The impact of extracellular matrix on the chemoresistance of solid tumors--experimental and clinical results of hyaluronidase as additive to cytostatic chemotherapy.

Chemoresistance is of outstanding importance for the limited results of chemotherapy in solid tumors. Chemoresistance of multicellular tumor tissues is more pronounced than that of single cells in vivo and in vitro. The enzyme hyaluronidase is able to loosen the cell-cell contact and the interstitial connective tissue and as such, in a number of preclinical and clinical trials, was shown to enhance the efficacy of cytostatic agents. Although proven to be very effective as additive to local chemotherapy, the systemic efficacy is not documented as well. We present a randomized trial done in high-grade astrocytomas with combined chemotherapy and radiation therapy with and without hyaluronidase. After very promising pilot results with systemic hyaluronidase in various tumor entities and also astrocytomas, this randomized study failed to show synergy to chemotherapy and radiation therapy in high-grade astrocytomas concerning survival. The promising preclinical data and the rather well documented activity in therapeutic use as additive to local chemotherapy seem to be an adequate motive to further elucidate the complex manner in which hyaluronidase is active in the interstitial tumor matrix and to obtain more information concerning the optimal route of application, the optimal dosage and the spectrum of tumor entities where it is synergistic with cytostatic chemotherapy and perhaps even radiation therapy.

Pleural and bone marrow metastasis from supratentorial oligoastrocytoma grade III.

We report a 62-year-old man with symptomatic metastasis to the pleural cavity and the bone marrow from a supratentorial oligoastrocytoma grade III, 24 years after the initial symptoms. Before tumor dissemination, the patient underwent brain surgery four times in 5 years. Six months after the last treatment, extraneural dissemination to the right pleural cavity was discovered. Despite resection of the pleural metastasis, local and distant spread to the bone marrow developed. The patient died 5 months after the occurrence of extraneural tumor metastasis. It is speculated that repeated brain surgery and extended survival may promote extraneural dissemination of supratentorial oligoastrocytoma grade III.

Light chain myeloma with oro-pharyngeal amyloidosis presenting as bulbar paralysis.

A 53-year old woman developed slowly progressive dysarthria, mild enlargement of the tongue and dysphagia since 1 year ago. All neurological differential diagnoses that could have explained the bulbar symptoms were excluded. The swallowing sequence was pathologic and immunoglobulins were markedly reduced. A bone marrow biopsy revealed light chain myeloma grade III. Amyloid deposits were found in the tongue but not in the kidneys. Oro-pharyngeal amyloidosis was held responsible for the described complaints. It is concluded that multiple myeloma must be considered in the differential diagnosis of bulbar paralysis and that biopsy of specific lesions is necessary to confirm local amyloidosis.

[Pamidronate in the treatment of tumor-associated hypercalcemia]. / Pamidronat in der Behandlung der tumorassoziierten Hypercalcämie.

After a 48-hour rehydration period 28 of 31 patients with cancer-associated hypercalcemia (serum calcium greater than or equal to 2.8 mmol/l) were treated intravenously with the bisphosphonate pamidronate. In three patients fluid repletion with 0.9% saline solution had already normalized serum calcium levels. Pamidronate was given in a single infusion on day 0, the dose of pamidronate adapted to the severity of hypercalcemia. If the serum calcium concentration was greater than or equal to 2.8 mmol/l on day 3, application of pamidronate was repeated. In all patients normocalcemia was restored; mean serum calcium decreased from 3.2 +/- 0.35 on day 0 to 2.15 +/- 0.32 on day 12. Hypercalcemia recurred in 11 patients, seven of these underwent pamidronate treatment according to the same therapeutical regimen. Normal calcium levels were attained in five cases. Side effects were of minor gravity: brief hyperthermia occurred in four patients and transient, asymptomatic hypocalcemia was noticed in nine cases.