A rare case of thyroid carcinosarcoma arising from recurrent papillary thyroid cancer: Case report and review of the literature.

BACKGROUND: Thyroid carcinosarcoma represents a rare subtype of thyroid cancer, distinguished by its unique histopathology-simultaneous malignant epithelial and mesenchymal cells. The occurrence of thyroid carcinosarcoma arising from recurrent papillary thyroid cancer is exceptionally infrequent. METHODS: Study outlines a patient's thyroid carcinosarcoma journey, covering presentation, recurrence, diagnostics, surgeries, and follow-up. A PubMed search gathered data on pathological features and treatment approaches for thyroid carcinosarcoma. RESULTS: The patient initially diagnosed with papillary thyroid cancer underwent thyroidectomy, neck dissection, and radioactive iodine therapy. Recurrence revealed thyroid carcinosarcoma, featuring papillary carcinoma, squamous cell carcinoma, and spindle cell components. Total laryngectomy followed by adjuvant radiotherapy and chemotherapy. The patient was followed for 17 months with no evidence of disease. CONCLUSIONS: This extraordinary case exemplifies a rare instance of local relapse in form of thyroid carcinosarcoma following an initial diagnosis of papillary thyroid carcinoma. Surgical resection and chemoradiotherapy show promising outcomes in managing this challenging condition.

Outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal dissemination from ovarian carcinosarcoma.

BACKGROUND: Ovarian carcinosarcoma (OCS) is an uncommon and aggressive malignancy, with poor response to current treatment approaches and no clear guidelines. Our aim is to evaluate the outcomes of an OCS cohort after cytoreduction with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A descriptive cohort study was performed. Patients who underwent CRS/HIPEC for peritoneal dissemination from tubo-ovarian malignancies (1999-2021) were retrospectively reviewed. Patients with confirmed histopathologic diagnosis of FIGO stage III/IV OCS were included. Overall (OS) and progression-free survival (PFS) were determined with the Kaplan-Meier method. RESULTS: Of 267 patients with tubo-ovarian malignancies reviewed, 7.5% (20/267) had OCS. Of these, 16 underwent CRS/HIPEC, including 9 for a new diagnosis and 7 for disease recurrence. Median age at surgery was 66.5 (IQR: 54.5-74.5) years. Nine (56.2%) patients were FIGO stage IV. Median peritoneal cancer index was 22 (IQR: 14-28). Complete cytoreduction was achieved in 15/16 (93.7%) cases. HIPEC agents included carboplatin (n = 7), cisplatin+doxorubicin (n = 4), and melphalan (n = 5). Major complications occurred in 4/16 (25%), with no 90-day mortality. Median follow-up was 41.8 months. Median PFS was 11.7 (95%CI: 10.5-17.1) months. Malignant bowel obstruction occurred in 3/16 (18.7%). Median OS from CRS/HIPEC was 21.3 (95%CI: 16.3-31.6) months, not reached for newly diagnosed vs 19.7 months for recurrent patients (p = 0.23). CONCLUSIONS: CRS/HIPEC showed promising survival and abdominal disease control with low rates of malignant obstruction in patients with advanced stage OCS. Collaborative studies with larger cohorts and longer follow-up may further elucidate the role of CRS/HIPEC in OCS.

Carcinosarcoma of the uterus: MRI findings including diffusion-weighted imaging and MR spectroscopy.

BACKGROUND: Recently carcinosarcoma has become regarded as a subset of endometrial carcinoma. Because the clinical course of carcinosarcoma is aggressive with poor prognosis, it should be differentiated from endometrial carcinomas for the appropriate surgical management and adjuvant therapy. PURPOSE: To clarify the magnetic resonance imaging (MRI) characteristics of uterine carcinosarcoma including diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement and MR spectroscopy (MRS) with quantitative metabolite evaluation. MATERIAL AND METHODS: MRI findings of 12 pathologically diagnosed uterine carcinosarcomas obtained on 3T MRI were retrospectively evaluated. The mean and minimum ADCs, and the lipid and choline concentration levels were compared with those of pathologically diagnosed 38 endometrial carcinomas. RESULTS: The mean and minimum ADCs in carcinosarcomas and endometrial carcinomas were not significantly different. The mean ADC of carcinosarcomas was significantly higher than that of higher grade (G2 and G3) endometrial carcinomas. The choline concentration in carcinosarcomas was significantly lower than that in endometrial carcinomas. High lipid peak was observed in 91% of carcinosarcomas and in 24% of endometrial carcinomas. CONCLUSION: Large, exophytic heterogeneous endometrial mass containing strongly enhanced areas, which may exhibit "tumor delivery", is a suggestive of carcinosarcoma. Relatively high mean ADC and low choline concentration considering its highly malignant nature due to intra-tumoral heterogeneity with necrosis and epithelial cystic components, and the presence of necrosis-associated high lipid peak may be compatible with carcinosarcoma.

Spatial oxygenation profiles in tumors during normo- and hyperbaric hyperoxia.

BACKGROUND: Inspiratory hyperoxia reduces tumor hypoxia, which is responsible for limited radiosensitivity of tumors. However, very little is known about the heterogeneity of intratumoral oxygenation during this supportive treatment. The study analyzes whether local hypoxia is still present during normobaric and hyperbaric inspiratory hyperoxia and whether the addition of CO2 to the inspiratory gas affects the spatial pO2 distribution. MATERIAL AND METHODS: Tumor oxygenation of experimental DS-sarcomas in rats was assessed by polarographic needle electrodes at 1 and 2 atm (bar) environmental pressure during pure O2 or carbogen (95 % O2 + 5 % CO2) breathing. Up to 320 individual pO2 measurements were performed in a strictly oriented grid resulting in an oxygenation profile in a horizontal tumor layer. RESULTS: In the experimental tumors used the oxygenation showed pronounced heterogeneities with closely adjacent hypoxic and oxygenated regions. This heterogeneity was still visible under normobaric hyperoxia where large confluent hypoxic regions were detectable. At 1 atm, the addition of CO2 improved tumor oxygenation significantly (at least in large tumors). At 2 atm, only very small local regions of hypoxia were detected. However, under this condition hypercapnia had no impact on tumor oxygenation. CONCLUSIONS: The data show that even under hyperbaric hyperoxia, hypoxic regions are detectable despite the average pO2 increased by a factor of 100. The results also clearly indicate that the oxygenation pattern improves disproportionally with increasing environmental pressure.

Uterine and ovary carcinosarcomas: outcome, prognosis factors, and adjuvant therapy.

OBJECTIVES: The aim of this study was to assess the outcome and the prognosis factors of uterine and ovarian carcinosarcomas. METHODS: From January 1993 to January 2010, data from 68 consecutively treated patients with uterine (n=59) and ovarian (n=9) carcinosarcomas were retrospectively analyzed in a single French comprehensive cancer center. RESULTS: The median follow-up was 24.2 months (interquartile range [IQR]: 13.5 to 54.6). The median age was 69 years (IQR: 63 to 77). Patients were classified as FIGO stage I (n=28; 41%) and FIGO stage II to IV (n=40; 59%), respectively. There were 33 (49%) and 29 (43%) homologous and heterologous type, respectively. The median disease-free survival and overall survival were 21.9 months (IQR: 7.9 to 22.3) and 27.1 months (IQR: 14.5 to 72), respectively. No statistical differences of survival were reported concerning the initial location of the carcinosarcoma (uterine vs. ovarian). Radiation therapy (hazards ratio [HR]=0.3; 95% confidence interval [CI], 0.16-0.67) and FIGO stage I (HR=0.4; 95% CI, 0.17-0.9) were associated with an increased disease-free survival. Homologous type (HR=3; 95% CI, 1.4-6.3) and FIGO stage II to IV (HR=2.64; 95% CI, 1.3-5.4) were associated with a decreased overall survival. There was no survival improvement for the 12% of patients receiving a multimodal adjuvant therapy. CONCLUSIONS: Uterine and ovary carcinosarcomas present a worse prognosis. On the basis of the present study data, although it should be prospectively confirmed, a sequential or multimodal adjuvant therapy should be proposed to patients with early-stage uterine and ovary carcinosarcomas.

Black race independently predicts worse survival in uterine carcinosarcoma.

OBJECTIVE: GOG 150 suggested that Black women had worse survival compared to White women with uterine carcinosarcoma. Our objective was to compare treatment and survival outcomes between Black and White women at a National Comprehensive Cancer Network (NCCN) cancer center serving a diverse racial population. METHODS: An IRB approved retrospective cohort study of uterine carcinosarcoma patients diagnosed between 2000 and 2012 was performed. Survival was compared by race and stratified by stage. Median progression free and overall survival (PFS and OS) were calculated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate survival analysis was performed with Cox proportional hazards model. RESULTS: 158 women were included: 93 (59%) were Black and 65 (41%) were White. 95 (60%) had early stage disease and 63 (40%) had advanced stage disease. Black women had a shorter PFS (7.9 vs. 14.2 months, p<0.001) and OS (13.4 vs. 30.8 months, p<0.001). There was no difference in survival between Black and White women with advanced stage disease (OS 8.5 vs. 11.8, p=0.18). However, PFS and OS were worse in Black women compared to White women with early stage disease (PFS 13.6 vs. 77.4, p=0.001), (OS 25.4 vs. 94.7, p=0.003). On multivariate analysis accounting for age, stage, BMI, and adjuvant treatment, Black race remained independently associated with risk of death (HR 2.0; 95% CI 1.25-3.23). CONCLUSIONS: Black women with uterine carcinosarcoma have worse survival compared to White women despite similar patient and treatment characteristics. This difference is largely due to differences in survival in early stage disease.

[Integrative management using Ayurvedic medicine in a patient with advanced malignant mixed Muellerian tumor - a case report]. / Integratives Management unter Einsatz von Ayurveda-Medizin bei einer Patientin mit fortgeschrittenem Malignen Müllerschen Mischtumor - ein Fallbericht.

BACKGROUND: Carcinosarcoma of the uterus is a rare malignant tumor with an extremely poor prognosis. Because there are just a few cases described, there is little evidence on possible treatment options. An improvement in the overall unsatisfactory therapeutic situation is required. CASE REPORT: The management of an advanced stage uterine carcinosarcoma, at the time of primary diagnosis in FIGO stage 4, in a 67-year-old woman is described, including multiple surgical interventions, radiotherapy, chemotherapy, and the complementary use of elements of Ayurvedic medicine. To this date, the 3-year follow-up revealed no evidence of distant metastasis. A high quality of life could be ensured continuously. CONCLUSION: Even with poor prognosis, tumor entities can be controlled by using all the available medical resources, enabling a satisfactory quality of life over a longer period of time. For this reason, the complementary use of the traditional medical system Ayurveda could be helpful.

[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report]. / Carcinosarcoma mamario una rara entidad con pronóstico fatal. A propósito de un caso.

BACKGROUND: breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67. CLINICAL CASE: we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease. CONCLUSIONS: metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.

Antecedentes: los carcinomas metaplásticos de la glándula mamaria son un grupo heterogéneo de neoplasias con pobre pronóstico en comparación con el carcinoma ductal invasor. Corresponden a menos de 1% del total de las neoplasias malignas de la glándula mamaria. Casi siempre se manifiestan como tumores de alto grado con menor índice de metástasis ganglionares y menor expresión de receptores de estrógeno y progesterona, Her2 y mayor expresión de Her1 y Ki-67. Caso clínico: se reporta el caso de una mujer de 52 años de edad con carcinosarcoma mamario que se manifiesta con un tumor mamario izquierdo, fungado, ulcerado, polipoide, de 18 cm de diámetro, con metástasis ganglionares al momento del diagnóstico. Recibió tratamiento multimodal con quimioterapia neoadyuvante seguida de mastectomía y quimioterapia complementaria; evolucionó con metástasis pulmonares y recurrencia local masiva. Falleció por complicaciones derivadas de la enfermedad.Conclusiones: los carcinomas metaplásticos de la glándula mamaria son padecimientos sumamente raros. Debido a la naturaleza de la enfermedad y su forma de presentación el pronóstico es pobre. Existen varios subtipos histológicos basados en estudios de hematoxilina y eosina o tinciones de inmunohistoquímica. El tratamiento debe ser multimodal (cirugía, radioterapia y quimioterapia) para obtener mejores resultados.

Teratocarcinosarcoma rinosinusal: reporte de un caso / Rhinosinusal teratocarcinosarcoma: a case report

Teratocarcinosarcoma rinosinusal es una neoplasia maligna infrecuente y rara, que combina elementos de teratoma y carcinosarcoma. Se compone de epitelio benigno o maligno (fibroblastos), mesénquima (cartílago, hueso o músculo liso) y elementos neurales. Hasta el año 2008 se han reportado un total de 63 casos de ubicación rinosinusal. Presentamos el caso de un teratocarcinosarcoma de fosa nasal, en un hombre de 67 años de edad, que consultó por obstrucción nasal rápidamente progresiva. La lesión se resecó completamente por abordaje endoscópico. El diagnóstico fue confirmado por histopatología e inmunohistoquímica. Se realizó tratamiento complementario con radioterapia, sin evidencia de recidiva al año después de la cirugía.

Rhinosinusal teratocarcinosarcoma is a rare malignant neoplasm, which combines teratoma and carcinoma elements. It is composed of benign or malignant epithelium (fibroblasts), mesenchymatic (cartilage, bone or smooth muscle) and neural elements. Until 2008, a total of 63 cases of rhinosinusal location have been reponed. We present the case of a nasal cavity teratocarcinosarcoma ín a 67 year old man that presented with rapidly progressing nasal obstruction. The lesion was completely resected by endoscopic approach. Diagnosis was confirmed by histological pathology and immunohistochemistry Additional treatment by radiotherapy was administered, with no evidence of recurrences a year after surgery.

Rationale for individualized therapy in Sinonasal Teratocarcinosarcoma (SNTC): case report.

BACKGROUND: Sinonasal Teratocarcinosarcoma (SNTC) is a very unusual and aggressive neoplasm characterized by the combination of malignant teratoma and carcinosarcoma features. We present the first case of malignant SNTC treated with individualized multimodal therapy including a histology-specific chemotherapy. CASE REPORT: A 31-year-old man presented with an obstruction of the right pansinus. Histology showed an SNTC with major parts of small cell, poorly differentiated carcinoma and a small proportion of highly differentiated embryonal rhabdomyosarcoma. An operation was performed followed by intraoperative application of a 5-FU ointment. Adjuvant chemotherapy with cisplatin, etoposid and ifosfamid were given in regard to the major components of this heterogeneous tumor. Radiotherapy up to 59.4 Gy was applied. CONCLUSION: 36 months after the end of therapy, there is no sign of tumor recurrence or metastasis in our patient. We suggest that surgery, radiotherapy and a histology-specific multidrug chemotherapy seems to be a therapeutic approach that is appropriate for this heterogeneous tumor.

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings.

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

OBJECTIVES: Uterine carcinosarcomas are uncommon, highly aggressive neoplasms that frequently recur after surgical treatment and adjuvant chemo-radiotherapy. Patients with recurrent disease respond poorly to salvage chemotherapy and irradiation. New therapeutic options are required for patients with metastatic disease. Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas. METHODS: We analyzed the expression of COX-2, c-KIT and HER-2/neu in 24 uterine carcinosarcomas and their correlation with clinical outcome. Disease-free interval and actuarial survival rates were the end points of the study. RESULTS: High staining intensity for COX-2 was observed in 8 cases (33.3%). C-KIT was expressed in 4 cases (16.7%) and HER-2/neu in 7 cases (29.2%). Patients with COX-2-positive tumors had a significantly poorer disease-free interval and survival (P = 0.01 and P = 0.05, respectively). All patients with c-KIT-positive tumors had early stage disease. In spite of this, their survival was not significantly better than that of c-KIT-negative cases. HER-2/neu expression did not show any correlation with clinical outcome. CONCLUSION: c-KIT, COX-2, and HER-2/neu were expressed in different proportions of uterine carcinosarcomas. COX-2 expression was a strong indicator of unfavorable prognosis. These results warrant further study to evaluate the possible role of a new molecularly targeted cancer therapy with COX-2 inhibitors in patients with uterine carcinosarcomas. The role of c-KIT expression and consequently the hypothetical use of STI571 should be tested in a larger series.

Primary sweat gland carcinosarcoma of the scrotal skin.

BACKGROUND: Carcinosarcoma is a biphasic tumor composed of malignant epithelial and mesenchymal elements. Although the tumors have been reported in different locations, they rarely occur in the skin and have not been reported in the skin of external genitalia. CASE REPORT: We present such a case in a 71-year-old Taiwanese man. He had had a long-term indolent nodule on scrotal skin, but it enlarged rapidly in 2 weeks. Wide excision of the tumor was performed. RESULTS AND DISCUSSION: The pathologic examination revealed a sweat gland carcinosarcoma consisting of admixed mucin-producing adenocarcinoma and solid spindle cell sarcoma. The two components exhibited contrasting immunohistochemical profiles with the epithelial component diffusely positive for epithelial markers and S-100 protein, while the sarcomatous component positive for vimentin and smooth muscle actin but negative for epithelial markers and S-100 protein. The immunoreactivity for S-100 protein in the epithelial component supports sweat gland origin. The tumor behaved aggressively. Local recurrence and distant metastases to lungs and brain occurred 6 months and 18 months later. The patient died of the disease 20 months after the initial diagnosis.

Results of treatment of primary liver cancer at Kaunas University of Medicine Hospital.

Though the results of treatment of primary liver cancer depend on many circumstances, the opportunity to perform a curative liver resection remains the main point in prognosis on survival. The aim of the study was to examine our first experience in the treatment of liver cancer. From 1996 to 2001 we observed 54 patients with liver cancer: 46 hepatocellular and 6 cholangiocellular carcinomas, 1 malignant carcinoid, and 1 carcinosarcoma. In presence of liver cirrhosis (21 patients, 38.8%) hepatic function was evaluated using Child Pugh classification. Lesions were multiple in 28 cases and single in 26 cases. Ten patients (18.5%) were radically resected, 12 patients (22.2%) were managed by laparotomy and biopsy, 2 by percutaneous ethanol injections, 1 by trans-ileocolic portal vein embolization + hepatic artery embolization. There were 7 deaths (28%) and 18 complications (72%) after the surgical treatment. The survival results of patients who underwent resection were better (median 240 days) compared with palliative treatment group (median 113.3 days); by Log-Rank test p=0.208. CONCLUSION. The use of liver resections in patients affected by single or monolateral liver cancer is effective and potentially radical treatment. Mortality and morbidity rate is high. Alternative therapies can be conveniently considered in case of multicentric Child B-C patients.

Metaplastic carcinoma of the breast: analysis of eight Asian patients with special emphasis on two unusual cases presenting with inflammatory-type breast cancer.

Metaplastic carcinoma of the breast is a rare form of breast cancer and has an uncertain prognostic significance. Cases from Asian countries have never been reported in the English literature. Between 1983 and 1998, we encountered 8 cases in our institution. There were 7 women and one man with a median age of 52.5 (37-73) years. Pathologic diagnosis included three poorly-differentiated adenosquamous carcinomas, two adenocarcinomas with spindle cell metaplasia, two matrix-producing carcinomas and one carcinosarcoma. Estrogen receptor was positive in 2 (25%) patients. Local recurrence or distant metastasis developed in 3 patients within one year of initial treatment. With a mean follow-up of 81 months (range, 19-183 months), 5 patients were disease-free at the time of this report. Interestingly, two of our patients had presented with huge-sized inflammatory breast cancer and were refractory to neo-adjuvant chemotherapy, but enjoyed an unexpected long disease-free survival after mastectomy. Although the clinical course of our patients appeared in general similar to that of the Western series, the two patients with inflammatory breast carcinoma ran a very unusual course, which may deserve further characterization.

[Changes in clonogenic properties of bone marrow and transplantable mice tumor cells during combined use of cyclophosphane and biological response modifiers of adaptogenic origin]. / Izmenenie klonogennykh svoistv kletok kostnogo mozga i perevivaemykh opukholei myshei pri kombinirovannom primenenii tsiklofosfana i modifikatorov biologicheskogo deistviia adaptogennoi prirody.

The clonogenic activity of tumors and blood marrow cells has been studied in experiments on CBA, BALB/C and C57B1/6 mice with the Ehrlich adenocarcinoma and Lewis lung carcinosarcoma treated with adaptogenic drugs of Rhodiola Rosea extract, a synthetic analog of Rhodiola phenol derivative, methyluracil and their combinations with cyclophosphamide. The extract and derivative are shown to protect the myelopoietic tissue from the toxic action of cyclophosphamide, retaining or increasing the suppressive effect of the latter towards clonogenic tumors cells. These data can be the reason for using the extract and derivative during the antitumor chemotherapy as biological response modifiers.

Effects of tumor necrosis factor-alpha on tumor blood flow and hyperthermic treatment.

The impact of recombinant human tumor necrosis factor-alpha (rhTNF-alpha), given alone or in combination with local hyperthermia, on perfusion and growth of a moderately rhTNF-alpha-sensitive rat tumor (DS-carcinosarcoma) was investigated. DS-carcinosarcomas were implanted into the hind foot dorsum of Sprague-Dawley rats. Tumor blood flow (TBF) was measured with the krypton-85 clearance technique. Treatment with either tumor necrosis factor-alpha (0.1-1.0 mg/kg) or hyperthermia (43.3 and 44.3 degrees C, 40 min) can decrease the perfusion of malignant tumors. The TBF reduction was fully established 2 h after rhTNF-alpha injection and lasted for at least 4 h. The application of local hyperthermia (T greater than 42 degrees C) 3 h after rhTNF-alpha administration further diminished tumor blood flow. Volume growth of the tumors was monitored during repeated treatment. rhTNF-alpha (0.2 and 1.0 mg/kg i.v.) combined with hyperthermia (43.3 and 44.3 degrees C, 40 min, starting 3 h after rhTNF-alpha injection) were given every third day from the fifth to the 20th day after tumor implantation. Monotherapies retarded tumor growth in a dose-dependent manner. Combined treatment was superior to either monotherapy leading to local tumor control in 40-50% of the animals treated. It is concluded that local hyperthermia can enhance the efficacy of rhTNF-alpha treatment by further reducing tumor perfusion.

Hyperthermia in cancer therapy.

Tumor hyperthermia is a rediscovered technique of oncotherapy which has confirmed value in many studies on cell cultures, rodent and mammalian tumors as well as first investigations on patients with tumors. The biological basis for using heat in the treatment of cancer is well established. Various direct and indirect mechanisms are significant for the effect of hyperthermia on tumor tissue. Whereas there are already extensive studies on the direct effects of hyperthermia on DNA, RNA, and protein synthesis, energy metabolism, and the membrane properties of tumor cells, the indirect effects have only been investigated more closely in recent years. These are likewise important for the damage to the tumor tissue and are mediated above all via alterations in the microcirculation and the environment. The recently gained increasing significance of this new technique in combination with other treatment modalities is well documented. Technical problems of heat application must be overcome, especially in deeper tumors and problems of thermometry must be solved in order to be able to apply tumor hyperthermia not only to selected advanced or recurrent tumors, but in order to use it as the fourth pillar of tumor therapy besides surgery, radiotherapy and chemotherapy. This article considers the biological basis and important aspects of hyperthermia therapy in combination with radiotherapy and chemotherapy.

Laser Doppler flowmetry in subepidermal tumours and in normal skin of rats during localized ultrasound hyperthermia.

Laser Doppler flowmetry has been applied to normal skin and to subepidermal tumours during localized ultrasound hyperthermia in the rat. In normal skin, 40 degrees C hyperthermia only induced a marginal increase in the red blood cell flux. Significant increases occurred after 20 min at 42 degrees C and after 4 min at 44 degrees C. During 44 degrees C hyperthermia maximum fluxes were reached after 24 min. Thereafter, the flow declined and finally approached preheating values. In contrast, in subepidermal tumours 40 degrees C hyperthermia on the average induced a slight decrease of the flux. During 42 degrees C hyperthermia a significant flow decrease was found after 40 min of heating. Following a transient increase in the laser Doppler flow during the heating-up period, 44 degrees C hyperthermia led to a significant impairment of the flux after 24 min. A total shutdown of RBC flux was observed in about 30 per cent of the tumours at 44 degrees C. Upon elevated tissue temperatures, pronounced inter-tumour variabilities in the time- and temperature-dependent changes of RBC flux were observed. Rhythmic oscillations of the RBC flux were found in some subepidermal tumours (0.40 +/- 0.05 cycles/min). Upon heating, these periodic flow variations slowed down significantly (0.20 +/- 0.04 cycles/min), whereas in normal skin the frequency of the flow fluctuations increased.