Hiromu Inai

Risk Factors for Loss to Follow-up During Active Surveillance of Patients with Stage I Seminoma

OBJECTIVE To elucidate the patterns and risk factors for loss to follow-up during active surveillance for Stage I seminoma. METHODS A total of 425 cases with Stage I seminoma underwent radical orchiectomy from 1985 to 2006 at 25 Japanese institutions, including 22 community hospitals and 3 university hospitals. The post-orchiectomy management selected was active surveillance for 186 patients, adjuvant radiotherapy for 182 patients and chemotherapy for 57 patients. The Kaplan-Meier method was used to estimate the recurrence-free survival and loss to follow-up rate. The risk factors for loss to follow-up were examined using Coxs proportional hazards model with multiple variables. RESULTS The 2-, 5- and 10-year loss to follow-up rates in the active surveillance group were 14.2, 37.8 and 71.3%, respectively, which were not significantly different in comparison with those in the active surveillance and adjuvant radiotherapy or chemotherapy groups. With regard to the active surveillance group, the multivariate analysis demonstrated that patients younger than 36 years at diagnosis, patients diagnosed since 2000 and patients treated at hospitals that enrolled more than 10 cases had a significant risk for loss to follow-up. No significant correlation between the loss to follow-up rate and pathological risk factors such as tumor size (≤4 versus >4 cm) and rete testis invasion (presence versus absence) was shown. CONCLUSIONS The loss to follow-up rates beyond 5 years were unsatisfactorily high during active surveillance. Further approaches to improve the quality of active surveillance are needed, especially for high-risk patients such as those of younger age.

Risk factors for chronic kidney disease after chemotherapy for testicular cancer

To elucidate the patterns of and risk factors for deterioration of renal function after chemotherapy in metastatic testicular cancer survivors using the estimated glomerular filtration rate.

Management of Ureteral Obstruction in Advanced Testicular Tumor with Lymph Node Metastasis

OBJECTIVE Ureteral obstruction is one of the complications of testicular tumor with retroperitoneal lymph node metastasis that requires ureteral stenting for management. We elucidated the clinical courses of ureteral obstructions and changes in renal functions in patients with indwelling ureteral stenting. METHODS The medical records of 56 patients who were treated for metastatic testicular tumors by chemotherapy at a single institute between 2002 and 2010 were retrospectively reviewed. RESULTS Among 56 patients, 12 patients needed ureteral stenting before chemotherapy. The proportion of patients requiring ureteral stenting was significantly higher in seminoma than non-seminoma (47 and 12%, respectively, P < 0.05). The ureteral stent was removed after chemotherapy or retroperitoneal lymph node dissection in all patients, except for one patient who died of cancer during chemotherapy. At retroperitoneal lymph node dissection, ureters were spared in three patients, a partial ureterectomy was needed in one patient, and no case underwent adjunctive nephrectomy. These 11 patients presented no local and distant recurrence at median follow-up of 44 months. Ureteral stenting increased the estimated glomerular filtration rate to more than 60 ml/min before chemotherapy in all patients, but it decreased to <60 ml/min in 6 of 11 patients after chemotherapy. CONCLUSIONS Ureteral obstruction due to testicular tumor was relieved after chemotherapy or retroperitoneal lymph node dissection. Ureteral stenting was effective to improve renal function before chemotherapy, although we should pay special attention to deterioration of renal function during or after chemotherapy.

Assessment and Management of Renal Impairment in Chemotherapy for Urogenital Cancer

The method of diagnosing chronic kidney disease by simple estimated glomerular filtration rate equations has demonstrated a high prevalence of chronic kidney disease among the genitourinary cancer patients. Approximately 30-50% of urothelial cancer patients have Grade 3 chronic kidney disease before chemotherapy, and the rate increases to around 80% in upper urinary tract cancer patients who have undergone radical surgery. Several gold-standard treatments, including cisplatin for urothelial/testicular tumors and anti-vascular endothelial growth factor therapy for kidney cancers, are known to be associated with the development of renal impairment. However, which renal function assessments are best to select a chemotherapy regimen remain unknown. Most testicular tumor patients are cured by intensive combined chemotherapy with cisplatin, but chemotherapy can induce chronic kidney disease in testicular cancer survivors. The prevalence of Stage 3 chronic kidney disease among the testicular cancer survivors is between 10 and 20%. Thus, the estimated glomerular filtration rate assessment is a useful tool for monitoring the development of chronic kidney disease among the cancer survivors, and assessment of renal function is mandatory before the treatment of these genitourinary cancer patients.

Oncological Outcomes of Metastatic Testicular Cancers under Centralized Management through Regional Medical Network

OBJECTIVE To investigate the dose intensity of induction chemotherapy and oncological outcomes of metastatic testicular cancer under centralized management through a regional medical network. MATERIALS AND METHODS We retrospectively analyzed the outcomes of 86 metastatic testicular cancer patients who were given induction chemotherapy at Tsukuba University Hospital and four branch hospitals between January 2000 and November 2010. Principally, management of patients with poor-prognosis disease and patients having risk factors for bleomycin, etoposide and cisplatin were referred to Tsukuba University Hospital before chemotherapy. For high-risk groups, etoposide and cisplatin or etoposide, ifosfamide and cisplatin was used as an alternative to bleomycin, etoposide and cisplatin. RESULTS Overall, 56 and 30 patients were treated at Tsukuba University Hospital and branch hospitals, respectively. Forty-seven, 18 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Eighteen of the 21 patients (86%) with poor-prognosis disease were treated at Tsukuba University Hospital from the beginning of induction chemotherapy. Induction chemotherapy with a high relative dose intensity was possible in most patients. The average relative dose intensity of each drug was >0.96. Treatment procedures other than induction chemotherapy were efficiently centralized; 74% of post-chemotherapy surgery and all second-line or subsequent chemotherapies were performed at Tsukuba University Hospital. The 5-year overall survival rates of the good-, intermediate- and poor-prognosis groups were 97, 93 and 84%, respectively. CONCLUSIONS Induction chemotherapy with high relative dose intensity, post-chemotherapy surgery and salvage chemotherapy was accomplished efficiently through centralization of management. Oncological outcomes were excellent, especially in patients with poor-prognosis disease, whose 5-year OS reached 84%.

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter's syndrome

Abstract

Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts.

p16(INK4a) (p16), a key molecule in bladder tumor development, inhibits the activities of cyclin-dependent kinases (CDKs) and maintains the retinoblastoma protein (pRb) in its active hypophosphorylated state. Following the finding that the p16 antitumor peptide dramatically inhibits the growth of aggressive leukemia/lymphoma through the restoration of p16 function using the Wr-T peptide transporter system, in this study, we developed a systemic therapy using mouse‑p16 peptide (m‑p16) in subcutaneous p16‑null mouse bladder tumors. In vitro analysis showed that the growth of p16‑null bladder tumor cells and the hyperphosphorylation of their pRbs were inhibited by p16 transduction in a concentration‑dependent manner. In an animal model, p16‑null MBT‑2 cells were injected subcutaneously into KSN/SKC nude mice. The systemic delivery of the m‑p16 peptide using Wr‑T by cardiac injection significantly inhibited the growth of solid MBT‑2 tumors compared with the control phosphate‑buffered saline (PBS) injection. Histological examination by TUNEL staining revealed that apoptosis was increased and pRb phosphorylation was inhibited. Thus, the systemic peptide delivery of p16 restores the hypophosphorylation of pRb and may be a useful tool for the treatment of bladder tumors.