Anastasios Machairas

Current Concepts in the Management of Necrotizing Fasciitis

Necrotizing fasciitis (NF) is a severe, rare, potentially lethal soft tissue infection that develops in the scrotum and perineum, the abdominal wall, or the extremities. The infection progresses rapidly, and septic shock may ensue; hence, the mortality rate is high (median mortality 32.2%). Prognosis becomes poorer in the presence of co-morbidities, such as diabetes mellitus, immunosuppression, chronic alcohol disease, chronic renal failure, and liver cirrhosis. NF is classified into four types, depending on microbiological findings. Most cases are polymicrobial, classed as type I. The clinical status of the patient varies from erythema, swelling, and tenderness in the early stage to skin ischemia with blisters and bullae in the advanced stage of infection. In its fulminant form, the patient is critically ill with signs and symptoms of severe septic shock and multiple organ dysfunction. The clinical condition is the most important clue for diagnosis. However, in equivocal cases, the diagnosis and severity of the infection can be secured with laboratory-based scoring systems, such as the laboratory risk indicator for necrotizing fasciitis score or Fournier’s gangrene severity index score, especially in regard to Fournier’s gangrene. Computed tomography or ultrasonography can be helpful, but definitive diagnosis is attained by exploratory surgery at the infected sites. Management of the infection begins with broad-spectrum antibiotics, but early and aggressive drainage and meticulous debridement constitute the mainstay of treatment. Postoperative management of the surgical wound is also important for the patient’s survival, along with proper nutrition. The vacuum-assisted closure system has proved to be helpful in wound management, with its combined benefits of continuous cleansing of the wound and the formation of granulation tissue.

Prosthetic repair of incisional hernia combined with elective bowel operation.

BACKGROUND AND AIMS Incisional hernia repair with mesh is considered a clean operation and it is not recommended to be perfomed at the same time with a potentially contaminated operation. The aim of this study is to assess the short-term results of a group of patients who underwent a colon operation and simultaneous incisional hernia repair with an onlay polypropylene mesh technique. PATIENTS AND METHODS From Novemberto June 2006, 19 patients underwent incisional hernia repair with polypropylene mesh, with simultaneous colonic operation. In 13 patients reestablishment of bowel continuity after a Hartmann procedure was done, whereas in four patients a loop colostomy was closed. Two patients underwent colectomy for cancer. RESULTS Post-operatively one patient had a seroma and two others had wound infections which required mesh removal. The mean follow-up was 70.15 +/- 48.40 months (range 3 to 142 months). During this period five patients died, four from progression of malignancy and one from myocardial infarction. Three patients (15.78%) developed recurrence, two patients with previous Hartmanns operation for complicated diverticulitis and wound infection and the third patient due to inappropriate mesh fixation with buttonhole hernia development. CONCLUSION Prosthetic repair of incisional hernias can be safely performed simultaneously with a colonic operation, with an acceptable rate of infectious complications and recurrence. It is unjustifiable to avoid the use of mesh in a potentially contaminated field when an appropriate technique is used.

Current Trends in Laparoscopic Ventral Hernia Repair

Background and Objectives: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. Database: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. Conclusions: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury.

Pre-treatment with low-dose endotoxin prolongs survival from experimental lethal endotoxic shock: Benefit for lethal peritonitis by Escherichia coli.

Although LPS tolerance is well-characterized, it remains unknown if it is achieved even with single doses of lipopolysaccharide (LPS) and if it offers protection against lethal bacterial infections. To this end, C57B6 mice were assigned to groups A (sham); B (saline i.p followed after 24h by i.p 30mg/kg LPS); and C (3mg/kg LPS i.p followed after 24h by i.p 30mg/kg LPS). Survival was monitored and animals were sacrificed early after lethal challenge for measurement of tumour necrosis factor-alpha (TNFα) in serum; isolation of splenocytes and cytokine stimulation; and flow-cytometry for apoptosis and TREM-1. Experiments were repeated with mice infected i.p by Escherichia coli after challenging with saline or LPS. Mortality of group B was 72.2% compared with 38.9% of group C (p: 0.020). Serum TNFα of group C was lower than group B. Expression of TREM-1 of group C on monocytes/neutrophils was greater than group B. Release of TNFα, of IFNγ and of IL-17 from splenocytes of group C was lower than group B and the opposite happened for IL-10 showing evidence of cellular reprogramming. In parallel, apoptosis of circulating lymphocytes and of splenocytes of group C was greater compared with group B. Pre-treatment of mice challenged by E. coli with low dose LPS led to 0% mortality compared with 90% of saline pre-treated mice; in these mice, splenocytes improved over-time their capacity for release of IFNγ. It is concluded that single low doses of LPS lead to early reprogramming of the innate immune response and prolong survival after lethal E. coli challenge.

Gastrointestinal Stromal Tumors (GISTs): An Updated Experience

BackgroundGastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors of the digestive tract characterized by c-KIT mutations. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors.MethodsThe stomach is the most commonly involved site for these tumors in the digestive tract. Computed tomography and endoscopy can usually establish the diagnosis. The study of certain specific immunohistochemical markers may contribute to better characterization of these tumors.ResultsSurgical resection of GISTs has been the most effective therapy. In addition, targeted therapy with tyrosine kinase inhibitors may reduce the development of recurrence or decrease the disease progression in patients with metastatic disease.ConclusionsThe introduction of tyrosine kinase inhibitors has resulted in significant improvement in the overall prognosis of these patients. Furthermore, preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs.

Improvement of gastric emptying by enhanced recovery after pancreaticoduodenectomy

BACKGROUND Enhanced recovery after surgery (ERAS) has improved postoperative outcomes particularly in colorectal surgery. This study aimed to assess compliance with an ERAS protocol and evaluate its effect on postoperative outcomes in patients undergoing pancreaticoduodenectomy. METHODS Fifty patients who had received conventional perioperative management from 2005 to 2009 (conventional group) were compared with 75 patients who had received perioperative care with an ERAS protocol (fast-track group) from 2010 to 2014. Mortality, complications, readmissions and length of hospital stay were evaluated and compared in the groups. RESULTS Compliance with each element of the ERAS protocol ranged from 74.7% to 100%. Uneventful patients had a significant higher adherence to the ERAS protocol (87.5% vs 40.7%; P<0.001). There were no significant differences in demographics and perioperative characteristics between the two groups. Patients in the fast-track group had a shorter time to remove the nasogastric tube, start liquid diet and solid food, pass flatus and stools, and remove drains. No difference was found in mortality, relaparotomy, readmission rates and overall morbidity. However, delayed gastric emptying and length of hospital stay were significantly reduced in the fast-track group. The independent effect of the ERAS protocol in reducing delayed gastric emptying and length of hospital stay was confirmed by multivariate analysis. CONCLUSION ERAS pathway was feasible and safe in improving gastric emptying, yielding an earlier postoperative recovery, and reducing the length of hospital stay.

Predictors affecting in-hospital mortality of ruptured abdominal aortic aneurysms: a Greek multicenter study.

BACKGROUND Endovascular aortic repair (EVAR) is being used with increasing frequency for the treatment of ruptured abdominal aortic aneurysms (rAAAs), although conflicting results have been reported concerning perioperative mortality. The aim of our study was to evaluate potential difference in mortality rates between EVAR and open surgical repair (OSR) and identify independent risk factors for in-hospital mortality in rAAAs. This study also aimed to evaluate the Glasgow Aneurysm Score (GAS) in predicting in-hospital mortality. A time-trend analysis of EVAR for ruptured AAAs was also performed. METHODS Prospectively collected data from 7 public hospitals in Greece concerning rAAA repairs between January 2006 and April 2012 were analyzed. Primary outcome was in-hospital mortality. Multivariate logistic regression analysis was used to identify independent risk factors. The receiver-operator characteristic curve was used to determine the value of the GAS in predicting in-hospital death. Time-trend analysis, depicting annual changes (%), concerning EVAR for ruptured AAAs was also conducted. RESULTS A total of 418 patients (92.3% men, mean age = 74.3 ± 8.8) with rAAAs were recorded during the study period. Among them, 113 patients (27%) underwent EVAR. Overall in-hospital mortality was 45.2%, whereas in-hospital mortality after EVAR and OSR was 20.4% and 54.3%, respectively (P < 0.001). Multivariate analysis evidenced that hemodynamic instability (P < 0.001), OSR (P < 0.001), age ≥80 years (P < 0.001), coronary artery disease (P < 0.001), and renal insufficiency (P = 0.02) independently increased in-hospital mortality. Area under the curve of GAS was 0.80 (95% confidence interval [CI] = 0.75-0.85, P < 0.001) for OSR and 0.64 (95% CI = 0.51-0.77, P = 0.04) for EVAR. Annual increase of proportion (%) of EVAR for rupture was 5% (P = 0.004). CONCLUSIONS EVAR is being used with increasing frequency for the treatment of rAAAs and it appears to be associated with lower in-hospital mortality compared with OSR, after adjustment for hemodynamic instability and known atherosclerotic risk factors. Preoperative predictors of in-hospital mortality such as GAS should be probably modified in these patients.

From Clinical Standards to Translating Next-Generation Sequencing Research into Patient Care Improvement for Hepatobiliary and Pancreatic Cancers

Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA. It is a pity that multiple Phase III randomized control trials testing the efficacy of targeted agents have negative results. Failure in the development of effective drugs probably reflects the poor understanding of genome-wide alterations and molecular mechanisms orchestrating therapeutic resistance and recurrence. In the post-ENCODE (Encyclopedia of DNA Elements) era, cancer is referred to as a highly heterogeneous and systemic disease of the genome. The unprecedented potential of next-generation sequencing (NGS) technologies to accurately identify genetic and genomic variations has attracted major research and clinical interest. The applications of NGS include targeted NGS with potential clinical implications, while whole-exome and whole-genome sequencing focus on the discovery of both novel cancer driver genes and therapeutic targets. These advances dictate new designs for clinical trials to validate biomarkers and drugs. This review discusses the findings of available NGS studies on HBP cancers and the limitations of genome sequencing analysis to translate genome-based biomarkers and drugs into patient care in the clinic.

The role of remote ischemic preconditioning in the treatment of atherosclerotic diseases

Remote ischemic preconditioning (RIPC) is the application of a transient and brief ischemic stimulus to a distant site from the organ or tissue that is afterward exposed to injury ischemia, and has been found to reduce ischemia–reperfusion injury (IRI) in various animal models. RIPC appears to offer two distinct phases of endothelial IRI protection, which are presumably mediated through neuronal and humoral pathways.

Synchronous well differentiated neuroendocrine tumour and gastrointestinal stromal tumour of the stomach: a case report

BackgroundWell differentiated neuroendocrine tumours (carcinoids), arising from cells of the diffuse neuroendocrine system, represent the most commonly encountered gastric endocrine tumours. Gastrointestinal stromal tumours (GISTs), which stem from interstitial Cajal cells located within the wall of the gastrointestinal tract and have a characteristic immunoreactivity for CD117 (c-kit protein), account for the majority of gastrointestinal mesenchymal neoplasms. Simultaneous occurrence of a GIST with a well differentiated neuroendocrine tumour in the stomach is very rare.MethodsClinical history, endoscopy and histopathological findings were utilized for our diagnostic considerations.ResultsWe report the coexistence of a high risk GIST with a well differentiated neuroendocrine tumour of benign clinical behavior, both located in the stomach, in a 62-year-old man previously operated for a gastric well differentiated neuroendocrine tumour with uncertain malignant behaviour.ConclusionsEven single well differentiated, sporadic, NETs of small size may coexist with GISTs. An appropriate initial therapeutic approach combined with a scrupulous follow-up seems to play a significant role in terms of preventing a metastatic disease.