A comparison between radioimmunotherapy and hyperthermic intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis of colonic origin in rats.

BACKGROUND: Cytoreductive surgery (CS) followed by heated intraperitoneal chemotherapy (HIPEC) is considered the standard of care for the treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC). These surgical procedures result in a median survival of 2 years at the cost of considerable morbidity and mortality. In preclinical studies, radioimmunotherapy (RIT) improved survival after CS in a model of induced PC of colonic origin. In the present studies we aimed to compare the efficacy and toxicity of CS followed by adjuvant RIT in experimental PC to the standard of care, HIPEC. METHODS: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in three groups of Wag/Rij rats. Treatment comprised CS only, CS + RIT or CS + HIPEC, immediately after surgery. RIT consisted of intraperitoneal administration of 74 MBq Lutetium-177 labeled MG1. HIPEC was performed by a closed abdomen perfusion technique using mitomycin C (16 mg/L during 60 minutes). The primary endpoint was survival. RESULTS: CS only or combined with RIT was well tolerated. Rats receiving CS + HIPEC were lethargic, suffered from diarrhea, and lost significantly more weight in the first postoperative week. Median survival of rats treated with CS + RIT was significantly longer than after CS alone (97 and 57 days, respectively, P < .004), whereas survival after CS + HIPEC or CS alone were not significantly different (76 and 57 days, respectively, P = .17). CONCLUSION: Survival after CS was significantly improved by RIT with Lutetium-177-MG1 in rats with PC of colorectal origin. Adjuvant HIPEC did not improve survival and was more toxic than adjuvant RIT.

Radioimmunotherapy and colorectal cancer.

BACKGROUND: Despite the success of radioimmunotherapy (RIT) using radiolabelled monoclonal antibodies (Mabs) directed against tumour-associated antigens in the treatment of non-Hodgkin's lymphoma, therapeutic success in solid tumours has been modest. In the past decade, a dozen Mabs have been investigated clinically for their potential usefulness in RIT of colorectal cancer. METHODS: The application of radiolabelled Mabs for the treatment of solid cancers is discussed, and clinical trials investigating RIT for colorectal cancer listed in the Medline and Embase databases are reviewed. RESULTS: Uptake of radiolabelled Mabs in tumour and, consequently, the therapeutic efficacy of RIT is inversely correlated with tumour size. The bone marrow is the most important dose-limiting organ. Twenty-three phase I/II studies were found that investigated the feasibility and efficacy of RIT using five radionuclides and 15 Mabs against carcinoembryonic antigen, tumour-associated glycoprotein 72, epithelial cellular adhesion molecule, A33 or colon-specific antigen p, mainly in patients with advanced colorectal cancer. A few responses were recorded but no particular antibody construct seemed superior. CONCLUSION: RIT might be an effective adjuvant treatment modality in colorectal cancer. Future studies should focus on its application in patients with small-volume or minimal residual disease.

[A new irrigation-suction boring system facilities low-pressure intramedullary boring of isolated swine femurs]. / Ein neues Spül-Saug-Bohrssystem ermöglicht die druckarme Markraumbohrung an isolierten Schweinefemora.

AIM: Intramedullary nailing is the treatment of choice for the stabilization of fractures of long tubular bones. An important disadvantage of this method is the increase in intramedullary pressure and the resulting release of fat into the venous blood system during reaming of the medullary canal. We have developed a new type of rinsing-suction-reamer (SSB) in order to minimize these disadvantages. Trials were initiated to investigate whether it is possible to ream the medullary canal with the SSB without pressure increase in comparison with the standard AO-reamer (AOB). METHODS: Reamed intramedullary nailing was performed in 20 isolated pig femora. The intramedullary pressure was recorded continuously. RESULTS: While stepwise reaming was performed, the pressure only rose above the physiological level in AOB. During insertion of the guide wire and the nail, comparable values were measured for AOB and SSB. CONCLUSION: Our experiments show that reaming of the medullary canal is possible without a pressure increase using the SSB in comparison with AOB.

In vitro construction of urinary bladder wall using porcine primary cells reseeded on acellularized bladder matrix and small intestinal submucosa.

BACKGROUND: Partial or radical cystectomy requires replacement of the urinary reservoir normally achieved by using small or large bowel segments. Our aim was to establish tissue engineering of an bioartificial bladder wall using primary cultures of porcine urothelial (pUC) and bladder smooth muscle cells (pSMC) to be reseeded on different acellular biological matrices. METHODS: Primary porcine cultures of pUC and pSMC were established from open bladder biopsy material 25 mm2 in size. Acellular matrix was generated either from a) porcine bladder wall segments or b) tubular small intestinal submucosa with the still attached decellularized muscularis layer. Reseeding of these matrices with primary cells was done in a two-dimensional static model and in a three-dimensional rotating bioreactor perfused with cell culture medium for a period of 6 weeks. RESULTS: Prior to reseeding the cultured cells were characterized as pUC and pSMC by immunohistochemical staining with either anti-keratin 7 or anti-alpha actin. For both matrices a reseeded double layer cell system of pUC and pSMC could be identified after incubation in the described systems for 6 weeks. CONCLUSIONS: Our results document successful generation of tissue engineered urinary bladder wall, which can be used in further large animal transplantation experiments.

Metastatic pattern of CC531 colon carcinoma cells in the abdominal cavity: an experimental model of peritoneal carcinomatosis in rats.

BACKGROUND: Peritoneal spread of tumour cells is a major source of morbidity and mortality in patients with colorectal cancer. In order to develop strategies to prevent intraperitoneal dissemination and to treat peritoneal carcinomatosis, the spread of tumour cells in the peritoneal cavity was studied. METHODS: Two million CC531 colon carcinoma cells were administered intraperitoneally in five groups of eight rats. The rats were killed after 1, 2, 4 and 8 hours and 3, 7, 14 and 21 days. After inspection of the abdominal cavity, samples of blood and ascites were taken. Liver, spleen, omentum, mesentery, diaphragm, parathymic lymph nodes and lungs were removed for histology and immunohistochemistry. RESULTS: No abnormalities were seen in the abdominal cavity until day 3. Subsequently the peritoneum and omentum became thickened and after 21 days all rats had haemorrhagic ascites and peritoneal carcinomatosis. The abdominal fluid contained tumour cells at all stages. The number of tumour cells decreased in the first 8 hours, and increased thereafter. At microscopy the peritoneum was completely covered by tumour cells after 3 days. Tumour cells concentrated in the milky spots (MS) of the omentum within 4 hours. The size of the MS increased as a result of an increase in number of tumour cells and macrophages. After 7--21 days the MS were completely replaced by tumour cells and new MS were formed. In the diaphragm tumour cells invaded the lymphatic lacunae after 8 h, and obliterated these after 3--7 days. Also invasion of the muscle fibres was seen after 3 days. Microscopically no tumour cells were found in blood, liver, spleen, parathymic nodes and lung. CONCLUSION: After intraperitoneal administration of CC531 colon carcinoma cells, tumour cells spread throughout the abdominal cavity, and concentrate in the milky spots of the greater omentum, the paracolic gutters, the subhepatic and subphrenic spaces and in the lymphatic lacunae of the diaphragm.

The prognostic significance of a previous malignancy in operable non-small cell lung cancer.

There is little data in literature on survival of patients with lung cancer as a second primary (SP) malignancy. This retrospective study was undertaken to investigate whether a previous malignancy has prognostic significance in operable non-small cell lung cancer (NSCLC). Sixty-six patients with SP NSCLC were compared with 75 'first primary' (FP) NSCLC patients without a previous malignancy. All the 141 patients had been surgically treated with curative intent at The Netherlands Cancer Institute (NKI) between 1977 and 1996. Patients who had undergone resections for lung metastases were excluded. Clinical and pathological characteristics were collected and a multivariate analysis on all the 141 patients was carried out. All the previous malignancies were invasive cancers associated with metastatic potential and predominantly located in the aerodigestive tract. Female-male ratio was higher in the SP group (29 vs. 15%, P = 0.06). Tumour diameter was smaller in the SP group (3.0 vs. 4.7 cm, P < 0.0001). Pneumonectomy was performed less frequently in the SP group. Five-year survival rate was higher in the SP group (61 vs. 34%, P = 0.04). Univariate favourable prognostic factors were; small tumour diameter, female gender, favourable pTNM-stage, favourable pT-stage, favourable cTNM-stage, no post-operative radiotherapy and a history of previous malignancy. Multivariate analysis showed tumour diameter, female gender and pTNM-stage to be the major potential confounders. When adjustments were made for these three variables, the prognostic advantage of the SP group disappeared. It was concluded that SP NSCLC has a similar prognosis when compared with FP NSCLC. NSCLC diagnosed during the follow-up of a previous malignancy, and deemed operable, therefore, warrants the same diagnostic and therapeutic approach as NSCLC as first malignancy.

[Children with stumbling gait due to acute spinal cord compression]. / Kinderen met een wankel looppatroon door acute ruggenmergcompressie.

Three previously healthy children, two girls aged 2 and almost 5 years and a boy aged 20 months, developed a progressively stumbling gait within days. In two this occurred after a period of weeks during which they complained of, or seemed to have back pain. In all three cases acute spinal cord compression by a malignant tumour was diagnosed. Histological examination revealed Ewing sarcoma, granulocytic sarcoma and T-cell lymphoma. Surgical decompression led to complete neurological recovery. Although rare, acute spinal cord compression during childhood is a medical emergency because of the risk of neurological morbidity. Back pain, weakness and a stumbling gait usually are the first symptoms. Sensory symptoms and sphincter dysfunction may develop later. Early recognition is essential, as prognosis depends on neurological findings and duration of symptoms when treatment is started.