Gene therapy for ovarian cancer using carbonyl reductase 1 DNA with a polyamidoamine dendrimer in mouse models.

Ovarian cancer (OC) in which carbonyl reductase 1 (CBR1) is highly expressed has good prognosis. The aims of this study were to determine the optimal conditions for delivering CBR1 DNA to OC cells via a polyamidoamine (PAMAM) dendrimer and to examine the therapeutic effectiveness of using a CBR1/PAMAM dendrimer to treat OC. The ratio for mixture of the PAMAM dendrimer and CBR1 plasmid DNA was defined as the ratio of the number of moles of phosphate groups in plasmid DNA to the number of moles of amino groups in PAMAM, which was expressed as N/P ratio. Mice were intraperitoneally injected with OC cells (HRA) to create peritoneal carcinomatosis. CBR1 DNA/PAMAM dendrimer complexes were administered on alternate days after injection of HRA cells. Cells transfected with CBR1 DNA at N/P ratio of 20:1 for 48 h produced the highest level of CBR1 expression. All the mice in control group died prior to day 25. However, all the mice administered the CBR1 DNA/PAMAM dendrimer survived (P<0.001). Use of a PAMAM dendrimer allowed CBR1 DNA to be delivered to cancer cells. The results suggested that CBR1 DNA/PAMAM dendrimer complexes may represent a potent gene therapy for the treatment of advanced OC.

A case of ovarian small cell carcinoma of the pulmonary type that was observed as it developed.

INTRODUCTION: In the case reported here, the authors observed ovarian small cell carcinoma of the pulmonary type as it developed. CASE: The patient was a 48-year-old woman who underwent a hysterectomy for CIN3 in 2007. A year later, the woman underwent screening for ovarian cancer. A gradually growing ovarian mass was noted. This mass was found to be a mixed tumor. This mixed tumor grew to 36 mm in size, and six months later it had enlarged to 119 mm. After surgery, the tumor was pathologically diagnosed as an ovarian small cell carcinoma of the pulmonary type with a neuroendocrine nature that was positive for CD56 and synaptophysin. Postoperatively, the patient received six courses of combined therapy with irinotecan and cisplatin (CPT-P therapy), and the patient has survived disease- free for over two years. CONCLUSION: Findings suggested that ovarian small cell carcinoma of the pulmonary type is a type I ovarian malignancy that develops through an adenoma-carcinoma sequence.

Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis.

UNLABELLED: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. INTRODUCTION: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. METHODS: Ambulatory patients aged ≥ 55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. RESULTS: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was -0.23 % (95 % CI -0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = -1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. CONCLUSIONS: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis.

Efficacy of combined treatment with alendronate (ALN) and eldecalcitol, a new active vitamin D analog, compared to that of concomitant ALN, vitamin D plus calcium treatment in Japanese patients with primary osteoporosis.

UNLABELLED: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. INTRODUCTION: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). METHODS: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. RESULTS: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18% in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. CONCLUSION: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium.

Smoking habits in relation to reproductive events among Japanese women: findings of the Japanese Nurses' Health Study.

OBJECTIVE: The purposes of this study were to examine smoking habits in relation to the reproductive events of pregnancy and menopause and clarify the reasons for smoking cessation among ex-smokers. METHOD: This is a cross-sectional study based on a baseline survey of a prospective cohort study. From 2001 to 2007, a self-administered questionnaire survey was conducted on 49,927 female nurses from all 47 prefectures in Japan. Logistic regression models were used to estimate age-adjusted odds ratios. RESULTS: Of the respondents, 17.2% were current smokers, 11.6% were ex-smokers and 69.8% had never smoked. The prevalence of smoking during pregnancy was 7.8%. Among ex-smokers, 30.3% gave "reproductive events" as their reason for smoking cessation. Current smoking and the number of cigarettes smoked per day before menopause were significantly related to onset of menopause. CONCLUSION: Women's smoking habits have mutual relationships with reproductive events such as pregnancy and menopause. Although "reproductive events" were an important reason for smoking cessation among women, 7.8% of women still smoked during pregnancy. Smoking was correlated with onset of menopause. Support for smoking cessation is an important healthcare issue throughout women's lifetimes.

Impact of rewarming preservation by continuous machine perfusion: improved post-transplant recovery in pigs.

BACKGROUND: Utilization of grafts from donors after cardiac death (DCD) greatly expands the organ pool. However, implementation of such a strategy requires the development of novel preservation methods to achieve recovery from changes owing to warm ischemia. METHODS: To assess potential methods, porcine livers harvested after 60 minutes of warm ischemic time (WIT) were perfused and preserved under the following conditions: Group 1 (n = 3), 2-hour simple cold storage and 2-hour machine perfusion (MP) at 8°C; group 2 (n = 3), 2 hours at 25°C and MP at 25°C and group 3 (n = 3), 2-hour simple cold storage and gradual rewarming to 25°C by MP. The preserved liver grafts were transplanted orthotopically into recipients. RESULTS: The aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hyaluronic acid (HA) levels in recipient blood at 2 hours after reperfusion were significantly lower among group 3: AST, 789 ± 258.8, 1203 ± 217.0, and 421 ± 55.8 IU/L; LDH, 1417 ± 671.2, 2132 ± 483.9, and 634 ± 263.9 IU/L; and HA, 1660 ± 556.5, 1463 ± 332.3, and 575 ± 239.0 ng/mL for groups 1, 2 and 3, respectively. Histologically, necrosis and swelling of hepatocytes were less severe among group 3 than groups 1 and 2. Group 3 animals showed better vital responses and started spontaneous breathing within 2 hours after reperfusion; 1 recipient survived for >24 hours, although all animals in groups 1 and 2 died within 2 to 3 hours after reperfusion. CONCLUSION: Rewarming by MP preservation may facilitate recovery and resuscitation of DCD liver grafts.

Temperature controlled machine perfusion system for liver.

Organ preservation using machine perfusion is an effective method compared with conventional preservation techniques using static cold storage. A newly developed MP preservation system to control perfusate temperatures from hypothermic to subnormothermic conditions is introduced. This system is useful not only for liver preservation, but also for evaluation of graft viability for recovery. This novel method has been proposed for preservation of porcine liver grafts. An innovative preservation system is especially important to obtain viable organs from extended criteria or donation after cardiac death donors. In this study, we introduce a new machine perfusion preservation system (NES-01) to evaluate graft viability for recovery of liver functions, using porcine grafts.

A basic consideration for porcine liver preservation using a novel continuous machine perfusion device.

INTRODUCTION: The aims of this study were to compare extracellular and intracellular-type University of Wisconsin (UW) solutions for liver grafts and to assess oxygenation in this perfusion system. MATERIALS AND METHODS: The organ preservation system consisted of 3 circulating systems for the portal vein, hepatic artery, and maintenance of the perfusion solution. The portal vein or hepatic artery system had a roller pump, a flow meter, and a pressure sensor. In this study, we perfused livers with UW or extracellular type UW-gluconate at 4°C-6°C for 4 hours. The flow rates at the entrance were 0.5 mL/min/g liver in the portal vein and 0.2 mL/min/liver in the hepatic artery. Orthotopic liver transplantation was performed in pigs: group 1-a, grafts procured after acute hemorrhagic shock were preserved by a solution without O(2); group 1-b, grafts were preserved with O(2); group 2-a, grafts were perfused using intracellular type solution (UW); and group 2-b, grafts were perfused using extracellular-type solution (UW-gluconate). RESULTS: Effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in group 1-b were lower than those in group 1-a. Survival rates in group 2-a and group 2-b were 1/4 and 3/3, respectively. Effluent AST and LDH levels in the perfusate of group 2-b were lower than group 2-a. Histological study revealed necrosis of hepatocytes and sinusoidal congestion in group 2-a. CONCLUSION: A beneficial effect of extracellular-type solution with oxygenation in a novel continuous machine preservation system yielded well-preserved liver graft function.

Functional recovery of donation after cardiac death liver graft by continuous machine perfusion preservation in pigs.

INTRODUCTION: Grafts from donation after cardiac death (DCD) will greatly contribute to the expand the donor pool. However, these grafts may require the development of the preservation methods because of primary nonfunction and severe ischemic bile duct injury. METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. Each system for the portal vein or the hepatic artery had a roller pump, a flow meter, and a pressure sensor. The livers were perfused with University of Wisconsin (UW)-gluconate at 4°C-6°C for 3 hours after 2 hours simple cold storage (CS). The portal vein flow rate was 0.5 mL/min/g liver (pressure, 10 mm Hg) and the hepatic artery flow rate was 0.2 mL/min/g liver (pressure, 30 mm Hg). Orthotopic liver transplantation was performed in pigs comparing Group 1 (n = 4) procured after acute hemorrhagic shock preserved by MP, Group 2 (n = 3) procured after warm ischemia time (WIT) of 30 minutes with CS preservation, and Group 3 (n = 4) procured with 30 minutes of WIT and MP preservation. RESULTS: Collected effluent aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the perfusion solution and serum AST and LDH were significantly lower in Group 1. AST and LDH results were lower in Group 3 than Group 2. Survival rates in Groups 1 and 3 were 3/4, but 0/3 in Group 2. CONCLUSION: MP preservation was a useful promising preservation mode for DCD liver grafts.

Pretransplant screening and evaluation of liver graft viability using machine perfusion preservation in porcine transplantation.

A novel method using machine perfusion for pretransplant screening and evaluation of the viability of liver grafts has been proposed, seeking to prevent severe ischemia-reperfusion injury and to reduce the risk of primary graft nonfunction. This study sought to evaluate the viability of critical grafts, which were obtained from expanded criteria donors or donation after cardiac death donors during preservation with a new machine preservation perfusion system (NES-01). The normalized pressure transition in the hepatic artery was employed as an evaluation index for liver viability. As a result, the normalized pressure (p/p(0)) in the hepatic artery showed a distinctive transition under each experimental conditions controlled by warm ischemic time (WIT). The high viability graft, obtained under the condition of WIT as 0 minutes (WIT0), showed a quick response to hepatic artery pressure after initiating perfusion, whereas the normalized pressure showed a sudden decrease. In contrast, the normalized pressure among WIT60, which may cause the graft to lose viability, showed a poor hepatic artery response. These findings corresponded to the cumulative release of enzymes. The findings of our study suggest that monitoring of the pressure drop rate in the hepatic artery during machine perfusion can be used to evaluate liver graft viability.

Efficacy and safety of monthly oral minodronate in patients with involutional osteoporosis.

UNLABELLED: Monthly minodronate at 30 or 50 mg had similar efficacy as 1 mg daily in terms of change in bone mineral density (BMD) and bone turnover markers with similar safety profiles. This new regimen provides patients with a new option for taking minodronate. INTRODUCTION: Minodronate at a daily oral dose of 1 mg has been proven to have antivertebral fracture efficacy. In the present study, the efficacy and safety of oral minodronate at monthly doses of either 30 mg or 50 mg were compared with a daily dose of 1 mg. METHODS: A total of 692 patients with involutional osteoporosis were randomized to receive minodronate at either 30 or 50 mg monthly or a daily dose of 1 mg. The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at 12 months. Total hip BMD, bone turnover markers, serum calcium (Ca), and parathyroid hormone (PTH) levels were also evaluated. RESULTS: Minodronate at monthly doses of 30 or 50 mg were noninferior to the 1 mg daily dose in terms of change in LS-BMD. Changes in total hip BMD were also comparable. Although a transient decrease in serum Ca and increase in PTH levels were observed in all three groups at slightly different magnitudes and time courses, changes in bone turnover markers were comparable among the different dosage groups with a similar time course. Safety profiles were also comparable. CONCLUSION: Minodronate at monthly doses of 30 or 50 mg has similar efficacy to the daily 1 mg dose in terms of BMD and bone turnover markers with similar tolerability.

A case of granulosa cell tumor of the ovary detected from metastatic foci.

The authors report a case of granulosa cell tumor of the ovary that followed a rare clinical course, where the primary focus did not appear as a mass, and disseminated foci grew in the abdominal cavity. In 2008, a 70-year-old patient, gravida 6 and para 3, was diagnosed with a perihepatic mass, peritoneal dissemination, and an abdominal wall mass as confirmed by computed tomography (CT) scanning. There was no mass lesion in the pelvis. The pathological diagnosis based on the resected mass in the abdominal wall was malignant mesothelioma. During follow-up, abdominal bloating developed from April 2009. CT scans indicated growth of the intraperitoneal lesions. Therefore, the patient received two cycles of combination therapy with cisplatin and pemetrexed. The treatment was discontinued due to lack of efficacy. The intraperitoneal lesions grew but the clinical course was slow and inconsistent with that of malignant mesothelioma. Central pathological review was requested in April 2011, and a granulosa cell tumor was diagnosed. The patient was referred to the department for detailed examination and treatment. The patient underwent incision of the intraperitoneal tumors, simple total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The final pathological diagnosis was normal-size adult-type granulosa cell tumor originating from the left ovary. It was a case of granulosa cell tumor without ovarian enlargement where growth of the metastatic foci was the major observation. As complete surgical resection was achieved and no additional therapy was given, the subject was followed on an outpatient basis and no recurrence was identified.

Can malignant transformation in mature cystic teratoma be preoperatively predicted?

PURPOSE OF INVESTIGATION: The study aimed to determine whether malignant transformation of mature cystic teratoma (MCT) can be preoperatively predicted by presenting two cases of MCT with malignant transformation and comparing their clinical factors with those of benign MCT encountered at around the same time. MATERIALS AND METHODS: Age, maximum tumor diameter, tumor marker levels (serum squamous cell carcinoma (SCC) and carbohydrate antigen (CA) 19-9, the presence of solid tumor masses, and the presence or absence of contrast enhancement in pelvic magnetic resonance imaging (MRI) were investigated in two cases of MCT with malignant transformation and 76 cases of benign MCT in which surgery was performed and a pathological diagnosis given by the department from 2004 to 2010. RESULTS: The mean ages of the two cases with malignant transformation and the cases of benign MCT were 42.5 years and 34.2 years, respectively. The mean maximum diameter of the two tumors with malignant transformation and the cases of benign MCT were 130 mm and 73.6 mm, respectively. The mean serum levels of SCC in the two cases with malignant transformation and the cases of benign MCT were 31.5 ng/ml and 0.92 ng/ml, respectively. Contrast enhancement and the presence of solid masses in images of MCT with malignant transformation were apparent. CONCLUSION: In order to accurately detect malignant transformation of MCT, the authors found it to be important to determine whether tumors larger than 100 mm in diameter were present and to check for the presence of solid masses enhanced in pelvic MRI examination, as well as to measure at least serum SCC and CA19-9 even in relatively young patients.

Clinical usefulness of a low-dose maintenance therapy with transdermal estradiol gel in Japanese women with estrogen deficiency symptoms.

OBJECTIVES: To determine the efficacy and safety of low-dose maintenance therapy with transdermal estradiol (E2) gel in Japanese women with climacteric disorder and estrogen deficiency symptoms. METHODS: Women (n = 209) aged 37-59 years who had climacteric disorder or estrogen deficiency symptoms received a standard dose of transdermal E2 gel (1.8 g/day, containing E2 1.08 mg/day) for 8 weeks as induction treatment. A total of 177 women in whom the number of daily hot flushes had decreased to less than one-third of the baseline value (marked improvement) at week 8 were double-blindly randomized to receive low-dose E2 (n = 88, 0.9 g/day, containing E2 0.54 mg/day) or E2-free placebo (n = 89) for 16 weeks. RESULTS: Improvement rates in the number of daily hot flushes at the final evaluation (primary endpoint) in the low-dose E2 group (marked 90.8%, moderate 6.9%, mild 1.1%, no change 1.1%, worsening 0%) were significantly greater than in the placebo group (marked 77.0%, moderate 10.3%, mild 4.6%, no change 2.3%, worsening 5.7%) (p = 0.0097), showing an inhibitive effect on the flare-up of climacteric symptoms. The incidence of treatment-related adverse events in the low-dose group (21.6%) was similar to that in the placebo (22.5%) but was lower than that in the standard-dose treatment (32.5%). CONCLUSIONS: Low-dose maintenance therapy that was half the standard dose of transdermal E2 gel (0.9 g/day) applied to women who had achieved marked improvement in the number of hot flushes at the standard dose (1.8 g/day) was demonstrated to be effective (inhibition of recurrence) and safe for the treatment of climacteric disorder and estrogen deficiency symptoms.

Presentation of a patient with pT2bN1M0 small cell carcinoma of the uterine cervix who obtained long-term survival with maintenance chemotherapy, and literature-based discussion.

BACKGROUND: Small cell carcinoma of the uterine cervix is a rare cervical carcinoma that advances early and is associated with a poor prognosis. We present a case of this disease which invaded the parametrium and metastasized to the pelvic lymph node. The patient underwent postoperative concurrent chemoradiotherapy (CCRT) followed by maintenance chemotherapy and obtained long-term survival. CASE: A 26-year-old patient, who had conceived on two occasions without giving birth and had smoked for ten years, underwent radical hysterectomy with a diagnosis of Stage Ibl cervical carcinoma in December 2006. The patient showed parametrial invasion, and metastasis to the left external iliac node and vaginal stump. With a diagnosis of pT2bN1M0, the patient underwent CCRT with weekly nedaplatin as postoperative therapy. For the maintenance chemotherapy, from May 2007, ten courses of PE therapy (CDDP, 15 mg/body; VP-16, 100 mg/body x 3) were performed. No recurrent signs have been observed for 39 months after the first operation. CONCLUSION: PE therapy may be useful as maintenance therapy, although there are no established treatments for small cell carcinoma of the uterine cervix.

Hypercholesterolemia accelerates bone loss in postmenopausal women.

OBJECTIVES: To clarify the effect of lipid profiles on postmenopausal bone loss using a longitudinal method and to determine whether cytokines are involved in bone loss. METHODS: The subjects were Japanese residents participating in the Iwaki Health Promotion Projects. Women with one or more of the following factors were excluded: a history of surgical menopause, current or past users of bisphosphonates or current user of other drugs known to influence bone and lipid metabolism, and current medication for diabetes or hypertension. Consequently, 99 postmenopausal women (61.2 ± 7.7 years old) and 85 premenopausal women (41.2 ± 8.6 years old) were selected for this study. The osteo-sono-assessment index (OSI) of the left calcaneal bone was obtained twice at 1-year intervals and the annual percentage change in OSI was calculated. Serum total cholesterol, high and low density lipoprotein cholesterol, triglycerides, homocysteine and cytokines such as adipocytokines, interleukins and tumor necrosis factor-α were measured. Postmenopausal women were grouped into three groups according to their basal cholesterol level, and the relationship between basal cholesterol level and annual change in OSI was studied. RESULTS: The annual percentage change in OSI in postmenopausal women with a serum total cholesterol level ≥240 mg/dl was significantly higher compared to those with a normal total cholesterol level, suggesting that hypercholesterolemia accelerates postmenopausal bone loss. No significant differences were seen in any of the cytokines that presumably cause bone resorption. CONCLUSION: These results showed that hypercholesterolemia has an inverse effect on bone loss independent of cytokines presumed to mediate bone loss.

Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers.

PURPOSE: Photodynamic therapy (PDT) is a new approach to cancer treatment that utilizes photochemical reactions induced by a combination of an oncophilic photosensitizing agent and laser light. With an aim to apply PDT for intraperitoneal disseminated foci of advanced or recurrent ovarian cancers, the present study was conducted to evaluate the antitumor effect of PDT using a methyl ester of 5-aminolevulinic acid (Methyl-ALA) on various types of human ovarian cancer in a subcutaneous xenograft model in nude mice and to elucidate the mechanism of its antitumor effect. METHODS: HTOA, MCAS, and TOV21G cell lines derived from human ovarian serous, mucinous, and clear cell adenocarcinoma, respectively, were used in this study. The mice in the treatment group and in the control group received an intraperitoneal injection of 250 mg/kg of Methyl-ALA and PBS alone, respectively. PDT was administered by 10 min irradiation using a 150 W halogen light, 3 h after Methyl-ALA or PBS injection. Each mouse received PDT twice a week for 3 weeks. RESULTS: Methyl-ALA-PDT significantly suppressed the growth of HTOA tumors as compared to control, whereas there was no significant effect on the growth of MCAS or TOV21G tumors. Methyl-ALA-PDT significantly increased apoptosis in implanted HTOA tumors as well as cultured cells. Western blot analysis showed that amount of expression of milk fat globule-EGF-factor 8, which binds to apoptotic cells and thereby facilitates their phagocytosis, significantly increased in HTOA tumors receiving Methyl-ALA-PDT, compared with untreated HTOA tumors. In addition, reduced vascular endothelial growth factor and CD34-positive microvessel density were found in solid HTOA tumors treated by Methyl-ALA-PDT, suggesting that the antitumor effect of Methyl-ALA-PDT is due to induction of apoptosis and reduction of angiogenesis. In comparison with HTOA cells, HPLC analysis demonstrated a significantly smaller intracellular amount of protoporphyrin IX (PpIX) in MCAS and TOV21G cells. PpIX is readily converted from Methyl-ALA and elicts photocytotoxicity. CONCLUSION: We conclude that Methyl-ALA-PDT could be an effective treatment in ovarian cancer and should be tested to apply intraperitoneally disseminated micro-foci during surgery.

A case of recurrent yolk sac tumor as spindle cell sarcoma of the abdominal wall.

Few studies report on tissue morphology in recurrence of yolk sac tumor. The case of the recurrence of a yolk sac tumor as a spindle cell sarcoma of the abdominal wall is presented. A 27-year-old woman was referred to our hospital due to suspicion of an ovarian tumor. Right salpingo-oophorectomy, partial omentectomy, and extirpation of disseminated foci as fertility-preserving surgery was done since the intraoperative pathological diagnosis was yolk sac tumor. Final pathological examination showed a germ cell tumor of which yolk sac tumor formed the major component including a small area that appeared to be immature nerve tissue. Although residual tumor was not less than 1 cm, clinical complete remission was reached after the sixth course of BEP regimen. However, the recurrence of a yolk sac tumor as an unclassified spindle cell sarcoma of the abdominal wall was found about two years after the initial surgery. Thereafter, the patient expired due to progression of the intraperitoneal disseminated lesions. The mesenchyme-like component of the yolk sac tumor is characterized by spindle cells originating from epithelial elements, and is likely to give rise to a chemoresistant, diversely differentiated sarcoma. This report suggests that the sarcoma reported in the case here also arose when spindle cells of the mesenchyme-like component underwent sarcomatous change during or after chemotherapy, subsequently relapsed as a chemoresistant tumor, and metastasized.