First successful case of non-invasive in-utero treatment of twin reversed arterial perfusion sequence by high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has excellent potential as a non-invasive therapeutic tool in various fields of medicine. We present a case of twin reversed arterial perfusion sequence, in which non-invasive blood flow occlusion in the acardiac fetus was successfully achieved by means of HIFU exposure from outside the maternal abdomen. HIFU was applied to blood vessels of the acardiac fetus at the point at which the umbilical cord entered the body in a series of four procedures at 3-day intervals starting at 13 weeks' gestation, and in a final procedure with higher power at 17 weeks. The HIFU intensity was set at approximately 2300 W/cm(2) for the initial series of procedures and at 4600 W/cm(2) for the final procedure, with exposure periods of 10 s. As color Doppler examination revealed absence of blood flow to the acardiac fetus after the second round of HIFU exposure, we concluded that complete occlusion of target vessels had been achieved. Delivery was by Cesarean section at 37 weeks' gestation. A male neonate (the pump fetus) was born weighing 1903 g with Apgar scores of 8 and 9 at 1 and 5 min, respectively. At the time of writing, the baby was healthy and growing normally, with the exception of congenital pseudarthrosis.

[Clinical effect of the cauterization for emphysematous bulla].

The purpose of performing pleural cauterization is developing heat denaturation, and we can induce pleural thickening and also reduce the bullae by shrinking the pleura It originates in a method of the cauterization whether there will be tissue damage. So a safe and reliable method of cauterization is required. Here, we investigated the indications for and effectiveness of cauterization techniques performed at our facility. We perform cauterization while dropping saline solution, so when using a Salient Monopolar Sealer, we can avoid excessive thermo-coagulation and more easily control cauterization. Furthermore, on the basis that only emphysematous pleura will turn white on cauterization, bullae can be distinguished, which is particularly effective in the case of lesions with unclear borders. In the case of a large emphysematous bulla, shrinkage of the bulla by cauterization can provide a sufficient surgical field, and a smaller lesion can then be stapled.

Application of high-intensity focused ultrasound for umbilical artery occlusion in a rabbit model.

OBJECTIVES: To investigate the application of high-intensity focused ultrasound (HIFU) for fetal umbilical artery blood flow occlusion in a rabbit model. METHODS: A prototype HIFU transducer in combination with an imaging probe with Doppler capability was constructed. Using this transducer, HIFU was applied at 1.4, 2.75 or 5.5 kW/cm(2) through the maternal abdominal skin to the fetal intra-abdominal umbilical arteries of four time-mated Japanese White rabbits (11 fetuses) on gestational day 25. Courses of 5-s HIFU exposure were performed until cessation of umbilical blood flow and cardiac arrest were confirmed by Doppler ultrasonography. Fetal necropsy was performed and exposed lesions were assessed by microscopic histological analysis. RESULTS: The mean diameter of the fetal umbilical artery was 0.6 +/- 0.2 mm and the mean peak systolic velocity of arterial blood flow was 44.7 +/- 18.5 cm/s. When HIFU was applied at 5.5 kW/cm(2), blood flow was completely occluded within 15 courses. HIFU exposure brought about vacuolar degeneration and destruction of elastic fibers in the tunica media of the artery. CONCLUSIONS: HIFU can be used to occlude umbilical artery blood flow in fetal rabbits.

Study of p53 gene alteration as a biomarker to evaluate the malignant risk of Lugol-unstained lesion with non-dysplasia in the oesophagus.

Mutations of the p53 gene are detected frequently in oesophageal dysplasia and cancer. It is unclear whether Lugol-unstained lesions (LULs) with non-dysplastic epithelium (NDE) are precursors of oesophageal squamous cell carcinoma (ESCC). To study the genetic alterations of NDE in the multistep process of oesophageal carcinogenesis, we determined the relationship between p53 mutations and LULs-NDE. Videoendoscopy with Lugol staining was performed prospectively in 542 oesophageal cancer-free subjects. Lugol-unstained lesions were detected in 103 subjects (19%). A total of 255 samples, including 152 LULs (NDE, 137; dysplasia, 15) and 103 paired samples of normal staining epithelium, were obtained from 103 subjects. After extraction of DNA and polymerase chain reaction analysis, direct sequencing method was applied to detect mutations of the p53 gene. The p53 mutation was detected in five of 137 samples with LULs-NDE (4%) and in five of 15 samples with dysplasia (33%). A hotspot mutation was found in 20% of LULs-NDE with p53 mutation and in 40% of dysplasia with p53 mutation. In contrast, no p53 mutations were found in 103 paired NDE samples with normal Lugol staining. In biopsy samples from oesophageal cancer-free individuals, the p53 missense mutations containing a hotspot mutation were found in NDE, which was identified as an LUL. These findings suggest that some LULs-NDE may represent the earliest state of oesophageal squamous cell carcinoma in Japanese individuals.

Detection of p53 mutations in the plasma DNA of patients with ovarian cancer.

Mutation of p53 is one of the most common genetic abnormalities detected in up to 81% of cases of ovarian cancer. To evaluate the use of plasma DNA analysis as a method for somatic mutation screening, we measured the presence of p53 mutations in DNA isolated from plasma and cancer tissue from patients with ovarian cancer. We analyzed the plasma DNA for the presence of p53 mutations (exons 5-8). Of 27 cases of ovarian cancer, 12 cases (44%) had mutations of p53 in cancer tissue. In two of the 12 cases (16.7%), identical mutations were detected in DNA of their preoperative plasma. In our follow-up of the two patients with p53 mutations in their plasma, mutant DNA was undetectable in their plasma after surgery. In one case, the p53 mutation re-surfaced in their plasma 16 months after surgery, and the patient died 2 months later. We have shown that tumor-derived DNA can be detected in the plasma of some patients with ovarian cancer, particularly in those with more advanced stage.

Pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth.

We sought to clarify pathological features and genetic alterations in colorectal carcinomas with characteristics of nonpolypoid growth. Colorectal carcinomas resected at Showa University Hospital in Tokyo included 86 with characteristics of polypoid growth (PG) and 21 with those of nonpolypoid growth (NPG). Mutations of APC, Ki-ras, and p53 genes, as well as microsatellite instability (MSI), were analysed using fluorescence-based polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). Carcinomas with an NPG pattern were smaller than PG tumours (P<0.0001). Carcinomas with a PG pattern were more likely to harbour Ki-ras mutations (36%) than NPG tumours (0%; P<0.0001). Mutation types in the APC gene differed significantly between PG and NPG carcinomas (P=0.0189), including frameshift mutations in 66% of PG carcinomas but no NPG carcinomas. Presence of a p53 mutation at a 'hot spot' also was more likely in PG carcinomas (37%) than in NPG carcinomas (0%; P=0.0124). No significant difference in presence of MSI was evident between carcinomas with PG and NPG patterns. In conclusion, significant genetic differences were evident between carcinomas with PG and NPG patterns. Genetic changes in NPG carcinomas differed from those of the conventional adenoma-carcinoma sequence. Assuming that some nonpolypoid growth lesions transform rapidly into advanced carcinomas, 20% of all colorectal carcinomas may progress in this manner.

Silent mixed corticotroph and somatotroph macroadenomas presenting with pituitary apoplexy.

We discuss three unique cases of pituitary macroadenoma presenting with pituitary hemorrhage but without typical endocrine symptomatology. Immunohistochemical analysis indicated positive reactivity for adrenocorticotropic hormone (ACTH) and growth hormone (GH), and in situ hybridization indicated the expression of proopiomelanocortin (POMC) and GH mRNA. We designated these cases silent mixed corticotroph and somatotroph adenoma. Patient 1 was a 30-year-old man, patient 2 was a 29-year-old woman, and patient 3 was a 59-year-old woman. All patients presented with a headache of sudden onset and visual disturbance. The patients did not exhibit typical Cushing's or acromegalic features. Serum ACTH level was remarkably elevated in patient 1, and slightly elevated in patients 2 and 3. In all patients, serum GH levels were within normal range and magnetic resonance imaging revealed an intra- and suprasellar mass with pituitary hemorrhage. Transnasal pituitary surgery in the three patients disclosed a pituitary adenoma producing ACTH and GH. In patient 2, the residual adenoma reappeared along with an intratumoral hemorrhage, and was resected by secondary transnasal surgery. Silent mixed corticotroph and somatotroph adenomas are characterized by the following: no endocrine symptoms; presentation dominated by mass effect symptoms; macroadenoma presenting with acute pituitary hemorrhage; and production of both ACTH and GH.

Simultaneous squamous cell carcinomas of the uterine cervix and upper genital tract: loss of heterozygosity analysis demonstrates clonal neoplasms of cervical origin.

Five cases of cervical squamous cell carcinoma with synchronous superficial squamous cell carcinoma in the upper genital tract were genetically analyzed to demonstrate the possibility of a clonal neoplastic process. In these cases, the cervical lesions were squamous cell carcinoma in situ (cases 1, 2, and 3) and invasive squamous cell carcinoma (cases 4 and 5). Loss of heterozygosity (LOH) analyses with a panel of microsatellite markers revealed a monoclonal process in four of the five cases. Homogeneous LOH throughout the microdissected lesions was most frequently detected on 6p and 6q (3 cases), followed by 11p and 11q (2 cases), loci known to be commonly lost in typical cervical squamous cell carcinoma. In two cases, genetic progression in terms of additional LOH was found in the upper genital tract but not in the cervix. Most of these squamous cell carcinomas were monoclonal neoplasms originating from the cervical mucosa with subsequent superficial migration of the tumor clone to the upper genital mucosa, and in some cases, genetic progression.

Corticotroph cell adenoma without typical manifestations of Cushing's disease presenting with cavernous sinus syndrome following pituitary apoplexy.

This report presents a unique case of corticotroph cell adenoma in a 30-year-old man without acromegaly or features typical of Cushing's disease, who developed cavernous sinus syndrome following pituitary apoplexy. Magnetic resonance imaging revealed a large intrasellar/suprasellar mass with pituitary hemorrhage and extension of a hematoma to the anterior base of the skull. Urgent transnasal pituitary surgery revealed an acidophilic pituitary adenoma, with immunoreactivity for ACTH and GH and expression of proopiomelanocortin (POMC) and GH messenger ribonucleic acid (mRNA) demonstrated by in situ hybridization. To our knowledge, a silent corticotroph cell adenoma with GH production has never been reported. This type of adenoma may potentially enlarge and develop tumoral hemorrhage because it is free of endocrinological symptoms.

Steroid sulfatase expression in ovarian clear cell adenocarcinoma: immunohistochemical study.

OBJECTIVE: Steroid sulfatase (STS) is an important enzyme that converts biological inactive steroid sulfate to active free steroid. As estrogen is thought to play an important role in cell proliferation in gynecological cancer, the existence of STS may have particular significance in the prognosis of ovarian cancer. In the present study, we determined the STS expression of ovarian clear cell adenocarcinoma (OCCA), which has the poorest prognosis among various ovarian cancers, immunohistochemically to clarify the biological nature of OCCA and also to determine whether STS expression is one of the prognostic factors in OCCA. METHODS: Forty-five archival, formalin-fixed, paraffin-embedded tissues from patients with OCCA and other epithelial ovarian cancers who were first operated on from 1987 to 1998 were subjected to analysis. Twenty-eight of forty-five (60.9%) OCCA cases coexisted with endometriosis. They were subclassified into papillary, solid, and tubulocystic types with respect to architectural pattern. Immunohistochemical staining of STS was performed using anti-human STS polyclonal rabbit antibody that had been immunized with purified STS from human placenta. RESULTS: STS was immunohistochemically stained positively in 70% (32/45) of OCCA, 33.3% of serous adenocarcinoma (6/18), and 50.0% of mucinous adenocarcinoma (4/8) specimens and was localized in the cytoplasm of neoplastic epithelial cells. No significant relationship was found between STS staining and FIGO staging. However, patients diagnosed as papillary type had a significantly lower survival rate and showed significantly more positive staining of STS (P < 0.05) than those with solid type. Stage, STS expression, and architectural type yielded a significant association with survival rate. CONCLUSION: It was proven that STS is present in the cytoplasm of patients with OCCA by an immunohistochemical method. OCCA patients with papillary tumor with positive STS expression are considered to have a poor prognosis.

[Reconstruction of the sellar floor during transnasal pituitary surgery using ceramics composed of a combination of hydroxyapatite and tricalciumphosphate].

Our clinical experience with reconstruction of the sellar floor during transnasal-transsphenoidal surgery for pituitary tumors using ceramics composed of a combination of hydroxyapatite and tricalciumphosphate (pituitary plate) is described. A pituitary plate was used to reconstruct the sellar floor in 15 patients with pituitary tumors that included 13 pituitary adenomas and 2 Rathke's cleft cysts. This method is indicated for cases of reoperation and cases in which there is of much cerebrospinal fluid leakage during surgery. This material is provided as a pituitary plate 12 x 12 mm round and 2 mm thick. There are four holes in the center by which the plate can be held with regular bipolar forceps. At the time of closing the sellar floor window, a pituitary plate was carved with scissors into a suitable shape and slipped inside the bony defect. The postoperative position of the pituitary plate could be clearly identified on skull roentgenogram and magnetic resonance imaging. No displacement or migration of the implanted pituitary plate was observed in any patient during follow-up radiological examinations. Infections such as a pituitary abscess or meningitis were not observed clinically or radiologically in any patient. In three patients who underwent repeated transnasal surgery for regrowth of the tumor, the pituitary plate that had been placed at the initial procedure was covered with a thin fibrous capsule and the plate was well preserved. These results indicate that a pituitary plate can be useful for reconstruction of the sellar floor in transnasal-transsphenoidal surgery.

Staged resection of large hypervascular vestibular schwannomas in young adults.

Two young adults underwent resection of large hypervascular vestibular schwannomas (acoustic neuromas) via two-stage surgery. The first patient, a 27-year-old woman with hydrocephalus, had a large hypervascular vestibular tumor in the left cerebellopontine angle (CPA) supplied by the left anterior inferior cerebellar artery (AICA) and posterior inferior cerebellar artery (PICA). The second patient, a 34-year-old woman, had a large AICA-supplied hypervascular vestibular tumor in the left CPA that displaced the brain stem significantly. At the initial stage, only the lateral aspect of the tumor was debulked due to excessive bleeding from the tumor bed. Angiography 1 or 2 months after the initial operation showed that the tumor was hypovascular. At the second stage, the remnant medial aspect of the tumor was relatively avascular and nonadherent to the brain stem. Without blood transfusion during the second stage, the tumor was removed totally in the first patient and subtotally in the second patient. Pathological examination revealed that dilatated blood vessels were prominently increased at the first surgery; however, at the second surgery, the number of blood vessels had decreased, showing necrosis and degeneration. Although there are no absolute indications for the staged resection of vestibular schwannomas, this procedure may represent one of the safest options for these difficult lesions in young adults.

Fatal severe vasospasm due to rewarming following hypothermia--case report.

A 37-year-old female died of cerebral vasospasm as a complication of rewarming following hypothermia therapy for severe head injury. She presented with severe consciousness disturbance and anisocoria after falling down a flight of stairs. Computed tomography (CT) revealed a right acute subdural hematoma and temporal contusion. Following surgery, mild hypothermia was started and rewarming was completed by the 11th day. Neurological examination showed no abnormalities, but intracranial pressure (ICP) suddenly increased and she manifested anisocoria on the 13th day. Repeat CT revealed a low density area in the right middle cerebral artery region and cerebral angiography showed diffuse narrowing of the main arterial trunks. A cerebrospinal fluid (CSF) sample was collected using an intraventricular ICP monitoring catheter. The CSF level of 8-hydroxy-2'-deoxyguanosine was elevated during the rewarming period, indicating substantial deoxyribonucleic acid (DNA) oxidation. She died on the 15th day due to uncontrollable ICP. Histological examination at autopsy of the narrowed artery found the waving phenomenon in the internal elastic lamina and invasion of inflammatory cells into the adventitia. These findings constitute the possible evidence that free-radical-mediated oxidative DNA damage may be important in the genesis of severe vasospasm due to rewarming following hypothermia.

Congenital ureteral diverticulum coexistent with hydronephrosis caused by vascular compression involving the uterine artery and umbilical ligament: report of a case.

Coexistence of congenital ureteral diverticulum and hydronephrosis caused by vascular compression is a rare entity. The authors experienced a case of congenital ureteral diverticulum coexistent with hydronephrosis caused by aberrant vascular compression by uterine and umbilical arteries in a 14-year-old girl. The authors could not diagnose accurately this abnormality preoperatively by 3-dimensional computed tomography. After partial ureterectomy, including resection of the saccular lesion and ureteroneocystostomy, the frequency of urinary tract infection decreased.

The effect of an oral administration of Lactobacillus casei strain shirota on azoxymethane-induced colonic aberrant crypt foci and colon cancer in the rat.

The preventive effect of oral administration of viable Lactobacillus casei strain Shirota (LcS) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and colon cancers in the rat was investigated. The study consisted of two experiments; in a short-term experiment (Exp-I), the inhibitory effect of 8- and 12-week treatments with LcS. Forty rats each received weekly a subcutaneous injection of AOM at a dose of 15 mg/kg of body weight for 5 weeks. Eight and twelve weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon and the mesenteric lymph nodes (MLN) were removed. The number of ACFs and the surface marker of lymphocytes derived from the MLN were investigated. The large ACF (those comprising four or more aberrant crypts per focus) had significantly decreased in the rats which had consumed the LcS diet. And oral administration of viable LcS significantly recovered CD8 positive lymphocytes to the levels in the control group. In a long-term experiment (Exp-II), 30 rats each received weekly a subcutaneous injection of AOM at a dose of 7. 4 mg/kg of body weight for 10 weeks. Twenty-five weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon were removed. The number and incidence of colon cancers were investigated. The number of rats with colon cancers and the number of colon cancers per rat, were significantly decreased in the rats which had consumed the LcS diet. LcS inhibited chemically-induced colon carcinogenesis in the rat. CD8 positive T lymphocytes may play a key role in the preventive effect against colon carcinogenesis.

A surgical case of solitary plasmacytoma of rib origin with biclonal gammopathy.

Localized solitary plasmacytoma of the bone (SPB) is a rare disease and is characterized by only one or two isolated bone lesions with no evidence of disease dissemination. A previously healthy 44-year-old male was admitted for evaluation of an abnormal radiographic shadow in the left middle lung field with symptoms of left back pain. Radiological evaluation revealed a peripheral opacity in the left chest wall, which was highly suspected to be a chest wall tumor. CT-guided transcutaneous needle biopsy of the tumor was performed and the specimens showed a monomorphous population of mature plasma cells. The bone marrow biopsy findings revealed no evidence of myeloma and bone scanning revealed only abnormal accumulation in the left seventh rib. He had mild M-proteins in a urine sample and Bence-Jones protein was detected. Immunoelectrophoresis revealed mild biclonal gammopathy of Bence-Jones protein of both the kappa and lambda light-chain types. Under a diagnosis of solitary bone plasmacytoma, preoperative radiation therapy with doses of 40 Gy for the tumor was performed. He underwent complete en bloc resection of the chest wall, including one-third of the left sixth and seventh ribs, the intercostal muscle and the parietal pleura. The protein abnormalities in the urine sample disappeared following surgical resection. Adjuvant chemotherapy using melphalan and prednisolone was performed. He is doing well without evidence of tumor recurrence 2 years following his initial diagnosis.

Fournier's gangrene caused by Candida species as the primary organism.

Fournier's gangrene is a rare entity caused by polymicrobial aerobic and anaerobic bacteria. We report a case of Fournier's gangrene caused by Candida as the primary organism. A 65-year-old man presented with perineal soft-tissue infections. He underwent surgical debridement and suprapubic cystostomy with both antifungal and antimicrobial therapy. The histopathologic examination revealed necrotizing fasciitis with Candida species as the sole initial pathogen. The case suggests that primary fungal pathogens should be considered as a causative organism of Fournier's gangrene.

[Metastatic skull tumors from cancers associated with subcutaneous mass lesions].

The incidence of metastatic brain tumors is increasing because of the recent progress in the detection and management of primary cancer. However, metastatic skull tumors from cancers associated with giant subcutaneous mass lesions are rare. We present four patients with metastatic skull tumors: two from hepatic cancer, one from lung cancer, and one from mamma cancer. In these patients, plain skull X-ray and bone CT showed osteolytic lesions. Angiograms revealed a tumor stain fed by abnormal vessels from the external carotid artery. MRI demonstrated masses with marked homogeneous enhancement with the "dural tail sign" in the dura adjacent to the tumors in three skull tumors from hepatic and mamma cancers, and a mass with slightly enhancement without the "dural tail sign" in a skull tumor from lung cancer. At surgery, hemorrhagic well-demarcated tumors were totally removed. The histological diagnosis was skull metastases from cancers in all cases. In cases with the "dural tail sign" on MRI, no tumor cells were seen in the inner layer of the dura and the dura adjacent to the tumors. It is possible that the "dural tail" is due to increased vascular permeability of the dural vessels. The recurrence of these skull tumors was not observed during the follow-up period. Surgical treatment for the metastatic skull tumors from cancers may be indicated to prevent deteriorating neurological symptoms affecting the quality of life.