Role of gelatinases (matrix metalloproteinases 2 and 9), vascular endothelial growth factor and endostatin on clinicopathological behaviour of rectal cancer.

AIM: The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs), their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] and activators [membrane-type MMPs (MT1-MMPs)], vascular endothelial growth factor (VEGF) and endostatin on clinicopathological variables and prognosis in patients with rectal cancer. METHOD: Paired samples of tumour tissue and normal tissue were obtained from patients with rectal cancer who underwent curative surgery (n = 34). Gelatin zymography for MMP-2 and MMP-9, an activity assay for MT1-MMP and enzyme-linked immunoassays for TIMP-2, VEGF and endostatin were performed using extracts from the paired tissue samples. RESULTS: Active MMP-9 showed statistically significant relationships with metastatic disease and perineural invasion (P = 0.002 and P = 0.042). A significant relationship was observed between the levels of tumoral pro-MMP-2 and pro-MMP-9 and the presence of lymph node metastasis (P = 0.012 and P = 0.021, respectively). Tumoral TIMP-2 levels showed a significant relationship with tumour recurrence (P = 0.011). A significant relationship was also observed between tumour VEGF levels and the presence of perineural invasion (P = 0.044), and VEGF levels were correlated with the size of the tumour (P = 0.009, r = 0.454). CONCLUSION: These results might contribute to further investigation of a possible prognostic significance in rectal cancer.

Single-dose oral ciprofloxacin compared with single-dose intravenous cefazolin for prophylaxis in inguinal hernia repair: a controlled randomized clinical study.

The aim of this study was to compare the efficacy of single-dose intravenous cefazolin prophylaxis with single-dose oral ciprofloxacin prophylaxis in patients undergoing tension-free inguinal hernia repair with polypropylene mesh. In a prospective and randomized setting, 395 patients received either a single dose of 500 mg of ciprofloxacin orally, 1--2h before the operation, or a single dose of 1g cefazolin intravenously on induction of anaesthesia. The primary outcome was to determine the wound infection rate within one year. The overall infection among the entire study population was 2% (eight of 395) including 2% (four of 199) of those receiving intravenous cefazolin and 2% (four of 196) of those treated with oral ciprofloxacin. There was no statistically significant difference between groups (P=0.59). All the infections were superficial incisional surgical site infections, and none progressed to a deep infection. Escherichia coli was the most commonly isolated bacterium. None of the infected patients developed recurrence of hernia. The rate of recurrence was 1.3% (five of 395) at one year including 2% (four of 199) of those receiving cefazolin and 0.5% (one of 196) of those receiving ciprofloxacin. Oral ciprofloxacin prophylaxis was found to be an attractive option with its wide antibacterial spectrum, low cost and ease of administration in patients undergoing tension-free inguinal hernia repair with polypropylene mesh.

Desmoplasia measured by computer assisted image analysis: an independent prognostic marker in colorectal carcinoma.

AIMS: The assessment of desmoplasia by traditional semiquantitative methods does not provide reliable prognostic data. The aim of this study was to quantify desmoplasia by computerised image analysis in primary colorectal carcinomas and to investigate its ability to predict overall survival. METHODS: In total, 112 colorectal adenocarcinomas, with a median follow up of 66 months, were studied. The representative tumour sections were stained by the van Gieson method, which stains collagen rich stroma red. For quantitative histochemical measurement, digital images were analysed by a computerised image analysis program to calculate the percentage of red stained tissue area. The percentage of desmoplasia (PD) was related to conventional clinicopathological prognostic factors and overall survival. RESULTS: The mean (SD) PD was 4.85 (3.37). PD was found to be significantly associated with lymph vessel and venous invasion. By Kaplan-Meier analysis, PD was associated with survival-patients with PD > 4 had a shorter survival than those with PD

Locoregional recurrence (non hepatic abdominal recurrence) of rectal cancer.

Thirty percent of deaths are related to locoreional recurrence. All patients with nonhepatic abdominal recurrence (NHAR) were considered as having locoregional failure. The aims of this study are firstly to retrospectively evaluate the results of potentially curative resection and palliative treatment modalities for a group of 25 patients with NHAR from rectal cancer. The second aim is to determine the effectiveness of R1 resection in these patients in terms of survival. In this study we have followed 25 patients with NHAR of which 10 were able to undergo potentially curative salvage resection, whilst the remaining 15 had either a palliative (R2) or no resection. The goals of treatment for recurrent rectal cancer are palliation of symptoms, a good quality of life, and if possible, cure with a low rate of treatment--related complications. Indications for salvage surgery depend on several factors including the extent of disease, the presence of concomitant illness and the surgeons experience. Systemic disease, systemic disease with peritoneal implants, multiple hepatic metastases, or extensive pelvic involvement preclude surgical treatment for cure. Curative and noncurative surgical procedures were performed width acceptable complications in the series presented hereThe mean survival for the group undergoing R0 resection was 50 months versus 55 months for the group undergoing R1 resection (not significant). Mean survival were 7,3 and 6 months in the groups undergoing R2, NR and NS respectively. The 5-year survival for the 10 patients who had potentially curative resection was 30 per cent versus 0 per cent for 15 patients who had non-curative procedures (p = 0.001). There was 1 post-operative 30 day mortality in the series of 19 patients who underwent surgery. Five patients (6 per cent) developed one or more post-operative complications. Two of them required reoperation.

Glucose transporter-1 (GLUT-1): a potential marker of prognosis in rectal carcinoma?

The aim of the study is to evaluate the pattern and level of expression of glucose transporter-1 (GLUT-1) in rectal carcinoma in relation to outcome as a potential surrogate marker of tumour hypoxia. Formalin-fixed tumour sections from 43 patients with rectal carcinoma, who had undergone radical resection with curative intent, were immunohistochemically stained for GLUT-1. A mean of three sections per tumour (range 1-12) were examined. Each section was semiquantitatively scored; 0, no staining; 1, <10%; 2, 10-50%; 3, >50% and a score given for the whole section, the superficial (luminal) and deep (mural) part of the tumour. Staining was seen in 70% of tumours. Increased staining was noted adjacent to necrosis and ulceration. A diffuse and patchy pattern of staining, with and without colocalisation to necrosis was seen. Patients with high GLUT-1-expressing tumours (score 3 vs 0-2) had a significantly poorer overall survival (P=0.041), which was associated with poorer metastasis-free survival with no difference in local control. No significant correlation was seen with other prognostic factors. There was a strong correlation between the score for the superficial and deep parts of the tumour (r=0.81), but a significant relationship with outcome was only found in the deep part (P=0.003 vs P=0.46). In conclusion, increased GLUT-1 expression in rectal tumours was an adverse prognostic factor and is worth further evaluation as a predictive marker of response to therapy.

Evaluation of prosthetic mesh closure in semiopen-abdomen patients.

BACKGROUND: To avoid the adverse consequences of abdominal compartment syndrome and to reduce the high mortality the celiotomy wound in patients with abdominal sepsis was closed without tension using prosthetic mesh. This produces a semiopen situation that permits staged reinterventions together with the functional reconstitution of the continuity of the abdominal wall. MATERIAL AND METHODS: Twenty-five patients with intra-abdominal sepsis of various causes were evaluated retrospectively to assess the results of semiopen management of the septic abdomen and reoperations on demand in severe peritonitis. All of the patients were in a state of neglected peritonitis, and had at least one failing organ system. The Mannheim Peritonitis Index (MPI) scoring system was used for stratification of abdominal sepsis. RESULTS: The mean MPI score of 25 patients was 24, ranging 10 to 33. Eight (32%) patients were reexplored (MPI=21). There were overall 9 (36%) complications in patients with mean MPI score of 23. Six (24%) mesh-related complications (infection and enterocutaneous fistulas) developed (MPI=19). The mean MPI score of patients without complications was 24. Four (16%) patients died with index MPI score of 26 due to fulminant hepatitis, myocardial infarction, and multiple organ failure. The admission period averaged 63 days. CONCLUSIONS: In 25 critically ill patients with abdominal sepsis the mortality was lower than expected, relative to heterogeneous data from the literature; also, major complications occurred less frequently although the mean MPI score was high. The authors conclude that this approach is a reliable contribution to the complex treatment of these patients.

Does the administration route of leucovorin have any influence on the impairment of colonic healing caused by intraperitoneal 5-fluorouracil treatment?

Intraperitoneal chemotherapy with 5-fluorouracil (5-FU) is a new, promising alternative in adjuvant treatment of advanced colorectal cancer. Leucovorin (LV), a biomodulator of 5-FU, potentiates the antineoplastic effect of 5-FU. The aim of this study was to determine whether the administration routes of LV had any influence on the impairment of colonic healing caused by intraperitoneal 5-FU treatment. 48 male Wistar rats were subjected to left colonic resection and anastomosis, and randomized to 1 of 4 groups: control group (receiving intraperitoneal NaCl, intravenous NaCl); ipFU group (receiving intraperitoneal 5-FU, intravenous NaCl); ipFU+ivLV group (receiving intraperitoneal 5-FU, intravenous LV), and ipFU+LV group (receiving intraperitoneal 5-FU+LV, intravenous NaCl). Treatment was started after surgery and continued for 5 days with daily injections. The animals were sacrificed on the 7th day postoperatively. Anastomotic complications were more common in the ipFU, ipFU+ivLV, and ipFU+LV groups (p < 0.05) compared to the control group. The anastomotic breaking strength was significantly reduced in the ipFU, ipFU+ivLV, ipFU+LV groups (p < 0.05) than in the control group, but it did not differ between the ipFU, ipFU+ivLV, and ipFU+LV groups. The hydroxyproline content of the anastomotic segment was also significantly reduced in the ipFU, ipFU+ivLV and ipFU+LV groups (p < 0.05) compared to the control group. However, there was no difference between the anastomotic hydroxyproline content of the ipFU, ipFU+ivLV, and ipFU+LV groups. In this experiment, colonic healing was impaired after intraperitoneal 5-FU administration as judged by the higher rates of anastomotic complications, reductions in anastomotic breaking strength and hydroxyproline content; but LV administration either intravenously or intraperitoneally did not cause further deterioration in colonic healing.

Prognostic significance of angiogenesis in rectal cancer: a morphometric investigation.

BACKGROUND: Neo-angiogenesis is crucial for tumor growth and metastasis and has been proposed as an independent prognostic factor for survival in patients with solid tumors. In this study the quantitative expression of angiogenesis was investigated by direct stereologic assessment of the vascular surface density in rectal carcinoma to determine the possible correlation of angiogenesis with clinicopathological factors and prognosis. PATIENTS AND METHODS: Sections from formalin-fixed paraffin-embedded tissue blocks of 29 primary rectal carcinomas were resected and immunostained for endothelial cell factor-VIII-related antigen. The vascular surface density (VSD), number of vessels per square mm (NVES), maximum NVES (NVESmax) according to the three maximum values of NVES and number of vessels in the unit area (N) were assessed by means of morphometry. The results were related to the main prognostic variables and the survival of patients. RESULTS: There were no significant differences between survivors and non-survivors in terms of the angiogenesis parameters that were investigated. The overall survival rate was not significantly different for sex, age, tumor size and differentiation, extrahepatic metastasis, depth of invasion and the mode of adjuvant therapy. However, a significantly lower overall survival rate was observed in patients with liver metastatic disease (p<0.001), lymph node involvement (p=0.04) and incomplete resection (p<0.001). Multivariate analysis indicated that only the number of vessels in the unit area (HR = 1. 028, p = 0. 04), hepatic metastases (HR=14.94, p=0.007) and type of resection (HR=23.81, p=0.004) predicted overall survival. CONCLUSION: These findings suggest that increased tumoral vascularity, consistent with previous studies, adversely affects survival in rectal cancer patients. Liver metastatic status and completeness of the surgical resection were the most powerful criteria to predict the final outcome of these patients. Thus, neo-angiogenesis is indeed an important and key step in tumorigenesis, but it may not be the single overwhelming factor that determines recurrence and metastasis in rectal carcinoma.

Prognostic value of CD44 expression in colorectal carcinomas.

BACKGROUND: CD44 has diverse functions in cell-cell and cell-matrix interactions and its expression appears to be an indicator of invasive and metastatic behaviour in carcinomas. However, contradictory data have been reported about the correlation between CD44 expression and prognosis in colorectal carcinomas. We aimed (i) to establish whether immunohistochemically detectable CD44 expression is related to tumor aggressiveness, (ii) to correlate CD44 expression with the degree of tumor differentiation and (iii) to determine the relationship between CD44 expression and patient survival and other conventional clinicopathological features. PATIENTS AND METHODS: The immunohistochemical expression of CD44 in a series of 111 colorectal carcinomas was examined using the monoclonal mouse anti-human phagocytic glycoprotein-1, CD44 (clone DF 1485) in correlation with clinicopathological variables. To achieve a reliable semi-quantitative evaluation, not only the staining intensity but also the distribution of positive tumor cells were analyzed. RESULTS: CD44 staining was high-grade positive in 42 and low-grade positive/negative in 69 tumor tissues. There was no association between CD44 expression and tumor size, histological differentiation, depth of invasion, lymph node involvement, clinical stage of the disease, or the radicality of surgical resection. CD44 expression was not correlated significantly with recurrence and distant metastases. Multivariate analysis showed that only the modified Astler-Coller (MAC) staging system was an independent prognostic factor of recurrence (HR=15.267; 15.267-6.808, 95% CI; p=0.001) and survival (HR=37.064; 13.309-103.220, 95% CI; p=0.001). Kaplan-Meier curves showed that there was no significant association between CD44 expression and recurrence and overall survival in either MAC B or C colorectal cancer. CONCLUSION: Expression of CD44 was not associated with any conventional clinicopathological features. CD44 cannot be considered as a prognostic predictor of recurrence, metastasis and overall survival.

Relationship of angiogenesis and p53 protein expression in colorectal carcinomas.

OBJECTIVE: Recently, new functions have been attributed to the p53 protein, particularly a prominent role in the regulation of angiogenesis. Tumours expressing mutant forms of p53 protein may be associated with increased angiogenesis. The aim of this study is to investigate the relationship between p53 protein expression and the quantitative expression of tumour angiogenesis in colorectal carcinomas. PATIENTS AND METHODS: Sections from paraffin-embedded blocks from 46 patients with primary colorectal carcinomas that had been completely removed were analysed. p53 protein expression and all vascular structures were evaluated by immunohistochemistry. The vessel parameters of angiogenesis including vascular surface density (VSD), number of vessels per mm2 (NVES) and number of vessels in unit area (n) were assessed by morphometry. Mann-Whitney U-test was used for comparing the extent of neovascularization in p53-positive and -negative cases. RESULTS: Twenty-four (52%) cases were p53+ and 22 (48%) were p53-. Mean VSD, NVES and n values for p53 protein-positive and -negative groups were as follows: VSD 96.7 +/- 65.4/mm vs 79.6 +/- 45.24/mm; NVES 104.8 +/- 97.5/mm2 vs 62.2 +/- 44.3/mm2; n 79.7 +/- 74.2 vs 52 +/- 35.7, respectively. There was no association between the angiogenesis parameters and p53-positive and -negative cases, when VSD (P=0.226) or n (P=0.176) were considered, but a statistically significant difference was obtained for NVES values (P=0.035). CONCLUSION: The authors concluded that tumoural angiogenesis assayed by morphometric investigation in colorectal carcinomas might be related to p53 protein expression when NVES is considered. This finding supports the possible role of p53 protein in increased angiogenesis in colorectal tumours.

Multivisceral resections for primary advanced rectal cancer.

Fixation of the locally advanced rectal tumor at the time of operation is an important prognostic variable. It may be difficult to determine whether fixation is caused by inflammatory adhesions or by direct tumor extension tethering the tumor to the surrounding pelvic structures. Extended en bloc removal of the locally advanced rectal cancer with involved adjacent organ(s) increases the resectability rate. We examined the perioperative mortality and morbidity and the prognosis of patients undergoing multivisceral resections for advanced primary rectal cancers. Of 83 patients with rectal cancers 20 (24%) had locally advanced tumors. Cases were divided into Gunderson-Sosin stages B(3) and C(3) and were further stratified into those with histologically confirmed carcinomatous invasion of the adjacent organ and those with inflammatory adhesions. Perioperative mortality was 5%. Only five patients (24%) showed histopathological confirmation of carcinomatous adhesion into adjacent organ(s)/structure(s). Histological confirmation of contiguous tumor spread was higher in C(3) patients. There was no significant difference between patients with positive and negative histopathological confirmation of malignant spread in terms of survival rates. Multivisceral resections can be performed safely for locally advanced rectal cancers with acceptable mortality and morbidity rates. The presence of local tumor extension does not mean incurability, and sound surgical judgement should dictate that in the face of a tethered lesion one must extend the surgical intervention radically to resect any tumor en bloc.

Retroperitoneal fibrosis mimicking a rectal tumor: report of a case.

PURPOSE: The study contained herein was undertaken to report an original case of retroperitoneal fibrosis that resembled a rectal tumor both symptomatically and radiologically. METHOD: Reported is a case of retrorectal fibrosis with a brief literature review of the topic. RESULT: Although many forms of retroperitoneal fibrosis have been reported, extension below the pelvic rim is very unusual. Compression of the rectum and right ureter, with constipation as a chief complaint, made this case presentation unusual. Although computerized tomographic findings and needle biopsies supported the diagnosis of retroperitoneal fibrosis, an exploratory laparotomy was necessary to rule out a malignancy and to release the ureter. CONCLUSION: A fibrotic mass involving the retrorectal region may mimic a rectal tumor. To reach a final diagnosis, an exploratory laparotomy may be necessary, despite sophisticated evaluation techniques, because it is difficult to differentiate whether the mass is malignant.

Which technique for treatment of pilonidal sinus--open or closed?

PURPOSE: After excision of the pilonidal sinus, some surgeons leave the wound open, and others close the wound primarily. The aim of this study is to compare length of hospital stay, length of time to return to work, wound infection rate, and recurrence rate in chronic pilonidal sinus patients, after modification of both closed and open techniques. METHODS: One hundred ten patients who had chronic-stage pilonidal sinus were randomly assigned to receive one of two excisional surgical procedures. One-half were treated by surgical excision and primary closure (closed technique, Group A). The other one-half were treated with Obeid's surgical excision (open technique, Group B). RESULTS: Ninety-one (46 in Group A and 45 in Group B) of 110 patients were followed for a period four months to three years. Although patients with primary closure had significantly longer hospital stays (P < 0.05) than patients in the open group, they returned to work significantly earlier (P < 0.05). In Group A and Group B, infection rates were 3.6 percent and 1.8 percent (P > 0.01), and recurrence rates were 4.4 percent and 0 percent (P > 0.01), respectively. CONCLUSION: Because both techniques have very low complication rates, treatment of chronic pilonidal sinus should be based on patient preference and characteristics, especially employment status.

Gallstone recurrence after shock wave therapy.

Fifty-three patients with complete clearance of all gallstone fragments after combined extracorporeal shock wave lithotripsy (ESWL) oral litholytic therapy were included in the study. Eight patients had recurrence of gallstones within the first year at follow-up evaluation. The rate of gallstone recurrence was 15.2 percent within the first year. Four of these eight patients reported biliary pain, the other four remained asymptomatic. The incidence of gallstone recurrence was high in patients who had multiple stones before ESWL treatment (p < 0.05). Age above 60 years was also associated with a higher rate of gallstone recurrence (p < 0.05).

Extracorporeal shockwave lithotripsy and litholytic therapy in cholelithiasis.

Extracorporeal shockwave lithotripsy (ESWL) and litholytic therapy were used in 100 patients over a period of 16 months. ESWL was carried out with a Lithostar Plus and chenodeoxycholic acid was used as the lytic agent, given until 3 months after complete disappearance of stones. Within a period of 8-12 months, stones disappeared completely in 82 per cent of the patients who had a single stone less than or equal to 20 mm in diameter and in 50 per cent of those with a single stone greater than 20 mm in size or with multiple stones. Complications requiring surgery developed in five patients: three had acute cholecystitis and two developed acute pancreatitis. Of the patients in whom complete stone clearance was achieved, two of 11 followed up developed recurrence of stones 4 months after cessation of lytic therapy.

Principal causes of mechanical bowel obstruction in surgically treated adults in western Turkey.

A retrospective study of the principal causes of mechanical bowel obstruction occurring in Western Turkey between 1979 and 1989 was undertaken. The records of 14,777 operations performed in the general surgery departments of two hospitals were reviewed. Mechanical bowel obstruction occurred in 582 patients. Among the causes of mechanical bowel obstruction, adhesions were most common (44.0 per cent), followed by strangulated hernia (23.9 per cent), volvuli (12.7 per cent) and colonic carcinomas (10.1 per cent). A previous appendicectomy appeared to be the most important cause of adhesions causing mechanical bowel obstruction.