Modulation of pain perception through transcranial alternating current stimulation and its nonlinear relationship with the simulated electric field magnitude.

BACKGROUND: Oscillatory activities observed in multiple regions are closely associated with the experience of pain. Specifically, oscillatory activities within the theta- and beta-frequency bands, observed in the left dorsolateral prefrontal cortex (DLPFC), have been implicated in pain perception among healthy individuals and those with chronic pain. However, their physiological significance remains unclear. METHODS: We explored the modulation of pain perception in healthy individuals by theta- and beta-band transcranial alternating current stimulation (tACS) over the left DLPFC and examined the relationship between the modulation effect and magnitude of the electric field elicited by tACS in the left DLPFC using computational simulation. RESULTS: Our findings revealed that both theta- and beta-tACS increased the heat pain threshold during and after stimulation. Notably, the simulated electric field magnitude in the left DLPFC exhibited an inverted U-shaped relationship with the pain modulation effect for theta-tACS. CONCLUSIONS: Our study findings suggested that there would be an optimal electric field strength to produce a high analgesic effect for theta-tACS. SIGNIFICANCE: The application of theta- and beta-tACS interventions targeting the left DLPFC might facilitate the treatment of chronic pain. Furthermore, the attainment of effective pain modulation via theta-tACS over the DLPFC warrants the use of optimal stimulus intensity.

Ovarian cancer presenting as a metastasis to a trocar tract used for a gasless lift-laparoscopy to resect a benign ovarian cyst: an unusual case report.

BACKGROUND: Metastasis to a trocar tract (port-site metastasis, PSM) is an uncommon but serious complication that possibly compromises the prognosis of cancer patients treated laparoscopically. CASE: A 42-year-old Japanese woman had a 20-cm benign right ovarian cyst resected using gasless lift-laparoscopy. Five years and eight months postoperatively, she noticed a three-cm subcutaneous tumor involving the trocar tract. She was also found to have a pelvic mass and an exploratory laparotomy revealed left ovarian cancer. Based on the histopathological findings, the subcutaneous tumor was diagnosed as a metastasis from the ovarian cancer. CONCLUSIONS: This case suggested that PSM could occur without direct or indirect wound contamination during laparoscopic surgery.

Metastatic gastric cancer mimicking an advanced cervical cancer: a case report.

BACKGROUND: Metastasis to the uterine cervix from non-gynecologic neoplasms is rare. However, metastatic tumors sometimes precede the diagnosis of a primary tumor, and may lead to diagnosis of the primary tumor. CASE: A 50-year-old woman was referred to us complaining of increasing right flank pain. Computed tomography scan demonstrated an enlarged uterus with right-sided hydronephrosis and hydroureter. Cervical cytology revealed adenocarcinoma. She was considered to have a Stage IIIB cervical adenocarcinoma. Although no cervical lesion was seen colposcopically, histopathology from biopsies of the uterine cervix revealed poorly differentiated adenocarcinoma infiltrating around the normal endocervical glands. A metastasis from the gastrointestinal tract was suspected. The patient underwent gastroscopy and was found to have Borrmann type IV gastric cancer. Biopsies confirmed a poorly differentiated adenocarcinoma with signet ring cells. CONCLUSION: Physicians should bear in mind that metastatic tumors may precede the diagnosis of a primary tumor and could manifest by mimicking advanced cervical cancer.

Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes.

Thirteen patients with epithelial ovarian cancer, who did not show any detectable lesion after cisplatin-containing chemotherapy following primary operation, were treated with adoptive transfer of tumor-infiltrating lymphocytes (TIL group). Eleven patients with almost equivalent conditions of disease, who were treated with only chemotherapy following primary operation, served as a control group. The median time of follow-up was 36 (range, 23-44) months in the TIL group and 33 (range, 14-48) months in the control group. The estimated 3-year overall survival rate of disease-free patients in the TIL group and in the control group was 100% and 67.5%, respectively. A significant difference was noticed between the overall survival rate of the TIL group and the control group (P < 0.01). Furthermore, the estimated 3-year disease-free survival rate of the patients in the TIL group and in the control group was 82.1% and 54.5%, respectively. The disease-free survival rate of patients in the TIL group and in the control group was significantly different (P < 0.05). These results suggest that the adoptive transfer of TILs after all chemotherapy has been finished might be one promising method to achieve complete cure of advanced epithelial ovarian cancer.

Choriocarcinoma in a term placenta with pulmonary metastasis.

This is a case report of choriocarcinoma in the placenta of a patient who had a term delivery at the 38th week of pregnancy. The pregnant woman had hemoptysis at the 26th week of pregnancy, and a chest X-ray revealed a tumor in the left lung. She had suffered from a hydatidiform mole in a previous pregnancy in 1989. The patient's serum level of beta-human chorionic gonadotropin (hCG) had been below the normal level before the present pregnancy. Choriocarcinoma was histologically found at 3 sites in the placenta. Her urine hCG levels decreased rapidly after delivery. A partial lobectomy was performed after 2 courses of chemotherapy, and no choriocarcinoma was recognized histologically, because the lesions were hemorrhagic and necrotic. At present, the mother is free of disease, and the baby is growing normally. The placenta should be examined in a detail in post-molar pregnancy.

Enhancement of T cell receptor signaling of tumor-infiltrating lymphocytes by retrovirally mediated fyn gene transduction.

We conducted retrovirally mediated transduction of fyn gene into tumor-infiltrating lymphocytes (TILs) in an attempt to augment T cell receptor-CD3 complex signal transduction, using TILs obtained from six patients with epithelial ovarian cancer. The expression of the transduced gene was more than five times that of endogenous fyn gene. In all preparations, the cytolytic activity of the TILs against autologous tumor cells, but not allogeneic tumor cells, was significantly enhanced (P < 0.01) by transduction of fyn gene. In addition, when TILs were treated with anti-CD3 antibody to stimulate T cell receptor-CD3 complex, fyn-gene-transduced TILs showed about two times higher proliferation (P < 0.05) and secreted 2.2 to 11.7 times more tumor necrosis factor-beta (P < 0.05) than nontransduced TILs. These results could have important implications for TILs-mediated gene therapy for cancer.

[Pharmacokinetics of carboplatin in a patient under hemodialysis].

A patient with ovarian cancer under long-term hemodialysis was treated with carboplatin at 240 mg/m2 via intravenous drip infusion for 30 min. Hemodialysis was performed 1 or 2 hrs after the administration of carboplatin. The pharmacokinetics of carboplatin were determined, plasma total and free carboplatin-derived platinum (total Pt and free Pt) levels declined rapidly in the former. The AUC, T1/2 and Cmax of total and free Pt were estimated to be 7.14 and 3.14 mg/ml x min, 35.1 and 18.2 h, and 15.1 and 10.0 micrograms/ml, respectively. Plasma total and free Pt levels showed the same as normal control in the latter. The AUC, T1/2 and Cmax of total and free Pt were estimated to be 8.70 and 5.09 mg/ml x min, 27.6 and 21.9 h, and 13.2 and 13.2 micrograms/ml, respectively. No severe side effect was observed after administration of carboplatin. In conclusion, carboplatin may be given to the patient 2 hrs before hemodialysis in view of the pharmacokinetics.

Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes.

The immunomodulation determined by natural killer cell activity, delayed-type hypersensitivity to purified protein derivative and phytohemagglutin, and phenotypic changes of peripheral blood lymphocytes was characterized in 12 patients with epithelial ovarian cancer who received adoptive transfer of tumor-infiltrating lymphocytes (TILs) after cisplatin-containing chemotherapy (TIL group). As a control, 10 patients with epithelial ovarian cancer who did not receive infusions of TIL were also examined in the same fashion. In the TIL group, peripheral blood lymphocytes showed increased percentages of cells bearing the CD8 antigen, in contrast to stable percentages of CD4 antigen-bearing cells, resulting in a decreased ratio of CD4+ to CD8+ cells. The percentages of CD16 and CD56 antigen-bearing cells also increased in proportion to augmentation of natural killer cell activity against K562 cells. Additionally, with regard to cell-mediated immunity determined by delayed-type hypersensitivity to phytohemagglutin and purified protein derivative, significantly and slightly enlarged erythema was observed 2 and 8 weeks, respectively, after the injection of TILs (phytohemagglutin, P < 0.05; purified protein derivative, not statistically significant). The control group showed no major changes in any of the immunological markers. These results suggest the possibility that the adoptive transfer of TILs induces immunoactivation of cellular immunity and enhances natural killer activity in patients with epithelial ovarian cancer.

Solid-phase anti-CD3 antibody activation and cryopreservation of human tumor-infiltrating lymphocytes derived from epithelial ovarian cancer.

The effect of solid-phase anti-CD3 antibody activation and cryopreservation was evaluated on thirteen samples of tumor-infiltrating lymphocytes (TILs) derived from epithelial ovarian cancer. Seven preparations of TILs were cultured with or without solid-phase anti-CD3 antibody in addition to 100 units/ml of recombinant interleukin-2 (rIL-2). The proliferation rate of all of the seven TIL preparations stimulated by anti-CD3 antibody on the fourth or fifth day of culture was 3.4 to 9.8 times greater than that of lymphocytes cultured with rIL-2 alone. Furthermore, in an experiment with five TIL samples activated with anti-CD3 antibody, three of them showed augmented cytotoxic activity against autologous fresh tumor cells. The population of CD3+/CD8+ TILs was increased after 4-5 weeks of cultivation and CD8+ lymphocytes amounted to over 70% in all of seven preparations tested, whereas two of seven preparations not activated by anti-CD3 antibody were CD3+/CD4(+)-dominant. In addition, nine preparations of TILs cultured with rIL-2 were cryopreserved for several weeks; after recovery from cryopreservation, no major change was observed in cell surface markers, in growth rate or in cytotoxic activity. These results suggest that cryopreserved and/or anti-CD3 antibody-activated lymphocytes could conveniently be employed in a clinical trial of adoptive immunotherapy employing TIL.

[A case of isocyanate-induced hypersensitivity pneumonitis and a compression-air mask thought to be effective in its prevention].

A 41-year-old paint sprayer, who had worked with polyurethane paint since the spring of 1989, developed exertional dyspnea and dry cough and entered hospital on December 4, 1989. Plain chest X-ray film and a computed tomogram of the lung revealed diffuse micronodular shadows in both lower lung fields. DLco was shown to be significantly decreased in a pulmonary function test. A sample of bronchoalveolar lavage fluid showed increased T lymphocytes and a decreased CD4/8 ratio. A lung biopsy specimen revealed alveolitis, but neither Masson body nor granulomas were seen. Serum antibody specific to TDI-HSA was detected, and an environmental provocation test was positive. From these results, the patient was diagnosed as having isocyanate-induced hypersensitivity pneumonitis. We advised him to wear a compression-air mask when he worked, because he did not want to quit his job. Respiratory symptoms have not been seen since then, but careful observation was thought to be necessary. The involvement of type III humoral and type IV cellular immunity was suspected in this case.

Suppressed mastoid pneumatization in cholesteatoma.

Mastoid pneumatization size was studied by X-ray in 289 patients with otitis media (134 with cholesteatoma and 155 with chronic suppurative otitis media (COM) and 73 patients with traumatic tympanic membrane perforation (controls). The results demonstrated that mastoid pneumatization in the diseased ear of cholesteatoma patients was greatly suppressed. In these patients, the contralateral ear also showed significant suppression compared with controls; mastoid pneumatization size in the healthy ear contralateral to cholesteatoma was similar to that in patients cured of otitis media with effusion (OME). Hence, we conclude that cholesteatoma is a sequela of OME in childhood.

Relation between the onset of chronic middle ear inflammation and the development of the middle ear air cell system.

The relation between the onset of chronic middle ear inflammation and the degree of pneumatization was investigated in porcine tympanic bullae, which closely resemble the human mastoid air cell system. Pneumatization was inhibited in all inflamed ears, and the later the induction of otitis media, the lesser the degree of inhibition of pneumatization. It was concluded that chronic middle ear inflammation inhibits the development of the middle ear air cell system, and the time of onset plays an important role in the degree of pneumatization.

The effect of chronic middle ear inflammation on the pneumatization of the tympanic bulla in pigs.

The effect of chronic middle ear inflammation on the pneumatization of the tympanic bulla was investigated in piglets. The pig tympanic bulla has an air cell system which is divided by trabeculae and closely resembles the human mastoid air cell system. The tympanic bulla and its air cell system in normal ears were well developed because of the bone formation and the bone resorption inside the cortex, whereas the tympanic bulla affected by chronic otitis media in the early stages of life exhibited retardation of pneumatization arising from the disturbed bone resorption by inflammatory stimulus. It was concluded that affliction with chronic middle ear inflammation in the early stages of life causes inhibition of pneumatization by hindering the development of the air cell system.