Effective treatment of intractable cutaneous metastases of breast cancer with electrochemotherapy: Ten-year audit of single centre experience.

PURPOSE: Electrochemotherapy (ECT) is the application of electric pulses to tumour tissue to render the cell membranes permeable to usually impermeant hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to ascertain whether ECT can be an effective palliative treatment for cutaneous metastases of breast cancer. METHODS: This work reports data from the European Standard Operating Procedures for Electrochemotherapy trial (EudraCT Number: 2004-002183-18). In combination with systemic and/or intratumoural bleomycin, optimised electric pulses were delivered to locally recurrent or metastatic cutaneous breast cancer lesions. Follow-up continued until December 2014. RESULTS: Between February 2004 and December 2014, twenty-four patients were treated. All patients had received prior multimodal therapy. In total, the patient cohort had, or developed, 242 lesions. Two hundred and 36 lesions were treated, with 34 lost to follow-up. An objective response was seen in 161 of 202 lesions (79.7%), with a complete response observed in 130 (64.3%). Thirty-nine lesions (19.3%) did not respond, while 2 (1%) progressed following ECT. 17 (73.9%) patients received two or fewer treatments. A minimum of a partial response was seen in at least 50% of treated lesions in 18 of the 24 (75%) patients. Smaller lesions were more likely to have an objective response (Chi-square test for trend, p < 0.001). CONCLUSIONS: Electrochemotherapy is an effective treatment for cutaneous breast cancer lesions that have proven refractory to standard therapies. As smaller lesions were found to be more responsive, we suggest that ECT should be considered as an early treatment modality, within multimodal treatment strategies.

The impact of COVID-19 on emergency surgical presentations in a university teaching hospital.

INTRODUCTION: The Coronavirus-19 (COVID-19) pandemic has led to a 50-70% reduction in acute non-COVID-19 presentations to emergency departments globally. AIM: To determine the impact of COVID-19 on incidence, severity, and outcomes of acute surgical admissions in an Irish University teaching hospital. METHODS: Descriptive data concerning patients presenting with acute appendicitis, diverticulitis, and cholecystitis were analysed and compared from March-May 2020 to March-May 2019. RESULTS: Acute surgical admissions decreased in March from 191 (2020) to 55 (2019) (55%), before increasing by 28% in April (2019: 119, 2020: 153). Admissions due to acute cholecystitis reduced by 33% (2019: 33, 2020: 22), with increased severity at presentation (P = 0.079) and higher 30-day readmission rates (P = 0.056) reported. Acute appendicitis presentations decreased by 44% (2019: 78, 2020: 43, P = 0.019), with an increase in severity (P < 0.001), conservative management (P < 0.001), and post-operative complications (P = 0.029) in 2020 compared to the same period in 2019. CONCLUSION: COVID-19 has potentiated a significant reduction in acute surgical presentations to our hospital. Patients presenting with acute appendicitis during the pandemic had more severe disease, were more likely to have complications, and were significantly more likely to be managed conservatively when compared to historical data.

Successful maintenance of process and outcomes for oesophageal cancer surgery in Ireland during the first wave of the COVID-19 pandemic.

INTRODUCTION: The emergence of the novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the coronavirus disease COVID-19 has impacted enormously on non-COVID-19-related hospital care. Curtailment of intensive care unit (ICU) access threatens complex surgery, particularly impacting on outcomes for time-sensitive cancer surgery. Oesophageal cancer surgery is a good example. This study explored the impact of the pandemic on process and short-term surgical outcomes, comparing the first wave of the pandemic from April to June in 2020 with the same period in 2019. METHODS: Data from all four Irish oesophageal cancer centres were reviewed. All patients undergoing resection for oesophageal malignancy from 1 April to 30 June inclusive in 2020 and 2019 were included. Patient, disease, and peri-operative outcomes (including COVID-19 infection) were compared. RESULTS: In 2020, 45 patients underwent oesophagectomy, and 53 in the equivalent period in 2019. There were no differences in patient demographics, co-morbidities, or use of neoadjuvant therapy. The median time to surgery from neoadjuvant therapy was 8 weeks in both 2020 and 2019. There were no significant differences in operative interventions between the two time periods. There was no difference in operative morbidity in 2020 and 2019 (28% vs 40%, p = 0.28). There was no in-hospital mortality in either period. No patient contracted COVID-19 in the perioperative period. CONCLUSIONS: Continuing surgical resection for oesophageal cancer was feasible and safe during the COVID-19 pandemic in Ireland. The national response to this threat was therefore successful by these criteria in the curative management of oesophageal cancer.

Buried bumper syndrome: a case report of an early PEG gastropexy-associated complication in a patient with gastric volvulus.

Buried bumper syndrome (BBS) is a rare complication associated with percutaneous endoscopic gastrostomy (PEG) tubes. It develops when the internal bumper migrates through the gastric wall, lodging anywhere along the gastrostomy tract leading to overgrowth of gastric mucosa thereby encasing the tube. BBS can lead to bleeding, perforation, peritonitis and intra-abdominal sepsis. Our case is a 71-year-old female presenting with tenderness, erythema and purulent discharge at the PEG tube site 2-weeks post-insertion. Computer tomography scan demonstrated the PEG had dislodged with the internal bumper in the subcutaneous tissue and the distal tip lying within the tract beyond the stomach wall. The PEG was removed by simple external traction. The patient clinically improved and discharged home on day three. Although BBS usually occurs late post-PEG insertion, it can also occur acutely. Preventative measures should be adopted at ward-level and emphasized with appropriate PEG tube care information provided to patients to avoid and recognize such complication.

The effect of a pre- and post-operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): Study protocol for a randomised controlled trial.

BACKGROUND: Advances in peri-operative oncological treatment, surgery and peri-operative care have improved survival for patients with oesophagogastric cancers. Neoadjuvant cancer treatment (NCT) reduces physical fitness, which may reduce both compliance and tolerance of NCT as well as compromising post-operative outcomes. This is particularly detrimental in a patient group where malnutrition is common and surgery is demanding. The aim of this trial is to assess the effect on physical fitness and clinical outcomes of a comprehensive exercise training programme in patients undergoing NCT and surgical resection for oesophagogastric malignancies. METHODS: The PERIOP-OG trial is a pragmatic, multi-centre, randomised controlled trial comparing a peri-operative exercise programme with standard care in patients with oesophagogastric cancers treated with NCT and surgery. The intervention group undergo a formal exercise training programme and the usual care group receive standard clinical care (no formal exercise advice). The training programme is initiated at cancer diagnosis, continued during NCT, between NCT and surgery, and resumes after surgery. All participants undergo assessments at baseline, post-NCT, pre-surgery and at 4 and 10 weeks after surgery. The primary endpoint is cardiorespiratory fitness measured by demonstration of a 15% difference in the 6-min walk test assessed at the pre-surgery timepoint. Secondary endpoints include measures of physical health (upper and lower body strength tests), body mass index, frailty, activity behaviour, psychological and health-related quality of life outcomes. Exploratory endpoints include a health economics analysis, assessment of clinical health by post-operative morbidity scores, hospital length of stay, nutritional status, immune and inflammatory markers, and response to NCT. Rates of NCT toxicity, tolerance and compliance will also be assessed. DISCUSSION: The PERIOP-OG trial will determine whether, when compared to usual care, exercise training initiated at diagnosis and continued during NCT, between NCT and surgery and then during recovery, can maintain or improve cardiorespiratory fitness and other physical, psychological and clinical health outcomes. This trial will inform both the prescription of exercise regimes as well as the design of a larger prehabilitation and rehabilitation trial to investigate whether exercise in combination with nutritional and psychological interventions elicit greater benefits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03807518 . Registered on 1 January 2019.

Effective tumor treatment using optimized ultrasound-mediated delivery of bleomycin.

Bleomycin is a nonpermeant, hydrophilic macromolecule with a high intrinsic anticancer cytotoxicity. However, the cytotoxic potential of the drug is restricted by its low membrane permeability. Application of low-intensity ultrasound to growing tumors enhances intracellular delivery of bleomycin after IP or intratumoral administration, thereby potentiating its cytotoxicity. Optimization of ultrasound parameters for in-vivo bleomycin delivery was undertaken, and an effective antitumor effect was demonstrated in solid tumors of both murine and human cell lines. Cell death after treatment was shown to occur by an apoptotic mechanism. The results achieved in these experiments were equivalent to those achieved using electroporation to mediate delivery of bleomycin-electrochemotherapy. We found that, although temperature rises of up to 5 degrees C occur using the optimized ultrasound conditions, this effect is not responsible for the potentiated drug cytotoxicity. This technique could be used with focused ultrasound or with endoscopic ultrasound probes to develop a localized and effective anticancer treatment with little or no systemic toxicity. (E-mail: Geraldc@ccrc.ie).

Focus on quality in healthcare in Ireland.

PURPOSE: The purpose of this paper is to summarise the recent debates and issues on the healthcare system in Ireland, which have come to the fore through media exposure. The implications for these debates on quality are suggested and questions are raised to stimulate further debate. DESIGN/METHODOLOGY/APPROACH: Recent reports and media opinion articles are reviewed in the light of the health reform programme and the increased prosperity due to the Celtic Tiger era in Ireland. FINDINGS: The Health Service in Ireland is not what it should be. Progress has been made but resistance at all levels is significant due to the mistrust and miscommunication between the managerial and clinical personnel which have built up during the past number of years. The trust of the public is at an all-time low. However, once patients are within the system they are satisfied with their care. ORIGINALITY/VALUE: This is a discussion paper which raises more questions than answers and is timely with the focus on quality in healthcare, particularly now as Ireland prepares for a general election for a new government with healthcare a priority issue.

The clinical utility of pre-operative neutrophil-to-lymphocyte ratio as a predictor of outcomes in patients undergoing elective laparoscopic cholecystectomy.

BACKGROUND: In recent years, there has been an increasing trend towards day-case surgery for patients undergoing laparoscopic cholecystectomy (LC). We investigated the predictive value that pre-operative neutrophil-to-lymphocyte ratio (PNLR) had on surgical outcomes. METHODS: A review of all patients who underwent LC during a 6-year period in a single institution was performed and PNLR recorded. A PNLR cutoff value of 3 was utilised. We compared operation time, length of stay (LOS), and conversion to open between those with PNLR less and greater than 3. RESULTS: A total of 567 patients underwent elective LC. Those with PNLR>3 had associated prolonged operation time (p < 0.005), prolonged LOS (p < 0.005), and higher rates of conversion to open surgery (p < 0.005). CONCLUSIONS: PNLR correlates with outcomes following LC. It is useful in delineating patients that have higher risk of conversion or prolonged length of hospital stay and is helpful in assessing suitability of day-case surgery.

Subcapsular haematoma following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is now considered the gold standard treatment for symptomatic gallbladder disease. Over the last two decades, a reduction in postoperative morbidity, mortality and hospital stay have seen a complete shift from open surgery to a laparoscopic approach. Intrahepatic subcapsular haematoma (ISH) is a rare and potentially life-threatening complication of LC. A 34-year-old female underwent LC for uncomplicated cholelithiasis. No complications were observed intra-operatively. 2 h postoperatively, the patient developed severe abdominal pain and tachycardia. Ultrasonography demonstrated an echogenic collection adjacent to the gallbladder fossa. Laparoscopy showed an ISH involving the right and left lobes of the liver, and no evidence of any intra-abdominal haemorrhage. Subsequent urgent triphasic CT identified a large ISH and a hypervascular lesion on the right lobe of the liver. This lesion demonstrated delayed enhancement with contrast filling suggestive of a hepatic haemangioma. This case report demonstrates the impact of imaging on postoperative management and the importance of postoperative patient monitoring in patients who have undergone laparoscopic surgery. Imaging explorations have a decisive role in the detection and characterization of haematomas.

Gastric motor dysfunction: is eosinophilic mural gastritis a causative factor?

Delayed gastric emptying caused either by gastric motor dysfunction or by gastroparesis is a profoundly debilitating disorder. When unresponsive to medical therapy, patients may undergo radical surgery including near-total gastro-oesophageal, with varied symptomatic improvement. We describe two patients who presented with symptoms consistent with gastro-oesophageal reflux, unresponsive to medical management. After fundoplication both developed symptoms of profound gastric motor dysfunction and subsequently proceeded to near-total gastro-oesophageal with symptomatic improvement. Histological examination of both excised gastric specimens revealed eosinophilic mural gastritis. To our knowledge, these are the first cases to demonstrate the association of mural eosinophilia and symptomatic gastric motor dysfunction. We propose that patients with gastric motor dysfunction, refractory to medical management, progress to laparoscopy and mural biopsy before gastrectomy. This would allow histological analysis of the gastric wall, and in the event of a positive finding of mural eosinophilic gastritis would allow a trial of medical therapy that could include an eosinophilic stabilizer such as the leukotriene D4 receptor antagonist montelukast or intravenous corticosteroid therapy, which may alleviate the symptoms.

Cocaine-associated lower limb ischemia.

Cocaine-associated thrombosis has been reported in the literature with reports of vascular injuries to cardiac, pulmonary, intestinal, placental, and musculoskeletal vessels; however, injury of the pedal vessels is rare. We report on a 31-year-old man who presented 2 months following a cocaine binge with limb-threatening ischemia without an otherwise identifiable embolic source. Angiography confirmed extensive occlusive disease of the tibioperoneal vessels. The patient improved following therapy with heparin and a prostacyclin analogue. Cocaine-induced thrombosis should be considered in patients presenting with acute arterial insufficiency in the lower limb without any other identifiable cause.