Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection.

BACKGROUND: Drain amylase content in the days immediately after major pancreatic resection has been investigated previously as a predictor of postoperative pancreatic fistula (POPF). Its accuracy, however, has not been determined conclusively. The purpose of this study was to evaluate the accuracy of drain amylase content on the first day after major pancreatic resection in predicting the occurrence of POPF. METHODS: A literature search of the MEDLINE, Embase and Scopus(®) databases to 13 May 2015 was performed to identify studies evaluating the accuracy of drain amylase values on day 1 after surgery in predicting the occurrence of POPF. The area under the hierarchical summary receiver operating characteristic (ROC) curve (AUChSROC ) was calculated as an index of accuracy, and pooled estimates of accuracy indices (sensitivity and specificity) were calculated at different cut-off levels. Subgroup and meta-regression analyses were performed to test the robustness of the results. RESULTS: Thirteen studies involving 4416 patients were included. The AUChSROC was 0·89 (95 per cent c.i. 0·86 to 0·92) for clinically significant POPF and 0·88 (0·85 to 0·90) for POPF of any grade. Pooled estimates of sensitivity and specificity were calculated for the different cut-offs: 90-100 units/l (0·96 and 0·54 respectively), 350 units/l (0·91 and 0·84) and 5000 units/l (0·59 and 0·91). Accuracy was independent of the type of operation, type of anastomosis performed and octreotide administration. CONCLUSION: Evaluation of drain amylase content on the first day after surgery is highly accurate in predicting POPF following major pancreatic resection. It may allow early drain removal and institution of an enhanced recovery pathway.

Neoadjuvant chemotherapy and primary-first approach for rectal cancer with synchronous liver metastases.

AIM: Up to a quarter of patients with rectal cancer have synchronous liver metastases at the time of diagnosis. This is a predictor of poor outcome. There are no standardized guidelines for treatment. We reviewed the outcomes of our patients with synchronous rectal liver metastases treated with a curative intent by neoadjuvant chemotherapy with or without chemoradiotherapy followed by resection of the primary tumour and then liver metastases. METHOD: Between 2004 and 2012, patients who presented with rectal cancer and synchronous liver metastasis were treated with curative intent with peri-operative systemic chemotherapy as the first line of treatment. Responders to chemotherapy underwent resection of the primary tumour with or without preoperative chemoradiotherapy followed by hepatic resection. RESULTS: Fifty-three rectal cancer patients with 152 synchronous liver lesions were identified. After a median follow-up of 29.6 months, the median survival was 41.4 months. Overall survival was 59.0% at 3 years and 39.0% at 5 years. CONCLUSION: Rectal resection before hepatic resection combined with neoadjuvant chemotherapy is associated with promising clinical outcome. It allows downstaging of liver lesions and removal of the primary tumour before the progression of further micrometastases. Furthermore, patients who do not respond to chemotherapy can be identified and may avoid major surgical intervention.

Survival analysis after pancreatic resection for ampullary and pancreatic head carcinoma: an analysis of clinicopathological factors.

BACKGROUND AND OBJECTIVES: Surgery remains the only curative option for the treatment of pancreatic and ampullary carcinomas. To examine the survival differences between ampullary and pancreatic head carcinomas after pancreaticoduodenectomy. METHODS: A retrospective review of patients with ampullary or pancreatic head adenocarcinoma undergoing curative resection during a 6-year period prior to 2000. RESULTS: A total of 104 patients underwent pancreaticoduodenectomy for pancreatic head and ampullary carcinomas (n = 65 and n = 39, respectively). Histologically, pancreatic cancer was worse, with more lymph node involvement and more positive resection margins and vascular and perineural invasions than found in ampullary carcinoma. The median disease-free and overall survival rates were significantly better for ampullary cancer when compared with pancreatic cancer (17 vs. 9 months [P = 0.001] and 35 vs. 24 months [P = 0.006], respectively). The actuarial 5-year disease-free and overall survival rates were 4.4% and 10.5%, respectively, for pancreatic carcinoma and 27.9% and 31.8%, respectively, for ampullary carcinoma. Multivariate analysis showed that microscopic resection margin involvement (P = 0.02) and involvement of over three nodes (P < 0.001) were significant factors affecting the overall survival for pancreatic and ampullary carcinomas, respectively. CONCLUSIONS: In this study, patients with ampullary carcinoma have a better prognosis and survival than those with pancreatic carcinoma.

Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry-based study.

OBJECTIVES: The proportion of women delivering with known HIV status in sub-Saharan Africa is not well described. Risk of HIV transmission to newborns is a major concern, but there may also be increased risks for other adverse pregnancy outcomes. DESIGN: Hospital registry. SETTING: North East Tanzania (1999-2006). POPULATION: Singletons (n = 14,444). METHODS: Births were grouped by maternal HIV status and socio-demographic factors predicting HIV status, and associations between status and pregnancy outcomes were studied. MAIN OUTCOME MEASURES: Maternal HIV status, perinatal mortality, prematurity, small for gestational age (SGA), birthweight and low Apgar score. RESULTS: The proportion of mothers with known HIV status increased from 7% before 2001 to 78% after 2004. Single motherhood, rural residence, low maternal education, maternal and paternal farming and higher paternal age were associated with unknown HIV status. About 7.4% (95% CI 6.7-8.1%) of women were HIV infected, with increased likelihood of infection with higher gravidity, single motherhood, rural residence, maternal business or farming occupations and paternal tribe. Compared with HIV-uninfected women, the untreated HIV-infected women had a higher risk of SGA births (adjusted risk ratio [ARR] 1.6; 95% CI 1.1-2.4), preterm birth (ARR 1.8; 95% CI 1.1-2.7) and perinatal death (ARR 1.9; 95% CI 0.95-3.8). Women with unknown HIV status had moderately increased risks. Treated HIV-infected women had a risk similar to that of the HIV-uninfected women for all outcomes, except for low Apgar score. CONCLUSION: HIV testing and infection were associated with socio-demographic factors. Untreated HIV-infected women had higher risks of adverse pregnancy outcomes, and risks were also increased for women with unknown HIV status. There is still a need to increase availability of HIV testing, education and adequate therapy for pregnant women.

Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu.

In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.

Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.

Stem cells as a treatment for chronic liver disease and diabetes.

Advances in stem cell biology and the discovery of pluripotent stem cells have made the prospect of cell therapy and tissue regeneration a clinical reality. Cell therapies hold great promise to repair, restore, replace or regenerate affected organs and may perform better than any pharmacological or mechanical device. There is an accumulating body of evidence supporting the contribution of adult stem cells, in particular those of bone marrow origin, to liver and pancreatic islet cell regeneration. In this review, we will focus on the cell therapy for the diseased liver and pancreas by adult haematopoietic stem cells, as well as their possible contribution and application to tissue regeneration. Furthermore, recent progress in the generation, culture and targeted differentiation of human haematopoietic stem cells to hepatic and pancreatic lineages will be discussed. We will also explore the possibility that stem cell technology may lead to the development of clinical modalities for human liver disease and diabetes.

A modified radiofrequency-assisted approach to right hemihepatectomy.

AIMS: To evaluate a modified radiofrequency-assisted approach to right hemihepatectomy. METHODS: Following a bilateral subcostal incision and intraoperative ultrasonography, the liver was mobilized in the standard manner, and a cholecystectomy was performed. The portal vein was isolated, encircled, and ligated. After demarcating the liver parenchyma, coagulation necrosis was achieved using a radiofrequency-assisted device along the line demarcated for transecting the liver parenchyma. The actual transection of the liver parenchyma and the right portal vein was done using a surgical scalpel along the radiofrequency-coagulated line. The right hepatic vein was coagulated using the radiofrequency sealer or by stitching in the resection plane. The hepatic artery was not dissected and was sealed together with the bile ducts in the resection plane using the radiofrequency instrument. The hepatic vein was not divided. RESULTS: Between July 2005 and July 2006, a total of 49 liver resections were performed in our unit. Of these, the radiofrequency-assisted technique was used in 33 cases with metastatic disease; 14 of these cases had right hemihepatectomies, including 2 repeat resections. The mean operation time was 180min (range, 120-240min), and the average blood transfusion was 0.14U (range, 0-2U). Postoperatively, there was no morbidity, such as bleeding, infection, or biliary fistula, related to the liver resection technique, and no patients died as a result of surgery. In 8 out of the 14 right hemihepatectomies, a right-sided pleural effusion was observed; 3 of them required evacuation. CONCLUSION: This paper describes a modified radiofrequency-assisted hemihepatectomy, which allows one to obtain control of the portal blood flow going into the resected part of liver. The modified approach appears to be simple and safe.

Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters.

The presence and type of mutations of the p53 tumor suppressor gene were determined in 40 patients undergoing curative hepatic resection for metastatic colorectal carcinoma. This represents the largest series in the literature on the screening of p53 mutations for liver metastases. The analysis was performed in exons 5-9 by denaturing gradient gel electrophoresis followed by direct sequencing. Forty-five percent of tumors showed mutation in p53, and this was observed only in exons 5-8. Mutations at codon positions 167, 196, 204, 213, 245, 281, 282, 286, and 306; deletion of codon 251 and of the first nucleotide of codon 252; and Leu residue (CTC) insertion downstream codon 252 are reported for the first time in colorectal liver metastasis. Mutations at codon positions 163, 248, and 273 have been reported previously. Correlation of p53 status with clinical parameters showed that patients with mutated p53 had a statistically higher number of lesions when compared with patients with wild-type p53 (P<0.050). In particular, of patients with mutated p53, 41% had three or more metastases compared with 14% of patients with wild-type p53. Synchronous metastases were present in 70% of the patients with p53 mutations and in only 29% of patients with wild-type p53 (P<0.025). In addition, patients with p53 mutations are more likely to develop recurrence (73%) compared with patients with wild-type p53 (33%; P<0.001). Other factors considered, including preoperative carcinoembryonic antigen level, bilobar distribution, and size of the lesion(s), did not show significant correlation with p53 status. These results suggest that p53 status might be an important prognostic indicator to predict the pattern and likelihood of treatment failure after hepatic resection.

A phase I/II study of hepatic artery infusion with wtp53-CMV-Ad in metastatic malignant liver tumours.

Colorectal cancer (CRC) is the second commonest cause of cancer death in the UK, with greater than 40% of these patients destined to die of the disease despite current medical management. Death is commonly due to liver metastases with sequelae including progressive liver dysfunction. Most patients with liver metastases present with tumours that are unresectable and incurable with existing therapies. The median survival for CRC patients after diagnosis with liver metastases is approximately 6 months or less. The human p53 gene is a tumour suppressor gene involved in the control of cell proliferation. Loss of wild-type p53 function is associated with the uncontrolled growth of many types of human cancers. The reintroduction and expression of wild-type p53 into p53 altered tumour cells has been shown to suppress tumour growth or induce apoptosis in both in vitro and in vivo models. In our experience greater than 50% of CRC tumours have p53 alterations. This study seeks to evaluate the safety, biological efficacy and the effectiveness of wtp53-CMV-Ad treatment which is a recombinant adenoviral vector containing the wild-type human p53 gene. It will be administered by infusion via the hepatic artery, for the regional gene therapy of malignant liver tumours. Study patients will have incurable metastatic (CRC) malignant tumours of the liver with evidence of p53 alteration in their liver tumours. In vitro studies have demonstrated p53-specific antiproliferative effects of wtp53-CMV-Ad on human liver tumour cells and in vivo studies have demonstrated p53-specific antiproliferative effects on human liver tumour cells. The vector Ad-p53 is a recombinant, replication-defective adenovirus based on adenovirus serotype 5. It contains a sequence encoding wild-type p53 whose expression is under the control of the human cytomegalovirus immediate early promoter-enhancer. This construct will be growth in 293 cells which contain the adenoviral E1A and E1B coding sequences which have been removed from the vector to render it replication defective. The study design is an open-label, non-randomised, single-dose, dose escalation Phase I/II clinical trial anticipated to involve a maximum of 19 patients. wtp53-CMV-Ad will be administered by infusion in a reservoir connected to the hepatic artery, for regional gene therapy (surgically implanted pump) in 3 escalating doses to successive cohorts of 3 patients each until the maximum tolerated dose is determined. Subsequently, 10 patients will be treated with this dose. Regional wtp53-CMV-Ad therapy will be administered as a single bolus infusion via hepatic artery catheter. The route of administration of wtp53-CMV-Ad via hepatic artery infusion is designed to maximise gene therapy exposure to the malignant tumours while minimising exposure to normal tissues outside the liver. The clinical protocol is designed to monitor treatment toxicity. Another objective is to evaluate the biological efficacy, including efficiency and stability of gene transfer by analysis of tumour tissues following therapy. As an important part of this objective the pharmacokinetics of wtp53-CMV-Ad will be studied. Clinical evidence of anti-tumour efficacy will also be collected. In addition, the safety and efficacy of different doses levels of wtp53-CMV-Ad will be studied.

E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Syncytia formation in HIV-1 infected cells is associated with an increase in cellular oleic acid.

Infection of cells with the human immunodeficiency virus type-1 (HIV-1) usually results in the formation of giant multinuclear cells (syncytia) [(1986) Nature 322, 470-474; (1986) Nature 322, 725-728; (1985) Hum. Pathol. 18, 760-765; (1987) Ann. Neurol. 21, 490-496]. The appearance of syncytia is associated with an increase in the monounsaturated oleic acid content. This report describes experiments which compare the activity of known antiviral agents with that of saturated fatty acid derivatives in inhibiting oleic acid and syncytia formation. A concept is introduced which proposes that infection of cells with the human immunodeficiency virus causes a rise in cellular oleic acid which leads to increased membrane fluidity.

The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines.

It has been suggested the E1B 55 kDa mutant adenovirus dl1520 can selectively kill p53-deficient human tumor cells. In this study, we examined the cytotoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with different p53 genetic and functional status. The results showed that HCC cell lines with deleted or mutant p53 gene and reduced p53 transcriptional activities were more susceptible to dl1520-induced cytolysis. Hep3B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cytolysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21(Waf-1/Cip-1) was downregulated 24 hours after dl1520 infection in HepG2 cells and increased when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infection. Bax expression increased in dl1520-infected HepG2 cells but not in Hep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 80 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but not in HepG2 cells. These results suggest that the susceptibility of HCC cells to dl1520-induced cytolysis is related to both p53 genotype and functional status, and is mediated by both cell cycle disturbance and apoptosis.

Fatty acid composition of normal and malignant cells and cytotoxicity of stearic, oleic and sterculic acids in vitro.

The aim of this study was to investigate the hypothesis that saturated fatty acids are differentially cytotoxic to cancer cells. Three studies were undertaken to: (1) measure the toxicities of stearic and oleic acids to normal and malignant cells in vitro, (2) assess if there is any relationship between toxicity and relative fatty acid composition and (3) determine whether the relative fatty acid composition of a cancer cell line could be modified by sterculic acid, an inhibitor of delta-9-desaturase. Stearic (18:0) and oleic (18:1) acids inhibited the colony-forming abilities of five human cancer cell lines and two non-neoplastic cell lines in a dose-dependent fashion. The concentration of oleic acid required to reduce colony formation ability by 50% was 2.5-6.0-fold greater than that of stearic acid. Addition of sterculic acid to a cancer cell line resulted in steady-state levels of stearic acid and increasing percentage of oleic acid.

Liver resection using total vascular exclusion, scalpel division of the parenchyma, and a simple compression technique for hemostasis and biliary control.

Recent improvements in perioperative morbidity and long-term outcome following liver surgery have led surgeons to attempt larger and more technically challenging liver resections. Total vascular exclusion (TVE) of the liver during resection has been proposed as a technique that will facilitate these difficult resections while minimizing blood loss. Total vascular exclusion is performed by obtaining complete isolation of the vascular pedicle of the liver. Once the hepatic vein is clamped, rapid resections may be performed with a loss of only the blood volume contained within the liver itself. Safe performance of total vascular exclusion of the liver requires a thorough understanding of hepatic anatomy, patient selection criteria, and the physiologic changes incurred by hepatic exclusion and subsequent ischemia and reperfusion. The following report discusses these issues, gives a detailed description of the steps involved in obtaining safe total vascular exclusion, and presents a technique using rapid parenchymal excision with a scalpel and capsular compression to obtain hemostasis and prevent bile leaks. We briefly discuss our experience with 144 consecutive resections in which this technique was used.

Aggressive surgical management of fibrolamellar hepatocellular carcinoma in puberty.

Extensive right hepatectomy and replacement of the invaded inferior vena cava were performed in a 14-year-old girl with fibrolamellar liver carcinoma. Despite the graft thrombosis the patient was discharged on the 50th post-operative day. After 3 years a solitary lung metastasis was resected and the patient remains with no sign of intra-abdominal or intrathoracic recurrence.

Chromosome 17 allele loss in hepatocellular carcinoma but not in synchronous liver adenoma.

A 51-year-old female underwent resection of two synchronous liver tumours, a hepatocellular carcinoma and an adenoma. DNA analysis revealed allele loss on chromosome 17 (17p13, near the locus of p53 tumour suppressor gene) in the hepatocellular carcinoma but not in the adenoma. This finding may support the view that loss of p53 tumour suppressor gene is associated with tumour progression.

Patient survival with liver metastases from colorectal cancer--a district hospital experience.

In a retrospective review of 301 newly diagnosed tumours of the colon and rectum, 61 patients (20%) presented with liver metastases. The mean survival for this group was 7.4 months. Five patients with solitary metastases were found who may have been helped by further surgery. There was a 20% operative mortality. No significant association between the grade, differentiation, lymph node status or venous invasion of the primary lesion was demonstrated. Operative palliative resection of the primary lesion did not improve survival. These results confirm the poor prognosis for patients with liver metastases, justifying all efforts into the earlier detection and prevention of colorectal carcinoma.

Study of the histochemical changes in mucus from normal and tumour bearing mucosa in patients with colorectal cancer.

The prognosis in colorectal cancer is related to the stage of the tumour. Thus, early detection of developing tumours will significantly improve the overall prognosis. This study assessed the histochemical changes in mucus from normal and tumour bearing mucosa to determine possible premalignant changes. Eighty patients with colorectal cancer and ten normal subjects were studied. Biopsies were taken from the tumour and from adjacent 'normal' mucosa and from both resection edges. Sections were stained with high iron diamine-alcian blue to distinguish sulphated from sialomucins. All normal mucosal biopsies showed a predominantly sulphated mucin pattern. By contrast, all 70 tumour mucosal biopsies showed a marked sialomucin staining. In transitional mucosa adjacent to the tumour, 30 patients showed marked increase in sialomucin (2+), 42 a moderate increase (+) and the remaining eight a normal pattern (-ve). Twenty-one (15%) patients had increased sialomucin at either surgical resection margins, all of whom had similar changes adjacent to the tumour, suggesting a wide field change in the mucus pattern. Since these changes in mucus are associated with malignant transformation then estimation of mucus pattern may give early prediction of malignant change in patients at risk of developing primary or recurrent carcinoma.

Alpha 2 interferon in the prevention of N-nitroso-methyl urea induced breast cancer in rats.

Human interferons have been shown to be effective treatment for hairy cell leukaemia and are now commercially available. Their role in treatment of solid tumours has yet to be established. This study assessed the value of alpha 2 interferon (IFN) in an experimental breast cancer model. Four groups of female Sprague-Dawley rats were studied. The first received three intravenous injections (7 mg/kg) of N-nitroso-methyl urea (NMU) at weeks 0, 3 and 7. The second received the same NMU dosage regime plus IFN (100,000 IU, twice weekly for 3 weeks). A third received IFN alone and the fourth was a control group receiving three intravenous injections of normal saline. At week 16, 19 of 20 rats in the NMU alone group had developed tumours significantly more than four of 15 rats with tumour in the NMU plus IFN group (P less than 0.001). Both the mean tumour number/rat and the mean tumour weight/rat was significantly more in the NMU group than the NMU plus IFN group P less than 0.05). No rats in the IFN alone or control group developed tumour. These data suggest that IFN prevents carcinogen induced breast cancer in rats. It may have a role in the prevention and treatment of human breast cancer.