Retrospective Investigation of Cutaneous Squamous Cell Carcinoma on the Lip Treated with Peplomycin Administered Through a Superficial Temporal Artery.

BACKGROUND: Continuous intra-arterial (IA) administration of peplomycin (PEP) through a tumor-feeding artery is one of the most effective treatments for cutaneous squamous cell carcinoma (cSCC) in cosmetic areas. PATIENTS AND METHODS: In order to determine the effective and safe dose of PEP and the curative rate of IA-PEP, we retrospectively investigated a case series of 24 patients with cSCC on the lips who were treated with IA-PEP. RESULTS: IA-PEP reduced the tumor mass in all 24 cases (100%). A complete response occurred in 17 patients (70.8%), and a partial response occurred in seven (29.2%). Moreover, 17 patients (70.8%) were cured, three patients developed cervical lymph node metastasis (12.5%), and four developed local recurrence (16.7%). Three out of the 24 patients developed interstitial pneumonia (12.5%). CONCLUSION: Low-dose IA-PEP administered through a superficial temporal artery was a highly effective treatment that achieved a curative response for 70.8% of patients with cSCC on the lips.

Immunomodulatory effects of peplomycin on immunosuppressive and cytotoxic cells in the lesional skin of cutaneous squamous cell carcinoma.

BACKGROUND: Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for cutaneous squamous cell carcinoma (SCC) on cosmetic areas. Although this reagent is useful for the treatment of SCC, its immunomodulatory effect on the tumor microenvironment is still unknown. OBJECTIVE/METHODS: In this study, we investigated the immunomodulatory effects of PEP on the tumor-infiltrating regulatory T cells and tumor-associated macrophages as well as CD8(+)TIA-1(+) cytotoxic T cells in the lesional skin of 5 patients with SCC on the lips. RESULTS: Our data suggest that, in addition to the direct antitumor effects, PEP decreased immunosuppressive cells and increased cytotoxic T lymphocytes at the tumor sites, which might maintain antitumor immune response against SCC.

Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients.

INTRODUCTION: Patients with muscle-invasive bladder cancer (MIBC) often undergo various preoperative treatments to improve survival; however, their efficacy and safety remain unclear. MATERIALS AND METHODS: The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC + R, n = 79). RESULTS: Pathological complete responses were observed in 17.6%, 22.0%, and 43.0% of patients in the SC, IAC, and IAC + R groups, respectively, with respective 5-year overall survival rates of 42.0%, 46.7%, and 50.3%. Multivariate analysis showed that successful IAC + R protocol administration was a significant predictor for survival (hazard ratio = 0.16, p = 0.028). The incidence of severe adverse events was higher in the IAC + R group (36.7%) than in the SC (9.8%) and IAC groups (16.0%). CONCLUSIONS: IAC + R was useful for patients with MIBC. Successful completion and optimal patient selection were important for this treatment strategy.

Two cases of retroperitoneal metastasis from a completely regressed burned-out testicular cancer.

INTRODUCTION: Primary extragonadal germ cell tumors (EGCT) are rare and it is still a matter of debate if they have to be considered as primary extragonadal issues or metastases from a primary testicular neoplasm. We describe two cases of the so-called burned-out seminoma, a primary testicular germ-cell tumor that spontaneously regressed after demonstration of retroperitoneal metastases. CASES PRESENTATION: Two patients (35 and 50 years old, respectively) presented with CT findings of retroperitoneal masses. In both cases physical examination of the testis was not suspicious, and only scrotal ultrasound (SUS) showed parenchymal alterations such as scarring, calcifications and nodular lesions. Left orchiectomy and chemotherapy were then performed in both cases. Currently, they are both free of disease. CONCLUSIONS: Although primary germ cell tumors may be of retroperitoneal origin, the likelihood of metastasis from a testicular primary origin should always be carefully considered in order to avoid misdiagnosis and to apply the best treatment schedule for the patients. Therefore, a testicular ultrasonography is mandatory in patients presenting CT findings of retroperitoneal adenopathy, even if patients are completely asymptomatic and their physical examination appears normal.

The effect of chemotherapy or radiotherapy on thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in cancer of the uterine cervix.

OBJECTIVE: Levels of 5-FU metabolic or related enzymes, particularly thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD), have been investigated in various cancer types, including uterine cervical cancer. Intratumoral TP levels have been reported to increase in response to several chemotherapeutic agents or irradiation in both xenografts and clinical studies. In cervical cancer, however, only a few studies about changes in TP and DPD expression associated with cancer treatment have been published. We evaluated the effect of chemotherapy and/or irradiation on TP and DPD expression in cervical squamous cell carcinoma. STUDY DESIGN: Of 27 patients in this study, 12 patients underwent neoadjuvant chemotherapy consisting of nedaplatin, ifosfamide, and/or peplomycin followed by radical surgery, and 15 patients underwent radiotherapy (n=8) or chemoradiotherapy with nedaplatin (n=7) as initial treatment. Tumor specimens were obtained from biopsies acquired before treatment and after administration of chemotherapy (2 weeks after the first and second cycles), and after irradiation with 10 Gy, 20 Gy, and 30 Gy. These specimens were used to measure TP and DPD levels by ELISA. RESULTS: In the 12 patients who received neoadjuvant chemotherapy, intratumoral TP and DPD levels did not change. In contrast, in the 15 patients who underwent radiotherapy or chemoradiotherapy with nedaplatin, TP or DPD expression appeared to be slightly increased or decreased, respectively, after irradiation with 20 Gy, and consequently the TP/DPD ratio was significantly higher after irradiation with 20 Gy than before irradiation. CONCLUSIONS: These results suggest a clinical advantage of chemoradiotherapy with capecitabine or doxyfluridine over radiotherapy alone via the elevation of the TP/DPD ratio in cervical squamous cell carcinoma. However, no advantage of combination chemotherapy with these 5-FU derivatives was demonstrated. Therefore, further evaluation with a larger number of patients or with other chemotherapeutic agents is required to confirm these observations.

Results of concomitant chemoradiation for cervical cancer using high dose rate intracavitary brachytherapy: study of JROSG (Japan Radiation Oncology Study Group).

The purpose of this study was to clarify outcome for concurrent chemoradiation (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized retrospective analysis of 226 patients treated with definitive CT-RT or radiotherapy alone (RT alone) in nine institutions between 2001 and 2003. External irradiation consisted of whole pelvic irradiation and pelvic side wall boost irradiation, using a central shield during the latter half of the treatment with the anteroposterior parallel opposing technique. The external beam irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy, platinum based drugs were used alone or in combination with other drugs such as 5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone, respectively. There was no significant difference between CT-RT and RT for overall survival and disease free survival. Univariate analysis suggested that loco-regional control was better with CT-RT, but multivariate analysis could not confirm this finding. Compared to RT alone, CT-RT caused significantly more acute and late complications. Thus, late complication (grade 3-4) free survival rate at 50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window with concomitant radiochemotherapy and HDR brachytherapy may be narrow, necessitating a close control of dose volume parameters and adherence to systems for dose prescription.

A successful IVF-pregnancy in a patient who underwent conservative surgery followed by a regimen of cisplatin, vinblastine and peplomycin to treat an advanced ovarian mixed germ cell tumour: a case report.

Mixed germ cell tumours of the ovary, one type of malignant ovarian germ cell tumours (MOGCTs), are rare gynaecologic cancers usually affecting young women. We report the case of a patient with an advanced ovarian mixed germ cell tumour who underwent fertility-saving surgery followed by a chemotherapy regimen of cisplatin, vinblastine and peplomycin. The patient was disease-free 8 years after initial presentation. She conceived and gestated dichorionic twins after IVF-embryo transfer. To the best of our knowledge, the patient is the first to be treated successfully with the combination chemotherapy regimen and then conceive safely using assisted reproductive technology (ART).

Granisetron reduces clinical and histological response to intra-arterial neoadjuvant chemotherapy in oral squamous cell carcinoma.

Intra-arterial neoadjuvant chemotherapy (TPP) with pirarubicin, cisplatin and peplomycin produced strong primary effects on oral squamous cell carcinoma, using metoclopramide (MCA) as an anti-emetic. After clinical application of granisetron (GRN), the clinical responses to TPP observed previously were weakened. In this paper, the influence of GRN on TPP is discussed. Sixty-three cases were evaluated with regard to the primary effects of TPP and anti-emetics. GRN was used in 42 cases of the GRN group, and MCA in 21 cases of non-GRN group. The clinical response rate (complete response, CR or partial response, PR) was 95.2% in the non-GRN group, and 76.2% in the GRN group. The rate of CR in the non-GRN group was 47.6%, whereas it was 9.5% in the GRN group. The histological effects in the GRN group were significantly lower (P<0.05) than those of non-GRN group. Concerning the relationship between the clinical responses and the histological responses, 4 of the 18 CR+PR cases (22.2%) in the GRN group showed good histological responses, compared with 6 of the 14 CR+PR cases (42.9%) showing in the non-GRN group. The histological responses in the GRN group were significantly lower (P<0.05) than in the non-GRN group. Our data indicate that GRN reduces the clinical and histological responses of chemotherapy.

Apoptosis in cervical cancer after balloon-occluded arterial infusion of anticancer drugs.

BACKGROUND: This study was designed to investigate the relationship between apoptosis and Bcl-2 and Bax expressions in uterine cervical cancer after balloon-occluded arterial infusion (BOAI). MATERIALS AND METHODS: Twenty-four specimens were obtained before and after BOAI. The occurrence of apoptosis was examined with molecular biochemical techniques. The expressions of Bcl-2 and Bax proteins were investigated by immunohistochemical staining. RESULTS: Labelling of DNA in situ indicated that apoptotic cells were sporadically seen before BOAI (6.1 +/- 1.9). Apoptotic cells apparently increased at 5 days (25.1 +/- 6.4) after BOAI The autoradiographic analysis revealed that the DNA-ladder was identified at 5 days after BOAI. Although Bcl-2 immuno-reactivity was faintly detected, the expression of Bax increased at 3 days (49.4 +/- 10.4%) after BOAI. CONCLUSION: The results indicated that treatment with BOAI resulted in transient increases of apoptosis in cervical cancer in association with the increased expression of Bax.

Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of the maxillary sinus.

OBJECTIVE: This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy. METHODS: A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients. RESULTS: The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P < 0.0001) and T classification (P < 0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P < 0.0005) and T classification (P < 0.05) were identified as significant prognostic factors for LCP and OAS. CONCLUSIONS: This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study.

Yolk sac tumor of the ovary during pregnancy: a case report.

BACKGROUND: There is a therapeutic dilemma for the pregnant patient with malignancy requiring chemotherapy. CASE: We had a case of a 30-year-old pregnant woman with a yolk sac tumor who underwent right salpingo-oophorectomy at 22 weeks gestation. Chemotherapy during pregnancy was postponed because of concern with the risks of the chemotherapy to the fetus. After the operation, L2 fraction of alpha-fetoprotein (AFP) depending on the affinity for Lens culinaris agglutinin (LCA) as an indicator for a maternal source of AFP had been detectable since 30 weeks gestation and elevated rapidly with advancing gestation. Tumor recurrence was confirmed clinically at 34 weeks gestation. She was induced, delivering a healthy baby, and received seven complete chemotherapy courses (cisplatin, etoposide, and peplomycin). Currently, the mother (39 months after last chemotherapy) and child are doing well. CONCLUSION: AFP-L2 may be a sensitive indicator for a yolk sac tumor derived AFP, leading to an earlier detection of tumor recurrence during pregnancy.

Expression of caveolin-1 and its correlation with cisplatin sensitivity in oral squamous cell carcinoma.

PURPOSE: Cisplatin (CDDP) is widely used for chemotherapy of oral squamous cell carcinoma (OSCC). However, the mechanism of resistance to CDDP is unclear. Recently, caveolin-1 was identified as being associated with both metastasis and multidrug resistance. In the present study, we showed that caveolin-1 expression is significantly related to chemosensitivity in OSCC. METHODS: We established a CDDP-resistant cell line, H-1R, from the parental OSCC cell line, H-1. Caveolin-1 expression was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) in both cell lines. We analyzed expression of caveolin-1 in 30 OSCC biopsy specimens and investigated the relationship between expression of caveolin-1 and patients' clinicopathological parameters and chemotherapeutic responses. RESULTS: The 3-(3,4-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that H-1R has a ten-times greater resistance to CDDP than H-1 has. The level of caveolin-1 expression in H-1R was significantly decreased in comparison with that in H-1 by real-time RT-PCR analysis. Positive caveolin-1 immunostaining correlated positively with a complete response (16/20, 80.0%). However, negative immunostaining was found in 6/7 (85.7%) cases with no response. Positive immunohistochemical staining of caveolin-1 correlated positively with chemosensitivity to CDDP-based combination chemotherapy (P=0.02). CONCLUSIONS: These results suggest that overexpression of the caveolin-1 gene may provide novel diagnostic markers associated with CDDP sensitivity in OSCC.

Radiotherapy for uterine cervical cancer: results of the 1995-1997 patterns of care process survey in Japan.

OBJECTIVE: The aim of this study is to establish Japanese national practice patterns for uterine cervical cancer patients who received radiotherapy without surgery. METHODS: The Japanese Patterns of Care Study (JPCS) conducted a national survey of 73 institutions using two-stage cluster sampling, and collected specific information on 591 patients with uterine cervical cancer treated by radiotherapy without planned surgery between 1995 and 1997. RESULTS: The median age of the patients was 70 years. Karnofsky performance status (KPS) was >/=90 for 37%. Most patients (95%) had histology of squamous cell carcinoma. Ten percent were stage I, 29% stage II, 48% stage III and 13% stage IVA. Photon beams of 10-14 MV were the most used for external beam radiotherapy (EBRT). The beam energy utilized varied significantly by institution strata. Midline block was used in approximately 70% of institutions. Intracavitary brachytherapy (ICBT) was performed in 77%. Institution strata correlated significantly with the ICBT application. The majority of patients (89%) were treated with high-dose-rate (HDR) ICBT. The median single point A dose of HDR-ICBT was 600 cGy. The median summated point A dose from EBRT and HDR-ICBT was 5800 cGy (range: 1196-8600). The median overall treatment time including ICBT was 49 days. Twenty-four percent of the patients received chemotherapy. Concurrent chemoradiation was performed in 5%. CONCLUSIONS: The JPCS established the Japanese national practice patterns of care for uterine cervical cancer patients treated with radiotherapy without planned surgery between 1995 and 1997. This survey demonstrated that the institutional strata significantly affected several practice patterns.

[A case of primary and solitary bone metastasis of testicular seminoma after orchiectomy].

A 40-year-old man with stage I left testicular seminoma who had been followed for 18 months after orchiectomy, complained of pain in his left upper extremity and dysbasia. Magnetic resonance imaging (MRI) and bone scintigraphy suggested multiple bone lesions in the thoracic vertebrae and right ischium, and bone biopsy revealed metastasis of seminoma. There was no evidence of other metastatic lesions. After he was treated with 2 courses of first-line chemotherapy consisting of peplomycin, etoposide, and cisplatin, which were followed by 2 courses of high-dose chemotherapy with carboplatin, etoposide, and ifosfamide, the metastatic lesions were nearly in complete response on MRI and bone scintigraphy and the result of fluorodeoxyglucose-positron emission tomography was negative, but the hCG-beta level remained slightly elevated. In most advanced testicular tumors, bone metastasis usually coexists with other metastatic lesions and appears as a secondary lesion. Herein, we report this rare case of primary and solitary bone metastasis from testicular seminoma after orchiectomy.

Neoadjuvant high-dose intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration in patients with stages IIIa-IVa cervical cancer.

OBJECTIVE: The objective of this study was to evaluate the response rate and survival of patients with locally advanced uterine cervical cancer who were treated with intraarterial infusion chemotherapy under percutaneous pelvic perfusion with extracorporeal chemofiltration (PPPEC). METHODS: Twenty-three untreated patients with stages IIIa-IVa cervical cancer were enrolled in the study. PPPEC was administered twice at 2 weeks interval using high-dose cisplatin alone (140-250 mg/m(2)) or high-dose cisplatin plus mitomycin C (7 mg/m(2)), pepleomycin (7 mg/m(2)) and 5-fluorouracil (700 mg/m(2)). Eighteen patients in whom the tumor downstaging was confirmed underwent radical surgery following PPPEC, whereas in the remaining five patients, radiotherapy was administered. RESULTS: Two weeks after the second PPPEC, the median volumetric tumor reduction and tumor response were 76% and 87%, respectively. Histologic response was 96%, while the tumor downstaging reached 83%. The curative surgery rate achieved was 89%. Five-year progression-free survival was 47% and 5-year survival rate was 74%. CONCLUSION: High-dose intraarterial infusion chemotherapy under PPPEC effectively achieved tumor downstaging and resulted in the favorable performance of the subsequent radical surgery and improved the 5-year survival rate of patients with locally advanced uterine cervical cancer.

[Clinical practice of 99mTc-peplimycin imaging and radio guided surgery for lung neoplasms].

BACKGROUND & OBJECTIVE: Intraoperatively,the routine method to differentiate malignant lung neoplasms from benign lesions is by the judgment of naked eye or frozen section. It is not accurate to judge by naked eye and will take long time by frozen section. Using a gamma-detecting probe (GDP) to accurately detect the tumors and the metastases, the operators could decide the resection range and the treatment plan. This study was preliminary clinical practice of tumor imaging and radioimmunoguided surgery (RGS) using (99m)Tc-PPM (peplomycin) as a tumor tracer. METHODS: Thirty-seven patients were administered with injection of (99m)Tc-PPM. The images were taken preoperatively. Region of interest (ROI) method was performed and tumor-to- normal-tissue (T/NT) ratio was calculated on the image. The radioactivity of the specimens resected from the patients was detected using GDP at the time of surgery. T/NT ratio was obtained by comparing the radioactivity of the tumor tissue with the normal lung tissue. RESULTS: The uptake ratios (T/NT) of (99m)Tc-PPM were different between malignant and benign lesion (P< 0.01). The ratio (T/NT, x+/-2s) was regarded as the threshold for differentiation of malignant and benign lesions. The sensitivity, specificity, and accuracy of identifying malignant lesion were 90%, 87.5%, and 89.3%, respectively; GDP could be used to accurately detect the invasive range of the tumors, with the sensitivity, specificity, and accuracy of identifying lymph node metastases of 91%, 88%, and 90%, respectively. CONCLUSION: (99m)Tc-PPM is a useful agent in differentiating malignant lung neoplasm from benign lesions, and as a tumor tracer can be used in detecting tumor by GDP intraoperatively. The RGS is a simple method that can help the surgeon in the intraoperative assessment of the tumor and the lymph node metastases.

[Neoadjuvant intraarterial chemotherapy with nedaplatin, peplomycin and mitomycin C for advanced cervical cancer].

The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.

[A case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with radical chemoradiotherapy].

We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a 46-year-old man. Clinical staging was T3bN2M0. The patient received 50 Gy external radiation combined with intraarterial and systemic chemotherapy. Pathological complete response was found both in bladder and regional lymph nodes when he underwent radical cystectomy and lymph node dissection. The patient has been alive without evidence of disease for two years postoperatively.

Dysgerminoma in a patient with a tumor of the neck. Empiric treatment of stage IV dysgerminoma.

The evolution of therapy for malignant ovarian germ cell tumors is one of the true success stories in oncology. Treatment outcome has improved greatly thanks to cisplatin-based combination chemotherapy. According to the well-established treatment guidelines for advanced cases, we treated a case of stage IV undifferentiated germ cell tumor in which we were able to preserve the patient's fertility. We concluded that the PEP regimen is an effective treatment for the patient with metastatic germ cell tumor.

Blood flow after intraarterial infusion chemotherapy in a patient with advanced cervical cancer.

We presented a case of locally advanced cervical cancer treated by intraarterial infusion chemotherapy, and evaluated the blood flow of uterine arteries before and after chemotherapy by using a transvaginal ultrasonic color Doppler device. Pulsatility index (PI) of each uterine artery increased after first course of chemotherapy compared to that of before chemotherapy. But PI did not change after second course in spite of a significant reduction in tumor size. Blood flow change assessed by Doppler ultrasound may be a limited but useful parameter for the efficacy of neoadjuvant chemotherapy in patients with cervical cancer.