Young Tak Kim

Loss in 3p and 4p and gain of 3q are concomitant aberrations in squamous cell carcinoma of the vulva.

Neoplasm of the vulva is a rare malignancy accounting for <5% of all female genital-tract cancer. However, in recent years the incidence of vulva intraepithelial neoplasia, known to serve as a precursor to carcinoma, has increased in young women generating considerable interest in its pathogenesis. Genetic changes at the molecular level in precursor or invasive vulvar tumors are not well investigated, and DNA copy number changes have not been reported until now. We used comparative genomic hybridization (CGH) to analyze genetic alterations in 10 primary invasive squamous cell carcinomas of the vulva. Chromosomal aberrations were identified in 8/10 cases. The most frequent chromosomal losses were 4p13–pter (five cases), 3p (four cases), and 5q (two cases), and less frequent losses were detected at 6q, 11q, and 13q (one case each). The most frequent chromosomal gains were 3q (four cases) and 8p (three cases), and less frequent gains were found in 9p, 14, 17, and 20q (one case each). The pattern of chromosomal imbalance in vulvar cancer detected by CGH was revealed to be very similar to that in cervical cancers, despite regional differences in their prevalence. These results suggest that the pathogenic pathways in vulvar and cervical carcinomas may be similar and that the genetic background may be common to these two squamous cell carcinomas.

Comparative study of neoadjuvant chemotherapy before radical hysterectomy and radical surgery alone in stage IB2-IIA bulky cervical cancer

OBJECTIVE To compare the efficacy of neoadjuvant chemotherapy with paclitaxel plus platinum followed by radical hysterectomy with radical surgery alone in patients with stage IB2-IIA bulky cervical cancer. METHODS From November 1999 to September 2007, stage IB2-IIA cervical cancers with tumor diameter >4 cm, as measured by MRI, were managed with two cycles of preoperative paclitaxel and platinum. As a control group, we selected 35 patients treated with radical surgery alone. RESULTS There were no significant between group differences in age, tumor size, FIGO stage, level of SCC Ag, histopathologic type and grade. Operating time, estimated blood loss, the number of lymph nodes yielded and the rate of complications were similar in the two groups. In surgical specimens, lymph-vascular space invasion (LVSI), nodal metastasis and parametrial involvement did not differ significantly between the two groups. In the neoadjuvant group, pathologic tumor size was significantly smaller and fewer patients had deep cervical invasion. Radiotherapy, alone and in the form of concurrent chemoradiation, was administered to more patients treated with radical surgery alone (82.9% vs. 52.9%, p=0.006). No recurrence was observed in patients who could avoid adjuvant radiotherapy owing to improved risk factors after neoadjuvant chemotherapy. There were no significant differences in 5-year disease free and overall survival. CONCLUSION As neoadjuvant chemotherapy would improve pathologic prognostic factors, adjuvant radiotherapy can be avoided, without worsening the prognosis, in patients with locally advanced bulky cervical cancer. Neoadjuvant chemotherapy would be improving the quality of life after radical hysterectomy in patients with bulky cervical cancer.

Progesterone increases mRNA levels of pituitary adenylate cyclase-activating polypeptide (PACAP) and type I PACAP receptor (PAC1) in the rat hypothalamus

Pituitary adenylate cyclase-activating polypeptide (PACAP) regulates pituitary hormone biosynthesis and secretion through its cognate receptors. PACAP also plays an important role in the regulation of ovarian steroid biosynthesis. If so, there might be a feedback regulation of hypothalamic PACAP synthesis by the pituitary and by ovarian steroids. In the present study, we used RNase protection assays to determine changes in mRNA levels of PACAP and type I PACAP receptor (PAC(1)) under the conditions of ovariectomy and replacement with ovarian steroids. Progesterone (P) alone or in combination with estradiol (E) induced significant increases in PACAP mRNA level in the medial basal hypothalamus (MBH) and PAC(1) mRNA levels in MBH and the preoptic area (POA). This finding suggests that feedback regulation takes place between the ovary and hypothalamic PACAP neurons. P is known to be a major regulatory feedback factor for hypothalamic luteinizing hormone-releasing hormone (LHRH) neurons, but P receptor is not present in these neurons. Therefore, we examined a possible involvement of PACAP in the feedback regulatory pathway of P to LHRH neurons. After an antisense PAC(1) oligodeoxynucleotide (ODN) was i.c.v.-injected into the third ventricle of E and P-treated rats, LHRH mRNA levels were determined. The ODN markedly decreased the P-induced increase in the LHRH mRNA level. Taken together, the present data suggest that PACAP may play a role as a mediator in the regulation of LHRH synthetic machinery by stimulatory feedback of P.

Reproductive outcomes after laparoscopic radical trachelectomy for early-stage cervical cancer

Objective The objective of this study was to estimate the reproductive outcome of young women with early-stage cervical cancer who underwent fertility-sparing laparoscopic radical trachelectomy (LRT). Methods We performed a retrospective review of the medical records of patients with early-stage cervical cancer who underwent LRT. Clinicopathological data were obtained from patient medical records, and reproductive outcome data were obtained from patient medical records and telephone interviews. Results Fifty-five patients who underwent successful LRT were included in this study. The median age of patients was 32 years (range, 22 to 40 years), and the median follow-up time after LRT was 37 months (range, 3 to 105 months). Menstruation resumed in all patients after LRT, with fifty patients (90.9%) and five patients (9.1%) reporting regular and irregular menstruation, respectively. Six patients (10.9%) presented with cervical stenosis, which was manifested by regular but decreased menstrual flow and newly-developed dysmenorrhea. These patients underwent cervical cannulation and dilatation. Eighteen patients (32.7%) attempted to conceive, with six out of 18 patients receiving fertility treatments. Fourteen pregnancies (i.e., four missed abortions, six preterm births and four full-term births) occurred in 10 patients after LRT. Nine out of 10 patients gave birth to 10 healthy babies. The pregnancy rate after LRT was 55.6% (10/18). The spontaneous abortion rate and live birth rate were 28.6% (4/14) and 71.4% (10/14), respectively. The preterm birth rate was 60% (6/10). Conclusion Pregnancy and live birth rates after LRT were promising; however, the preterm birth rate was relatively high. Cervical stenosis also occurred in a small percentage of patients.

Amplification at 9p in cervical carcinoma by comparative genomic hybridization

DNA copy number changes were studied by comparative genomic hybridization on 10 tumor specimens of squamous cell carcinoma of cervix obtained from Korean patients. DNA was extracted from paraffin‐embedded sections after removal of non‐malignant cells by microdissection technique. Copy number changes were found in 8/10 tumors. The most frequent changes were chromosome 19 gains (n=6) and losses on chromosomes 4 (n=4), 5 (n=3), and 3p (n=3). A novel finding was amplification in chromosome arm 9p21‐pter in 2 cases. Gains in 1, 3q, 5p, 6p, 8q, 16p, 17, and 20q and losses at 2q, 6q, 8p, 9q, 10p, 11, 13, 16q, and 18q were observed in at least one of the cases.

Time Course and Characteristics of Astrocyte Activation in the Rat Brain after Injury

Objective After injury to the central nervous system (CNS), glial scar tissue is formed in the process of wound healing. This can be is a clinical problem because it interferes with axonal regeneration and functional recovery. It is known that intracellular proteins, including the glial fibrillary acidic protein (GFAP), nestin, and vimentin increase in the astrocytes after an injury to the CNS. By studying the time course and co-expression pattern of these intracellular proteins, this study will attempt to prove that these proteins are involved in the processes of glial scar formation. Methods Twenty-five male Sprague-Dawley rats were used in this study. Bregma of the cerebral cortex, an area was incised with a sharp blade, and perfusion was performed. The expressions of the intracellular proteins were assayed, while the co-localization of the intermediate filament (GFAP, nestin, and vimentin) and A2B5 were examined. Results At 12 hours, the GFAP was expressed in the white matter underlying the lesion, and in the cerebral cortex. Nestin was expressed in the astrocytes in the perilesional area after 3 days, while A2B5 was observed in the edge of the wound at 12 hours post-injury, with its expression reaching a peak at 7 days. Vimentin was detected in the white matter at 12 hours, and in the cortex, reaching a peak at 7 days. Conclusion In the processes of glial scar formation, nestin, vimentin, and A2B5 were revealed in the astrocytes, and these factors may be involved in the division, proliferation, and transportation of the astrocytes.

Spontaneous Spinal Epidural Hematoma on the Ventral Portion of Whole Spinal Canal: A Case Report

Spontaneous spinal epidural hematoma is an uncommon but disabling disease. This paper reports a case of spontaneous spinal epidural hematoma and treatment by surgical management. A 32-year-old male presented with a 30-minute history of sudden headache, back pain, chest pain, and progressive quadriplegia. Whole-spinal sagittal magnetic resonance imaging (MRI) revealed spinal epidural hematoma on the ventral portion of the spinal canal. Total laminectomy from T5 to T7 was performed, and hematoma located at the ventral portion of the spinal cord was evacuated. Epidural drainages were inserted in the upper and lower epidural spaces. The patient improved sufficiently to ambulate, and paresthesia was fully recovered. Spontaneous spinal epidural hematoma should be considered when patients present symptoms of spinal cord compression after sudden back pain or chest pain. To prevent permanent neurologic deficits, early and correct diagnosis with timely surgical management is necessary.

Nail Gun Induced Open Head Injury: A Case Report

Increasing use of the nail gun has led to higher injury rates from the use of tools with sequential actuation. Nail gun injury can occur to various parts of the body. Very deep penetration in the brain can have fatal results. A 46-year-old male fired shots from a nail gun into his brain in a suicide attempt. This case demonstrated successful surgical management of the resultant open head injury.

Pituitary Carcinoma with Mandibular Metastasis: A Case Report

Pituitary carcinomas are rare primary adenohypophyseal tumors with cerebrospinal or extracranial metastasis. The present case, the first report of the disease in Korea, involved a 36-yr-old woman who presented with a 3-week history of headache. Brain magnetic resonance imaging revealed a 2.5-cm sellar and suprasellar mass showing heterogeneous enhancement with suspicious invasion of both cavernous sinuses. The patient underwent gross-total resection. The tumor cells were composed of polygonal cells singly or in variable-sized nests. The nuclei were large and round with prominent nucleoli. The cytoplasms was acidophilic and granular. Marked pleomorphism and frequent mitoses (3 per 10 HPFs) were found. By immunohistochemistry, tumor cells were strongly positive for prolactin, but negative for ACTH and GH. Additional immunostainings for cytokeratin, vimentin, and glial fibrillary acidic protein (GFAP) were negative. After the surgery, the patient received radiotherapy because of the atypical histologic features. The prolactin level fell from 123.17 ng/mL to 5.17 ng/mL after surgery. Nine months after the initial diagnosis, the patient died from mandibular metastasis associated with the pituitary carcinoma.

Will Fluoroscopic Follow-up after Stent-Assisted Coiling of Cerebral Aneurysms Provide Information on Recanalization?

Fluoroscopic images for comparison (FICs) can be easily obtained for follow-up on an outpatient basis. This study retrospectively assessed the diagnostic performance of a set of FICs for evaluation of recanalization after stent-assisted coiling, with digital subtraction angiography (DSA) as the reference standard. A total of 124 patients harboring 144 stent-assisted coiled aneurysms were included. At least one month postembolization they underwent follow-up angiograms comprising a routine frontal and lateral DSA and a working-angle DSA. For analysis, FICs should be compared with the mask images of postprocedural DSAs to find recanalization. Instead of FIC acquisition, the mask images of follow-up DSAs were taken as a substitute because of the same view-making processes as FICs, full availability, and perfect coincidence with follow-up DSAs. Two independent readers evaluated a set of 169 FICs and DSA images for the presence of recanalization one month apart. Sensitivity, specificity, and interreader agreement were determined. Recanalization occurred in 24 (14.2%) cases. Of these, nine (5.3%) cases were found to have significant recanalization in need of retreatment. Sensitivity and specificity rates were 79.2% (19 of 24) and 95.9% (139 of 145) respectively for reader 1, and 66.7% (16 of 24) and 97.9% (142 of 145) for reader 2. Minimal recanalization was identified in seven out of all eight false negative cases. Excluding minimally recanalized cases in no need for retreatment from the recanalization group, calculation resulted in high sensitivity and specificity of over 94% for both readers. Interreader agreement between the two readers was excellent (96.4%; κ = 0.84). FICs may be a good imaging modality to detect significant recanalization of stent-assisted coiled aneurysms.