Tornwaldt's cyst formation after concurrent chemoradiotherapy for nasopharyngeal carcinoma.

The complications of concurrent chemoradiotherapy for nasopharyngeal carcinoma include dryness of mouth, sensorineural hearing loss, dental caries, trismus, pituitary dysfunction, myelitis, paralysis of cranial nerves IX-XII, massive neck fibrosis and pharyngeal wall necrosis. Tornwaldt's cyst formation after concurrent chemoradiotherapy for nasopharyngeal carcinoma has not been reported previously in the world literature. Tornwaldt's cyst, a persistent pharyngeal bursa, is found in about 3 per cent of the adult population, although the majority of these are asymptomatic. We describe the previously unreported complication of Tornwaldt's cyst formation after concurrent chemoradiotherapy for nasopharyngeal carcinoma.

Rapid flow carbon dioxide laparoscopy disperses cancer cells into the peritoneal cavity but not the port sites in a new rat model.

BACKGROUND: The role of carbon dioxide (CO2) in the pathogenesis of tumor recurrence after laparoscopy remains controversial. Using a new rat model, we studied the effect of different CO2 flow rates on the dispersal of free cancer cells. METHODS: A novel model of desufflation without trocar was developed, and 55 Fischer rats were randomized into three flow groups: group A (rapid, 0.67 l/min; n = 20), group B (slow, 0.44 l/min; n = 20), and group C (gasless, n = 15). We vented CO2 via a portless surgical valve that filtered cells. After the abdominal wall had been suspended to create space, half of the animals in each group (nonrecovery) received 7.5 x 10(6) immunolabeled rat colon cancer cells (RCC2) intraperitoneally, whereas the other half (recovery) received 7.5 x l0(6) viable RCC2 before insufflation or gasless laparoscopy. Nonrecovery animals were killed after 20 l of insufflation. Parietal peritoneal and port-site specimens were examined for RCC2 by fluorescence microscopy (FM) and flow cytometry (FC). The recovery animals were killed at 4 weeks for evidence of wound recurrence. RESULTS: Nine of 10 nonrecovery animals in A had RCC2 on FM or FC, as compared with 2 animals in each of the nonrecovery groups B and C (p = 0.018, Fisher's exact test). Two of the nine animals in group A also had RCC2 in their portless valves. Two recovery (A) animals developed wound recurrence as compared with none in the other groups (p = 0.315). CONCLUSION: In this model, rapid CO2 flow dispersed free cancer cells into the peritoneal cavity, but not into the port sites, thus supporting a role for CO2 in the intraperitoneal dispersal of free cancer cells, but not in wound recurrence.

Metachronous colorectal cancers.

BACKGROUND: Up to 9 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers. There is no consensus on the detection and management of such cancers. METHODS: The literature was reviewed exhaustively regarding the incidence, clinical characteristics, detection, treatment and molecular genetics of metachronous colorectal cancers. This was based on a Medline search from 1966 to December 1997 for articles on metachronous colorectal cancers. A manual search was also performed on references quoted in these articles. All publications relevant to this study were included. RESULTS: Although the underlying causes for metachronous colorectal cancers are yet to be elucidated, risk factors for the disease have been identified. These include the presence of synchronous polyps or cancers, a history of metachronous cancers, and hereditary non-polyposis colorectal cancer (HNPCC). CONCLUSION: Preoperative colonoscopy and postoperative colonoscopic surveillance are essential in identifying patients at risk of metachronous colorectal cancer. A total colectomy and ileorectal anastomosis should be considered for some patients, certainly for those with HNPCC.

Genetic instability in patients with metachronous colorectal cancers.

BACKGROUND: Nearly 7 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers several years later. A molecular marker that could identify patients susceptible to metachronous cancers would be of clinical importance. METHODS: Twenty-four colorectal cancers from 15 individuals with metachronous colorectal cancer were investigated for microsatellite instability at five loci by single stranded conformational polymorphism analysis. A control group of 14 colorectal cancers from individuals who had only developed one sporadic colorectal cancer each was analysed similarly. RESULTS: Microsatellite instability was demonstrated in 17 of 24 cancers from individuals with metachronous cancer compared with one of 14 cancers from individuals with a single colorectal cancer. CONCLUSION: These results suggest that testing for microsatellite instability may be useful in recognizing patients at high risk of developing metachronous colorectal cancers.

[The effect of the physico-chemical properties of suture materials and the surface structure on adherence of tumor cells]. / Vliv fyzikálne-chemických vlastností sicího materiálu a jeho povrchové struktury na adherenci nádorových bunek.

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastigmatic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

Detection of free malignant cells in the peritoneal cavity before and after resection of colorectal cancer.

PURPOSE: This study was designed to select the best monoclonal antibody to stain malignant cells in peritoneal wash fluid, and to investigate the incidence of free malignant cells in preresection and postresection colorectal cancer peritoneal washings using a combination of conventional cytology and immunocytochemistry. METHODS: Peritoneal washings were taken from 35 consecutive patients undergoing colorectal cancer resection. RESULTS: Malignant cells were isolated on a density gradient and identified by conventional cytology and an indirect immunoperoxidase stain. Malignant cells were identified in peritoneal washings from 15 patients (preresection only n = 3, postresection only n = 4, both n = 8). The origin of free malignant peritoneal cells in 11 preresection-positive washings must be the serosa. The origin of these cells in the four postresection-positive patients is uncertain: serosal and luminal spillage were considered unlikely and no circulating cells were found in the mesenteric vessels near the tumor. CONCLUSION: Tumor cells may have leaked out from lymphatics cut during the dissection.

Influence of suture physicochemical and surface topographic structure on tumor cell adherence.

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastomotic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1.

The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.

Anti-epithelial membrane antigen monoclonal antibodies and radioimmunolocalization of colorectal cancer.

The monoclonal antibodies LICR-LON M8 and 77-1, which react with epithelial membrane antigen, showed a strong reaction with colorectal cancer on immunohistochemistry. In a radioimmunolocalization study in patients with colorectal cancer, 111In-labelled M8 detected 13 of 16 tumour sites present in 16 patients. 111In-labelled 77-1 detected 10 of 15 tumour sites present in 14 patients. The high radioactive background in the liver prevented the detection of hepatic metastases in eight patients (five in the M8 and three in the 77-1 group). The mean (s.d.) tumour to normal colon ratio was 2.5(1.2) for M8 and 1.6(0.5) for 77-1 at day 6 after antibody administration. The mean (s.d.) tumour to blood ratio was 4.9(3.7) for M8 and 3.6(1.5) for 77-1. There was no statistical difference between these results. All scan-positive cancers reacted with M8 and 77-1 on immunohistochemistry. The results suggest that these monoclonal antibodies may have a role in the immunolocalization of colorectal cancer.

Immunolocalisation of an anti-EMA monoclonal antibody to a renal carcinoma xenograft.

The monoclonal antibody 77-1 originally raised to a membrane extract of human bladder cancer reacted with a human renal carcinoma xenograft XK1 on immunoperoxidase staining. This suggested a potential role for its immunolocalisation to renal carcinoma, and prompted a localisation study of the I-125 and In-111 labelled 77-1 to the xenograft. The uptake of the radiolabelled antibody by the xenograft was measured as a tumour to blood ratio taken at 24 hour intervals for up to 72 hours. Four animals were used for each time point and the mean tumour to blood ratio obtained. A monoclonal antibody 48-1, non reactive with XK1, was similarly radiolabelled and administered to another group of animals bearing the xenografts to act as a control. Statistical analysis using the unpaired Student't' test showed that the uptake of the 1-125 and In-111 labelled 77-1 by the xenografts was significantly higher than the non-specific antibody 48-1 at all time points (p less than 0.002-0.018), demonstrating that a specific localisation to the xenograft XK1 by the radiolabelled 77-1 had occurred.

Immunoscintigraphy of colorectal cancer with an antibody to epithelial membrane antigen (EMA).

Immunoperoxidase staining of LICR-LON M8, a mouse monoclonal antibody reactive with epithelial membrane antigen, showed a strong reaction with colorectal cancer. This finding prompted an immunoscintigraphic study of colorectal cancer patients using this antibody. Sixteen patients had external gamma scintigraphy after intravenous injection of indium 111-labeled M8. Positive scans were obtained in 11 of the 13 patients with primary colorectal cancers, and 2 of the 3 patients with recurrent tumors. The high indium 111 background in the liver prevented the detection of hepatic metastases in 5 patients. Twelve patients had samples taken of tumor, normal colon, and venous blood at the time of surgery. The ratio of labeled antibody uptake in tumor to that of blood was 5.1 (+/- 3.6 S.D.), which was significantly different (P = 0.001) to that of the similar ratio for normal colon (2.0 +/- 1.6 S.D.). The tumor to normal colon uptake ratio was 2.6 (+/- 1.3 S.D.). These results suggest a specific uptake of indium 111-labeled M8 by colorectal cancer.

A comparison of carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) in human colorectal cancer.

The development of monoclonal antibodies (MAbs) to tumour-associated antigens has allowed the successful radioimmunolocalization of a variety of tumours and has provided a basis for targeted therapy. In patients with colorectal cancer, antibodies to CEA have been the most widely used for imaging, but their role in targeted therapy may be inhibited by their reaction with normal tissues and with circulating CEA. Epithelial-membrane antigen (EMA) is expressed by most epithelial tumours, including colorectal cancers, and antibodies to EMA may provide a satisfactory alternative. We therefore compared two high-affinity MAbs, one to CEA (C46) and one to EMA (ICR2), in tissues obtained from 31 patients with cancer (18 primary colonic, 6 nodal metastases and 7 liver metastases), 14 patients with adenomatous polyps and 17 with normal colon. The indirect immunoperoxidase staining reaction was used and the results classified as either positive or negative. A heterogeneous pattern of staining was found for both antibodies. ICR2, the anti-EMA, reacted with slightly fewer colonic cancers than C46, the anti-CEA antibody (83% vs. 100%) and a similar number of metastases. Most noticeable was the minimal reaction of anti-EMA with normal colon (12% vs. 71%) and benign polyps (7% vs. 79%) in comparison to anti-CEA. This would suggest a possible role for ICR2 in the radioimmunolocalization and targeting of colorectal cancer.

Monoclonal antibodies reacting with colorectal tumours.

25 mouse monoclonal antibodies were screened for cell surface reactivity with colorectal tumours using the indirect immunoperoxidase method. Five antibodies of the IgG subclasses were selected. LICR-LON-M8 was raised against human milk fat globule membrane (HMFGM). The remaining four antibodies 48-1, 3-48-2, 77-1, and 8-30-3 were raised against human bladder metastases. M8, 77-1, and 8-30-3 which showed epithelial membrane antigen (EMA) - like reactivity exhibited greater selectivity for colorectal cancer compared with normal colon. M8 and 77-1 are being evaluated for immunoscintigraphy of colorectal carcinoma.