Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer.

BACKGROUND: We explored the predictive significance of BRCA1, TXR1 and TSP1 expression in non-small-cell lung cancer (NSCLC) patients treated with docetaxel in association with cisplatin or gemcitabine. METHODS: To analyse BRCA1, TXR1 and TSP1 mRNA expression from microdissected primary tumours of 131 patients with stage IIIB (wet) and IV NSCLC, RT-qPCR was used. RESULTS: The mRNA levels of TXR1/TSP1 were inversely correlated (Spearman's test: -0.37; P=0.001). Low TXR1 mRNA levels were associated with higher response rate (RR; P=0.018), longer median progression-free survival (PFS; P=0.029) and median overall survival (mOS P=0.003), whereas high TSP1 expression was correlated with higher RR (P=0.035), longer PFS (P<0.001) and mOS (P<0.001). Higher BRCA1 mRNA expression was associated with higher RR (P=0.028) and increased PFS (P=0.021), but not mOS (P=0.4). Multivariate analysis demonstrated that low TXR1/high TSP1 expression was an independent factor for increased PFS (HR 0.49; 95% CI 0.32-0.76; P<0.001) and mOS (HR 0.37; 95% CI 0.2-0.58; P<0.001), whereas high BRCA1 expression was correlated with increased PFS (HR 0.53; 95% CI 0.37-0.78; P=0.001). CONCLUSIONS: These data indicate that TXR1/TSP1 and BRCA1 expression could be used for the prediction of taxanes' resistance in the treatment of NSCLC.

Kallikrein 10 (KLK10) methylation as a novel prognostic biomarker in early breast cancer.

BACKGROUND: We evaluated the prognostic significance of KLK10 exon 3 methylation in patients with early-stage breast cancer since it has been shown to have a significant impact on biological characteristics of breast tumors. MATERIALS AND METHODS: Using methylation-specific PCR, we evaluated the specificity of KLK10 methylation in 10 breast tumors and matching normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and in a testing group of 35 patients. The prognostic significance of KLK10 methylation was validated in an independent cohort of 93 patients. RESULTS: KLK10 was not methylated in normal breast tissues and fibroadenomas while it was in 5 of 10 breast tumors and in 1 of 10 matching normal tissues. In the testing group of 35 patients, KLK10 methylation was detected in 70.0% of patients who relapsed (P = 0.001) and in 77.8% of patients who died (P = 0.025). In the independent cohort, 53 of 93 (57.0%) patients were found positive for KLK10 methylation. During the follow-up period, 24 of 93 (25.8%) patients relapsed and 19 of 93 (20.4%) died. Disease-free interval (DFI) and overall survival (OS) were significantly associated with KLK10 methylation (P = 0.0025 and P = 0.003). Multivariate analysis revealed that KLK10 methylation was an independent prognostic factor for DFI and OS. CONCLUSION: KLK10 exon 3 methylation provides important prognostic information in early breast cancer patients.

Selection for beta 2-microglobulin mutation in mismatch repair-defective colorectal carcinomas.

Novel peptide antigens complexed with human leukocyte antigen (HLA) and beta 2-microglobulin (beta 2M) molecules are presented at the cell surface to cytotoxic T lymphocytes (CTLs), provoking lysis of the antigen-presenting cell [1]. In tumor cells, genetically altered or abnormally expressed proteins provide a source of peptides that can be presented to CTLs; the resulting anti-tumour CTL responses may provide part of the body's defence against cancer. Disabling mutations in the HLA and beta 2M proteins required for peptide presentation allow a tumour cell to escape destruction by CTLs. Cells with deficient DNA mismatch repair have high spontaneous mutation rates [2] and produce many altered proteins that are a potential source of numerous unique peptides. Mutator tumour cells might therefore be particularly vulnerable to immune surveillance and CTL attack. Mutator phenotypes [3,4] and loss of beta 2M (or HLA) expression [5,6] are both relatively common among sporadic colorectal tumours. We have compared the frequency of beta 2M mutations in sporadic colorectal and other tumours with and without a mutator phenotype. Mutations were more frequent among colorectal tumours with the microsatellite instability indicative of a defect in DNA mismatch repair. The inactivating beta 2M mutations were predominantly frameshifts, which is consistent with the underlying mismatch repair defects. Evasion of immune surveillance by acquiring beta 2M mutations therefore occurs at high frequency in tumour cells with a mutator phenotype due to defective DNA mismatch repair.

Angiosarcoma of the heart: case report and review of the literature.

BACKGROUND: Primary angiosarcoma of the heart is an extremely rare malignant disease. PATIENTS AND METHODS: A 32-year-old female with primary angiosarcoma of the heart at an advanced stage with lung and bone metastases is presented. The tumor showed extensive expression of c-erb-B2 and a moderate expression of c-kit. Chemotherapy (cisplatin, epirubicin and ifosfamide) was administered. Herceptin as well as glivec were added to the above combination. RESULTS: There was a good partial response and the lung deposits almost disappeared. The duration of response was 6 months. CONCLUSION: This case of angiosarcoma of the heart is presented because of the extreme rarity of this disease, and its responsiveness to chemotherapy in combination with imatinib and herceptin.

Loss of transporter in antigen processing 1 transport protein and major histocompatibility complex class I molecules in metastatic versus primary breast cancer.

We studied by immunohistochemistry the HLA-allelic, beta 2-microglobulin, and TAP-1 expression in primary breast carcinomas and related lymph node metastases. Thirty-three of the primary tumors and 44% of the lymph node metastases had a complete HLA class I loss. The higher incidence of antigenic loss in metastatic tumors suggests that recognition of HLA class I antigens by the host immunity could have an important role in the metastatic evolution of breast cancer. We observed a simultaneous defective expression of all three components involved in HLA class I expression. Since the controlling genes of heavy chain and TAP-1 are located in different chromosome than beta 2-microglobulin, it could be that a common factor exists regulating HLA class I antigenic expression. Five of 25 (20%) primary and metastatic tumors from HLA-A2-positive individuals also had a selective loss. The high incidence of HLA class I loss in breast cancer patients shows that adjuvant immunotherapy to induce HLA class I expression could be of value in a subgroup of patients.

Human apurinic endonuclease 1 expression in a colorectal adenoma-carcinoma sequence.

Human apurinic endonuclease 1 (HAP1) plays a key role in the repair of baseless sites in DNA. HAP1 is also known to be a potent regulator of the binding activity of a number of transcription factors. We have examined the immunohistochemical expression of the HAP1 protein in normal colorectal mucosa, hyperplastic polyps, tubulovillous adenomas, and carcinomas. In normal colonic mucosa, the predominant staining was nuclear in the less differentiated cells located at the lower part of the crypt, but it was cytoplasmic in the more differentiated superficial colonic epithelium. HAP1 expression was nuclear in 3 of 30 adenomas (10%) and 5 of 44 carcinomas (11%), but it was cytoplasmic in 11 of 30 adenomas (37%) and 22 of 44 carcinomas (50%) and both nuclear and cytoplasmic in 16 of 30 adenomas (53%) and 17 of 44 carcinomas (39%). The observed staining in stromal fibroblasts and endothelial cells was nuclear, whereas that in macrophages was cytoplasmic. Our data indicate that HAP1 is expressed in different subcellular compartments during normal differentiation and that this pattern is disrupted in adenomas and carcinomas. The differential localization may be relevant to the two different proposed functions of HAP1.

The distribution of the deleted in colon cancer (DCC) protein in human tissues.

A gene called deleted in colon cancer (DCC) has been identified on a region of chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene encodes a protein belonging to the immunoglobulin superfamily with similarity to the N-CAM transmembrane proteins and is a putative tumor-suppressor gene. Alternative splicing of transcripts of transmembrane proteins, including N-CAM, is known to occur, resulting in different isoforms of the protein. Using five antibodies against the DCC gene product (three monoclonal antibodies raised in our laboratory, one commercially available antibody, and a rabbit polyclonal antibody), we have demonstrated by immunostaining a DCC protein isoform in reticuloendothelial cells in human thymus, tonsil, and lymph node. This can be distinguished from another isoform described in normal colonic epithelium, because this latter is not demonstrable with the antibodies we have used. It could not be detected in normal colonic epithelium, polyps or colorectal carcinomas. This restrictive distribution suggests that not all DCC gene products are important in colonic cancer.

Intramuscular administration of estrogen may promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia.

OBJECTIVE: Promoting angiogenesis may be an effective treatment for patients with diffuse peripheral vascular disease. This study investigated whether estrogen can promote angiogenesis and perfusion in a rabbit model of chronic limb ischemia. METHODS AND RESULTS: Ischemia was induced in one hindlimb of 24 oophorectomized New Zealand White rabbits. Ten days later (day 0), they were randomized into 4 groups for intramuscular treatment in the ischemic limb: controls receiving saline at day 0; Estrogen-1 group receiving estradiol valerate, modified release (EVMR), 1 mg/kg at day 0; Estrogen-2 group receiving EVMR 1 mg/kg at days 0 and 15; and Estrogen-3 group receiving EVMR 2 mg/kg at day 0. Revascularization was evaluated by clinical indexes, such as ischemic/normal limb systolic blood pressure (BPR), and capillary density/muscle fiber in the abductor muscle of the ischemic limb at the time of death (day 30). At day 30 the BPR was increased in all groups (0.39+/-0.08 in the controls, 0.52+/-0.11 in the Estrogen-1 group, 0.65+/-0.13 in the Estrogen-2 group and 0.61+/-0.16 in the Estrogen-3 group, F=2.39, P=0.04). The capillary/muscle fiber at day 30 was 0.87+/-0.09, 1.08+/-0.15, 1.01+/-0.14 and 1.10+/-0.9 (F=5.01, P=0.01), respectively, in the 4 groups. The capillary/muscle fiber was related to BPR (r=0.48, P<0.02) and to 17-beta estradiol plasma levels of day 15 (r=0.58, P=0.003) and of day 30 (r=0.46, P<0.02). CONCLUSION: Administration of estrogen promotes angiogenesis and perfusion in ischemic rabbit hindlimbs. Thus, estrogen may represent a new therapeutic modality in the management of arterial insufficiency.

Preconditioning limits myocardial infarct size in hypercholesterolemic rabbits.

BACKGROUND: Hypercholesterolemia predisposes to coronary artery disease and causes endothelial dysfunction; some reports suggest that endothelial derived substances are involved in ischemic preconditioning. OBJECTIVE: Our aim was to examine the possibility that preconditioning maybe attenuated in a clinically relevant animal model of hypercholesterolemia with atherosclerosis. METHODS: Male rabbits were fed with cholesterol enriched diet and then divided into two groups (A and B) without and with preconditioning, respectively. A second series of rabbits fed a normal diet were similarly divided into two groups (C and D) without and with preconditioning, respectively. All the animals were subjected to 30 min ischemia and 180 min reperfusion. Blood samples were collected for cholesterol assessment; arterial and heart samples were harvested at the end for histopathological examination. Infarct (I) and risk areas (R) were delineated with Zn-Cd particles and TTC staining. RESULTS: Cholesterol in groups A and B was 58.3+/-8.7 mg% at baseline and 1402+/-125 mg% at 8 weeks (P<0.0001) and in groups C and D 57.5+/-5.8 mg% before the surgical procedure. I/R% was 39. 3+/-6.3% in group A, 16.7+/-3.9% in B (P<0.01), 41.4+/-7.5% in C and 10.8+/-3.3% in D (P<0.01). CONCLUSION: We conclude that preconditioning is unlikely to be attenuated by hypercholesterolemia.

Expression of xenobiotic-metabolizing enzymes by primary and secondary hepatic tumors in man.

PURPOSE: To determine the immunohistochemical expression of xenobiotic-metabolising enzymes (XME) in normal livers, primary hepatocellular carcinomas (hepatomas) and secondary hepatic tumors from colonic primary tumors. METHODS AND MATERIALS: The expression of XME in primary (n = 16) and secondary (n = 21) hepatic tumors and patients with no malignancies (n = 20) were investigated using polyclonal antibodies raised against the following rat enzymes CYP1A1, CYP2B1, CYP2C6, CYP3A1, CYP4A1, cytochrome P-450 reductase, epoxide hydrolase and testosterone UDP-glucuronyl transferase. The rat cytochrome P-450 antibodies recognize various human isoenzymes within the same gene family. Immunohistochemistry was undertaken using the immunoperoxidase and alkaline phosphatase anti-alkaline phosphatase techniques. RESULTS: There was a reduction in the overall expression of all XME by tumor tissue compared to adjacent nonneoplastic liver cells (p = 0.008), more in livers with secondary tumors (p < 0.0001) and reduced expression of XME by hepatomas and secondary liver tumors compared to livers with no malignancy. A tendency for higher expression of all XME by nonneoplastic liver cells from patients with hepatomas relative to nonmalignant livers was observed, with significantly higher expression of CYP3A4/5 and testosterone UDP-GT enzymes (odds ratio 3.12; CI 1.59-6.10). CONCLUSION: The expression of XME by tumor tissue is reduced in primary and secondary hepatic malignancies. The expression of XME by nonneoplastic liver cells is higher in patients with hepatomas than patients with no hepatic malignancies. These alterations in XME activities may have important therapeutic implications in the response and toxicity to systemic anti-cancer therapy, due to altered pharmacokinetics. In addition, differential expression of these enzymes by normal and malignant cells may be important for the rational design of selective anti-tumor drugs.

Pulsed field gel electrophoresis on frozen tumour tissue sections.

The application of pulsed field gel electrophoresis (PFGE) to the molecular genetic analysis of solid tumours has been restricted by the requirement for whole single cells as a DNA source. A simple technique which allows for the direct analysis of histologically characterised solid tumour material by pulsed field gel electrophoresis was developed. Single frozen tissue sections obtained from colonic carcinoma specimens were embedded without further manipulation in molten, low melting temperature agarose. The tumour DNA contained within the agarose plug was subjected to restriction enzyme digestion and PFGE. Sufficient high molecular weight DNA is yielded by this method to obtain a hybridisation signal with a single copy probe. Histological examination of adjacent tissue sections may also be carried out, permitting correlation between molecular analysis and tumour histology.

Expression of aminopeptidase-n (CD 13) in normal tissues and malignant neoplasms of epithelial and lymphoid origin.

AIMS: To provide a detailed knowledge of the distribution of the CD13 molecule, also known as the protease aminopeptidase-N, on both normal tissues and malignant neoplasms of epithelial and lymphoid origin. METHODS: CD13 antigen was examined by immunocytochemistry, using a recently produced antibody (VS5E) alongside a commercially available anti-CD13 monoclonal antibody. The VS5E recognising CD13 was produced by immunising a doxorubicin resistant breast cancer cell line (MCF-7-ADr). A striking feature of this antibody was that it stained the doxorubicin resistant cells but not the parental cell line. Both antibodies were tested on a broad range of normal tissues and three common types of epithelial malignancy (colon n = 28, lung n = 30, breast n = 35), and 12 cases of Hodgkin's and 52 of non-Hodgkin's lymphomas. RESULTS: CD13 was expressed on many tissue and cell types outside the haematopoietic system. In particular it was present on breast epithelium and in 20% (seven of 35) of breast carcinomas, but absent in normal and neoplastic colonic and bronchial tissues and lymphomas. CONCLUSIONS: This study provides not only detailed information about the expression of the CD13 antigen, but also raises the important possibility that CD13 expression may correlate with drug resistance in breast carcinomas.

Angiogenesis and p53 expression in the colorectal adenoma-carcinoma sequence.

Angiogenesis, the formation of new vessels, is essential for tumor growth and metastasis. Mutations of p53 tumor suppressor gene are frequent and play an important role in colorectal oncogenesis. A role of p53 as an angiogenesis inhibitor has also been proposed. We evaluated angiogenesis and p53 expression in 16 hyperplastic polyps, 35 solitary tubular and tubulovillous adenomas, and 47 cases of sporadic colorectal carcinomas arising on the basis of preexisting adenomas, with standard immunohistochemical techniques. The mean microvessel density (MVD) in carcinomas was significantly higher compared with the respective adenomatous part of the same tumor (27.9 vs. 7; P=0.0001). Linear regression analysis of MVD between cancerous and adenomatous areas showed a significant correlation (P = 0.0001, r = 0.56), raising the possibility that carcinomas arising from better vascularized adenomas might show increased vascularity. The MVD was significantly higher in stage C compared with stage A cases (P=0.04). p53 positivity was detected in 26 of 47 cancerous (55%) and in 14 of 47 adenomatous areas (30%; P = 0.0002). All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78). We conclude that angiogenesis and p53 play a critical role in colorectal neoplasia, and the process of malignant transformation in tumors arising from highly angiogenic adenomas, particularly those carrying p53 mutations, is accelerated with rapid tumor progression from stage to stage, indicating a more aggressive tumor phenotype.

TAL1 gene deletions and TAL1 protein expression in sporadic melanoma.

Studies on cytogenetic abnormalities and cell lines have implicated chromosome 1p32 as being important in the pathogenesis of melanoma. Genetic linkage studies have also mapped a melanoma-susceptibility locus to chromosome 1p. The gene TAL1 is present on chromosome 1p32, and deletions within it are the commonest chromosomal abnormality in T-acute lymphoblastic leukaemia (T-ALL). A melanoma cell line harbouring a 1p32 deletion involving the TAL1 gene and the presence of TAL1 protein in developing mouse melanocytes led us to investigate whether TAL1 deletions and/or TAL1 protein expression occur in sporadic melanomas. DNA extracted from 32 fresh melanomas was amplified by standard polymerase chain reaction for the four common deletions of the TAL1 gene that occur in T-ALL. In addition, frozen and paraffin-embedded sections of these melanomas were stained with monoclonal antibodies that detect full-length and truncated TAL1 protein. The results of the study show that deletions of TAL1 do not occur in melanoma. Indeed, full and truncated TAL1 protein also could not be detected immunohistochemically in the paraffin-embedded and frozen sections of the melanomas. We conclude that the TAL1 gene and its protein are probably not directly involved in the oncogenesis of melanomas.

Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.

Platelet-derived endothelial cell growth factor (PDECGF) also called thymidine phosphorylaze (TP) has been shown to have considerable angiogenic activity. 141 cases of early stage non-small cell lung cancer were stained for TP and vascular grade using the P-GF.44C and JC70 MoAbs, respectively. The early steps of TP activation could be identified in 27 cases, where one or two foci of cancer cell TP overexpression occurred within a general pattern of negative/weak staining. Thirty-three foci of overexpression were analyzed for the local microvessel density in the adjacent stroma, assessed by microvessel counting (MC) and Chalkley Score (CS) comparatively with the remaining TP negative tumor areas. The degree of local inflammatory (lymphocyte and macrophage) infiltration was also assessed. A statistically significant increase of mean MC and mean CS was observed in areas of TP overexpression in both low and high angiogenesis cases. Overall, the mean MC in overexpressing areas, assessed in 250x fields, was 20.4 +/- 12.8 vs. 13.6 +/- 9.5 in areas with no TP expression (p = 0.0001). The mean CS was 5.7 +/- 3.3 and 4.0 +/- 2.1, respectively (p = 0.0003). Ten out of 19 (54%) cases with low lymphocytic infiltration showed marked stromal lymphocytic infiltration in the area of focal TP overexpression (p = 0.01). The present study provides further evidence of a direct association of TP and the process of angiogenesis in non-small cell lung cancer.

Assessment of vascular maturation in lung and breast carcinomas using a novel basement membrane component, LH39.

LH39, is a monoclonal antibody recognizing an epitope located at the lamina lucida of mature small veins and capillaries but not in newly- formed vessels of several pathological conditions including cancer. We examined the ratio of mature/immature vessels in 50 breast and 81 lung carcinomas and correlated the vascular maturation index (VMI) to different clinicopathological variables including angiogenesis. Mature vessels were defined by staining with antibodies to both LH39 and CD31, using double immunohistochemistry, whereas immature vessels stained only for CD31. VMI was defined as the percentage fraction of mature vessels (LH39 positive)/total number of vessels (CD31 positive). VMI in breast carcinomas ranged from 0-47% (median 8.75%), which was significantly lower than that observed in the normal breast cases (range 54%-70%; median 68%). The median VMI in the non-small cell lung carcinomas was 46% (range 15%-90%). There was a significant inverse correlation between high tumor VMI and absence of nodal involvement in both breast and lung tumors examined (p=0.01). Thymidine phosphorylase (TP) expression, but not vascular endothelial growth factor (VEGF) expression, was related to a low VMI showing an intense vascular remodeling in TP expressing cases. Thus, assessment of vessel maturation might be complementary to microvessel number to aid the identification of patients who might benefit from specific antiangiogenic therapies or vascular targeting treatment.

Non-small cell lung cancer: c-erbB-2 overexpression correlates with low angiogenesis and poor prognosis.

Tumour angiogenesis is an important prognostic factor in non-small cell lung cancer. Recently, EGFR and c-erbB-2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin-catenin complex. The role of c-erbB-2 protein in cell migration has been also reported. In this study we investigate the combined role of tumoral neoangiogenesis and c-erbB-2/EGFR expression in the metastatic behaviour and prognosis of operable non-small cell lung cancer. 107 tumour samples from patients suffering from operable non small cell lung cancer were examined. EGFR and c-erbB-2 were not correlated with each other. C-erbB-2 expression was associated with low angiogenesis, approaching statistical significance in adenocarcinomas (p = 0.08). The absence of expression of both c-erbB-2 and EGFR oncogenes in tumours with high angiogenesis, was most frequently observed in node negative cases (p = 0.04). C-erbB-2 overexpression defined a subgroup of node negative patients with low angiogenesis and prognosis similar to patients with tumours bearing high angiogenesis. These findings support the hypothesis that expression of the erb genes is a mechanism activated in non-small cell lung cancer to enable cancer cell migration. This pathway seems to be activated mainly in tumours with poor vasculature presumably lading to an unfavourable intratumoral nutritional and oxygen ambience.

Predicting distant failure in nasopharyngeal cancer.

In a prospective study of 78 patients with nasopharyngeal cancer, we examined the prognostic significance of T stage, histology, parapharyngeal involvement, and lymph node dimensions, size, and level concerning distant metastasis. AU patients were treated with radical radiotherapy alone and completed 3 to 7 years of follow-up. In univariate analysis of time to metastasis, there was a significant difference stratifying for T stage (T1 and 2 versus T3 and 4), node dimensions (less than 6 versus more than or equal to 6 cm), neck level (above versus below the thyroid notch), and parapharyngeal involvement, but not for bilaterality of lymphadenopathy. Histology was an important prognostic factor related to distant metastasis since none of the 24 World Health Organization class I cases showed distant metastasis versus 14 (26%) of 54 patients with World Health Organization class II/III carcinoma. A multivariate duration model of time to metastasis within the later histologic group suggested that lymph node dimensions, node level, and T stage were the most important factors related to distant metastases, with the hazard ratios being 3.98, 3.23, and 1.76, respectively. Multivariate analysis within the T3- to T4-stage group showed that node dimension was the only significant variable, with an associated hazard ratio of 4.09. Cases with upper-neck lymphadenopathy and node dimensions of less than 6 cm had a distant metastasis rate of <5%. We conclude that adjuvant chemotherapy for nasopharyngeal cancer is justified in T3- and T4-staged cases with nonkeratinizing or undifferentiated histology and with lymph nodes larger than 6 cm and/or located below the thyroid notch.

[A voluminous vascular leiomyoma of the pancreas treated by personal technique of resection of the pancreatic head without duodenectomy]. / Voluminoso leiomioma vascolare del pancreas trattato con tecnica personale di pancreatectomia cefalica senza duodenectomia.

A new technique variation of complete resection of the pancreatic head with preservation of the duodenum is described. The steps of this intervention are the partial mobilization of the duodenum, the mobilization of the gastric antrum, the section of the pancreatic neck and the complete resection of the pancreatic head with a meticulous dissection/section of the small blood vessels connecting the duodenum and the head of the pancreas. The terminal part of choledochus is removed with the specimen of the pancreas. The intervention is completed with cholecystectomy, end-to-side pancreaticojejunostomy, end-to-side choledocho-jejunostomy and side-to-side jejunojejunal anastomosis. The authors carried out this intervention on a 74-year old woman with a voluminous vascular leiomyoma of the pancreatic head. The patient, two years after the operation, is well with a normal clinical and laboratory follow-up.