Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform.

The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition of this isoform. We describe the use of these fragments in nude mice to target an aggressive tumor (grafted F9 murine teratocarcinoma). Imaging in real time was done by infrared photodetection of a chemically coupled fluorophore. The targeting was improved by use of affinity-matured fragments with low kinetic dissociation rates (koff = 1.5 x 10(-4) s-1) and also by engineering dimeric fragments via a C-terminal amphipathic helix.

[Tumoral degeneration occurring over a non-healing meningocele. Report of two cases]. / Degeneración tumoral en meningocele no intervenido. Descripción de dos casos.

A giant meningocelic sac has not been usually described in adult patients, due to the fact that it shows a low incidence and few newborn have survived to date though the malformation is benign. We report two cases of patients born with the described malformation and who were not operated at that time, so they reached adulthood with bigger sacs. They needed surgery to remove the sacs, for a different reason. The older one had a fistulous abcess but the LCR did not come out, and it did not improved by the application of topic and antibiotic treatment. The other patient showed a progressive growth of the malformation during the last year, skin hardening and pain. The histological study of the dried sacs proved the existence of a carcinomatous degeneration. In the patients we have treated, it seems that a chronic irritation of the LCR and the appearance of multipotent cells in the meningocele may favour the malignancy of the tissues surrounding the sac. This possible malignancy, already described in the bibliography, suggests a prompt elective surgical treatment of the patients with these congenital lesions as soon as possible.

Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice.

Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.

Shunt-related abdominal metastasis of cerebral teratocarcinoma: report of an unusual case and review of the literature.

OBJECTIVE AND IMPORTANCE: Internal drainage of cerebrospinal fluid to the abdominal cavity via a ventriculoperitoneal shunt (VPS) is a common procedure for therapy of obstructive hydrocephalus; because this condition is often caused by brain tumors blocking the natural cerebrospinal fluid pathways, the VPS as an artificial anastomosis can provide the means for the spreading of tumor cells by the cerebrospinal fluid. We report the case of a VPS-related abdominal metastasis of a teratocarcinoma and review the pertaining literature. CLINICAL PRESENTATION AND INTERVENTION: A 24-year-old man with a history of three brain tumors that were operated on when the patient was 14, 21, and 23 years of age developed an acute ileus 7 months after VPS insertion for cerebral teratocarcinoma. Intraoperatively, a massive abdominal tumor was observed, which turned out to be a peritoneal metastasis of the aforesaid brain tumor. The patient died as a result of his illness 1 month later. RESULTS: To date, 58 VPS-related metastases of brain tumors have been described. The male-to-female ratio is 1.6:1, the mean age at shunt insertion is 12.2 years, and the interval between shunt operation and diagnosis of metastases is 16.8 months. During the observation time, 69.2% of the patients died as a result of their illness or abdominal metastases. The most common sources of the metastases were germinomas (27.7%), medulloblastomas (19.1%), and endodermal sinus tumors (10.3%). CONCLUSION: The presented case is only the second VPS-related abdominal spreading of a cerebral teratocarcinoma. Metastases via VPS are rare but should be considered as a possible complication and mode of systemic spread in patients with primary intracranial malignancy.

[Computer-assisted control of CT-guided caudo-cranial puncture access route using the triangulation method]. / Computergestützte Kontrolle eines kaudo-kranialen Punktionsweges im CT bei Anwendung der Triangulationsmethode.

PURPOSE: To control the position of a puncture needle on an access route, which is not parallel to the CT-scan, using control scans not showing start and target points. METHODS: A software tool has been developed. After CT for biopsy planning x/y coordinates and table position of start and target points have to be determined on CT-scans. The software calculates x/y coordinates of the access route for every table position, which must be marked interactively on control scans. The accuracy of the programme was proven experimentally and the method was used in five patients. RESULTS: There was no difference between the calculated and measured access route in the experiment. Four of five patients were punctured successfully using our method. CONCLUSION: Our method is a promising procedure to control a CT-guided caudo-cranial biopsy access route.

[Paraneoplastic hyperthyroidism in a patient with metastasizing teratocarcinoma and excessively high HCG]. / Paraneoplastische Hyperthyreose bei metastasiertem Teratokarzinom mit exzessiver HCG-Erhöhung.

Clinically manifest hyperthyroidism is a rare paraneoplastic syndrome in patients with excessive HCG production due to testicular cancer. A 40-year-old patient with right testicular cancer (teratoma, embryonal cell carcinoma), diffuse pulmonary metastases and high serum HCG levels presented with symptomatic hyperthyroidism. The patient received immediately thyrostatic therapy and 4 cycles of PEI chemotherapy (Cisplatin, Etoposide, Ifosfamide). Thyroid function had returned to normal by the beginning of the second course of chemotherapy. After right orchiectomy and resection of residual pulmonary masses which revealed vital tumor cells, two additional courses of chemotherapy were performed. The patient is well and without evidence of disease 11 months after therapy. All patients with testicular cancer and excessive HCG production should be evaluated for biochemical and clinical signs of hyperthyroidism and treated accordingly with antithyroidal medication and immediate cytoreductive chemotherapy.

[Extragonadal germinal tumors of retroperitoneal localization]. / Tumores germinales extragonadales de localización retroperitoneal.

Extragonadal germ cells tumors can arise primarily in the retroperitoneum. It has been suggested that these neoplasms might be metastasis from an occult testicular lesion which would have regressed later. We report our experience with seven retroperitoneal germ cell tumors without testicular involvement. The most frequent symptoms were lumbar or abdominal pain and paraneoplastic syndrome. Abdominal palpable mass was noticeable in 85% of patients. We point out the computerized tomography and echography as the most sensitive exploration for diagnosis. The confirmation of retroperitoneal tumor was achieved preoperatively in all cases. Surgical and chemotherapy treatment was performed. Radiotherapy was employed in two cases. The mean survival was 9.5 months (6-24 m.). Retroperitoneal lymphadenectomy after chemotherapy has not improved the survival. Relapses of the diseases were noticed after and apparently partial or complete response to chemotherapy.

Sinonasal teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (SNTCS) is a distinctly rare tumor characterized by a variegated histologic architecture of epithelial and mesenchymal components. By reported accounts, SNTCS is a highly malignant tumor displaying rapid, aggressive growth. Prognosis is poor: less than 45% of all patients survive past 5 years. Combination surgery and radiotherapy currently appear to be the most effective treatment. This report presents a 76-year-old African American man with a SNTCS in the right nasal cavity and paranasal sinuses. The patient was treated with combination surgical excision and postoperative radiation therapy. The clinical and pathologic features and clinical course will be discussed.

Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies.

Far-red-emitting cyanine fluorochromes have many properties desirable for in vivo imaging: absorption and emission at wavelengths where blood and tissue are relatively transparent, high quantum yields, and good solubility even at high molar ratios of fluorochrome to antibody. Potentially, conjugation by multiple linkages should minimize hydrolysis in vivo. We conjugated two tumor-targeting monoclonal antibodies: anti-SSEA-1 (IgM, kappa) at ratios of 1.2-35 mol dye/mol antibody and 9.2.27 (IgG2a, kappa) at 0.6-6 mol dye/mol antibody, using the cyanine fluorochromes Cy3.18, Cy5.18, and Cy5.5.18. Nude mice were inoculated using the SSEA-1-expressing MH-15 teratocarcinoma or the 9.2.27 antigen-expressing SK-MEL-2 melanoma to give tumors at several sites. Conjugated antibody was injected, and mice were imaged immediately after injection and at appropriate intervals thereafter using a standard camera lens, dissecting microscope, or endoscopes. Images were acquired using either an image-intensified video camera or cooled CCD cameras. Immediately after injection, major blood vessels and the heart, liver, and kidneys were readily visualized. After 1 day, tumor-targeting antibody conjugates were concentrated in tumors and there was little circulating conjugate; however, the bladder and kidneys were still visible. Tumors labeled by specific antibody were the most fluorescent tissues at 2 days after injection, but non-specific antibody conjugates did not concentrate in the tumors. The small intestine was weakly visualized by both specific and non-specific antibody conjugates. These data support the possibility of visualizing tumor metastasis by optical means, including currently available endoscopes.

Extragonadal nonseminomatous germ cell tumour with hypercalcemia, masquerading as renal cell carcinoma: a case report.

Humoral hypercalcemia secondary to the production of parathyroid hormone-related peptide has been reported to occur in up to 17% of patients with renal cell carcinoma but has been reported only rarely in patients with other genitourinary cancers and never in patients with testicular or extragonadal nonseminomatous cancers. A 54-year-old man is reported who had an extragonadal nonseminomatous germ cell tumour with hypercalcemia that masqueraded as a renal cell carcinoma with metastases. The hypercalcemia was suspected to be humorally mediated.

Blastomatous tumor with teratoid features of nasal cavity: report of a case and review of the literature.

A case of blastomatous tumor with teratoid features is presented. The polypoid mass was observed in the left nasal cavity of a 72-year-old man. Histologically, the lesion was composed of neuroepithelial cells with blastomatous appearance, cystic squamous nests filled with keratin materials, many mucous glands, complex tubular and glandular structures with edematous fibroblastic stroma. Sinonasal neoplasms including teratoid components and immature neuroepithelium are exceedingly rare. We suggest that the term 'immature teratoma' is more suitable than blastoma or blastomatous tumor when there is no carcinomatous or sarcomatous component besides the immature neuroepithelium and teratoid elements.

Late pelvic recurrence of nonseminomatous testicular carcinoma after negative retroperitoneal lymph node dissection.

We report a case of pathologic Stage I teratoma recurring in the pelvis as embryonal carcinoma 12 years after radical orchiectomy and bilateral retroperitoneal lymph node dissection (RPLND). The patient received three cycles of chemotherapy (cisplatin, etoposide, bleomycin) followed by complete surgical excision of the pelvic mass. Successful treatment of these rare late recurrences usually requires chemotherapy and complete surgical excision. Pelvic relapse may potentially result from incomplete iliac node resection at the time of RPLND, altered lymphatic drainage from an incompletely resected spermatic cord, or a second primary extragonadal tumor focus. Our case emphasizes the importance of meticulous surgical technique during RPLND and the necessity for follow-up beyond 5 years in patients with testicular cancer.

A case report of sinonasal teratocarcinosarcoma.

A sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive malignant neoplasm histologically characterized by the combination of one or more epithelial elements and mesenchymal components. We report a case of a 78-year-old man with SNTCS involving the nasal cavity and paranasal sinuses. He complained of epiphora and exophthalmos with weight loss. Physical and diagnostic images resulted T4N0M0. The tumor was completely and widely resected via a trans-facial approach to perform total maxillectomy with orbital exenteration. The clinical presentation, pathologic features, and clinical course are described with a review of the literature.