophageal adenocarcinoma is an enigma. It has emerged, seemingly from nowhere, in the late 20th century to dominate the oesophageal oncological landscape. This review will examine whether the current outcome for adenocarcinoma is as good as it gets or whether additional treatment is necessary and if so whether neoadjuvant therapy is effective.

Are elective surgical operations cancelled due to increasing medical admissions?

BACKGROUND: Cancellation of operations increases theatre costs and decreases efficiency. We examined the causes of theatre cancellations in general surgery. METHODS: The Beaumont hospital database (ORSUS system) and theatre records were examined retrospectively between April 1997 and March 2002. The number and causes of theatre cancellations, the number of emergency admissions and their length of hospital stay were studied. RESULTS: The number of elective operations cancelled between April 1997-March 1998 and April 2001-March 2002 were 368 and 427 respectively. 'No bed' was the reason for theatre cancellation in 114 (31.0%) cases between April 1997-March 1998 and this increased to 267 (62.5%) cases between April 2001-March 2002. Between April 1997-March 1998 and April 2001-March 2002, general surgical emergency admissions decreased by 6.74% (3,116 to 2,906), and emergency surgical admissions across the specialties decreased by 2.02% (4,002 to 3,921). In the same time interval, general medical emergency admissions rose from 4,195 to 5,386 (a 28.39% increase), and emergency medical admissions across the specialties rose from 5,401 to 6,689 (a 23.84% increase). General surgical bed days for emergency admissions fell between April 1997-March 1998 and April 2001-March 2002 from 28,839 to 26,698 (7.4% decrease). There was a similar decrease from 38,188 to 36,004 (5.7% decrease) for all surgical specialties. Total bed days necessitated by general medical emergency admissions increased from 53,226 to 61,623 (15.8%). Across the medical specialties, an increase from 71,590 to 82,180 bed days (14.79%) was seen. CONCLUSIONS: Elective surgery cancellation is a significant problem with far-reaching consequences. While multifactorial in aetiology, increased bed usage by medical specialties is one important factor. This study has implications for doctors, training, administrators and patients.