The Effect of Supplementary Omegaven® on the Clinical Outcome of Patients With Advanced Esophagogastric Adenocarcinoma Receiving Palliative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy: A Phase II clinical trial.

BACKGROUND/AIM: Previous studies have shown anti-proliferative and anti-apoptotic effects of omega-3 fatty acids (Omegaven®) in vitro and in vivo. Whether this effect can be exploited in patients with advanced esophago-gastric adenocarcinoma is unknown. The present study intended to determine the tumour radiological response and toxicity profile of intravenous omega-3 fish oil infusion when combined with standard palliative chemotherapy, and present the effects of this treatment on plasma cytokine biomarkers. MATERIALS AND METHODS: Participants with advanced esophago-gastric adenocarcinoma were enrolled in a phase II single-arm clinical trial of palliative chemotherapy (epirubicin, oxaliplatin, and capecitabine; EOX) coupled with weekly infusion of Omegaven®. Outcomes were compared to those observed in 37 historical control patients who had received EOX alone. Toxicity was graded using the CTCAE v4.03 and radiological response was assessed using RECIST v1.1. Plasma cytokine levels of IL-1, IL-2, IL-6, TNF-α, and VEGF were evaluated by ELISA. RESULTS: Twenty participants were included in the analysis. Radiological responses were as follows: partial response (EOX plus omega-3 group 73% vs. EOX alone 39%, p=0.03), stable disease (EOX plus omega-3 21% vs. EOX alone 39%, p=0.24), and progressive disease (EOX plus omega-3 7% vs. EOX alone 18%, p=0.34). Grade 3 or 4 toxicity was less common (thromboembolism & gastrointestinal) in those who received EOX plus omega-3. This translated into fewer hospital admissions. There were significant reductions in the concentrations of IL-2 (p=0.009), TNF-α (p<0.0001) and VEGF (p=0.002) following each treatment. CONCLUSION: The treatment with supplementary omega-3 fatty acids reduced chemotherapy-related toxicity and resulted in better radiological responses. The combination treatment resulted in a shift towards a favourable anti-inflammatory cytokine profile. These findings should be evaluated in a randomised clinical trial.

Effects of Omegaven®, EPA, DHA and oxaliplatin on oesophageal adenocarcinoma cell lines growth, cytokine and cell signal biomarkers expression.

BACKGROUND: There is limited evidence assessing the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33 and OE19 cells. METHOD: The two oesophageal cells were treated with Omegaven® (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h. RESULTS: The following inhibitory effects were observed on OE33 cells: EPA reduced cell growth by 39% (p = 0.001), DHA by 59% (p < 0.000) and Oxaliplatin by 77% (p < 0.000). For OE19 cells, the EPA reduced growth by 1% (p = 0.992), DHA by 26% (p = 0.019) and oxaliplatin by 76% (p < 0.000). For both cells, Omegaven® resulted in reduced cell growth at intermediate concentrations (20-40 µM) and increased cell growth at low (10 µM) and high (50 µM) concentrations. DHA, Omegaven® and oxaliplatin were associated with significant downregulation of VEGF and p53 protein, and upregulation of p21 protein. DHA, Omegaven® and Oxaliplatin also led to significant downregulation of the total ERK1/2 and Akt proteins. CONCLUSION: DHA, Omegaven® and oxaliplatin were associated with downregulation of p53 and VEGF in both cells. Of the PUFAs studied, DHA alone or in combination (Omegaven®) had greater in vitro anti-cancer effects than EPA alone.

The "kidney-liver" multiorgan ex vivo perfused model improves the circuit's biochemical milieu during perfusion compared to the "liver-kidney" counterpart.

The multiorgan ex vivo perfused liver-kidney model allows studying the hepatic pathophysiology and purifying waste products. We tested if the addition of the kidney first followed by the liver (KL circuit) produces better results compared to the classic liver-first approach (LK). Intact livers and kidneys were obtained post mortem from ten female domestic white pigs, five experiments were conducted with the KL circuit and five with the LK. Bile, urine production, arterial blood gases, glucose, renal and liver tests were collected hourly during the perfusions. The KL circuit had values more close to physiological ranges, more stable over time and showed less variability compared to the LK circuit for urine production, glucose, PH, anion gap, lactate, urea, sodium, potassium and Alanine Transaminase (ANOVA test for repeated measures p < 0.05). The KL circuit produced a more physiological and reliable biochemical milieu.

Gastropericardial fistula after Roux-en-Y bypass for reflux disease.

A 49-year-old man was admitted to his local hospital with a 3-day history of left-sided chest pain which started after a coughing paroxysm. His surgical history included laparoscopic Toupet fundoplication 30 months earlier and revisional reflux surgery (Roux-en-Y gastric bypass) 11 months earlier. On admission, he was found to be tachycardic at 110 bpm, hypotensive (90/65 mm Hg). He had ST depression in ECG leads V2-5 with a normal troponin I level. Chest radiography indicated a pneumopericardium which prompted referral to the oesophagogastric surgery unit. Endoscopy and CT with oral contrast confirmed a gastropericardial fistula. This was managed by total gastrectomy through a left thoracoabdominal approach. The patient was discharged home 2 months later. We report the fourth case of gastropericardial fistula in the literature as a long-term complication of Roux-en-Y gastric bypass with a favourable outcome and mini literature review.

Case report of mannose-binding lectin (MBL) deficiency and postoperative sepsis and coagulopathy in a patient following total pancreatectomy for chronic pancreatitis.

CONTEXT: Complement plays a central role against infection and coordinates the activity of coagulation and fibrinolysis. In this report we present a patient that underwent total pancreatectomy experienced sepsis, coagulopathy and bleeding that endangered the postoperative course. CASE REPORT: A sixty-five-year-old woman underwent total pancreatectomy for intractable pain without islet transplant, this patient was diagnosed as AP and MBL deficient from a blood test performed preoperatively. On the postoperative course she experienced severe haemorrhages and sepsis for 3 weeks postoperatively. An analysis of serial perioperative serum samples conducted which showed further depletion of the alternate and MBL complement pathway without restoration to baseline levels. CONCLUSION: This is the first reported case of alternative and mannose-binding lectin pathways depletion associated with major postoperative bleeding and sepsis following pancreatic surgery. Future research should examine the relationship between complement pathways activity and postoperative complications in order to possibly introduce it as a preoperative screening and possible replacement therapy prior to any major surgical intervention.

Prognostic value of baseline FDG uptake on PET-CT in esophageal carcinoma.

AIM: To evaluate the influence of baseline maximum standardized uptake value (SUVmax) on survival in a cohort of patients, undergoing positron emission tomography-computed tomography (PET-CT) scan for esophageal carcinoma. METHODS: The pre-treatment SUVmax numeric reading was determined in patients with confirmed esophageal or junctional cancer having PET-CT scan during the time period 1(st) January 2007 until 31(st) July 2012. A minimum follow up of 12 mo was required. Patients were subdivided into quartiles according to SUVmax value and the influence of SUVmax on survival was assessed using univariate and multivariate analysis. The following pre-treatment factors were investigated: patient characteristics, tumor characteristics and planned treatment. RESULTS: The study population was 271 patients (191 male) with esophageal or junctional carcinoma. The median age was 65 years (range 40-85) and histologic subtype was adenocarcinoma in 197 patients and squamous carcinoma in 74 patients. The treatment intent was radical in 182 and palliative in 89 patients. SUVmax was linked to histologic subtype (P = 0.008), tumor site (P = 0.01) and Union for International Cancer Control (UICC) stage (P < 0.001). On univariate analysis, prognosis was significantly associated with SUVmax (P = 0.001), T-stage (P < 0.001) and UICC stage (P < 0.001). On multivariate analysis, only T-stage and UICC stage remained significant. CONCLUSION: Pretreatment SUVmax was not a useful marker in isolation for determining prognosis of patients with esophageal carcinoma.

A case of recurrent mesocolon myxoid liposarcoma and review of the literature.

Background. Liposarcoma is the second most common soft tissue sarcoma affecting predominantly the retroperitoneal space and extremities. Mesenteric liposarcoma is uncommon and occurs in the small bowel mesentery. In this paper we report the case of a recurrent mesocolon myxoid liposarcoma manifesting 6 years from the initial right hemicolectomy for the primary tumour. Case Report. A 41-year-old female presented with a 4-day history of signs and symptoms indicative of small bowel obstruction, subsequently confirmed on plain abdominal X-ray. In 2006 she underwent a right hemicolectomy for a myxoid liposarcoma of the mesentery. The patient was initially managed conservatively; however she showed no signs of improvement and was taken to theatre for an exploratory laparotomy and division of adhesional bands. During this procedure an incidental finding of a dark purple, smooth pelvic mass was identified with similar macroscopic appearance to that of splenic tissue. Histological examination revealed a recurrent mesocolon myxoid liposarcoma. Conclusion. Mesocolon myxoid liposarcoma is a rare soft tissue neoplastic pathology and carries a high risk of recurrence. Therefore, a symptomatic patient with a previous history of primary liposarcoma excision should be treated with a high index of suspicion and a longer period of followup should be considered.

An audit to determine if vitamin b12 supplementation is necessary after sleeve gastrectomy.

ABSTRACT: Sleeve gastrectomy has increased in popularity over the last five years and it is likely to supersede gastric banding. Nevertheless, it is unclear whether vitamin B12 supplementation is required after surgery. The aim of this short report is to identify any vitamin B12 deficiency and highlight the necessity of post laparoscopic sleeve gastrectomy vitamin B12 monitoring. PATIENTS AND METHODS: A review of 66 patients underwent LSG in our institution. 25 patients were excluded as they had no postoperative vitamin B12 screening. 41 patients were included as screened for vitamin B12 and other micronutrients including selenium, serum folate, ferritin, iron, zinc, copper, magnesium and vitamin D. RESULT: There were 5 male (12%) and 36 females (88%), 8/41 patients (20%) had Vitamin B12 deficiency, none of them developed macrocytic anaemia. 17/21 (81%) patient were vitamin D deficient and 9/21 (43%) exhibited low selenium. CONCLUSION: In this small group, a 20% prevalence of vitamin B12 was identified. As a consequence vitamin B12 monitoring and supplementation will be a standard of care in the early postoperative period after LSG at this institution.

Steps for the autologous ex vivo perfused porcine liver-kidney experiment.

The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.

Small bowel hamartoma: a huge diverticulum of small bowel.

A-20-year old male, with no significant medical history, presented with clinical features mimicking a perforated acute appendicitis. Because of features of peritonitis, a laparotomy was performed which showed a segment of small bowel with multiple large diverticula and mesenteric cysts. A segmental small bowel resection was performed. The patient made an uneventful recovery from surgery. Histology revealed features of a small bowel hamartoma.

Small bowel adenocarcinoma: a case of atypical CT scan appearance.

A 73-year-old man presented to the surgical assessment unit with recurrent episodes of central abdominal pain and vomiting for 18 months. He has the past medical history (PMH) of hypertension and has been using his denture for 35 years; he had no past surgical history; he drinks alcohol socially and not a smoker. This patient was investigated for iron deficiency anaemia with upper and lower gastrointestional endoscopy, as the patient had positive faecal occult blood; rectal biopsy showed no sign of inflammation and no evidence of malignancy; blood investigation showed Hb 9.8 g/dl, white cell count 14.8, mean cell volume 86.3, mean cell haemoglobin 26.9 and C reactive protein 13. This patient underwent a CT scan of the chest, abdomen and pelvis; the latest one showed that there is a short segment of the middle part of the small bowel that looks thickened and within which there is a high-density calcified shadow which is reported as an ingested foreign body or a tooth fragment; the patient underwent laparotomy and the histology results revealed 30 mm well differentiated/moderately differentiated adenocarcinoma.