Does gender affect laparoscopic cholecystectomy?

The relationship between sex and outcome after laparoscopic surgery for symptomatic cholelithiasis remains unclear. The purpose of this study was to determine the influence of sex on the clinical presentation of patients with symptomatic gallstone disease and the clinical outcomes of laparoscopic cholecystectomy. The rates of conversion to open cholecystectomy, complication rates, operative times, and lengths of hospital stay were compared between the sexes. Compared with female patients, males were significantly older and more likely to have coexisting cardiovascular disease, previous upper abdominal surgery, previous hospitalization for acute cholecystitis and pancreatitis, acute cholecystitis, and suppurative cholecystitis (such as empyema), conversions, and complications. The mortality rate was nil. Analyses revealed an independent effect of sex on the prevalence of complications, even when including all of the major confounding factors in the model. In contrast, the effect of sex on conversion to open cholecystectomy was not significant when controlling for patient age. Operative time and postoperative hospital stay were significantly longer in males than in females. The tendency of male patients to have cholecystitis of greater severity should remind surgeons of the need to inform patients about the higher conversion rate among male patients, to reduce the disappointment of a large laparotomy wound or prolonged recovery period. On the other hand, there may be an increased need for surgeons to strongly advice male patients with symptomatic cholelithiasis to undergo early intervention.     

Epigenetic editing and tumor-dependent immunosuppressive signaling in head and neck malignancies

Head and neck cancer (HNC) comprises a heterogeneous variety of malignant tumors, characterized by a relatively high tumor mutation burden. Previous data have revealed that immune system dysfunction appears to serve a key role in the development and progression of HNC and established immunosuppression is vital for evading the host immune response. Despite progress in chemotherapy and radiotherapy, the survival rate of patients with HNC is still low. Therefore, the present review discusses the development of novel immunotherapy approaches based on the various immune cell signaling routes that trigger drug resistance and immunosuppression. Additionally, the present review discusses the epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs that drive and support HNC progression. Furthermore, the role of cancer-associated fibroblasts, tumor macrophages and myeloid cells in tumor-related immunosuppression are considered. Specifically, the molecular immune-related mechanisms in the tumor microenvironment, which lead to decreased drug sensitivity and tumor relapse, and strategies for reversing drug resistance and targeting immunosuppressive tumor networks are discussed. Deciphering these molecular mechanisms is essential for preclinical and clinical investigations in order to enhance therapeutic efficacy. Furthermore, an improved understanding of these immune cell signaling pathways that drive immune surveillance, immune-driven inflammation and tumor-related immunosuppression is necessary for future personalized HNC-based therapeutic approaches.     

Intramedullary application of local antibiotic bullets for the treatment of long bone fracture related infection

Purpose

The optimal means of local antibiotic delivery for fracture related infection is unknown. Until now, intramedullary application of calcium sulphate based local antibiotics has been challenging. We report on the use of a newly available mode of preparation and delivery: the Stimulan Bullet Mat and Introducer (Biocomposites Ltd, Staffordshire, England).

Methods

A retrospective analysis of prospectively collected data for infection cases at two separate tertiary referral institutions was performed. We included cases of long bone FRI with a retained intramedullary nail, treated with a single stage protocol of metalwork removal, debridement, local antibiotic application using the novel mould and applicator, with additional bony stabilisation and soft tissue reconstruction where required.

Results

All 13 patients achieved infection remission rate with an average follow-up of 19.7 months (range 12–28). All 6 patients with infection around an unhealed fracture achieved union at an average 8 months (range 4–12) from debridement. No patients developed aseptic wound leak.

Conclusions

Antibiotic impregnated calcium sulphate can be used safely as part of a single stage treatment protocol for the treatment of long bone fracture related infection following intramedullary nailing. We have demonstrated high rates of infection remission and union, using a newly available intramedullary applicator.

     

Effect of haemodialysis on serum levels of tumour markers in patients with end-stage renal failure

SUMMARY: We studied the effect of haemodialysis on the serum levels of tumour markers in 78 patients, 49 men and 29 women with a mean age of 61 ± 2 years, who had been undergoing haemodialysis for 39 ± 10 months. No patient had any clinical evidence of malignancy. Serum values of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous-cell-carcinoma-related antigen (SCC), neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), CA 15-3, CA 19–9, and among males prostate-specific antigen (PSA) were determined before and after dialysis. Postdialysis values, after being corrected for haemoconcentration, were compared with predialysis values. A significant increase of 32% was observed in NSE levels ( P <0.001) and of 21% in CA 15-3 ( P <0.001) after haemodialysis. A lesser, but still statistically significant, increase (8-12%) was observed in SCC, AFP and CEA levels ( P <0.05), while the values of the remaining three markers remained unchanged. In conclusion, an increase in some tumour markers was found in our patients after dialysis, a finding which requires further investigation.     

Circulating VEGF levels in the serum of gastric cancer patients: correlation with pathological variables,patient survival,and tumor surgery

OBJECTIVE: To evaluate the clinical usefulness of serum vascular endothelial growth factor (VEGF) levels in gastric cancer patients. SUMMARY BACKGROUND DATA: Vascular endothelial growth factor plays an important role in the formation of new blood vessels involved in the growth and metastatic spread of solid tumors, but there is limited information regarding the clinical significance of serum VEGF levels in cancer patients. METHODS: Serum VEGF concentrations were measured by an enzyme linked immunosorbent assay in 61 healthy controls and in 58 gastric cancer patients before surgery, and then again at 7 and 30 days after surgery. The association between preoperative serum VEGF levels, clinicopathological features and patient survival, and their changes following surgery were evaluated. RESULTS: Serum VEGF levels in gastric cancer patients were significantly higher than those in controls. There was a significant association between serum VEGF levels and disease stage, as well as invasion depth of the tumor and the presence of distant metastases. Serum VEGF levels decreased significantly after radical resection of the primary tumor and increased in patients with unresectable tumors. Multivariate regression analysis showed that serum VEGF level is an independent prognostic factor for survival. CONCLUSIONS: Serum VEGF levels in gastric patients are significantly higher compared with normal controls and correlate with local tumor extent, disease stage, and the presence of distant metastases. Preoperative serum VEGF concentration decreases significantly after radical resection of the primary tumor and is an independent prognostic factor for patient survival suggesting that determination of serum VEGF levels may be clinically useful.     

Mycophenolate mofetil impairs the integrity of colonic anastomosis

BACKGROUND: The aim of this experimental study was to investigate the effect of mycophenolate mofetil (MMF) during the three phases of colonic anastomosis healing and specifically to check the effect of MMF on the expression of transforming growth factor-beta1 (TGF-beta1), one of the most important growth factors contributing to mechanical stability of colonic anastomosis. MATERIALS AND METHODS: Sixty male Wistar rats underwent colonic resection and end-to-end anastomosis. The animals were divided into two groups, a study group given MMF 40 mg/kg, intraduodenally and a control group given vehicle. The rats were sacrificed at 3, 7, and 14 days (10 animals in each group). The anastomoses were tested by measuring bursting pressure and hydroxyproline content. Histological examination and immunohistochemical expression of TGF-beta1 also were assessed. RESULTS: The mean bursting pressure in the study group was significantly lower on day 3 and 7, but there was no statistical significance on day 14. The mean hydroxyproline content was lower in the study group on days 3, 7, and 14. Histology showed decreased number of macrophages and fibroblasts on days 3 and 7 but no difference on day 14. The expression of TGF-beta1 was significantly reduced in the study group, with the difference being more pronounced on days 3 and 7. CONCLUSION: MMF weakens the integrity of colonic anastomosis, and this effect is more significant during the inflammatory phase of healing. MMF has a negative effect on macrophages and TGF-beta1 expression, resulting in decreased collagen accumulation at the anastomosis.     

Long-term evaluation of rabbit peripheral nerve repair with end-to-side neurorrhaphy in rabbits

This study was designed to quantitatively assess long-term end-to-side neurorrhaphy in rabbits. The cut right ulnar nerve was repaired and sutured to the median nerve, in which a perineurial window was created in an end-to-side fashion 3 cm above the elbow joint. Both the extent of the reinnervation and the integrity of the intact donor nerve were evaluated in 36 rabbits randomly treated with fresh or delayed nerve repair. Evaluations included motor nerve conduction velocity (MNCV), dry muscle weight (DMW), and histological examinations at 9 and 12 months postoperatively. The recovery rates of MNCV were 90.1% and 92.8% for the ulnar nerve, and 95.7% and 96.8% for the median nerve, compared to intact contralateral nerves at 9 and 12 months, respectively. MNCV was not detectable for the ulnar nerve in control animals, while it was normal for the median nerve. Recoveries of flexor carpi ulnaris dry muscle weight of about 90.7% and 94.5% were observed at 9 and 12 months postoperatively, respectively. However, muscle mass measurements revealed a recovery of only 31.3% and 27% for control groups at 9 and 12 months postoperatively. The differences between experimental groups and control groups were statistically significant (P < 0.01). Neurofilament and silver stains showed numerous sprouting axons originating from the median nerve to the ulnar nerve. The results indicate that end-to-side neurorrhaphy could induce axonal sprouting from the main nerve trunk of upper limbs in rabbits, leading to useful functional recovery.     

Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna

Background and Aim: We investigated the role of the prophylactic administration of the antioxidant 2‐mercaptoethane sulfonate (mesna) on the hepatocyte‐regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver. Methods: Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor‐κB (NF‐κB) activity were assessed. Results: Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF‐κB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF‐κB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle‐induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF‐κB, while attenuating liver injury after PH under Pringle. Conclusion: The excessive activation of NF‐κB is related to the suppression of hepatocyte‐regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle‐induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF‐κB activation.