John Spiliotis

The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery.

Wound dehiscence: is still a problem in the 21th century: a retrospective study

BackgroundThe aim of this study was to evaluate the risk factors of wound dehiscence and determine which of them can be reverted.MethodsWe retrospectively analyzed 3500 laparotomies. Age over 75 years, diagnosis of cancer, chronic obstructive pulmonary disease, malnutrition, sepsis, obesity, anemia, diabetes, use of steroids, tobacco use and previous administration of chemotherapy or radiotherapy were identified as risk factorsResultsFifteen of these patients developed wound dehiscence. Emergency laparotomy was performed in 9 of these patients. Patients who had more than 7 risk factors died.ConclusionIt is important for the surgeon to know that wound healing demands oxygen consumption, normoglycemia and absence of toxic or septic factors, which reduces collagen synthesis and oxidative killing mechanisms of neutrophils. Also the type of abdominal closure may plays an important role. The tension free closure is recommended and a continuous closure is preferable. Preoperative assessment so as to identify and remove, if possible, these risk factors is essential, in order to minimize the incidence of wound dehiscence, which has a high death rate.

Diagnosis and management of peritoneal metastases from ovarian cancer.

The management and the outcome of peritoneal metastases or recurrence from epithelial ovarian cancer are presented. The biology and the diagnostic tools of EOC peritoneal metastasis with a comprehensive approach and the most recent literatures data are discussed. The definition and the role of surgery and chemotherapy are presented in order to focuse on the controversial points. Finally, the paper discusses the new data about the introduction of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced epithelial ovarian cancer.

Acute cholangitis due to afferent loop syndrome after a Whipple procedure: a case report

IntroductionPatients with resection of stomach and especially with Billroth II reconstruction (gastro jejunal anastomosis), are more likely to develop afferent loop syndrome which is a rare complication. When the afferent part is obstructed, biliary and pancreatic secretions accumulate and cause the distention of this part. In the case of a complete obstruction (rare), there is a high risk developing necrosis and perforation. This complication has been reported once in the literature.Case presentationA 54-year-old Greek male had undergone a pancreato-duodenectomy (Whipple procedure) one year earlier due to a pancreatic adenocarcinoma. Approximately 10 months after the initial operation, the patient started having episodes of cholangitis (fever, jaundice) and abdominal pain. This condition progressively worsened and the suspicion of local recurrence or stenosis of the biliary-jejunal anastomosis was discussed. A few days before his admission the patient developed signs of septic cholangitis.ConclusionOur case demonstrates a rare complication with serious clinical manifestation of the afferent loop syndrome. This advanced form of afferent loop syndrome led to the development of huge enterobiliary reflux, which had a serious clinical manifestation as cholangitis and systemic sepsis, due to bacterial overgrowth, which usually present in the afferent loop. The diagnosis is difficult and the interventional radiology gives all the details to support the therapeutic decision making. A variety of factors can contribute to its development including adhesions, kinking and angulation of the loop, stenosis of gastro-jejunal anastomosis and internal herniation. In order to decompress the afferent loop dilatation due to adhesions, a lateral-lateral jejunal anastomosis was performed between the afferent loop and a small bowel loop.

Ovarian cancer screening and peritoneal carcinomatosis: standards, ‘omics’ and miRNAs for personalized management

Ovarian cancer is the most deadly gynecological cancer. Despite biomedical research advances, medical progress over recent years in early detection, effective treatment and cure rates has been slow. Only one in four women is diagnosed at Stage I of cancer associated with excellent oncological outcome, more than 70% of those with advanced tumors die of the disease. Here we discuss the advances and challenges of ‘-omics’-based early-detection biomarkers, hyperthermic intraperitoneal chemotherapy (HIPEC) or neoadjuvant treatment in combination with standard cytoreductive surgery for the treatment of advanced disease and the exciting perspectives of miRNAs for a new generation of biomarkers and drugs.

The practice of pediatric anesthesia in Greek district hospitals

SIR—In order to register the practice of pediatric anesthesia (PA) in the Greek general district hospitals (DH), we send questionnaires to all the 167 anesthesiologists who worked in these hospitals. Ninety-seven DH had not an organized pediatric surgical department, whereas four had a consultant pediatric surgeon. During the study period (January– June 2007), 70 anesthesiologists from 70 DH responded. Only six had some kind of special education in PA. Fortytwo of the 70 DH had equipment to provide anesthesia in all ages from 0 to 14 years old, and the remaining had equipment for anesthesia in ages >2 years old. Twenty of the 70 DH provided pediatric anesthetic equipment for emergency cardiopulmonary resuscitation. During the study period, 2783 pediatric operations (1360 emergencies) were performed in 44 of the 70 DH (63.2 cases per hospital in 6 months) (Table 1). All patients were 3 years old or older. Five hundred and fifteen operations (18.5%) were performed in the four hospitals which had a pediatric surgeon (280 scheduled). In the six DH which had anesthesiologist with special training in PA, were operated on 481 (17.2% of the 2783) cases (341 scheduled). There was one hospital which had both, an anesthesiologist with special training in PA and a pediatric surgeon and in this hospital were operated on 185 cases (150 scheduled). Thirty-five from the 44 hospitals had neither a pediatric surgeon nor an anesthesiologist with special training in PA. In these hospitals, 1972 pediatric operations were performed (the 70.8% of the total cases, 56.3 cases per hospital in 6 months and the 952 were scheduled ones). Respectively, in the same period, the number of the pediatric operations per hospital was 128.2 for the four hospitals which had a consultant pediatric surgeon and 80.1 for the six hospitals with anesthesiologist having a special training in PA. In the question that we asked whether pediatric anesthesia should become a subspecialty of anesthesia, 56 of the 70 anesthesiologist considered it necessary, but only 25 of them would like to engage with this specialty. Our results were not in accordance with the recommendations derived from the National Confintential Enquiry into Perioperative Deaths (NCEPOD) (1). In this important study were considered all children deaths within the first 30 postoperative days for surgeries that were performed during one year. The authors concluded that some deaths could be avoided. They suggested that surgeons and anesthetics involved in pediatric surgery should not undertake occasional practice as the outcome is related to their experience. Furthermore, nonpediatric hospitals in which children are operated should have an anesthesiologist with special post fellowship training in PA (1). The dilemma, who should do the PA that got out in two papers published on 1997, resulted in a centralization trend of the pediatric surgical cases (2,3). McNicol discussed the pros and cons of this centralization. The specialized pediatric hospitals are not uniformly distributed to the territory resulting in difficulties in the transfer of emergency cases and at the same time in parents’ agitation (2). There is engrossment about the safety of performing a simple operation (such as a bone fracture) in a child, in a district hospital without an organized pediatric surgical department. Furthermore, we could say that the accomplishment of more complicated operations belongs to the world of fantasy. If we want a decentralization of the pediatric surgery intended to improve the quality of care, we should take additional measures regarding the facilities, the equipment, and the stuff. In our study, pediatric operations were performed in 44 DH. Thirty-five of these hospitals had neither a pediatric surgeon nor an anesthesiologist with special training in PA and the remaining had not an organized pediatric surgical department. So, it is clear that some of the biggest Greek DH lack in special stuff. Excessive anesthesia-related morbidity and mortality in children has been explained in part by a lack of competency in pediatric anesthesiology (4). Occasional practice in pediatric surgery and anesthesia is not acceptable, both for surgeons and anesthesiologists unless for life threatening emergencies or minimal cases. Auroy et al. (5) studied the complications in PA and its relationship to pediatric practice in France. A significantly (P < 0.05) higher incidence of complications was found in the groups that performed 1–100 (7.0 ± 24.8 per 1000 anesthetics) and 100–200 pediatric anesthetics (2.8 ± 10.1 per 1000 anesthetics) than in the group that administered more than 200 pediatric anesthetics per year (1.3 ± 4.3 per 1000 anesthetics). The authors, despite the limitations of their study, recommended that a minimum case load of 200 pediatric anesthetics per year is necessary to reduce the incidence of complications and improve the level of safety in pediatric practice (5). In our study, a total of 2783 pediatric operations were performed in the 44 of the 70 DH. This corresponds at a mean of 63.2 cases per hospital per 6 months or 126.4 cases per year. In the majority of the Greek DH were children operated on and which had neither a pediatric surgeon nor an anesthesiologist trained in PA, the number of cases was 112.6 per year per hospital. Our questionnaire did not include questions regarding the major complications of PA. It is of Pediatric Anesthesia 2008 18: 667–692

Role of age on the outcome of liver surgery. A single institution experience

Objective:  The aim of the present study was to evaluate the role of age on different types of liver surgery.

Adjuvant S-1 Chemotherapy for Gastric Cancer and Peritoneal Wash

In the September issue of the World Journal of Surgery, Ito and colleagues evaluated the efficacy of postoperative S-1 chemotherapy in patients with stage II/III gastric cancer with detection by a real-time reverse transcription polymerase chain reaction (RT-PCR) of free intraperitoneal cancer cells [1]. Based on the results of a large-scale, appropriately designed, multicenter, Japanese, Phase III, randomized controlled trial (RCT) [2], postoperative S-1 chemotherapy has become a standard adjuvant treatment in Japanese patients with stage II/III gastric cancer after standardized gastrectomy with D2 lymphadenectomy. In this changing treatment study, adjuvant S-1 chemotherapy reduced peritoneal recurrence in the subgroup analysis. However, that trial was not designed to evaluate the efficacy of S-1 treatment in stage II/III patients with a positive peritoneal wash on RT-PCR. Ito and colleagues [1] looked at whether adjuvant S-1 treatment was effective also in the subgroup of patients with molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembryonic antigen (CEA) mRNA in peritoneal washes. From a total of 32 patients with CEA mRNA(?) gastric cancer, 20 patients (37.5%) relapsed, 10 of whom showed peritoneal relapse. The authors compared these findings with those of historical controls and found that the 3-year survival rates for the study population and the controls were similar (67.3% vs. 67.1%, respectively). The authors concluded that S-1 monotherapy seems not to be effective in eradicating free cancer cells in the abdominal cavity. If this is true, all patients with stage II/III should undergo a peritoneal wash during D2 surgery because CEA mRNA(?) may influence the decision-making about postoperative adjuvant S-1 treatment. However, this is a small retrospective comparison study with historical controls, which suggests major limitations in terms of drawing conclusions. The authors might better have performed a Phase II trial to assess a potential role of CEA mRNA. If such a study had positive results, a Phase III RCT could then be satisfied. Current efforts to improve oncologic outcomes of patients with stage II/III disease have focused on the addition of adjuvant radiotherapy to S-1 or cisplatin-based combination chemotherapy. Moreover, the positive results of a Phase III trial adding trastuzumab to HER2-positive patients with advanced or metastatic gastric cancer [3] drive new clinical trials of adjuvant treatment with trastuzumab plus combination chemotherapy. Exciting emerging research explores other mutated genes that influence other signaling pathways, such as HER1 and HER3 downstream pathways as well as signaling pathway networks important for gastric cancer metastasis. The advent of the latest DNA sequencing technology raises rational optimism for improving outcomes of patients with gastric cancer or other solid cancers [4–15].

Genotyping Gastric Cancer

Gastric cancer, like most solid tumors, is associated with wide variations in mutation. This heterogeneity reveals the complexity of cancer and the major difficulties in predicting prognosis or treatment response among individual patients with the same clinicopathologic features, tumor staging, and treatment. Genotyping provides an exciting opportunity to identify the genetic variations, such as single-nucleotide polymorphisms (SNPs), underlying individual tumors. Such features may have clinical implications as prognostic and predictive markers. This raises the question of whether genotyping of key single genes, such as for example matrix metalloproteinase (MMP) genes, could be translated into clinically useful information. In the December 2010 issue of World Journal of Surgery, Alakus and colleagues [1] reported results of their study of the potential clinical utility of gastric cancer genotyping. In their study, genotyping for the identification of SNPs was performed in samples from 135 patients with primary gastric carcinoma. Genotyping was performed for MMP-2(-1306C [ T), TIMP-2(303C [ T), and MMP7(-181A [ G). In addition, MMP-2 and TIMP-2 antigen expression in resected tumor tissues was detected immunohistochemically. There were no significant relationships between SNPs and traditional standard factors, such as tumor differentiation, pT, R category, or the TNM and Lauren classifications. However, there was a significant correlation between TIMP-2(303C [ T) and higher pN stages (P = 0.01) and more distant metastasis (P = 0.02) for patients with the CC genotypes. The presence of the TIMP-2(303C [ T) CC genotype was not associated with significant differences in survival. The authors conclude that TIMP-2(303C [ T) CC genotype was associated with more advanced pN and pM categories. This relatively small retrospective study reconfirms how hard is to identify robust biomarkers by simple genotyping of single genes. There was no significant correlation between patients with or without SNPs in MMP genes. Although MMP genes have an important role in tumorigenesis and metastases, increasing evidence suggests that multiple SNPs in many other genes, copy-number changes, and genomic rearrangements are involved in carcinogenesis, tumor growth, and metastasis. Moreover, it is still unknown how all these mutations result in gene deregulation. Even when the catalog of mutations involved in gastric cancer and other solid tumors has been completed, the next great challenge will be the understanding of gene expression regulation and the prediction of regulatory system interactions. Therefore, it may be naı̈ve to believe that SNPs alone can drive tumorigenesis and metastasis. Whole-genome sequencing, and not single-gene genotyping, appears to be a rational approach to gaining an understanding of the genetic basis of cancer. It appears that such knowledge is almost essential for developing biomarkers for a ‘‘true’’ personalized medicine. The latest high-throughput techniques and next-generation sequencing technology are currently in usein largescale systematic whole-genome studies designed to to provide deeper insight into structural and functional variations in cancer [2]. Most recently, high-quality experimental studies in model organisms [3, 4] have provided high hope for translating exciting research into structural and functional genome into clinical medicine [5–15]. J. Spiliotis (&) Department of Surgery, ‘‘METAXA’’ Cancer Memorial Hospital, Botosi 51, TK 18535 Piraeus, Greece e-mail: jspil@in.gr

Laparoscopic hyperthermic intraperitoneal chemotherapy for the management of advanced peritoneal carcinomatosis.

The role of laparoscopic HIPEC has been reported by several centers around the world as a promising and appealing therapeutical alternative in the management of patients suffering of advanced intra-abdominal malignancies and peritoneal carcinomatosis. Laparoscopic HIPEC is implemented as a neoadjuvant and adjuvant therapeutical modality before and after open cytoreductive surgery. The diagnostic and therapeutical impact of laparoscopic HIPEC is well appreciated and generally is associated with many advantages when compared to classical open HIPEC and simultaneous open cytoreductive surgery.