Carboplatin chemotherapy in a pregnant patient with undifferentiated ovarian carcinoma: case report and review of the literature.

There are already 12 reports of women treated by chemotherapy for epithelial ovarian cancer during pregnancy. However, most cases received chemotherapy of single cisplatin or cisplatin-based regime, and only four cases received carboplatin-containing chemotherapy. We report the case of a woman treated with single-agent carboplatin during pregnancy. The patient underwent bilateral salpingo-oophorectomy at 18 weeks of gestation and was diagnosed as having stage IC undifferentiated ovarian carcinoma. She was treated with four courses of carboplatin (area under the curve = 6.0) chemotherapy during pregnancy without severe toxicity. At 33 weeks of gestation, cesarean section was performed, followed by total hysterectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. No residual disease was histologically shown. The patient underwent additional chemotherapy with carboplatin and paclitaxel. After one year of follow-up, the baby shows normal growth and the patient has no evidence of disease. Postponing the termination of pregnancy by single-agent carboplatin chemotherapy during pregnancy might be considered as an option for therapy in selected women with ovarian malignancies.

What is the best method of detecting endometrial cancer in outpatients?-endometrial sampling, suction curettage, endometrial cytology.

OBJECTIVE: Office methods of endometrial sampling for outpatients with abnormal uterine bleeding should be minimally invasive. The purpose of this study was to determine the best method for detecting endometrial cancer in an outpatients setting. METHODS: In all, 114 symptomatic women who were suspected of having endometrial disease by their local gynaecologist were enrolled in this study. After pelvic examination and transvaginal ultrasonography, endometrial cytology, suction endometrial curettage, and four-site endometrial biopsy were performed, in this order without anaesthesia in each patient. After endometrial sampling, the patient was asked to comment on the intensity of any pain experienced during each procedure. Then the final histological diagnosis made from the surgical materials was compared with the results of the three pre-operative methods. RESULTS: Among the 114 consecutive patients, 56 had endometrial carcinoma, three had carcinosarcoma, six had endometrial hyperplasia, and 49 had benign conditions. The sensitivity of detecting malignancy was 88% (52/59) with endometrial cytology, 92% (54/59) with suction curettage, and 88% (52/59) with four-site biopsy. When endometrial cytology was combined with suction curettage, the sensitivity of detecting malignancy was increased from 92% to 98%, whereas the sensitivity was increased from 88% to 97%, when endometrial cytology was added to four-site biopsy. Suction curettage was significantly less painful than four-site biopsy. CONCLUSION: Our data indicated that suction curettage plus endometrial cytology was the best combination for pathological examination of outpatients with abnormal uterine bleeding.

Development of a cancer vaccine: peptides, proteins, and DNA.

Genetic changes leading to protooncogene activation qualitatively and/or quantitatively alter their gene products and are exclusively or largely restricted to transforming cells and their precursors. The overexpression of HER2 is among those changes and is often detected in adenocarcinomas such as breast, ovarian, lung, and gastric cancer. This provides a rationale for exploring the possibility that HER2 is a target of host immune responses against cancer cells. We have recently demonstrated that HER2 can be a target for tumor-rejecting immune responses against syngeneic murine HER2+ tumor cells. We defined two different peptides, HER2p63-71 and HER2p780-788, with a Kd anchor motif that can induce CD8+ cytotoxic T lymphocytes (CTLs). The growth of HER2+ syngeneic tumors was suppressed in mice immunized with HER2p63-71 or p780-788. Since murine Kd and human HLA-A24 share a similar anchor motif for peptides, HER2p63 71 and HER2p780-788 were examined for induction of CTLs in HLA-A24+ individuals. CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner. To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue. We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. We designed a simple protein delivery system: cholesteryl group-bearing polysaccharides, mannan or pullulan (CHM or CHP, respectively), complexed with the truncated HER2 protein containing the 147 N-terminal amino acids. These complexes were able to induce CD8+ CTLs against HER2+ tumors. CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen. The complete rejection of tumors also occurred when CHM-HER2 was applied early after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that this unique hydrophobized polysaccharide may help soluble proteins to induce cellular immunity. Such a novel vaccine may be of potential benefit in cancer prevention and cancer therapy.

Effect of aphidicolin on DNA synthesis in cultured human thyroid cells.

To investigate whether partial inhibition of DNA synthesis affects the growth of thyroid cells, human thyroid cells were cultured in the presence of aphidicolin for 24h. After removal of aphidicolin, the growth of thyroid cells was evaluated by [3H] thymidine uptake and analysis of cell cycle by flow cytometry. In Graves' thyroid cells, [3H] thymidine uptake and the percentage of cells in S+G2/M phase increased during 24 hours after washout of aphidicolin, whereas those were not augmented in normal thyroid cells. Thus, the acceleration of DNA synthesis occurred after the partial inhibition of it by aphidicolin in Graves' thyroid cells, but not in the normal thyroid cells. This phenomenon might, at least in part, explain the difference of growth regulation between Graves' and normal thyroid cells.

Changes of hemostatic molecular markers after gynecological surgery.

The authors evaluated the hemostatic abnormalities occurring in the postoperative period of eight patients with malignant tumors and compared them with those occurring in the postoperative period of eight patients with benign tumors. Two of the patients with malignant tumor presented pulmonary embolism after operation. Plasma fibrinogen and fibrin degradation product levels in patients with malignant tumors were already high before operation and further increased significantly after operation. The plasma levels of D-dimer, thrombin-antithrombin complex, and free-tissue factor pathway inhibitor were increased in both groups after operation, but they were higher in patients with malignant tumors than in patients with benign tumors. The plasma levels of protein C and antithrombin were significantly decreased in both groups after operation. but they were significantly lower in patients with malignant tumors than in those with benign tumors. The decreased activity of protein C or antithrombin may be not only a risk factor of thrombotic disease, such as pulmonary embolism, but also the cause of thrombosis. In patients with malignant tumors, the operation time was significantly longer than that in patients with benign tumors. This long operative period might cause vascular endothelial cell injury which is reflected by the plasma levels of free-tissue factor pathway inhibitor, antithrombin, and protein C.

Wegener's granulomatosis in a patient with a rheumatoid arthritis.

A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone.

Analysis of meat pigments with tissue spectrophotometer TS-200.

The colour of meat and rice flour pastes containing known amounts of myoglobin and the colour of intact beef and pork samples were analyzed with tissue spectrophotometer TS-200. The differences in the spectra of myoglobin among three types of derivatives were successfully distinguished with this instrument. In addition, there is a close relationship between I(HB) value, a parameter for estimating the content of pigments in animal tissues, and myoglobin content in model systems (rice flour paste and meat paste). Especially, the I(HB) value is proportional to myoglobin content in intact beef and pork meat whose myoglobin is mostly in the state of oxymyoglobin and/or deoxymyoglobin: y = 208·26 x + 6·72, where y is the I(HB) value, x is the myoglobin content (%) and r = 0·94.

[Serial cerebral computed tomography and magnetic resonance imaging in a case of hemolytic uremic syndrome with the complication of the central nervous system due to Escherichia coli O157:H7].

We report serial cerebral computed tomography (CT) and magnetic resonance imaging (MRI) in a case of hemolytic uremic syndrome (HUS) with the complication of the central nervous system due to Escherichia coli O157:H7. Although initial brain CT was normal, follow-up CT and MRI revealed lesions in the white matter and bilateral basal ganglia, representing brain edema and infarcts, respectively. Especially, lesions in the bilateral basal ganglia were very unique. Serial CT and MRI findings are useful to understand the mechanism of the complications of the central nervous system associated with HUS.

[A case of pulmonary metastasis of ovarian leiomyosarcoma responsive to CTP therapy].

One case of pulmonary metastasis of leiomyosarcoma responsive to CTP therapy was reported. The patient was a 44-year-old woman who had undergone total simple hysterectomy for uterine myoma 6 years before. Five years after the operation she underwent ovariectomy for ovarian tumor. Based on the histopathological findings, she was diagnosed to have leiomyosarcoma. One year later the patient was referred to use because of pulmonary metastasis. After admission to our hospital CTP therapy was started. Disappearance of the metastatic lesion was demonstrated by the chest X-ray findings at the end of five courses of treatment.

[Effects of combination chemotherapy using 5-FU, leucovorin, and CDDP (FLP therapy) for noncurative resected or recurrent stomach cancer in outpatients].

We performed combination chemotherapy consisting of 5-FU, leucovorin, and CDDP (FLP therapy) against noncurative resected or recurrent stomach cancer in outpatients as of August 1991. Seventeen outpatients patients underwent FLP therapy until February 1993. Therapeutic responses, survival time after the operation or recurrence, rate at home, and the improvement of performance status (PS) were studied. The response rate was 54.5%, median survival time was 410 days, the rate at home was 75.5 +/- 14.7%, and the rate of improvement of PS was 82.4%. Toxicities were observed in 70.6%. Thrombocytopenia must be followed carefully, but it was encountered in only a few patients. FLP therapy for advanced or recurrent stomach cancer in outpatients was expected to improve the QOL.

[Prolonging home residence and treatment of cancer in patients with recurrent stomach cancer].

A study was conducted on 27 patients with cancer of the stomach who died from a postoperative recurrence of the cancer, 26 of whom died in the hospital and one of whom died at home. The period from the manifestation of initial symptoms of the recurrence to confirmed diagnosis was less than two months in 20 of the 26 cases (77%). The period from confirmed diagnosis to terminal hospitalization was in excess of three months in 11 of the 26 cases (42%). Of these cases, there were some in which it appeared that the time spent at home could have been extended through means such as another operation, insertion of an intraperitoneal access apparatus, or insertion of a subselective movable catheter. Forty-six percent (46%) of the patients were notified of their diagnosis, but none of them were notified of the recurrence of the cancer, suggesting the difficulty of notifying a patient of a diagnosis of cancer recurrence. A private home-care medical system was used in the case of the patient who had died at home of terminal stomach cancer. There were no major problems with this system other than the complaint that it placed a great financial burden on the family.

[A patient with stage IV gastric cancer responding to combination chemotherapy with 5-FU, leucovorin and CDDP].

The patient was a 44-year-old male with gastric cancer accompanied by pancreatic invasion and metastasis to the periaortic lymph nodes. Combination chemotherapy with 5-FU, leucovorin (LCV) and CDDP (FLP therapy) was preoperatively given. Pancreaticoduodenectomy was carried out as absolutely noncurative resection. FLP therapy was continued postoperatively, and resulted in disappearance of the metastases in the periaortic lymph nodes on CT. As there were no findings of recurrence, the patient was regarded as being in complete response. In addition, the performance status improved from Grade 2 to Grade 0. Since the three-drug combination therapy induced only slight adverse reactions (Grades 1-2), it could be safely carried out at the outpatient department. Thus, combination therapy with 5-FU, LCV and CDDP is thought to be effective against gastric cancer.

[Usefulness of palliative care for the patients with recurrent gastric cancer by home-IVH].

Depending upon the type of cancer involved, the period of the end stage varies greatly, and with it decreases the quality of life (QOL). In gastric cancer, for example, the terminal stage is usually short and the QOL diminishes abruptly. Thus, it takes time keeping this decrease in QOL to minimum, despite the complications, so that the patient's last days will be even somewhat more acceptable. Improvement in QOL for the patient who cannot eat due to recurrent gastric cancer can be effectively achieved by alleviation through IVH. With this in mind, the conditions consonant with the application of home IVH are as follows: 1) The patient's pain can be kept under control at home. 2) The patient wishes to remain. 3)There is sufficient human support at home. The caretakers in the family, and especially the key person(s) must exert much effort and labor and they need rest as well. Home medical care in the terminal stage presupposes a social environment involving day care, short stay, and hospice nursing facilities of all kinds. At present, public services of this kind differ with the community, much remains uninformed to public, and clinic-hospital networking will be needed more than ever. In this difficult situation, the home-care medical services provided by the private sector are effective. These services are only for the short term, of course, and there will be a financial problem. Various measures (tax deduction, public assistance) must be considered to support the patients and caretakers.

[Evaluation of medicinal lymph node dissection in advanced gastric cancer].

In order to improve the results of surgical treatment in advanced gastric cancer, we performed preoperative targeted chemotherapy for metastatic lymph nodes. The solution which contained aclarubicin adsorbed on activated carbon was submucously injected around gastric tumor under endoscopic observation 2-7 days prior to the operation. We termed this method medicinal lymph node dissection (MLD). Our standard surgical treatment (SST) for gastric cancer consists of gastrectomy and extended lymph node dissection (N1 and N2 lymph nodes). Patients of curative resection with histologically positive lymph node metastasis were enrolled, as the subjects. We compared the cumulative survival rate in 47 patients treated with SST+MLD (MLD group) with that in 125 patients treated with SST only (control group). Five year survival rates in the MLD and control groups were 60% and 48%, respectively. The MLD group showed significantly higher survival rate in patients with N3, N4 and infrapyloric lymph node metastasis. A significant difference of the survival rate suggests the efficacy of SST+MLD against micrometastasis in N3 and para-aortic lymph nodes. The SST+MLD therapy is recommended to the advanced gastric cancer, especially in the lower third of the stomach.

Generation of dyspeptic symptoms by direct acid and water infusion into the stomachs of functional dyspepsia patients and healthy subjects.

BACKGROUND: The mechanisms of the development of symptoms in functional dyspepsia (FD) patients have not been fully elucidated. We previously reported that acid directly infused into the stomach causes dyspeptic symptoms in asymptomatic healthy controls (HCs); however, the response to acid infusion of FD patients was not determined. AIM: To investigate the severity of dyspeptic symptoms induced by direct acid infusion in FD subjects and HCs. METHODS: This was a multi-centre, cross-over, randomised, double-blind study in 23 FD subjects and 32 HCs. FD was defined using the Rome III criteria. All subjects were Helicobacter pylori negative. Each subject received two tests; 0.1 mol/L hydrochloric acid and water infused into the stomach. The presence and severity of 12 dyspeptic symptoms were assessed using a visual analogue scale. RESULTS: The proportion of subjects developing symptoms by acid or water infusion was significantly greater in FD subjects than HCs. All of the FD subjects experienced at least one symptom by water or acid infusion. In the FD subjects, the severity of symptoms was significantly greater with acid infusion than water infusion. The severity of symptoms in total and the scores for eight of the 12 symptoms induced by acid infusion was significantly greater in FD subjects than in HCs. CONCLUSIONS: The severity of dyspeptic symptom generation induced by direct acid infusion into the stomach was significantly greater in functional dyspepsia subjects than in healthy controls, suggesting that hypersensitivity to acid is one of the important mechanisms of the development of symptoms in functional dyspepsia patients.

NOD1 and NOD2 mediate sensing of periodontal pathogens.

In bacterial infection, Nucleotide-binding Oligomerization Domain (NOD) 1 and NOD2 induce innate immune responses by recognizing fragments of the bacterial component peptidoglycan (PGN). To determine the roles of these receptors in detection of periodontal pathogens, we stimulated human embryonic kidney cells expressing NOD1 or NOD2 with heat-killed Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum or their soluble PGNs (sPGNs). All bacteria and their sPGNs could stimulate activation of NF-kappaB. However, there were differences in NOD1- and NOD2-stimulatory activities among the species of bacteria. P. gingivalis showed weaker NOD1- and NOD2-stimulatory activities than did other bacteria. These differences in activities were confirmed by production of interleukin-8 from oral epithelial cells stimulated with sPGNs. These findings indicate that both NOD1 and NOD2 might be involved in the recognition of periodontal pathogens, and that the weak NOD-stimulatory property of P. gingivalis might be helpful for survival in the periodontal pocket.

Effect of monensin on DNA synthesis in cultured human thyroid cells.

Monensin is a carboxylic ionophore which perturbs the structure and function of the Golgi apparatus and lysosomes. In the present study, we investigated the functional significance of these organelle in the growth factor-mediated cell proliferation in cultured human thyroid cells from normal and Graves' disease. DNA synthesis was estimated by [3H]-thymidine uptake and flow cytometric analysis. Monensin inhibited both [3H]-thymidine uptake in a dose-dependent manner and the transition of G1 to S phase determined by flow cytometric analysis. Monensin partially blocked the effect of bovine TSH in normal thyroid cells. [3H]-thymidine uptake was suppressed to 56.7 +/- 37.3% of the control value with bTSH and monensin, but it was still higher than those with monensin alone (21.9 +/- 15.0% of the control). The percentage of cells in the S phase was also increased from 7.64 +/- 1.91% with monensin alone to 11.54 +/- 2.82% with bTSH at t = 24h. Forskolin or 12-O-tetradecanoylphorbol 13-acetate (TPA) could not mimic the action of TSH. On the other hand, insulin and EGF most effectively counteracted monensin-induced inhibition of DNA synthesis in Graves' thyroid cells. [3H]-thymidine uptake was not completely inhibited, being 73.5 +/- 24.0% with EGF, 105.0 +/- 25.4% with insulin, and 49.2 +/- 6.6% with monensin alone, respectively. The percentage of cells in the S phase also increased from 8.31 +/- 2.61% with monensin alone to 11.25 +/- 4.27% with EGF and 12.86 +/- 3.12% with insulin. In conclusion, the functional maintenance of the Golgi apparatus and lysosomes is necessary for DNA synthesis in both normal and Graves' thyroid cells, in which bTSH, insulin, and EGF might be differently involved in the regulation of DNA synthesis.