Clinical and genetic analysis of microtia in Japan.

Microtia is thought to have a multifactorial inheritance, but several investigators disagree. Here we report our survey of the hereditary factors and possible causes. We conducted a questionnaire survey of 428 patients with microtia who were being treated at two hospitals from September 2006 to September 2008. We recorded their age, sex, affected side, duration of gestation, birth weight, age of parents at patients' birth, accompanying malformations, number of siblings, familial occurrence, smoking habit of parents, and medication/disorders of mother during pregnancy, and analysed the results. There were preponderances of male (61%), unilateral (90%) and right-sided disease (59%). Other than the first and second branchial arch syndrome, microtia is often accompanied by other congenital deformities, in particular congenital heart disease; cleft lip, or palate, or both; vertebral defects; and anomalies of extremities. The occurrence in first-degree relatives was 2%. Most maternal disorders and medication taken during pregnancy were common and there was no clear link. Statistically, there was a tendency to low birth weight and high maternal age, but it is not possible to identify these as a specific cause of microtia. Multifactorial inheritance is unlikely to be the cause of microtia as there was only one finding in agreement with its widely accepted characteristics. However, we cannot completely discount it as there were too few cases in some groups to make a judgement.

The reverse superficial temporal artery flap from the preauricular region, for the small facial defects.

BACKGROUND: For the reconstruction of facial defects, the retroauricular flap is generally used. However, this flap has disadvantages, such as venous return disturbance and reddish skin colour peculiar to the retroauricular region. METHODS: Here, we report the reverse superficial temporal artery (STA) flap, elevated from the preauricular region. In our method, the flap is retrogradely elevated including the STA under the skin island in the preauricular region and the temporoparietal fascia around the superficial temporal vessels in the temporal region. The donor site is closed primarily or by the retroauricular flap. RESULTS: Five cases with a pedicled flap and one case with a free flap were treated using our method. In one case, a minor congestion of the flap occurred postoperatively, and temporary facial nerve palsy in another case. In all cases, the results were cosmetically good, and the scar at the donor site was inconspicuous. CONCLUSIONS: As compared to the retroauricular flap, our method is easier to perform and the flap has a reliable blood circulation. Moreover, it can be used with both a pedicled and a free flap, leaving an inconspicuous scar at the donor site, and a colour match without reddish skin. Therefore, when considering reconstruction of small-sized defects on the face, our method is more useful than the retroauricular flap.

Nose and upper lip reconstruction for purpura fulminans.

BACKGROUND: Purpura fulminans (PF) is a rare syndrome of intravascular thrombosis and haemorrhagic infarction of the skin. The initial symptom of PF is peripheral purpura which progresses to necrosis very rapidly. The prognosis of PF is poor, and the mortality is reported to be around 40%. Even if the patient survives, the patient may require amputation or reconstruction for limbs and facial necrosis. CASE REPORT: A 48-year-old male suffered from PF following a left cerebellopontine angle tumour excision. His nose and upper lip fell into necrosis afterwards. We performed nose and upper lip reconstruction at 8 months after the onset. We used a forehead flap for the nasal reconstruction and a free forearm flap for the lining. His upper lip was reconstructed with bilateral nasolabial orbicularis oris myocutaneous flaps. RESULTS: The colour and texture match of the reconstructed nose and lip is good. He could open his mouth wide enough and close completely. CONCLUSIONS: Facial reconstruction after PF is very difficult, because the patient has extensive scarring around the defect and there is little intact facial tissue. However, we performed a facial reconstruction using local flaps as much as possible, and obtained good results.

The relationship between exhaled carbon monoxide and human neutrophil function in the Japanese general population.

We have evaluated the relationship between exhaled carbon monoxide (CO) level and neutrophil-related functions such as reactive oxygen species (ROS) production capability, phagocytic activity and serum opsonic activity in the general population. Serum opsonic activity was determined by measuring the effects of serum on neutrophil ROS production capability using lucigenin- and luminol-dependent chemiluminescence (LgCL, LmCL). LgCL is associated with the detection of O(2)(-) , whereas LmCL mainly detects H(2)O(2) and HOCl, which are higher reactive oxygen radicals. In females, exhaled CO level was found to have positive associations with ROS production capability and LgCL. However, the opposite tendency was seen between exhaled CO level and LmCL in both genders. This result suggests that neutrophil ROS production in females may have contributed to oxidative stress, which led to the increases in intrinsic CO and exhaled CO consequently. Such changes then may have inhibited the process of changing reactive oxygen radicals into higher oxidizing potential levels.

New way to raise the V-Y advancement flap for reconstruction of the lower lip: bipedicled orbicularis oris musculocutaneous flap technique.

We describe a new way to raise the V-Y advancement flap, which is useful for reconstruction of the lower lip. Various other methods have been reported in the past, but it has been necessary to choose the most suitable method for each particular case. A V-Y advancement flap from the submandibular region is one of the useful techniques to reconstruct the lower lip, and it is suitable for a wide horizontal defect. However, the conventional V-Y flap is insufficiently mobile and the reconstructed vermilion is thin because of the limitation of the pedicle. In such a case, the reconstructed lip may sag or cause an embarrassing defect. We developed a new way to raise the flap to obviate these problems. We use the V-Y advancement flap from the inferior margin of the defect in a conventional way after excision of the tumour, and use a mucosal flap to reconstruct the vermilion border. The skin side of the V-Y flap is undermined, and the orbicularis oris muscles are preserved on both sides as pedicles. The flap is then raised as a bipedicled musculocutaneous flap, which has adequate movement. After the flap has been sutured, the superior margin of the flap is de-epithelialised, and used to create the volume of the vermilion border. Functionally and cosmetically good results were achieved.

The acute surgical management of injury to the helix and antihelix in patients with large body surface area burns.

Deformity or loss of the ear may be caused by superficial dermal burns or deep burns. The depth of ear burns is progressive because the ear protrudes from head and is easily affected by external pressure. Therefore, burn wounds of the ear should be debrided as early as possible, before irreversible changes of the cartilage, and covered with healthy tissue. We describe a surgical procedure for treatment of the extensively burned ear. With this technique, the helix is covered by a postauricular advancement flap, and the antihelix is covered by a skin graft. Because the procedure is straightforward and can be completed within a short time, it can be performed at the same time as other life-saving measures. The use of a skin flap permits adequate debridement in terms of both depth and width, minimising the risk of infection. The helix can be reconstructed to provide a natural appearance, and late ulcer formation due to external irritation is prevented. We have treated 15 ears on 11 patients with this procedure and have consistently obtained a satisfactory outcome.

[Clinical analysis of eight patients with primary follicular lymphoma in the duodenum].

We performed a clinical analysis on 8 patients with primary follicular lymphoma in the duodenum taken from among 26 cases of primary gastrointestinal malignant lymphoma treated in our division. The median age was 60 years (range 48 to 82 yr). The ratio of males to females was 4:4. The chief complaints were no symptoms in 4 cases, heartburn in 2 cases, lower abdominal pain in 1 case, and back pain in 1 case. All patients were in clinical stage I EA. Gastroendoscopic findings showed multiple whitish granules around the ampulla of Vater in all patients. Involvement of the site in 6 cases was only located at the second portion; lesions in the other 2 cases were located at the second portion, and at the third portion or fourth portion, respectively. A histological study showed follicular lymphoma grade 1, and an immunohistological study demonstrated that the lymphoma cells were positive for CD79a, CD10, CD20, and bcl-2. Five patients were positive for the FISH analysis fusion signal of IgH/bcl-2 genes. Rituximab with CHOP therapy was performed for 7 patients. Seven patients are currently alive, and one died of uterine cancer. At the medium-term 39 month-follow-up, 7 patients were in complete remission, and 1 patient was in partial remission. Rituximab with CHOP (CVP) therapy is a possible treatment for primary follicular lymphoma in the duodenum. Further consideration of appropriate therapy for this disease might be necessary.

A new technique for harvesting costal cartilage with minimum sacrifice at the donor site.

With conventional procedures for harvesting costal cartilage, several large, full-thickness cartilage blocks are harvested from the chest wall and are cut, shaped, and joined to create the desired form. Many pieces of unused cartilage are discarded excluding those preserved for future use. Conventional procedures for costal cartilage harvesting are also associated with severe problems such as pain, deformity of the chest wall, and a long scar. We developed a new technique that permits only the necessary size and shape of cartilage to be directly harvested with the use of a chisel. With this technique, both sides and the bottom of the cartilage remain intact at the donor site. The anterior perichondrium can be harvested simultaneously. This technique was performed in 28 patients. The required quantities could be harvested in all patients without severe complications such as perforation of the pleura and excessive bleeding. The procedure required 30 min or less in all patients. The length of the skin incision was less than 3 cm in 25 patients and greater than 3 cm in two obese patients and a young man who had hard subcutaneous connective tissue. Pain intensity was markedly lower than that after conventional techniques. Twenty-six patients could walk 1 day after the operation. There were virtually no deformities of the thorax, even in children younger than 10 years. The structure of the reconstructed site was maintained during at least 2 years follow-up in all patients. Our technique for harvesting costal cartilage is associated with smaller scars, less pain, and less deformity of the chest wall than conventional procedures. In addition, it is minimally invasive and can be performed in a short time.

Basaloid squamous-cell carcinoma of the lung in a young woman.

We report a rare case of basaloid squamous cell carcinoma of the lung in a young Japanese woman. An 18-year-old woman presented with productive cough. Chest radiogram and computed tomography (CT) revealed a tumor in the left hilum accompanied by partial atelectasis of the left upper lobe and pleural effusion. Transbronchial fine-needle aspiration cytology supported a tentative diagnosis of primary squamous-cell carcinoma of the lung. The clinical stage was T4N2M1, with multiple bone metastases. Despite a transient response to chemotherapy consisting of carboplatin and paclitaxel, the patient died because of tumor progression 2 months after the start of the chemotherapy. Necropsy established the diagnosis of basaloid squamous-cell carcinoma of the lung. Immunohistochemical studies of the necropsy specimen indicated that the tumor was positive for keratin, vimentin, and S100, and negative for chromogranin A, cytokeratin CAM5.2, and bcl-2. Besides the rarity of the disease itself, the present case seemed to have additional uniqueness in that the patient was 18 years old and female. This is the youngest patient with a case of basaloid squamous cell carcinoma of the lung ever reported.

Hypoxia-inducible factor-1 drives the motility of the erythroid progenitor cell line, UT-7/Epo, via autocrine motility factor.

OBJECTIVE: It is well known that hypoxic stress strongly enhances erythropoiesis, but the effect of hypoxia on erythroid progenitors has not been examined precisely. In the present study, using the erythropoietin-dependent cell line UT-7/Epo, which has characteristics of erythroid progenitors, we investigated a novel role of hypoxia in erythropoiesis. METHODS: UT-7/Epo and four other hematopoietic and lymphoid cell lines (HL-60, THP-1, Raji, and CEM) were cultured in 20%, 5%, or 1% O2. Morphology was observed under a phase-contrast microscope. Cell motility was evaluated using the Transwell migration assay. An analysis of the protein level of hypoxia-inducible factor-1 (HIF-1) alpha and autocrine motility factor (AMF) was conducted using Western blotting and immunocytochemistry, respectively. Reverse transcription polymerase chain reaction was performed to evaluate the expression of AMF mRNA. Human bone marrow stromal cells were used in cocultures with UT-7/Epo. Apoptosis of UT-7/Epo was examined by immunocytochemistry using an antiactive form of caspase 3 antibody. RESULTS: Among the five cell lines, UT-7/Epo exhibited active pseudopodial extension in hypoxia (1% O2), and cell motility was increased. HL-60, THP-1, Raji, and CEM did not show an increase in cell motility even in 1% O2. In addition, expression of the alpha-subunit of HIF-1 was activated by hypoxia, and expression of the mRNA and protein of AMF induced by HIF-1, increasing cell motility, was promoted. The addition of an HIF-1 inhibitor, cadmium chloride (CdCl2), or alpha-ketoglutarate (2-oxoglutarate) decreased the AMF mRNA expression, and an AMF inhibitor, erythrose 4-phosphate, decreased the cell motility. When UT-7/Epo was cocultured with human bone marrow-derived stromal cells that significantly inhibit the apoptosis of UT-7/Epo, the migration of UT-7/Epo under the stromal cells (pseudoemperipolesis) was increased in hypoxia. CONCLUSION: Under hypoxic conditions, erythroid progenitors may exhibit active migration in the bone marrow and the opportunity for contact with stromal cells increases, inhibiting apoptosis.

Monocyte/Macrophage-specific marker CD163+ histiocytic sarcoma: case report with clinical, morphologic, immunohistochemical, and molecular genetic studies.

We report a case of a very rare disorder, histiocytic sarcoma, from a review of our autopsy cases. The neoplastic cells that proliferated in organs throughout the body were large cells containing eosinophilic cytoplasm and pleomorphic nuclei with prominent nucleoli. In the bone marrow, erythrophagocytosis by neoplastic cells was observed. The neoplastic cells were positive not only for lysozymes and CD68 (KP-1, PG-M1, and Ki-M1P) but also for a monocyte/macrophage-specific marker, CD163. In contrast, the results of tests for markers of myeloid cells, lymphoid cells, and epithelial cells were all negative. In a polymerase chain reaction study of paraffin-embedded tissues, analyses for the rearrangement of immunoglobulin heavy chain and T-cell receptor-gamma genes were negative. The current World Health Organization diagnostic criteria for histiocytic sarcoma regard immunohistochemical investigation as crucial. In this regard, the highly specific positivity for CD163 in this patient indicates that immunohistochemical staining of CD163 is very useful for the diagnosis of histiocytic sarcoma.

Multiple myeloma complicated by autoimmune hemolytic anemia.

A 57-year-old man was admitted with severe anemia and hypergamma globulinemia. After a diagnosis of multiple myeloma and autoimmune hemolytic anemia was made, chemotherapy rapidly decreased the M-protein level and improved his anemia with normalization of the direct Coombs test. The immunoglobulin binding to the patient's red cells was immunoglobulin G kappa chain like the myeloma M-protein. However, monoclonal immunoglobulin G derived from short-term culture of the patient's bone marrow mononuclear cells did not bind to a panel of red cells. Therefore, the relationship between the M protein produced by his myeloma cells and hemolysis remained unclear.

Detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma by whole-body MRI: comparison with bone and 67Ga scintigraphies.

The aim of this study was to evaluate the diagnostic potential of whole-body MRI (WB-MRI) for the detection of bone marrow and extramedullary involvement in patients with non-Hodgkin's lymphoma. WB-MRI, which was performed on 34 patients, consisted of the recording of T1-weighted spin-echo images and a fast STIR sequence covering the entire skeleton. The WB-MRI findings for bone marrow and extramedullary involvement were compared with those from (67)Ga and bone scintigraphies and bone marrow biopsy results. Two MRI specialists reviewed the WB-MRI results and two expert radiologists in the field of nuclear medicine reviewed the bone and (67)Ga scintigraphy findings. Bone marrow and extramedullary involvement of non-Hodgkin's lymphoma were confirmed by follow-up radiographs and CT and/or a histological biopsy. The detection rate of WB-MRI was high. More bone marrow involvement was detected by biopsy, and more lesions were detected by scintigraphies. In total, 89 lesions were detected by WB-MRI, whereas 15 were found by biopsy, 5 by (67)Ga scintigraphy, and 14 by bone scintigraphy. WB-MRI could also detect more extramedullary lesions than (67)Ga scintigraphy; i.e., 72 lesions were detected by WB-MRI, whereas 54 were discovered by (67)Ga scintigraphy. WB-MRI is useful for evaluating the involvement of bone marrow and extramedullary lesions throughout the skeleton in patients with non-Hodgkin's lymphoma.

MLL/AF-1p fusion in therapy-related early pre-B acute lymphoblastic leukemia with t(1;11)(p32;q23) translocation developing in the relapse phase of acute promyelocytic leukemia.

We report the development of therapy-related early pre-B acute lymphoblastic leukemia in a patient administered a topoisomerase II inhibitor, etoposide, a consolidation therapy agent for acute promyelocytic leukemia. Our case is of interest because of simultaneous relapse of the original leukemia and onset of therapy-related leukemia and relatively rare t(1;11)(p32;q23) translocation with confirmed MLL/AF-1p fusion. This case suggests that careful monitoring for MLL gene rearrangements is necessary after administration of topoisomerase II inhibitors.

[Seven patients with stage I and II primary testicular lymphoma].

Seven patients with stage I and II primary testicular lymphoma (PTL) have been treated since 1990 to the present at Kawasaki Medical School. All patients, whose median age was 56 yrs, had initially complained of swelling of the scrotal contents. The lesions were on the right in two patients, on the left in five, and no patient had bilateral lesions. The histological diagnosis was diffuse large B-cell type in all patients. Five patients were classified as Ann Arbor stage I, and two at stage II. After high-orchiectomy for resection of tumor, two patients received chemotherapy alone, with a combination of chemotherapy and irradiation of the contralateral testis in the remaining five. Complete remission was achieved in all seven patients, but relapse occurred later in one. As it is recognized that, even in localized stage or low risk group PTL patients, the relapse rate in the central nervous system (CNS) and contralateral testis is quite high, chemotherapy, prophylactic CNS treatment and radiation of the contralateral testis after tumor resection should be included in the management of PTL.

[A case of fatal MALT lymphoma of pulmonary origin with systemic metastasis and manifesting macroglobulinemia].

The patient was a 61-year-old man whose chest radiography showed infiltration in both lung fields. MALT lymphoma was diagnosed from transbronchial lung biopsy (TBLB) specimens. The serum monoclonal IgM level then increased, and plasma cells and lymphoplasmacytoid cells were found in a bone marrow examination, indicating macroglobulinemia as a complication. Despite chemotherapy, systemic metastasis led to the patient's death. Our report is accompanied with a review of literature, because no report of MALT lymphoma of pulmonary origin complicated with macroglobulinemia exists, and it is considered that the macroglobulinemia in this case was related to the MALT lymphoma.

[Acute myelogenous leukemia associated with severe esophageal stricture after chemotherapy].

A 41-year-old woman with relapsed acute myelogenous leukemia was treated twice with idarubicin hydrochloride and cytarabine. She developed a 6-cm-long stricture in the lower esophagus 12 days after re-induction therapy. Although she had preceding candida infection, it is suspected that her stricture was caused by mucosal damage due to chemotherapeutic agents. This case suggests that the possibility of esophageal stricture should be considered in patients with swallowing disturbance after intensive chemotherapy.