Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.

Clinical practice guidelines for the surgical treatment of rectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO).

In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized.

Clinical practice guidelines for the surgical management of colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

Despite considerable improvement in the management of colon cancer, there is a great deal of variation in the outcomes among European countries, and in particular among different hospital centers in Greece and Cyprus. Discrepancy in the approach strategies and lack of adherence to guidelines for the management of colon cancer may explain the situation. The aim was to elaborate a consensus on the multidisciplinary management of colon cancer, based on European guidelines (ESMO and EURECCA), and also taking into account local special characteristics of our healthcare system. Following discussion and online communication among members of an executive team, a consensus was developed. Statements entered the Delphi voting system on two rounds to achieve consensus by multidisciplinary international experts. Statements with an agreement rate of ≥80% achieved a large consensus, while those with an agreement rate of 60-80% a moderate consensus. Statements achieving an agreement of <60% after both rounds were rejected and not presented. Sixty statements on the management of colon cancer were subjected to the Delphi methodology. Voting experts were 109. The median rate of abstain per statement was 10% (range: 0-41%). In the end of the voting process, all statements achieved a consensus by more than 80% of the experts. A consensus on the management of colon cancer was developed by applying the Delphi methodology. Guidelines are proposed along with algorithms of diagnosis and treatment. The importance of centralization, care by a multidisciplinary team, and adherence to guidelines is emphasized.

Adjuvant chemotherapy for colon cancer: a consensus statement of the Hellenic and Cypriot Colorectal Cancer Study Group by the HeSMO.

Colorectal cancer remains a major cause of cancer mortality in the Western world both in men and women. In this manuscript a concise overview and recommendations on adjuvant chemotherapy in colon cancer are presented. An executive team from the Hellenic Society of Medical Oncology was assigned to develop a consensus statement and guidelines on the adjuvant treatment of colon cancer. Fourteen statements on adjuvant treatment were subjected to the Delphi methodology. Voting experts were 68. All statements achieved a rate of consensus above than 80% (>87%) and none revised and entered to a second round of voting. Three and 8 of them achieved a 100 and an over than 90% consensus, respectively. These statements describe evaluations of therapies in clinical practice. They could be considered as general guidelines based on best available evidence for assistance in treatment decision-making. Furthermore, they serve to identify questions and targets for further research and the settings in which investigational therapy could be considered.

Predictive factors for post-ERCP pancreatitis: a large-scale single expertized endoscopist study.

BACKGROUND: Pancreatitis remains the most common and feared complication of therapeutic endoscopic cholangiopancreatography (ERCP) associated with substantial morbidity. The patient-related and procedure-related independent risk factors for post-ERCP pancreatitis (PEP) in a large case volume by a single experienced endoscopist have been investigated only by few studies. The aim of the study was to investigate patient-related and procedure-related risk factors for PEP collected by a defined protocol on patients who underwent therapeutic ERCP in a single endoscopic unit during the last 8 years. PATIENTS AND METHODS: Our retrospective cohort study included a total of 2688 therapeutic ERCPs enrolled in the final analysis. The impact of the risk factors on PEP development was investigated by univariate and multivariate analysis. PEP was diagnosed and its severity was graded according to the consensus criteria. RESULTS: With the exception of history of pancreatitis, there was no other statistically significant difference of patients' characteristics between patients with and without PEP. Female sex, age, difficult cannulation, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct, and suprapapillary fistulotomy were not found to be risk factors for PEP by univariate and multivariate analysis. Both univariate and multivariate analysis showed history of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization as independent risk factors for PEP. CONCLUSIONS: History of acute pancreatitis, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first-class and second-class pancreatic ductules, and acinarization were all identified as independent risk factors for PEP.

Risk factors for therapeutic ERCP-related complications: an analysis of 2,715 cases performed by a single endoscopist.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is now the exclusive endoscopic therapeutic modality for biliary as well as pancreatic diseases. The aim of the present study was to investigate patient- and procedure-related risk factors for post-ERCP complications in a large-scale study of procedures performed by a single experienced endoscopist. METHODS: This is a retrospective cohort study which included a total of 2,715 therapeutic ERCPs enrolled in the final analysis. Potential important patient- and procedure-related risk factors for overall post-ERCP complications, pancreatitis and post-endoscopic sphincterotomy (ES) bleeding were investigated by univariate and multivariate analyses. RESULTS: Following the first therapeutic ERCP, 327 patients suffered complications; pancreatitis was observed in 132 (4.9%) patients, hemorrhage in 122 (4.5%) patients, cholangitis in 63 (2.3%) patients, perforation in 3 (0.11%) patients, and basket impaction in 7 (0.26%) patients. History of acute pancreatitis was more common in patients with post-ERCP complications (P<0.001). Female gender, young age (<40 years), periampullary diverticulum, suspected sphincter of Oddi dysfunction, metal stent placement, opacification of main pancreatic duct and suprapapillary fistulotomy were not found to be risk factors for overall post-ERCP complications and post-ERCP pancreatitis (PEP). Multivariate analysis showed a history of acute pancreatitis, difficult cannulation, needle-knife papillotomy, transpancreatic sphincterotomy, opacification of first and second class pancreatic ductules and acinarization as independent risk factors for overall complications and PEP, whereas antiplatelet and anticoagulation drug use were not found to be independent risk factors for post-ES bleeding. CONCLUSIONS: The results of this study demonstrate that the endoscopist's experience reduces patient- and procedure-related risk factors for post-ERCP complications.

Upper gastrointestinal endoscopy for dyspepsia: exploratory study of factors influencing patient compliance in Greece.

BACKGROUND: Upper gastrointestinal endoscopy is the most preferable diagnostic examination for patients over fifty when upper gastrointestinal symptoms appear. However, limited knowledge exists in concerns to the compliance of primary care patients' to the doctors' recommendations for endoscopy. METHODS: Patients who visited primary care practices in Greece and experienced upper gastrointestinal symptoms within a 10 days screening study, were referred for an upper endoscopy exam. The patients which refused to complete the endoscopy exam, were interviewed by the use of an open- ended translated and validated questionnaire, the Identification of Dyspepsia in General Population (IDGP) questionnaire. A qualitative thematic analysis grounded on the theory of planned behavior was performed to reveal the reasons for patients' refusal, while socio-demographic predictors were also assessed. RESULTS: Nine hundred and ninety two patients were recorded, 159 of them (16%) were found positive for dyspepsia and gastro-esophageal reflux disease according to the IDGP questionnaire. Out of the above, 131 (83.6%) patients refused further investigation with endoscopy. Patients who refused upper endoscopy were predominantly female (87.8%) (p = 0.036) and over the age of 50. The lack of severe symptoms, fear of pain, concerns of sedation, comorbidity and competing life demands were reported by patients as barriers to performing an endoscopic investigation. CONCLUSIONS: Patients with dyspepsia in rural Greece tend to avoid upper gastrointestinal endoscopy, with two major axons considered to be the causes of patients' refusal: their beliefs towards endoscopy and their personal capability to cope with it. Future research examining reasons of low compliance should be carried out in combination with modern behavioral theories so as to investigate into the above.

Endoscopic management of occluded biliary uncovered metal stents: a multicenter experience.

AIM: To compare diverse endoscopic interventions in the management of occluded uncovered self-expanding metal stents (SEMSs) that had been placed for palliative treatment of unresectable malignant biliary obstruction. METHODS: A retrospective review was undertaken in 4 tertiary endoscopic centers to determine optimal management of different types of occluded SEMSs. The technical success of performed treatment in occluded SEMSs, the patency of the stent, the need for re-intervention and the financial costs of each treatment were analyzed. RESULTS: Fifty four patients were included in the analysis; 21 received Hanaro, 19 Wallstent and 14 Flexus. For the relief of obstruction, a plastic stent was inserted in 24 patients, a second SEMS in 25 and mechanical cleaning was performed in 5 patients. The overall median second patency rates between second SEMSs and plastic stents did not differ (133 d for SEMSs vs 106 d for plastic stents; P=0.856). Similarly, no difference was found between the overall survival of SEMS and plastic stent groups, and no procedure-related complications occurred. Incremental cost analysis showed that successive plastic stenting was a cost-saving strategy at least in Greece. CONCLUSION: Insertion of uncovered SEMSs or plastic stents is a safe and effective treatment for occluded uncovered SEMSs; insertion of plastic stents appears to be the most cost-effective strategy.

Upper gastrointestinal carcinogenesis: H. pylori and stem cell cross-talk.

Chronic inflammation of the gastric epithelium has been associated with the pathogenesis of gastric cancer, as it was postulated by Corea's model of gastric carcinogenesis. Helicobacter pylori (Hp) regulates this inflammatory process and promotes gastric carcinogenesis through induction of gene mutations and protein modulation. Recent data raise the cancer stem cell hypothesis, which implies a central role of multipotent cancer cells in oncogenesis of various solid tumors. This review provides a synopsis of gastric cancer initiation and promotion through Hp and stem cell signaling pathways. The expanding research field of Hp-related cancer stem cell biology may offer novel implications for future treatment of upper gastrointestinal cancer.

Malignant esophageal dysphagia palliation using insertion of a covered Ultraflex stent without fluoroscopy: a prospective observational study.

BACKGROUND: This study aimed to investigate the efficacy and safety of placing self-expandable metal stents (SEMSs) without fluoroscopy for palliation of malignant esophageal or esophagogastric strictures. METHODS: From January 2003 to June 2008, a prospective observational study investigated the placement of covered proximal-release Ultraflex stents without fluoroscopy in nonoperable malignant esophageal and esophagogastric strictures. The technical success as well as the early and late complications (perforation, migration, severe gastroesophageal reflux, hematemesis, and reobstruction due to tissue ingrowth or overgrowth) were recorded. Dysphagia before and after stent placement was scored on a 5-point scale. All the patients were observed monthly in the outpatient clinic or by telephone contact until death. RESULTS: The study enrolled 89 patients (16 women; mean age, 69.54±7.1 years) with dysphagia due to inoperable esophageal or esophagogastric malignant strictures (29 squamous cell cancers, 52 adenocarcinomas, and 8 obstructive malignant extrinsic compressions). The mean stricture length was 6.2±2.8 cm. Endoscopic deployment was achieved for 83 patients (93.2%), with accurate stent positioning in all the patients except one. An adequate relief of symptoms was noted for 82 of the patients (92.1%). During the follow-up period, 36 patients (43.4%) had recurrent dysphagia, caused by tumor overgrowth in 32 cases and stent migration in 4 cases, after an average time of 82 days (range 67-216 days). A stent-in-stent procedure was performed in 27 cases. For two patients, a third stent-in-stent needed to be placed after 85 and 216 days, respectively. CONCLUSION: In most cases, SEMSs can be accurately and safely positioned without fluoroscopy for palliative treatment of malignant esophageal dysphagia.

Sequential or simultaneous placement of self-expandable metallic stents for palliation of malignant biliary and duodenal obstruction due to unresectable pancreatic head carcinoma.

BACKGROUND: Pancreatic cancer is generally not amenable to curative resection, and self-expanding metallic stents have been used to relieve obstruction of bile duct and duodenum in patients with unresectable pancreatic cancer. However, both relative experience with sequential or simultaneous endoscopic stents placement in biliary and duodenal stricture and long-term efficacy of these stents are limited. The aim of this study was to present our experience on the effectiveness of this form of endoscopic treatment. PATIENTS AND METHODS: We performed a retrospective review of all patients undergoing sequential or simultaneous biliary and duodenal stent placement for biliary and symptomatic duodenal obstruction due to unresectable pancreatic head carcinomas in 4 tertiary endoscopic centers. Data were collected from endoscopy and outpatient clinic reports, x-rays, and telephone calls. All patients were followed until their death. Endpoints included technical and clinical success, stent long-term patency, and survival. RESULTS: Thirty-nine patients with unresectable pancreatic head cancer were included. Biliary or duodenal stenting was unsuccessful in 7 patients (17.9%). The remaining 32 patients (median age: 77 y; range: 52 to 82 y), with locally advanced (n=21) or metastatic disease (n=11), were studied. Twenty-one patients (65.6%) received at least first-line chemotherapy. Overall median survival was 9 months (range: 2 to 22 mo), being higher in locally advanced (median survival: 11.5 mo, range: 4 to 22 mo) than metastatic disease (median survival: 3 mo, range: 2 to 5.5 mo) (P<0.001). Median duodenal and biliary patency was 3 months (range: 1 to 12 mo) and 9 months (range: 2 to 22 mo), respectively (P<0.05). Nine of 32 patients (28.1%) required reintervention for recurrent symptoms. No major complications or death occurred in relation to endoscopic treatment. CONCLUSIONS: Placement of self-expandable metal stents is a safe and efficacious palliation method for biliary and duodenal obstruction due to unresectable pancreatic head carcinoma. The majority of patients do not require reintervention and those who require can usually be managed nonoperatively.

Partially covered vs uncovered sphincterotome and post-endoscopic sphincterotomy bleeding.

AIM: To prospectively compare partially covered vs uncovered sphincterotome use on post-endoscopic biliary sphincterotomy (ES) hemorrhage and other complications. METHODS: All patients referred for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to undergo ES either with a partially covered or an uncovered sphincterotome. Both patient and technical risk factors contributing to the development of post-ES bleeding were recorded and analyzed. The characteristics of bleeding was recorded during and after ES. Other complications were also compared. RESULTS: Three-hundred and eighty-seven patients were recruited in this study; 194 patients underwent ES with a partially covered sphincterotome and 193 with conventional uncovered sphincterotome. No statistical difference was noted in the baseline characteristics and risk factors for post-ES induced hemorrhage between the 2 groups. No significant difference in the incidence and pattern of visible bleeding rates was found between the 2 groups (immediate bleeding in 24 patients with the partially covered sphincterotome vs 19 patients with the uncovered sphincterotome, P = 0.418). Delayed bleeding was observed in 2 patients with a partially covered sphincterotome and in 1 patient with an uncovered sphincterotome (P = 0.62). No statistical difference was noted in the rate of other complications. CONCLUSION: The partially covered sphincterotome was not associated with a lower frequency of bleeding. Also, there was no difference in the incidence of other significant complications between the 2 types of sphincterotome.

Endoscopic hemostasis using monopolar coagulation for postendoscopic sphincterotomy bleeding refractory to injection treatment.

BACKGROUND: Endoscopic sphincterotomy (ES) is the cornerstone of therapeutic ERCP and bleeding is one of its most frequent and serious complications. Monopolar coagulation has been used effectively for many causes of gastrointestinal hemorrhages. We investigated the efficacy and safety of endoscopically delivered monopolar coagulation through a polypectomy snare in patients with ES-induced bleeding not responding to injection treatment. PATIENTS AND METHODS: The study included 672 consecutive patients who underwent ES between June 2007 and January 2009. Bleeding patterns (trickle, oozing, spurting) were recorded. Patients with bleeding not responding to spray irrigation or injection of 0.9% NaCl+epinephrine 1: 10,000 solution were treated with monopolar coagulation. Complications related to the technique were assessed. RESULTS: ES-induced bleeding occurred in 59 patients (8.78%). Visible bleeding patterns immediately after ES were: 32 trickle, 21 oozing, and 4 spurting. Delayed bleeding was observed in 2 patients. In 11 patients with intraprocedural bleeding (7 oozing and 4 spurting) not responding to spray irrigation and injection treatment with epinephrine solution, bleeding was successfully treated with monopolar coagulation. There were no procedure-related complications in this series. CONCLUSIONS: Monopolar coagulation is an effective and safe treatment modality and is recommended as an alternative method to other therapeutic modalities for post-ES bleeding not responding to injection treatment.

Double major papilla of Vater--a rare endoscopic finding during endoscopic retrograde cholangiopancreatography: a case report.

BACKGROUND: A double major papilla of Vater is a rare congenital anomaly with only three documented cases described in the literature. CASE REPORT: We report the case of a 19-year-old man, with chronic ulcerative pancolitis and congenital sphrerocytosis, who underwent endoscopic retrograde cholangiopancreatography because he had persistent elevation of liver enzymes and normal MRI cholangiography. During endoscopic retrograde cholangiopancreatography, a double papilla of Vater with separate drainage for the bile duct and the pancreatic duct was observed. CONCLUSION: Endoscopic retrograde cholangiopancreatography showed normal pancreatogram and findings compatible with sclerosing cholangitis.