Bleomycin Chemotherapy Research Articles

Clinical analyses of 81 infertile and 20 testicular tumor men with suspected X-chromosome-linked gene anomalies in Japan

A total of 101 cases of 81 infertile men and 20 men with testicular tumors were analyzed clinically for suspected X-chromosome-linked gene abnormalities. Among the 81 infertile men analyzed by testicular biopsy, 11 Klinefelter syndrome (KS) cases showed Leydig cell nodular hyperplasia with azoospermia. They had low levels of testosterone (131 ± 81 ng/dl) and high levels of luteinizing hormone (21 ± 7 mIU/ml) and follicle-stimulating hormone (36 ± 11 mIU/ml). From Leydig cell hyperplasia combined with atrophic tubules, X-linked androgen receptor dysfunctions in Sertoli and Leydig cells were judged in the KS cases. One azoospermia case of non-KS had primary yolk sac tumor of the mediastinum and liver. The removed yolk sac tumor showed complete necrosis after bleomycin, etoposide, and cisplatin (BEP) chemotherapy, which indicated cisplatin-sensitive apoptosis. X-linked inhibitor of apoptotic protein (XIAP) must exhibit an apoptosis-inducible mutation (XIAP-S87A) in the non-KS case. Subsequently, 20 testicular tumor cases were classified into ten with seminoma, eight with mixed germ cell tumors (MGCT), one with mature teratoma, and one with diffuse large B cell lymphoma. Although among the eight MGCT cases, six cases had high levels of α-fetoprotein (68–43647 ng/ml), their blood levels of human chorionic gonadotropin-β were <0.1 to 23 ng/ml with a good prognosis. Radiological examinations of the 20 cases showed nodular, hemorrhagic, or cystic changes in lung, liver, or periarterial lymph nodes, but no metastatic changes in bone or brain. Besides cisplatin-induced acute renal failure in one of the two seminoma cases treated with BEP chemotherapy, the two cases showed chronic renal failure (CRF) due to glomerular disturbance, but three treated MGCT cases did not. Their mutated humanin in spermatocytes, which located in X-chromosome and bound to podocytes, might have aggravated the CRF. Infertility and testis-related tumors were caused by X-chromosome-linked gene anomalies.

Parathyroid Adenoma and Chondrosarcoma After Treatment of Pediatric Hodgkin Disease

Treatment of Hodgkin disease (HD) with chemoradiotherapy in children is associated with increased risk for developing secondary neoplasms. Parathyroid adenoma (PTA) and chondrosarcoma (CS) are quite rare types of secondary neoplasms after HD. We describe a 5-year-old boy with stage IV HD, successfully treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone)/ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 35 Gy mantle radiotherapy who developed primary hyperparathyroidism because of benign PTA at the age of 20 years, and died of CS in thoracic vertebrae at the age of 22 years. Consecutive occurrence of PTA and CS after treatment of pediatric HD, to the best of our knowledge, has not been reported earlier.

Risk factors for mortality in AIDS-associated Kaposi sarcoma in a primary care antiretroviral treatment program in Malawi

AIDS-associated Kaposi sarcoma (AIDS-KS) is the most common HIV-related malignancy. The majority of cases are found in sub-Saharan Africa. This retrospective cohort study describes characteristics of patients with AIDS-KS and factors associated with mortality in an antiretroviral treatment (ART) program in rural Malawi. Of 11 122 patients enrolled on ART, 830 (7%) had AIDS-KS. Patients with AIDS-KS were more likely to be lost to follow-up (22% versus 14%, P < 0.001) and showed a higher mortality (22% versus 10%, P < 0.001) compared to patients without AIDS-KS. A CD4 count ≤150 cells/μl, advanced stage AIDS-KS, and absence of bleomycin chemotherapy were associated with increased mortality. Earlier diagnosis and improved treatment of AIDS-KS are urgently needed in order to reduce mortality.

BLMH1 single nucleotide polymorphism correlation with bleomycin chemotherapy in patients with testicular germ cell tumors.

e15100 Background: Bleomycin, the main component of chemotherapy protocol for metastatic testicular germ-cell tumor (TGCT), may be inactivated by bleomycin hydrolase, encoded by BLMH1 gene. SNP A1450G is thought to be involved in controling enzymatic activity and thus the level of bleomycin-induced DNA damage. We suggested hypotesis that this SNP A1450G might influence toxicity in TGCT patients. Methods: Fiftynine patients with metastatic TGCT (6 seminomas, 14 nonseminomas and 39 with mixed germ cell tumors) were treated with three (10 patients) or four cycles (47 patients) of BEP chemotherapy (bleomycin/etoposide/cisplatin), except for 2 patients with bleomycin toxicity who were treated with 1 and 2 cycles of BEP. Blood samples of 59 patients were analysed using the real-time PCR method performed by ABI PRISM 7000 Sequence Detection System (Applied Biosystems) and pre-developed TaqMan SNP genotyping assay (rs1050565) according to the manufactures' instructions Results: We observed a wide range of adverse events casued by toxicity of bleomycin: cough, dyspnea, pneumonitis, pulmonary fibrosis, nail changes, hyperpigmentation, hypersensitivity, pruritus, leukocytopenia, vomiting, nausea and the fever. Two patients revealed severe adverse events (who were treated with 1 and 2 cycles of BEP), one a pulmonary fibrosis (x-ray verified) and the second as a significant dyspnea.The most common adverse effects were dermatological (hyperpigmentation, pruritus, hypersensitivity and nail changes) as well as fever. Patients with AG or GG genotypes developed more adverse events (25) than patients with AA (16) although results didn't reach statistical significance. Conclusions: Our results suggests that application of SNPs in future as a routine method will enable individual approach and recognition of patients who are genetically predisposed for higher toxicological effects of bleomycin. It can be expected that as number of subjects in this cohort will increase statistical significance will be reached. No significant financial relationships to disclose.

Outcomes after bleomycin, etoposide and cisplatin combination chemotherapy in patients with ovarian yolk sac tumor

Objective: The aim of this study was to evaluate the oncologic and reproductive outcomes of patients with ovarian yolk sac tumor after bleomycin, etoposide, cisplatin (BEP) chemotherapy following surgery. Methods: Of 145 patients with histologically confirmed malignant ovarian germ cell tumor, 43 had yolk sac tumor and received BEP chemotherapy after surgery. A retrospective analysis of these patients was performed. Results: The mean age of 43 patients was 24.8 years (range, 7 to 59 years). Thirty eight patients were iparous. Of 179 BEP chemotherapy cycles, grade 1~2 hematologic and non-hematologic adverse events occurred in 46 cycles in 21 patients. Thirty nine patients showed complete remission, 1 patient showed partial remission, and 3 patient had progressive disease during BEP chemotherapy. After median follow-up time of 57 months (range, 3 to 153 months), 5 patients had recurrent disease and three of them died of disease. The 5-year recurrence free survival rate and overall survival rate were 86% and 94%, respectively. After chemotherapy, all but one premenarchal patients had normal menstruation. Of them 5 patients tried to conceive and 3 of them succeeded in pregnancy. Conclusion: BEP chemotherapy was very safe and effective in patients with ovarian yolk sac tumor. Survival outcomes are excellent and reproductive outcomes are promising after BEP chemotherapy.

A Case with Hodgkin Lymphoma and Fronto-temporal Lobular Degeneration (FTLD)-like Dementia Facilitated by Chemotherapy

We report a case of a 39-year-old man with Hodgkin lymphoma who developed depressive symptoms after starting adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy and later exhibited sexual disinhibition in addition to cognitive dysfunction (mainly executive dysfunction). Seven months after the start of adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy, he was finally diagnosed as having fronto-temporal lobular degeneration-like dementia facilitated by adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy. At the time of writing, the patient's condition has persisted for more than 6 months after the discontinuation of adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy, and the changes in brain function brought on by the adriamycin, bleomycin, vinblastine and dacarbazine chemotherapy may now be irreversible. This case points to the importance of being attentive to the appearance of neuropsychiatric symptoms and evaluating brain functions properly when performing anti-cancer chemotherapy.

Relapse with Malignant Transformation After Chemotherapy for Primary Mediastinal Seminoma: Case Report

This case report details a relapse with malignant transformation after the completion of bleomycin, etoposide and cisplatin chemotherapy for primary mediastinal seminoma, although the residual mass after chemotherapy was <3 cm in size and did not display an increased uptake of fluorodeoxyglucose when examined using positron emission tomography.

A case report: Primary extragonadal yolk sac tumor of penile shaft in a 2‐year‐old child

A 2-year-old boy, who had the chief complaints of penile swelling and pain, was brought to the hospital by his mother. Penile contusion/trauma was suspected and he was admitted the same day to undergo emergency surgery to eliminate hematoma. The surgery revealed that the origin of the bleeding was not trauma but a tumor lesion of the penile shaft. It was histopathologically identified as a yolk sac tumor and no tumorous lesions were found except that in the penis. Therefore the patient was diagnosed as definitely having a yolk sac tumor originating in the penis. The patient received four cycles of cisplatin, etoposide and bleomycin treatment as adjuvant chemotherapy. Although it was impossible to completely resect the tumor, cisplatin, etoposide and bleomycin chemotherapy was effective and a complete response was achieved. We plan to carefully monitor the patient in the future.

The impact of histopathologic diagnosis on the proper management of testis neoplasms

A 45-year-old man underwent a right orchiectomy for a rapidly growing testicular mass. After histologic and imaging examinations the patient was diagnosed with stage I (T1N0M0) seminoma. Approximately 2 months after surgery the patient began to complain of abdominal pain and a CT scan revealed a bulky retroperitoneal mass. The patient did not receive the planned prophylactic radiotherapy and was treated with combined cisplatin, etoposide and bleomycin chemotherapy; after the completion of this treatment he achieved complete remission. Three years later, and while still undergoing follow-up, the patient developed multiple neurological motor deficits. Brain MRI and CT-guided biopsy. Diffuse large B-cell lymphoma of the testis, relapsing in the central nervous system. High-dose methotrexate alone or in combination with high-dose cytarabine.

Combined chemotherapy using cisplatin, ifosfamide and bleomycin (PIB) in the treatment of advanced and recurrent cervical carcinoma.

Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.

A case of spermatic cord teratoma in low-stage testicular cancer managed by surveillance

A 25-year-old male presented to his local urologist with new-onset right testicular pain and swelling detected on self examination. A scrotal ultrasound scan showed a right testicular mass, suspicious for neoplasm. Serum levels of alpha-fetoprotein and human chorionic gonadotropin were found to be elevated at 920.2 microg/l and 637.4 U/l, respectively. The patient underwent right inguinal orchiectomy and was diagnosed with nonseminomatous germ cell tumor of the right testis, composed of yolk sac tumor, teratoma, and embryonal carcinoma with no evidence of metastatic disease. He opted to remain under surveillance rather than undergo primary chemotherapy or retroperitoneal lymph node dissection for his clinical stage I disease. Serologic relapse at 4 months after orchiectomy was successfully treated with bleomycin, etoposide and cisplatin (BEP) chemotherapy. Surveillance comprised regular clinic visits, measurement of serum levels of alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, chest X-ray and CT of the abdomen and pelvis. Pathology of the testicular mass was reviewed. A 1.7 cm nodule anterior to the right psoas muscle suspicious for metastatic disease that was seen on CT 16 months after orchiectomy was pathologically confirmed as recurrent mature teratoma in the spermatic cord. Additionally, one of eleven interaortocaval lymph nodes showed evidence of teratoma. Bilateral nerve-sparing retroperitoneal lymph node dissection with complete excision of the right spermatic cord was performed. The patient has since remained disease-free, with normal levels of serum tumor markers and no evidence of metastasis on chest X-ray and abdominal CT.

Optimal Management of Retroperitoneal Metastatic Nonseminomatous Testicular Cancer: Toward a Better Selection Between Scalpel and Needle

During the past decades, both surgery and systemic chemotherapy have emerged as critically important modalities in the treatment of nonseminomatous germ cell cancer. Before the advent of cisplatin-based chemotherapy, retroperitoneal lymph node dissection (RPLND) had been established to be potentially definitive treatment in many cases of low volume (stage IIA, 2 cm; stage IIB, 5 cm) retroperitoneal metastatic disease. A full, bilateral, or modified template RPLND is a technically demanding procedure and requires a skillful and experienced surgeon. Nonetheless, if uneventful and definitive, a RPLND is devoid of late toxicity. After the recognition of the high curative potential of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, even in the setting of widespread metastatic disease, many investigators have adopted primary chemotherapy also in stage IIA and IIB disease, reserving RPLND mainly to resect postchemotherapy residuals. At first glance, this approach seems straightforward given the greater than 90% disease-free survival and 95% disease-specific survival in good prognosis (low volume) metastatic disease by chemotherapy. Following primary RPLND, chemotherapy was also increasingly being used adjuvantly if pathologic stage II was confirmed, or to treat systemic relapse after RPLND. Hence, chemotherapy has increasingly been given as primary therapy. The prospect of primary chemotherapy to eradicate virtually all lowor limited volume retroperitoneal metastatic disease, and sparing most patients double treatment in terms of an additional RPLND, however, has not come true. Several studies using primary chemotherapy have demonstrated that up to 50% of patients with stage IIA and IIB retroperitoneal metastatic disease obtain no radiologic complete remission and even the tiniest remnants ( 5 mm in previously involved sites) may harbor remaining viable cancer, or residual mature teratoma. In the greater majority of patients who undergo postchemotherapy RPLND for radiologic residual disease, the resected specimens contain mature teratoma as the dominant histology. Although mature teratoma is considered benign, there is a lifetime risk of growth and secondary transition into malignancy. Therefore, mature teratoma should be considered potentially malignant, requiring surgical resection whenever feasible. Two large European databases have allowed determination of the incidence and histology of residual masses in the retroperitoneal area following full induction chemotherapy. In a study of the Medical Research Council in 287 patients, 222 of whom had stage IIA/B nonseminoma, viable cancer was found in 18% and mature teratoma was present in 51% of patients who underwent surgery for postchemotherapy residuals. The frequency of surgery and histological findings is summarized in Table 1. A subset analysis is also available of the stage IIA/B patients treated in the study led by the European Organisation for Research and Treatment of Cancer of three versus four cycles of BEP in good prognosis testicular cancer. Of the total 812 patients entered onto the study, 300 patients had stage IIA or IIB nonseminoma. Radiologic residual disease ( 1 cm) was reported in 132 patients (44%) after the completion of chemotherapy. Of these, 73 underwent surgery and 71 patients had complete resection of residual disease; in one

A kampo medicine, Yin‐Chiao‐san, Prevents bleomycin‐induced pulmonary injury in rats

Yin-Chiao-San (YCS), a kampo medicine, is widely used for patients with pulmonary disease and was applied for the treatment of SARS in Asia countries in 2003. For this reason, the present study investigated the preventive effect of YCS on bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. Animals were divided into four groups: (1) saline control group; (2) BLM-induced group, in which 15 mg/kg BLM was intraperitoneally injected three times per week for a period of 5 weeks; (3) BLM + vitamin E (10 mg/kg/day) as a positive group; (4) and BLM + YCS (1000 mg/kg/day). After 35 days, the rats were anesthetized, killed and then the lungs and bronchoalveolar lavage fluids (BALFs) were collected. The attenuation of pulmonary fibrosis was estimated according to the lung index, malondialdehyde (MDA), catalase (CAT), hydroxyproline (HP) and tumor necrosis factor-alpha (TNF-alpha) level in lung tissue and BALF. The serial sections of lung were stained with haematoxylin-eosin and Masson trichrome for histopathological observation of pulmonary fibrosis. The results indicated that YCS significantly reduced the lung index, MDA, HP and TNF-alpha, but YCS significantly enhanced the CAT level when compared with the BLM-induced group (p < 0.05). Additionally, the BLM group displayed severe histopathological change in the lung tissue, but YCS treatment could attenuate the BLM-induced PF. In conclusion, the results demonstrated that YCS possesses antioxidant and antiinflammatory activities and also inhibited collagen formation. Thus, YCS exhibited a preventive effect in BLM-induced PF and it is suggested that YCS may be applied to attenuate the side effects of BLM in chemotherapy.

Testicular sperm extraction in patients with persistent azoospermia after chemotherapy for testicular germ cell tumor

Sperm cryopreservation before chemotherapy in young males is recommended because of chemotherapy's gonadotoxic effects. However, many patients miss sperm banking, and consequently are often sterile. Two azoospermic patients presented to us after chemotherapy, and we obtained sperm from them by testicular sperm extraction (TESE). One patient was 32 years old and had been treated with six cycles of cisplatin, etoposide and bleomycin (BEP) chemotherapy and one cycle of high-dose chemotherapy for stage III non-seminoma. Histopathology of the testicular specimen showed germinal aplasia with focal islands of full spermatogenesis. Although two intracytoplasmic sperm injection (ICSI) cycles were performed, pregnancy was not achieved. The other patient was 33 years old who was treated with four cycles of BEP chemotherapy for stage II seminoma. Histopathology of the testicular specimen showed Sertoli-cell-only syndrome. Ongoing pregnancy was achieved after one ICSI cycle. TESE should be considered in patients with persistent azoospermia after chemotherapy if frozen sperm samples are not available.

Mutagenesis and crystallographic studies of the catalytic residues of the papain family protease bleomycin hydrolase: new insights into active-site structure.

Bleomycin hydrolase (BH) is a hexameric papain family cysteine protease which is involved in preparing peptides for antigen presentation and has been implicated in tumour cell resistance to bleomycin chemotherapy. Structures of active-site mutants of yeast BH yielded unexpected results. Replacement of the active-site asparagine with alanine, valine or leucine results in the destabilization of the histidine side chain, demonstrating unambiguously the role of the asparagine residue in correctly positioning the histidine for catalysis. Replacement of the histidine with alanine or leucine destabilizes the asparagine position, indicating a delicate arrangement of the active-site residues. In all of the mutants, the C-terminus of the protein, which lies in the active site, protrudes further into the active site. All mutants were compromised in their catalytic activity. The structures also revealed the importance of a tightly bound water molecule which stabilizes a loop near the active site and which is conserved throughout the papain family. It is displaced in a number of the mutants, causing destabilization of this loop and a nearby loop, resulting in a large movement of the active-site cysteine. The results imply that this water molecule plays a key structural role in this family of enzymes.

Radiological findings following postsurgical intratumoral bleomycin injection for cystic craniopharyngioma

Objectives The purpose of this study was to compare the radiological findings before and after intratumoral bleomycin injection in patients with cystic craniopharyngioma so as to define the role of adjuvant intracavitary bleomycin chemotherapy for cystic craniopharyngiomas. Patients and methods Eleven patients whose craniopharyngioma was confirmed cytologically and/or histologically were retrospectively reviewed. The follow-up duration ranged from 9 to 79 months (mean, 31.6 months). Only the solid portion of the cystic craniopharyngiomas was excised before repeated injections of bleomycin (15–180 mg in total) into the cystic portion through an Ommaya reservoir were given. The patients were evaluated neuroradiologically before and after bleomycin administration. Results After the completion of all treatment cycles, the disappearance or shrinkage of the tumor was initially noted in all cases on follow-up CT and/or MR imaging studies. However, tumor recurrence was seen in four cases with a mixed tumor type. Conclusion Postoperative bleomycin injection in cystic craniopharyngioma does not appear to totally eradicate the tumor and does not stop tumor recurrence unless the cyst is the only portion of the craniopharyngioma that is left. Nevertheless, postoperative bleomycin injection decreases and stabilizes tumor size, and thus may be considered as an option of treatment modalities in patients with predominantly cystic craniopharyngiomas.

One course of adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminomatous germ-cell tumors (NSGCT): Results of the German Prospective Multicenter Trial (Association of Urological Oncology [AUO]/German Testicular Cancer Study Group [GTCSG] Trial 01–94)

4512 Background: The incidence of relapse was analyzed in patients with clinical stage I (CS I) NSGCT after either retroperitoneal lymph node dissection (RPLND) or one course of adjuvant cisplatin, etoposide, and bleomycin (PEB) chemotherapy. Methods: Between September 1996 and February 2005, 382 patients with stage I NSGCT were included in the German Prospective Multicenter Trial. After orchiectomy, patients were randomized to either RPLND (191 patients) or one cycle of cisplatin 20 mg/sqm d1–5, etoposide 100 mg/sqm d1–5, and bleomycin 30 mg d1, 8, 15 (PEB, 191 patients). Pathological stage II after RPLND (18% of CS I) was followed by adjuvant chemotherapy (2 × PEB). The primary endpoint was relapse rate. The trial was powered to show an advantage for chemotherapy (planned sample size 360 patients, alpha 5%, power 80%) after a median follow-up of 3 years. Results: Thirty-six patients were excluded due to violation of the inclusion criteria. Of the remaining 346 eligible cases, 172 patients were treated by RPLND and 174 patients received one course of PEB. Median time of follow-up was 47 months, with 323 patients (93%) followed-up for at least 1 year. Of the evaluable patients 331 (96%) have remained disease-free. Thirteen (8%) patients experienced relapse after RPLND and 2 (1%) after one course of adjuvant PEB (p = 0.0028). All patients with relapse have been successfully treated. Five patients developed pulmonary metastases, 3 patients relapsed with retroperitoneal metastases, 3 patients showed marker elevations, and 2 patients had an inguino-scrotal relapse after RPLND. The patients with one cycle of PEB relapsed with a tumor marker elevation and a mature teratoma retroperitoneal metastases, respectively. Conclusions: This randomized trial revealed only two relapses among 174 patients treated with one course of PEB. The low risk of recurrence supports one course of PEB over RPLND for the treatment of patients with clinical stage I NSGCT. No significant financial relationships to disclose.

Long-Term Risk of Cardiovascular Disease in 5-Year Survivors of Testicular Cancer

To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC). We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis. After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk. Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.

Recurrent ovarian dysgerminoma after laparoscopy

To our knowledge, recurrent dysgerminoma at the site of tumor removal by laparoscopy in a patient with stage IA disease has not been previously reported. A woman with ovarian dysgerminoma treated by laparoscopy and tumor removed through the cul-de-sac recurred the 17 months later at the site of tumor removal. She was successfully treated with etoposide, bleomycin, and cisplatin chemotherapy with complete response. This case illustrates the potential for surgical site implant of an ovarian dysgerminoma; surgeons should follow strict guidelines when performing laparoscopic procedures for ovarian malignancies in order to prevent this type of incident.

Neutropenia and febrile neutropenia in patients with Hodgkin's lymphoma treated with doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy

When uncomplicated neutropenia during doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) chemoterapy for the treatment of Hodgkin's lymphoma is encountered, it is unclear whether or not treatment should be modified. In the present study, we determined the incidence of neutropenia, febrile neutropenia, and the relationship of febrile neutropenia to grade III/IV neutropenia and dose modification, in a large university patient population. We reviewed the charts of patients diagnosed with Hodgkin's lymphoma between 1 January 1990 and 31 December 2002 who were treated with ABVD chemotherapy, and seen at the University of Iowa with complete diagnosis, staging, and treatment dosing records. Adequate data was available on 894 treatments in 81 patients with Hodgkin's lymphoma treated with ABVD chemotherapy. Grade III/IV neutropenia was present on the scheduled day of treatment in 187 (20.9%) treatments in 64 (79%) patients. Grade III/IV neutropenia was most common at cycle 1 day 15. Febrile neutropenia developed nine times in eight patients, and eight episodes of febrile neutropenia developed when the treatment-day absolute neutrophil count (ANC) ⩾1000. Dose delay of >4 days and/or dose reduction to <80% of original doxorubicin dose following grade III/IV neutropenia occurred in 29 of 187 treatments, with no episodes of febrile neutropenia. With grade III/IV neutropenia on the day of therapy, 158 treatments were administered without dose reduction or dose delay with one subsequent episode of febrile neutropenia. Neutropenia during ABVD is common, and dose modification for uncomplicated neutropenia on the day of treatment may not reduce the risk of febrile neutropenia. It may be possible to maintain dose intensity in the face of uncomplicated neutropenia during ABVD therapy.