Carcinoma of the external auditory canal: histological and treatment groups.

OBJECTIVE: Evaluation of the clinical and pathological factors associated with the treatment and outcomes of external auditory canal (EAC) carcinomas. METHODOLOGY: A retrospective review of clinical and pathological analysis was performed on 23 patients who were histologically diagnosed with EAC carcinomas and treated at Hamamatsu University hospital. We evaluated the clinical staging, treatment methods, pathological diagnosis (particularly squamous cell carcinoma, SCC), and patient outcomes. Main outcome measures include staging, treatment procedures, pathological features, and estimated survival rates. RESULTS: The 5-year overall survival (OS) of study participants was 75.2% and the 10-year OS was 60.2% using the Kaplan-Meier method. The prognosis for SCC was poor compared with other carcinomas (p= 0.0462). The prognoses for SCC patients after treatment with surgery alone and after postoperative radiotherapy or chemoradiotherapy were significantly better than for patients with unresectable tumours (p = 0.0004 and p = 0.0001, respectively). There was no significant difference among the four tumour stage groups. Information about patients' survival status was obtained after a median follow-up period of 57.5 months (range, 7-151 months). CONCLUSION: Our survival analysis data for carcinoma of the EAC demonstrates that SCC and unresectable cases are associated with poor outcomes. Outcomes for patients with operable disease more closely parallel the survival curves of patients with advanced stage T4 disease. Patients with SCC should be strictly categorized as cases with severe disease.

Relevance of level IIb neck dissection in patients with papillary thyroid carcinoma.

BACKGROUND: Cervical nodal metastasis is a key prognostic factor in patients with papillary thyroid carcinoma. The role of lymph nodes in papillary thyroid carcinoma management and prognosis remains controversial. METHODS: Level IIb lymph nodes obtained from 44 patients with papillary thyroid carcinoma were histopathologically examined retrospectively. Specimens were classified as ipsilateral or contralateral. The number of dissected nodes and prevalence of level IIb metastasis were compared according to pre-operative clinical nodal stage. RESULTS: In the node-negative neck, the prevalence of contralateral and ipsilateral IIb nodes was 0 out of 20 and 0 out of 3, respectively. In the node-positive neck, the prevalence of contralateral and ipsilateral IIb nodes was 1 out of 13 (7.70 per cent) and 3 out of 41 (7.32 per cent), respectively. Clinically determined and pathologically confirmed level IIb node negativity were significantly associated. Thirty-four patients (77.3 per cent) developed accessory nerve complications from level IIb dissection. CONCLUSION: Level IIb neck dissection for papillary thyroid carcinoma may be required if pre-operative examination reveals multilevel, level IIa or suspicious level IIb metastasis.

Ring closure of carbon nanotubes.

Lightly etched single-walled carbon nanotubes are chemically reacted to form rings. The rings appear to be fully closed as opposed to open coils, as ring-opening reactions did not change the structure of the observed rings. The average diameter of the rings was 540 nanometers with a narrow size distribution. The nanotubes in solution were modeled as wormlike polymer chains, yielding a persistence length of 800 nanometers. Nanotubes shorter than this length behave stiffly and stay nearly straight in solution. However, nanotubes longer than the Kuhn segment length of 1600 nanometers undergo considerable thermal fluctuation, suggesting a greater flexibility of these materials than is generally assumed.

Low-dose MTX for the treatment of acute and chronic graft-versus-host disease in children.

We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m(2) weekly. Seven of ten patients (70%) with aGVHD responded well to MTX, thus resulting in the achievement of either a complete response (CR) or a partial response (PR). The dose of prednisone could be reduced to equal to or lower than 1 mg/kg in the responding patients at the end of MTX therapy. The median number of MTX administrations was five (range, 1-7). Ten (58.8%) of seventeen patients with cGVHD achieved CR or PR. The dose of prednisone could be reduced to lower than 0.4 mg/kg in 16 of 17 patients and seven patients could discontinue prednisone. The median duration of MTX administration was 18 months (range, 1-68). The toxicities of grade III to IV occurred in only six patients presenting cytopenias or elevated levels of serum transaminases. Low-dose MTX was tolerable and effective for the steroid-refractory or -dependent GVHD in reducing the dose of steroid without increasing the risk of opportunistic infection.

Emergent thyroidectomy with sternotomy due to acute respiratory failure with severe thyroid storm.

Huge cervical and mediastinal masses may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Thyroid storm is also a life-threatening endocrine emergency originating almost exclusively from uncontrolled Graves' disease. We report a case of a 42-year-old man with acute upper airway obstruction and tachycardia from progressive swelling of a giant thyroid, in conjunction with thyroid storm resulting from uncontrolled Graves' disease. Fibreoptic-assisted nasal intubation was performed while the patient was awake, immediately followed by emergency total thyroidectomy via a cervical and sternal approach. The patient had an uneventful postoperative course and recovered well. Respiratory failure due to swelling of a giant thyroid is a life-threatening condition and should be treated immediately with endotracheal intubation while the patient is awake following emergent total thyroidectomy, even with a sternotomy.

Allogeneic hematopoietic stem cell transplantation provides sustained long-term survival for patients with adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATLL) is a distinct peripheral T-cell neoplasm that is highly resistant to chemotherapy. Several groups, including ours, have reported encouraging results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with ATLL. To confirm our previous report and to establish the basis for a phase II clinical study, we analyzed 40 allo-HSCT for acute and lymphoma types of ATLL in seven institutions in Japan between 1997 and 2002. All evaluable cases entered complete remission (CR) after allo-HSCT and the median survival time was 9.6 months for all patients. The estimated 3-year overall and relapse-free survival, and disease relapse were 45.3, 33.8 and 39.3%, respectively. Among 10 cases with ATLL relapse, five cases achieved CR again: three by the reduction or cessation of immunosuppressive agents, which suggested a graft-versus-ATLL (GvATLL) effect. However, univariate or multivariate analysis did not show any benefit of graft-versus-host disease (GVHD) on the prevention of relapse. These results suggested that allo-HSCT was effective for some patients with aggressive ATLL, and that the GvATLL effect could be achieved even without GVHD. A new phase II trial to test the efficacy of allo-HSCT for ATLL is warranted.

Response of non-T, non-B acute lymphocytic leukemia cells to phorbol ester.

Non-T, Non-B acute lymphocytic leukemia cells were cultured in vitro with or without the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), a potential modulator of differentiation. The eight cases studied were representative of non-T, non-B acute lymphocytic leukemia (ALL) cells and expressed amounts of la antigens varying from 0.9 X 10(5) to 7.1 X 10(5) molecules/cell; these levels were measured in a cellular radioimmunoassay with 21w4 monoclonal antibody directed at a monomorphic human la determinant. With all cases, TPA caused a significant increase in the level of la. Cultures with TPA expressed 4.3 times the amount of la found on fresh ALL cells, and a correlation was observed (r = 0.92) between the level of la following culture with TPA and that found on fresh ALL cells. A 25% increase in the modal volume of ALL cells was also caused by TPA. There was no detectable induction of surface or cytoplasmic immunoglobulin and no change in the expression of the common ALL antigen. Inhibition of [3H]thymidine incorporation and stimulation of 14C-labeled amino acid incorporation were observed in the presence of TPA, suggesting that the increase in la level occurs concurrently with an increase in protein synthesis induced by phorbol ester. Following culture with TPA, a substantial increase in the ability of the ALL cells to stimulate in a mixed-lymphocyte reaction was obtained. These results suggest that ALL cells, like other cell types, are susceptible to the effects of TPA and respond by changes in cell volume, surface antigen expression, and mixed-lymphocyte reaction stimulating capacity.

Survival outcomes after surgical resection of pulmonary metastases of head and neck tumours.

BACKGROUND: There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers. METHODS: A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated. RESULTS: The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan-Meier method. The prognosis for patients with a disease-free interval of less than 24 months was poor compared to those with a disease-free interval of greater than 24 months (p = 0.0234). CONCLUSION: Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection.

Insulin and glucagon secretion after pancreatectomies. Correlation of secretion and hormonal contents of remaining pancreas.

We studied whether insulin and glucagon secretory capacities change in relation to the corresponding hormonal contents in the pancreas remnant after pancreas resection. The following groups of dogs were used: sham operated (S-O), left pancreatectomized (L-Px), right pancreatectomized (R-Px), subtotal pancreatectomized (St-Px), and total pancreatectomized (T-Px). Endocrine functions were assessed by intravenous glucose tolerance test (IVGTT) and insulin tolerance test (ITT) in each dog under anesthesia before surgery and 1 wk after. In these five groups, the insulin secretory capacities, assessed as the integrated incremental secretion of immunoreactive insulin (sigma delta IRI) from the IVGTT, decreased to 95 +/- 11, 78 +/- 9, 48 +/- 8, 12 +/- 8, and -4 +/- 4% of the respective preoperative values, and these values were proportional to the percentage residual weight (100, 64 +/- 2, 35 +/- 2, 13 +/- 2, 0%) and IRI content (100, 59 +/- 4, 45 +/- 3, 10 +/- 2, 0%) of the pancreas remnant. After surgery, glucagon secretory capacity, the integrated incremental secretion of immunoreactive glucagon (sigma delta IRG) during the ITT, decreased significantly in the L-Px, St-Px, and T-Px groups but not in the R-Px group. The sigma delta IRG values as percentages of the preoperative values were 109 +/- 25, 46 +/- 11, 89 +/- 13, 19 +/- 11, and 3 +/- 3%, respectively, for the five groups. These values were proportional to the percentage residual IRG contents of the pancreas remnants (100, 48 +/- 6, 65 +/- 8, 12 +/- 2, 0%) rather than to the percentage residual pancreatic weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Allogeneic hematopoietic stem cell transplantation for 27 children with juvenile myelomonocytic leukemia diagnosed based on the criteria of the International JMML Working Group.

Prognostic factors of juvenile myelomonocytic leukemia (JMML) have not been clarified because of its very low incidence and inaccuracy in the diagnosis. The purpose of this study was to evaluate children with JMML given an allogeneic hematopoietic stem cell transplantation (SCT) and the role of different variables potentially influencing outcome in a nationwide survey in Japan based on the newly proposed criteria by the International JMML Working Group. The study patients were 27 children who underwent SCT among 55 JMML patients retrospectively collected in the survey. The source of grafts was HLA-identical siblings in 12 cases, HLA-matched unrelated individuals in 10 and others in five. Total body irradiation was used in 18 cases. Event-free and overall survival (OS) at 4 years after SCT were 54.2 +/- 11.2% (s.e.) and 57.9 +/- 11.0% (s.e.), respectively. Six patients died of relapse and three of complications. Patients with abnormal karyotypes showed a significantly lower OS than those with normal karyotypes (P < 0.001). Patients below 1 year of age showed a significantly higher OS than those of 1 year of age or more (P = 0.02). Patients with grade 0-1 acute graft-versus-host disease (GVHD) or chronic GVHD had a more favorable OS than those without them, although they were not statistically significant (P > 0.05). Other variables studied were not associated with OS. A multivariate analysis of these factors yielded the abnormal karyotype as the only significant risk factor for lower OS (risk ratio: 11.0; 95% CI: 2.7-45.1).

High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.

An effective chemotherapeutic regimen for acute myeloid leukemia and myelodysplastic syndrome in children with Down's syndrome.

In recent pediatric collaborative studies of acute myeloid leukemia (AML), patients with Down's syndrome (DS) have better outcome than other patients when they were treated according to their intensive AML protocols. This may be attributed to enhanced sensitivity of DS AML cells to selected chemotherapeutic agents. We evaluated a less intensive chemotherapeutic regimen which was specifically designed for children with AML-DS. Remission induction chemotherapy consisted of daunorubicin (25 mg/m2/day for 2 days), cytosine arabinoside (100 mg/m2/day for 7 days), and etoposide (150 mg/m2/day for 3 days). Patients received one to seven courses of consolidation therapy of the same regimen. Thirty-three patients were enrolled on the study and their clinical, hematologic and immunophenotypic features were analyzed. Of the 33 patients, all were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia or myelodysplastic syndrome. All patients achieved a complete remission and estimated 8 year event-free survival rate was 80+/-7%. Three patients relapsed and two died due to cardiac toxicity and one due to septic shock. The results of our study showed that patients with AML-DS constitute a unique biologic subgroup and should be treated according to a less intensive protocol designed for AML-DS.

Clinical characteristics and the prognosis of rhabdomyosarcoma - a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

AIM: There have been no nationwide group studies for patients with rhabdomyosarcoma in Japan. This study aims to assess the actual state of treatments and their outcome. PATIENTS AND METHODS: From 1982 to 1996, 79 rhabdomyosarcomas were registered by the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area. The prognostic factors and treatments were assessed based on the 5-year survival rate. The staging was done according to the Intergroup Rhabdomyosarcoma Study (IRS) Clinical Grouping Classification. RESULTS: The 5-year survival rate for all patients was 39.1 %. The survival rates for each factor were as follows, according to 1) group; 77.8 % for Group I, 51.9 % for Group II, 33.7 % for Group III, and 20.2 % for Group IV; 2) primary site: 56.3 % for the head and neck, 43.8 % for the parameningeal region, 12.5 % for the extremity, 58.3 % for the genitourinary region, and 30.5 % for the others; 3) histology: 35.8 % for the embryonal type, 36.8 % for the alveolar type. CONCLUSIONS: Altogether, the outcome of this study was poor. To improve outcomes, a new nationwide group study for rhabdomyosarcoma, which we belong to, has just started in Japan.

Protracted dormancy of pre-leukemic stem cells.

Cancer stem cells can escape therapeutic killing by adopting a quiescent or dormant state. The reversibility of this condition provides the potential for later recurrence or relapse, potentially many years later. We describe the genomics of a rare case of childhood BCR-ABL1-positive, B-cell precursor acute lymphoblastic leukemia that relapsed, with an acute myeloblastic leukemia immunophenotype, 22 years after the initial diagnosis, sustained remission and presumed cure. The primary and relapsed leukemias shared the identical BCR-ABL1 fusion genomic sequence and two identical immunoglobulin gene rearrangements, indicating that the relapse was a derivative of the founding clone. All other mutational changes (single-nucleotide variant and copy number alterations) were distinct in diagnostic or relapse samples. These data provide unambiguous evidence that leukemia-propagating cells, most probably pre-leukemic stem cells, can remain covert and silent but potentially reactivatable for more than two decades.

Antitumor effect of transcatheter oily chemoembolization for hepatocellular carcinoma assessed by computed tomography: role of iodized oil.

The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82 patients with unresectable hepatocellular carcinoma (HCC) by computed tomography more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered to 40 cases. No significant differences were found in the patient background characteristics between the DOE-treated group and the EOE-treated group. Tumor regression of more than 50% of the product of two dimensions was observed in 26 DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No difference in antitumor effect was observed between DOE and EOE, although a sufficient dose per tumor volume would be required to manifest an antitumor effect on hepatocellular carcinoma.

Appraisal of combination treatment for hepatocellular carcinoma: long-term follow-up and lipiodol-percutaneous ethanol injection therapy.

Since 1988, 124 patients with hepatocellular carcinoma were treated in our departments. Among them, 31 cases treated by surgical resection and 30 cases administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte, France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-, and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy group. The follow-up results at less than 4 years after the procedures revealed that the survival rate with the combination therapy was slightly better than that with the surgical treatment. However, in the subsequent 4 years, the survival rate of the combination therapy group decreased rapidly. The reasons for this deterioration were local recurrence and/or new primary lesions of hepatocellular carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the ethanol so that the location of the injected ethanol could be easily confirmed. The effectiveness of L-PEIT was thus confirmed by computed tomography, performed on the following day. Defective Lipiodol accumulation in the tumor and/ or neighboring tissues was able to be corrected by additional ethanol injections. With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore, a better prognosis is expected.

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Needle tract implantation of hepatocellular carcinoma after percutaneous liver biopsy.

The authors report a case of needle tract implantation of hepatocellular carcinoma following percutaneous biopsy of the liver. The patient, a 62-year-old Japanese male, was found to have a small hepatocellular carcinoma diagnosed by needle biopsy; this was followed by transcatheter chemoembolization, a combination of transcatheter arterial infusion of adriamycin and transcatheter arterial embolization of Gelfoam, and right lobectomy. Eight months after the biopsy and the lobectomy, a nodule of hepatocellular carcinoma, measuring 3.5 cm in diameter, was found at the site of the previous biopsy and excised. The patient is doing well without further recurrence of tumor 23 months after the lobectomy and 15 months after the excision of the implanted tumor in the subcutis.

Cytoprotective effect of prostaglandin I2 on ischemia-induced hepatic cell injury.

The protective effect of prostaglandin I2 (PGI2) on ischemia-induced liver cell injury was investigated during 60-min, 75-min, and 90-min liver ischemia. Vehicle-treated rats tolerated the 75-min hepatic ischemia poorly. Only 25% of the rats in this group survived more than 7 days. However, the survival rate of PGI2-treated rats (350 ng/kg/min) significantly improved to 67%. Liver cell organelles were well-preserved by the PGI2 treatment. Adenosine triphosphate levels in the liver of the PGI2-treated rats were significantly higher than those of vehicle-treated rats at 60 min of reoxygenation following 75-min ischemia. Cyclic 3'-5' adenosine monophosphate levels markedly increased during 60-min PGI2 infusion. Cyclic 3'-5' guanosine monophosphate levels also significantly increased during the PGI2 infusion and were still higher than those of vehicle-treated rats at the end of the 75-min ischemia. Although the exact cytoprotective mechanism of PGI2 at the cellular level is still unclear, our results demonstrate that elevated ATP and cyclic nucleotides levels play an important role in liver cell preservation during ischemia.

Passive enhancement of rat heart allografts by xenogeneic antidonor sera raised in rabbits.

Antilymphocyte serum (ALS) was raised in rabbits immunized by administration of lymphoid cells from Sprague-Dawley (SpD) rats. The ALS was rendered specific for the SpD strain by complete absorption by Wistar rat lymphoid cells. The specificity was considered to be predominantly directed to SpD Ir gene-associated (Ia) antigens, since absorption by SpD erythrocytes failed to abolish lymphocytotoxic activities. Alloantibody production by Wistar rats sensitized with SpD spleen cells was completely inhibited by simultaneous injections of SpD-specific ALS. This effect was specific as normal alloantibody production occurred when Wistar rats were immunized with ACI cells, as a third party. Although this ALS exhibited restricted enhancing ability on skin allograft survival, it was capable of significantly prolonging the survival of heart allografts from SpD to Wistar rats. The ALS showed blocking activities on mixed lymphocyte culture (MLC) but had no effect on cell-mediated cytotoxicity (CMC). The enhancing activity was thus considered to be mediated by an afferent blockage of immune responses.