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.

Role of circulating fibrocytes in the diagnosis of acute appendicitis.

BACKGROUND: Improved diagnostic biomarkers are required for acute appendicitis. The circulating fibrocyte percentage (CFP) is increased in inflammatory states, but has not been studied in acute appendicitis. This study aimed to determine CFP in acute appendicitis and compare diagnostic accuracy with standard serological biomarkers. METHODS: A prospective cohort study was carried out between June 2015 and February 2016 at University Hospital Limerick. The CFP was determined by dual-staining peripheral venous samples for CD45 and collagen I using fluorescence-activated cell sorting, and correlated with histopathological diagnoses. The accuracy of CFP in determining histological acute appendicitis was characterized and compared with the white cell count, C-reactive protein concentration, neutrophil count, lymphocyte count and neutrophil : lymphocyte ratio. RESULTS: Of 95 adults recruited, 15 were healthy individuals and 80 had suspected appendicitis at presentation. Forty-six of these 80 patients had an appendicectomy, of whom 34 had histologically confirmed appendicitis. The CFP was statistically higher in patients with pathologically proven acute appendicitis than in healthy controls (median 6·1 (i.q.r. 1·6-11·6) versus 2·3 (0·9-3·4) per cent respectively; P = 0·008). The diagnostic accuracy of CFP, as determined using the area under the receiver operating characteristic (ROC) curve, was similar to that of standard biomarkers. In multinomial regression analysis, only raised CFP was retained as an independent prognostic determinant of acute appendicitis (odds ratio 1·57, 95 per cent c.i. 1·05 to 2·33; P = 0·027). CONCLUSION: The CFP is increased in histologically confirmed acute appendicitis and is as accurate as standard serological biomarkers in terms of diagnosis.

Management options for chronic anal fissure: a systematic review of randomised controlled trials.

INTRODUCTION: Anal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel blockers, botulinum toxin injection and sphincterotomy. The aim of this study was to review current options for the treatment of chronic anal fissure. METHODS: A comprehensive search identifying randomized controlled trials comparing treatment options for anal fissure published between January 2000 and February 2020 was performed. The primary outcome assessed was healing at 8 weeks post commencing treatment. Secondary outcomes included recurrence, intolerance of treatment and complications. RESULTS: A total of 2822 studies were identified. After removal of duplicates and non-relevant studies, we identified nine randomized controlled trials which met pre-defined criteria. There was a total of 775 patients. At 8 weeks, healing rates were 95.13% in those treated with sphincterotomy, 66.7% in the botulinum toxin group, 63.8% in the nitrate group, 52.3% for topical diltiazem and 50% for topical minoxidil. Recurrence was highest amongst those treated with botulinum toxin injection (41.7%) and lowest for sphincterotomy (6.9%). Although the absolute number is low, there was a risk of permanent incontinence with sphincterotomy. CONCLUSION: This review of the randomized control data demonstrates that healing was significantly higher amongst those treated with sphincterotomy versus more conservative modalities. Topical nitrites had similar outcomes to botulinum toxin injection but were poorly tolerated in comparison to other treatments. The benefit of sphincterotomy was at a cost of increased complications, notably permanent incontinence.

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.

Initial experience with a dual-console robotic-assisted platform for training in colorectal surgery.

BACKGROUND: Minimally invasive surgery is associated with several patient-related benefits, including reduced length of hospital stay and reduced blood loss. Robotic-assisted surgery offers many advantages when compared with standard laparoscopic procedures, including a stable three-dimensional binocular camera platform, motion smoothing and motion scaling, improved dexterity and ergonomics. There are limited data on the effectiveness of the dual-console DaVinci Xi platform for teaching resident surgeons. The goal of this study was to examine preliminary outcomes following the introduction of a dual-console robotic platform in our institution. METHODS: A retrospective review of our prospectively maintained patient database was performed. The first ten dual-console resident-performed procedures in colorectal surgery were compared with matched cases performed on a single console by the trainer. Patient demographics, operative times and patient outcomes were compared. RESULTS: Twenty patients were included in this study. There was no significant difference in console time (p = 0.46) or total operative time (p = 0.52) when residents and trainers were compared. Patient outcomes were equivalent, with no difference in length of stay, morbidity or mortality. CONCLUSIONS: The DaVinci Xi dual-console platform is a safe and effective platform for training junior surgeons. The dual-console system has the potential to alter surgical training pathways.

An analysis of medical students' attitude to surgical careers and pursuing intercalated research degrees.

INTRODUCTION: Major changes are occurring in surgical training in the UK and Ireland. Training time is reduced due to the introduction of run-through training and the EWTD. Streamlined training also may affect the number of trainees engaging in full-time higher degrees by research, in spite of the fact that those who do engage are more academically productive. This study assesses the attitudes of medical students towards a career in surgery and their attitudes to research, especially in the context of an intercalated degree programme. METHODS: 615 students comprising both undergraduates and postgraduates from RCSI were surveyed. The influence of a number of factors was ranked using five-point Likert scales. Students were asked to rate the importance of research to their future careers. RESULTS: 595 (97 %) of those surveyed completed the questionnaire satisfactorily. Those interested in surgery were more likely to be male, undergraduate students and younger. Factors encouraging students to pursue a surgical career were prestige, identification of a surgical mentor, financial reward and research opportunities on offer (p < 0.001 in all cases). Almost 27 % of students had already engaged with some form of research project. A significant proportion of those interested and not interested in surgery (26 and 29 % respectively) would consider taking time out to do an intercalated research degree as part of their primary medical studies. CONCLUSION: Surgical training faces significant challenges. One way to encourage the next generation of academic surgeons may be to offer some candidates intercalated research degrees while pursuing their medical qualification.

Can 'Hot Spotting' Prove to be a Useful Tool to Identify Disproportionate ED Use in the Rural General Hospital Setting?

'Hot spotting' allows the identification of areas with disproportionate use of Emergency Department (ED) services. To date, 'hot spotting' has focused on large urban centres. The aim of this study was to determine if there are geographic hotspots for ED use in the rural general hospital. ED attendances were logged between 1st July 2013 and 30th June 2014. Frequent users and super users were isolated. Addresses were cross referenced against national census data to determine number of users per 500 population in geographically distinct regions. The number of frequent users ranged from 1.00/500 population to 4.88/500 population. Four out of nineteen areas had > or equals; 4 frequent users per 500 population. There was no correlation between number of users and distance from MGH (p=0.44). 77% of frequent users presented with mixed aetiologies. Nineteen percent of frequent attenders presented via GP referral only, 13% attended via self-referral only and 88% attended via GP and self-referral routes.

Breaking Barriers to Successful Implementation of Day Case Laparoscopic Cholecystectomy.

Laparoscopic cholecystectomy is a common procedure performed in both emergency and elective settings. Our aim was to analyse the trends in laparoscopic surgery in Ireland in the public and private healthcare systems. In particular we studied the trend in day case laparoscopic cholecystectomy. National HIPE data for the years 2010-2012 was obtained. Similar datasets were obtained from the three main health insurers. 19,214 laparoscopic cholecystectomies were carried out in Ireland over the 3-year period. More procedures were performed in the public system than the private system from 2010-2012. There was a steady increase in surgeries performed in the public sector, while the private sector remained static. Although the ALOS was significantly higher in the public sector, there was an increase in the rate of day case procedures from 416 (13%) to 762 (21.9%). The day case rates in private hospitals increased only slightly from 29 (5.1%) in 2010 to 40 (5.9%) in 2012. Day case laparoscopic cholecystectomy has been shown to be a safe procedure, however significant barriers remain in place to the implementation of successful day case units nationwide.

Patterns of retroperitoneal trauma following gunshot violence: A case series.

INTRODUCTION: Abdominal trauma is defined as any injury to the abdomen and its containing viscera. Common penetrating injuries including gunshot or stab injuries are increasing worldwide. However, retroperitoneal gunshot injuries have a lower incidence than trans-abdominal trauma and can have substantially different outcomes. CASE REPORT: We report a series of three family members involved in gunshot violence over an18-month period. Each sustained retroperitoneal gunshot injuries with varying injuries patterns and treatment courses. Interestingly, one patient had a delayed small bowel perforation on day 6 post injury. DISCUSSION: Retroperitoneal trauma following gun violence has a lower incidence than trans-abdominal trauma. There is a paucity of literature describing injury patterns following this type of injury and their subsequent management. In the context of penetrating retroperitoneal trauma, the retroperitoneal organs are at risk and therefore serial clinical and/or radiological assessment is necessary. Delayed small bowel injury as a consequence of retroperitoneal gunshot is an unusual finding, with no reports to our knowledge in the literature. CONCLUSION: this case series highlight that penetrating retroperitoneal trauma can produce a variety of injury patterns. Therefore a wide clinical acumen is needed to ensure a successful outcome. The trajectory of the bullet may help ascertain potential injuries, but serial assessment and observation are also important. Ultimately, individual cases must be treated accordingly, based on clinical stability, severity of injury and radiological findings. Despite initial stability, patients should always be observed for delayed complications.

Alveolar rhabdomyosarcoma originating between the fourth and fifth metatarsal--case report and literature review.

We report a case of alveolar rhabdomyosarcoma arising between the fourth and fifth metatarsal. A 13-year-old boy presented to outpatients with a history of pain and swelling in the lateral aspect of his left forefoot. Plain radiographs and MRI showed a soft tissue mass displacing the fourth metatarsal. Percutaneous biopsy revealed an alveolar rhabdomyosarcoma. Staging scans showed advanced metastatic disease. The patient was treated with chemotherapy. This highly malignant lesion remains challenging to diagnose, and difficult to treat successfully.

Highly stable ultrabroadband mid-IR optical parametric chirped-pulse amplifier optimized for superfluorescence suppression.

We present a 9 GW peak power, three-cycle, 2.2 microm optical parametric chirped-pulse amplification source with 1.5% rms energy and 150 mrad carrier envelope phase fluctuations. These characteristics, in addition to excellent beam, wavefront, and pulse quality, make the source suitable for long-wavelength-driven high-harmonic generation. High stability is achieved by careful optimization of superfluorescence suppression, enabling energy scaling.

Tunable enhancement of a soliton spectrum using an acoustic long-period grating.

We demonstrate a scheme for tunable shaping of a soliton spectrum. Specifically, we show a local enhancement of 6 dB in the pulse spectrum by propagating the pulse through a fiber containing micro-bends generated by a flexural acoustic wave - an acoustic long-period grating (LPG) - followed by nonlinear propagation through uniform fiber. The location of the enhancement peak can be tuned by external control of the acoustic frequency of the LPG. We discuss the potential application of this scheme to tunable supercontinuum sources.

Nonlinear propagation effects in antiresonant high-index inclusion photonic crystal fibers.

We experimentally and numerically investigate femtosecond-pulse propagation in a microstructured optical fiber consisting of a silica core surrounded by airholes that are filled with a high-index fluid. This fiber combines the resonant properties of hollow-core bandgap fibers and the high nonlinearity of index-guiding waveguides. A range of nonlinear optical effects can be observed, including soliton propagation, dispersive wave generation, and a Raman self-frequency shift. Tuning the center wavelength of the laser and varying the refractive index of the fluid lead to different propagation effects, mediated by the strongly wavelength-dependent group-velocity dispersion in these photonic bandgap confining structures.

Nonlinear pulse propagation at zero dispersion wavelength in anti-resonant photonic crystal fibers.

We experimentally and numerically investigate femtosecond pulse propagation in a microstructured optical fiber consisting of a silica core surrounded by air holes which are filled with a high index fluid. Such fibers have discrete transmission bands which exhibit strong dispersion arising from the scattering resonances of the high index cylinders. We focus on nonlinear propagation near the zero dispersion point of one of these transmission bands. As expected from theory, we observe propagation of a red-shifted soliton which radiates dispersive waves. Using frequency resolved optical gating, we measure the pulse evolution in the time and frequency domains as a function of both fiber length and input power. Experimental data are compared with numerical simulations.

In-band OSNR and chromatic dispersion monitoring using a fibre optical parametric amplifier.

This paper presents an all-optical, in-band optical signal-to-noise ratio (OSNR) and chromatic dispersion monitor. We demonstrate monitoring over the 1 nm bandwidth of our signal, which is a 10 GHz pulse train of 8.8 ps pulses. The monitor output power, as measured on a slow detector, has a 1.9 dB dynamic range when the signal OSNR is varied by 20 dB, and a 1.6 dB dynamic range when +/- 150 ps/nm of chromatic dispersion is applied. Cascaded four-wave mixing occurring in the optical parametric amplifier provides the nonlinear power transfer function responsible for the monitoring. An analysis using the signals' probability density functions show that the nonlinear power transfer function provides preferential gain to clean undispersed pulses when compared to noisy and/or dispersed pulses. Our analysis includes a consideration of the applicability of the device to high duty cycle systems, and simulations on monitoring of a 40 Gb/s pulse train with a 50% duty cycle.

Compact tunable microfluidic interferometer.

We demonstrate a compact tunable filter based on a novel microfluidic single beam Mach-Zehnder interferometer. The optical path difference occurs during propagation across a fluid-air interface (meniscus), the inherent mobility of which provides tunability. Optical losses are minimized by optimizing the meniscus shape through surface treatment. Optical spectra are compared to a 3D beam propagation method simulations and good agreement is found. Tunability, low insertion loss and strength of the resonance are well reproduced. The device performance displays a resonance depth of -28 dB and insertion loss maintained at -4 dB.

Simultaneous residual chromatic dispersion monitoring and frequency conversion with gain using a parametric amplifier.

We demonstrate that chromatic dispersion induced pulse-width broadening can be effectively monitored by a simple average power measurement of the filtered output from a parametric amplifier when additional four-wave mixing interactions are introduced. This all-optical technique also provides all-optical frequency conversion of the signal being monitored and signal gain.