George Basdanis

Prognostic significance of mucinous component in colorectal carcinoma

BackgroundMany factors influence survival in colorectal cancer patients, one of them is the mucinous component of the tumour. Mucinous adenocarcinoma is characterized by the extracellular mucin of more than 50% of the tumour volume.MethodsFrom 1970 to 1999, 1160 patients were admitted to our clinic for colorectal cancer. They were divided into four groups according to mucinous character of the tumour, in two time periods of 15 years.ResultsThere was an increase in the incidence of mucinous tumours from 20.8 to 30.5% in the second period. These tumours were more advanced (Dukes’ C) and especially right sided (34.5% vs. 17.9%). Five-year survival was increased during the second period but was of a lesser degree in the mucinous group (51.5% vs. 65.5%).ConclusionsColorectal mucinous carcinomas present at a more advanced stage, predominantly in men, with higher right colon location rate, and a worse overall 5-year survival rate than the non-mucinous colorectal cancers.

Randomized clinical trial of stapled hemorrhoidectomy vs open with Ligasure for prolapsed piles

BackgroundThe aim of the study was to compare the results in 95 patients randomly allocated to undergo either stapled or open hemorrhoidectomy using Ligasure.MethodsNinety-five patients with grade III and IV hemorrhoids were randomly allocated to undergo either stapled (50 patients) or open using Ligasure (45 patients). Stapled hemorrhoidectomy was performed with the use of a circular stapling device. Open hemorrhoidectomy was accomplished according to the Milligan-Morgan technique by using Ligasure. Postoperative pain was assessed by means of a visual analog scale (VAS). Recovery evaluation included return to pain-free defecation and normal activities. A 6-month clinical follow-up and an 18 (12-24) month median telephone follow-up were obtained in all patients.ResultsOperation time for open hemorrhoidectomy using Ligasure was shorter [median 13 (range 9.2-16.1) min vs 15 (range 8-17) minutes, p < 0.05]. Median range of VAS score in the stapled group were significantly lower [VAS score after 8 h: 3 (2-6) vs 5 (3-8), p < 0.01; VAS score after first defecation: 5 (3-8) vs 7 (3-9), p < 0.001. The stapled hemorrhoidectomy was associated with an increased incidence of intraoperative bleeding in 18 cases (36%) vs four cases (8.8%) of the Ligasure group. There were three cases (6%) from the stapled group with recurrence of the hemorrhoids and none from the open technique.ConclusionsHemorrhoidectomy with a circular stapler device is easy to perform, but one more line of clips must be added to the device to avoid intraoperative bleeding from the cut line. Hemorrhoidectomy performed using Ligasure is more painful postoperatively but is a more radical operation.

A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: A Hellenic Cooperative Oncology Group study

BackgroundColon cancer is a public health problem worldwide. Adjuvant chemotherapy after surgical resection for stage III colon cancer has been shown to improve both progression-free and overall survival, and is currently recommended as standard therapy. However, its value for patients with stage II disease remains controversial. When this study was designed 5-fluorouracil (5FU) plus leucovorin (LV) was standard adjuvant treatment for colon cancer. Irinotecan (CPT-11) is a topoisomerase I inhibitor with activity in metastatic disease. In this multicenter adjuvant phase III trial, we evaluated the addition of irinotecan to weekly 5FU plus LV in patients with stage II or III colon cancer.MethodsThe study included 873 eligible patients. The treatment consisted of weekly administration of irinotecan 80 mg/m2 intravenously (IV), LV 200 mg/m2 and 5FU 450 mg/m2 bolus (Arm A) versus LV 200 mg/m2 and 5FU 500 mg/m2 IV bolus (Arm B). In Arm A, treatments were administered weekly for four consecutive weeks, followed by a two-week rest, for a total of six cycles, while in Arm B treatments were administered weekly for six consecutive weeks, followed by a two-week rest, for a total of four cycles. The primary end-point was disease-free survival (DFS) at three years.ResultsThe probability of overall survival (OS) at three years was 0.88 for patients in Arm A and 0.86 for those in Arm B, while the five-year OS probability was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.436). Furthermore, the probability of DFS at three years was 0.78 and 0.76 for patients in Arm A and Arm B, respectively (P = 0.334). With the exception of leucopenia and neutropenia, which were higher in patients in Arm A, there were no significant differences in Grades 3 and 4 toxicities between the two regimens. The most frequently recorded Grade 3/4 toxicity was diarrhea in both treatment arms.ConclusionsIrinotecan added to weekly bolus 5FU plus LV did not result in improvement in disease-free or overall survival in stage II or III colon cancer, but did increase toxicity.Trial registrationAustralian New Zealand Clinical Trials Registry: ACTRN12610000148077

Colorectal cancer in patients over 70 years of age: determinants of outcome.

BackgroundThe aim of this study was to evaluate operative risk factors, the mortality, morbidity and survival in old patients with colorectal cancer.MethodsFrom 1160 patients with colorectal cancer, 398 patients aged 70 years or older, from 1970 to 2000, were followed-up. Dukes’ classification, differentiation, sex, anatomical site and survival were compared with patients <70 years old.ResultsLong-term results have been proved to be similar both in young and old patients. Relative survival rate for patients aged 70–95 (70.5%) were similar to those for patients less than 70 years old (71.6%) and also comparable between male (72.3%) and female (68%) patients.ConclusionsElderly patients have a lower capacity to react to postoperative complications, but the relative survival is similar to younger patients. Advanced age alone should not be used as a criterion to deny surgery for colorectal cancer.

Fluorouracil and Leucovorin with or without Interferon Alfa-2a as Adjuvant Treatment, in Patients with High-Risk Colon Cancer

Background: It has been shown in randomized studies that adjuvant treatment with the combination of fluorouracil (FU) and levamisole reduced the risk of recurrence and deaths of patients with stage III colon cancer. Pharmacological studies of FU led to its use in combination with a number of modulating agents including interferon-α and leucovorin (LV) that appear to enhance its activity in vitro. Furthermore, a meta-analysis suggested that the combination of FU with LV increased the response rate as compared to FU monotherapy in patients with advanced colorectal cancer. Purpose: To evaluate the impact of adjuvant treatment with the combination of FU and LV with or without interferon alfa-2a (IFN) on disease-free survival (DFS) and overall survival (OS) for patients with stage II or III colon cancer. Patients and Methods: From August 1989 to July 1997, 280 patients with stage II and III colon cancer entered the study and were randomly assigned to receive either the combination of FU (600 mg/m2/week × 6, followed by a 2-week rest) and LV (500 mg/m2/week × 6 as a 2-hour infusion, followed by a 2-week rest) for 4 cycles (group A, 139 patients), or the same chemotherapy plus recombinant IFN (3 MU subcutaneously 3 times a week) for 1 year (group B, 141 patients). Results: A total of 109 patients (78.9%) of group A and 119 (84.4%) of group B completed four cycles of chemotherapy. Also, 51.4% of patients of group A and 53.9% of group B received ≥80% of the planned dose of FU. One patient (group A) was found to be ineligible and was not included in the analysis. The median relative dose intensity of FU in the two groups was 0.90 and 0.85, respectively. As of August 1998, after a median follow up of 4 years, there was no significant difference in either 3-year DFS (group A, 83.1%; group B, 75.9%, p = 0.14) or OS (group A, 84.5%; group B, 80.0%, p = 0.27). In the Cox model, stage of disease, number of infiltrated nodes, tumor grade and presence of regional implants were identified as significant prognostic factors for OS. Grade 3–4 toxicities, mainly diarrhea, were observed in 26.1% of patients of group A and in 24.8% of group B. There were no treatment-related deaths. Conclusions: The addition of IFN to the combination of FU with LV postoperatively does not improve DFS and OS of patients with stage II or III colon cancer.

Manometric and clinical evaluation of patients after low anterior resection for rectal cancer

The aim of this study was to examine the anorectal physiological and clinical changes that occur after low anterior resection for rectal cancer. Since 1998, 30 patients underwent laboratory tests of anorectal function, preoperatively and 1 month and 6 months after low anterior resection. Postoperatively all patients presented with increased bowel frequency, 60% of the patients with mild soiling and 30% with urgency for defecation. Six months after surgery there was a significant improvement of these symptoms. The anal resting pressure was significantly decreased postoperatively, while maximum squeezing pressure remained unchanged. The rectoanal inhibitory reflex was absent in 80% of the patients and at 6 months after surgery it tended to recover. Rectal capacity and compliance were reduced in all patients. In the current study, the majority of patients demonstrated manometric anorectal changes and clinical anorectal function disorders during the first year after surgery. We observed that these disorders correlated with the low level of the anastomosis.

Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer

BackgroundThe aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC).MethodsPatients were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A, FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status were also assessed.ResultsBetween 2005 and 2008, 441 patients were enrolled, with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5–83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9–83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4–89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one–two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions.ConclusionsNo significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size.Trial registrationANZCTR 12610000509066. Date of Registration: June 21, 2010.

Surgical treatment of haemorrhoids with the use of the circular stapler and open haemorrhoidectomy. A comparative study

Abstract The surgical treatment of haemorrhoids with the use of a circular stapler is a novel method. A comparative retrospective study of two groups of patients treated surgically for third- and fourth-degree haemorrhoids was conducted. Fifty patients (group A) underwent a surgical intervention with the circular stapler in the rectal mucosa 4 cm above the dentate line. In another group of 50 patients (group B), the standard open haemorrhoidectomy (Milligan-Morgan) was carried out. The new method (group A) compared with the standard haemorrhoidectomy (group B) was found to be less time consuming (mean time, 10±2 minutes vs. 35±5 minutes, p<0.001). The majority of patients (28) in group A experienced mild pain (VAS, 3–5) while pain for the majority of patients in group B was 5–7 on the VAS scale (p<0.01). The duration of postoperative hospitalisation was 1±1 days for the patients of group A and 5±2 days for the patients of group B (p<0.05). The early postoperative bleeding rate was 6% in group A and 12% in group B (p<0.01). None of the patients of group A developed incontinence and 6 (12%) patients in group B developed mild liquid incontinence during the first postoperative month. During the period of follow-up (12 months to 3 years, median length 18 months in outpatient visits), no patient in either group developed recurrence of haemorrhoids or rectal prolapse. In conclusion, the surgical treatment of haemorrhoids with the circular stapler seems to be an efficient alternative to the standard open haemorrhoidectomy when this is indicated.

Cecal obstruction due to primary intestinal tuberculosis: a case series

IntroductionPrimary intestinal tuberculosis is a rare variant of tuberculosis. The preferred treatment is usually pharmaceutical, but surgery may be required for complicated cases.Case presentationWe report two cases of primary intestinal tuberculosis where the initial diagnosis was wrong, with colonic cancer suggested in the first case and a Crohns disease complication in the second. Both of our patients were Caucasians of Greek nationality. In the first case (a 60-year-old man), a right hemicolectomy was performed. In the second case (a 26-year-old man), excision was impossible due to the local conditions and peritoneal implantations. Histopathology revealed an inflammatory mass of tuberculous origin in the first case. In the second, cell culture and polymerase chain reaction tests revealed Mycobacterium tuberculosis. Both patients were given anti-tuberculosis therapy and their post-operative follow-up was uneventful.ConclusionsGastrointestinal tuberculosis still appears sporadically and should be considered in the differential diagnosis along with other conditions of the bowel. The use of immunosuppressants and new pharmaceutical agents can change the prevalence of tuberculosis.

Intraperitoneal application of phospholipids for the prevention of postoperative adhesions: a possible role of myofibroblasts

BACKGROUND Peritoneal adhesions, organized as fibrous bands after abdominal surgery, are related with considerable morbidity and repeated hospitalization. Phospholipids, natural constituents of the peritoneal fluid, seem to display excellent antiadhesive properties. The aim of this study was to investigate whether intraperitoneal application of phospholipids is capable of reducing postoperative adhesions and the possible underlying mechanisms. MATERIALS AND METHODS Twenty male Wistar rats were subjected to a midline laparotomy and a standard peritoneal and cecum abrasion trauma. Before laparotomy closure, a bolus of 3 mL of phospholipids (12 mg/mL) or NaCl (placebo) was given intraperitoneally. Seven days later, the quality and the quantity of adhesions, as well as serum proinflammatory and/or profibrotic mediators, were blindly assessed. Human colonic subepithelial myofibroblasts were isolated from normal controls and cultured with transforming growth factor-β1 (TGFβ1, 5 ng/mL) in the presence of phospholipids (30-300 μg/mL). Collagen production in culture supernatants and migratory activity of myofibroblasts were also assessed. RESULTS Phospholipids reduced intra-abdominal adhesions (P < 0.001), with respect to their intensity and area, and serum levels of cytokines (interleukin 1β, interleukin 6, platelet-derived growth factor-1, and TGFβ1) compared with placebo-treated rats. Stimulation of myofibroblasts with TGFβ1 significantly increased (P < 0.001) the basic collagen production. The presence of phospholipids significantly reduced (P < 0.001) both the TGFβ1 induced and the basic collagen production. Using a wound healing assay, phospholipids were found to reduce the basic and the TGFβ1-induced migration of myofibroblasts in a concentration-dependent manner. CONCLUSIONS Intraperitoneal phospholipids might be involved in the prevention of postoperative adhesions formation via the reduction of proinflammatory and/or profibrotic mediators and by inhibiting fibrogenic properties of mesenchymal cells.