Assessing the histological type and grade of primary parotid carcinoma by fine-needle aspiration and frozen section.

OBJECTIVE: The aim of this study is to compare preoperative fine needle aspiration cytology (FNAC) and intraoperative frozen section (FS) for the correct identification of malignancy, histological grade, and histological type. METHODS: FNAC was performed on all 105 patients and FS on 71 patients with parotid carcinoma. RESULTS: The rate of correctly determining the histological grade by FNAC and FS was 32% and 73%, respectively. The correct diagnosis rate for both the histological type and grade by FNAC and FS was 20% and 48%, respectively. CONCLUSIONS: The correct grading of both high and low/intermediate grade carcinoma is possible in 70-80% of patients by FS. If the histological grade is identified correctly, the extent of resection can usually be decided appropriately. Therefore, we should put emphasis on determining the histological grade.

Radiotherapy concurrent with S-1 and radiotherapy alone for T2N0 glottic carcinoma: a retrospective comparative study.

OBJECTIVE: We examined the completion rate, safety, and adverse events in patients with T2N0 glottic carcinoma who received chemoradiotherapy with S-1 (tegafur-gimeracil-oteracil potassium). METHODS: In T2N0 glottic carcinoma patients, we retrospectively compared the local control rate and outpatient therapy completion rate between 20 patients who received radiotherapy plus S-1 (S-1 group) and 20 who received radiotherapy alone (RT group). RESULTS: Local recurrence was not detected in any of the 20 subjects from the S-1 group, whereas local recurrence was found in 4 of the 20 subjects (20%) from the RT group (p<0.05). Outpatient treatment was completed by 15 of the 20 subjects from the S-1 group and 17 of the 20 subjects from the RT group (p=0.43). CONCLUSION: We investigated chemoradiotherapy with S-1 in patients who had T2N0 glottic carcinoma and found a higher local control rate when compared with radiotherapy alone as well as comparable safety for outpatient delivery.

Novel differential diagnostic method for superficial/deep tumor of the parotid gland using ultrasonography.

BACKGROUND: The purpose of this study was to prepare the ultrasonographic diagnostic criteria on parotid tumors for preoperative differentiation of superficial and deep tumors. METHODS: We evaluated 154 patients with a benign parotid tumor who underwent surgery. The minimum thickness of normal parotid gland tissue between the parotideomasseteric fascia and tumor (minimum fascia-tumor distance [MFTD]) was measured on preoperative ultrasonography and compared among tumors at different locations, and the optimum cutoff value to differentiate a deep tumor was identified. RESULTS: The MFTD showed significant differences between superficial and deep tumors and between inferior pole and deep tumors. The sensitivity, specificity, and accuracy of an MFTD ≥3 mm for the differentiation of deep tumors were 85%, 91%, and 89%. CONCLUSION: A tumor with an MFTD ≥3 mm on preoperative ultrasonography is very likely to be a deep tumor based on a new differentiation method for deep parotid tumors considering those present at other locations.

Role of cytokines in lavage or drainage fluid after hemithyroidectomy in wound healing: involvement of histamine in the acceleration and delay of wound healing.

Wound healing is a sophisticated biologic process. In the case of hemithyroidectomy, the operation time is relatively short with small tissue damage and without skin excision, and bacterial contamination before, during, and after the operation is uncommon. Here, we explored which cytokine(s) affected the rates of healing of skin wounds after hemithyroidectomy of 29 patients. We assessed the amounts of cytokines (e.g., interleukin-6, platelet-derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and tumor necrosis factor-α) in either the preoperative or postoperative lavage fluids, or in the drainage fluids on postoperative days (PODs) 1-8. All of these cytokines showed a similar pattern; after reaching a peak on POD1, the production fell sharply on POD2-8, revealing that wound healing commenced on POD1. The rates of wound healing were inversely related to the levels of histamine in six patients (i.e., those with the three largest and those with the three smallest total volumes of drainage fluid on POD1): high (or low) levels of histamine in the postoperative lavage fluids with low (or high) levels in the drainage fluids on POD1 caused earlier (or the delay of) wound healing, suggesting involvement of histamine in the acceleration and delay of wound healing.

Late nodal metastasis of T2 oral cancer can be reduced by a combination of preoperative ultrasonographic examination and frozen section biopsy during supraomohyoid neck dissection.

CONCLUSION: The occult metastasis rate for T2 oral cancer can be reduced by ultrasonography (US). Also, the late metastasis rate is considered to be reduced by combining US with frozen section biopsy (FSB) during supraomohyoid neck dissection (SOHND). OBJECTIVES: Early oral cancer has been reported to show occult metastases in 15-53% of patients, but the criteria or methods for the diagnosis of cervical lymph node metastasis are unclear in many studies, and there is no clear definition of occult metastasis. In patients with T2 oral cancer, the diagnosis of lymph node metastasis by US and its pathological diagnosis (pN) after neck dissection were compared to evaluate the usefulness and limitations of US, occult metastasis rate, significance of SOHND as preventive neck dissection, and use of FSB. METHODS: A total of 73 patients with T2 oral cancer were investigated retrospectively. Modified radical neck dissection (MRND) was performed in N+ patients, and SOHND was carried out in N0 patients. FSB was performed in all patients undergoing SOHND. US and pN diagnoses were compared. RESULTS: The occult metastasis rate was 18% when occult metastases were limited to those detected by SOHND and 22% when late nodal recurrences were also included.

Diagnostic criteria of ultrasonographic examination for lateral node metastasis of papillary thyroid carcinoma.

CONCLUSION: Considering the incidence of metastasis from papillary thyroid carcinoma (PTC) with respect to the lateral cervical regions and limited detection on preoperative ultrasonography (US), level II to IV dissection may be essential when lateral node metastasis (LNM) is detected on preoperative US. OBJECTIVES: LNM is frequent in patients with PTC. However, a consensus regarding its preoperative diagnosis and the indication/extent of lateral node dissection (LND) has not been reached. We prepared criteria for diagnosing LNM from PTC using US. Furthermore, we investigated the usefulness and limits of US and appropriate extent of dissection. PATIENTS AND METHODS: We conducted a retrospective study in 70 patients with PTC (80 sides) in whom LNM was detected preoperatively, and level II to V LND was performed. We compared the results of the preoperative diagnosis of LNM using US in accordance with the criteria with those of histopathological diagnosis after LND. RESULTS: Diagnostic criteria for LNM were a minor axis of 6 mm or more and a minor/major axis ratio of 0.5 or more. Histopathologically, metastasis was detected in 467 lymph nodes. Of these, 199 (43%) were detected on US, and met the diagnostic criteria.

Planned fractionated boron neutron capture therapy using epithermal neutrons for a patient with recurrent squamous cell carcinoma in the temporal bone: a case report.

BACKGROUND: We describe the first case of extensive squamous cell carcinoma in the temporal bone recurring after surgery, conventional radiotherapy, and chemotherapy, which was treated using planned fractionated boron neutron capture therapy (BNCT). METHODS: A 42-year-old patient received BNCT twice with a 1-month interval to ensure neutron capture in the deep lesion. We used an epithermal neutron beam as the neutron source and boronophenylalanine as the boron compound. The total radiation doses in the tumor beneath the skin, at the deepest point of the tumor, and in the skin around the right auricle were estimated as 41.8, 36.9, and 15.8 Gy-Eq, respectively. RESULTS: Radiological studies performed 6 months after the first BNCT showed obvious tumor shrinkage and no evidence of residual tumor. CONCLUSION: We believe that planned fractionated BNCT is an effective treatment option for patients with inoperative extended carcinomas in the temporal bone.

Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation.

Chromosomal translocations (CTs) between immunoglobulin (Ig) genes and the BCL6 proto-oncogene are frequently associated with diffuse large B-cell lymphomas (DLBCLs) and follicular lymphomas (FLs) and are implicated in the development of these lymphomas. However, whether Ig/BCL6 translocation per se is sufficient to drive malignant transformation is not clear. To understand the biology of Ig/BCL6-translocated cells prior to their malignant transformation, we developed a system capable of detecting 1 to 3 Igmu/BCL6 CT cells in 1 million mixed cells through the detection of chimeric Imu-BCL6E2 and BCL6E1-Cmu1 transcripts that reflect reciprocal Igmu/BCL6 translocations. The chimeric transcripts that existed in the vast majority of normal lymphoid tissues are due to Igmu/BCL6 CT and were not generated from trans-splicing. Both Imu-BCL6E2 and BCL6E1-Cmu1 transcripts were coexpressed in the same cell populations. The Ig/BCL6 recombination junctions themselves were isolated from B-cell subpopulations expressing the Imu-BCL6 transcripts. The appearance of Igmu/BCL6 CT was associated with cells expressing germinal center but not naive B-cell markers. This study shows that Ig/BCL6 translocations occur in germinal center-stage B cells in healthy humans, and that Ig/BCL6 CTs per se are not likely sufficient to cause the malignant transformation in the context of human B cells.

IFN-gamma: a cytokine essential for rejection of CTL-resistant, virus-infected cells.

We recently demonstrated differential susceptibility of cells expressing viral antigen to killing by antigen-specific cytotoxic T lymphocytes (CTLs). In addition, interferon-gamma (IFN-gamma) has been implicated in the clearance of some viruses from tissues. We explored the role of IFN-gamma in the cytotoxicity of Sendai virus-specific CTLs against virus-infected RL(male symbol)1 (T cell leukemia) or Meth A (fibrosarcoma) cells, as well as the growth of subcutaneously (s.c.) transplanted, virus-infected cells in IFN-gamma(+/+) or IFN-gamma(/) mice of the syngeneic strain (BALB/c). Sendai virus-specific CTLs were cytotoxic against virus-infected RL(male symbol)1 cells, and s.c. transplanted, virus-infected RL(male symbol)1 cells were acutely rejected from IFN-gamma(+/+) or IFN-gamma(/) mice. In contrast, the CTLs were inactive toward virus-infected Meth A cells, but s.c. transplanted, virus-infected Meth A cells were acutely rejected from IFN-gamma(+/+) but not IFN-gamma(/) mice. The s.c. growth of virus-infected Meth A cells in the mutant mice was markedly inhibited by s.c. injections of IFN-gamma, and the rejection from IFN-gamma(+/+) mice was delayed after specific elimination of macrophages by intravenous (i.v.) injections of dichloromethylene diphosphonatecontaining liposomes. These results suggest an essential role of IFN-gamma and involvement of macrophage in the rejection of CTL-resistant, virus-infected cells.

IgE production after four routes of injections of Japanese cedar pollen allergen without adjuvant: crucial role of resident cells at intraperitoneal or intranasal injection site in the production of specific IgE toward the allergen.

The production of specific IgE antibodies directed toward cedar pollen correlates well with the onset of allergic rhinitis; but the mechanisms of allergen recognition as nonself and Ig class switch to IgE by the immune system are still not fully understood. In the present study, we injected cedar pollen into mice through 4 different routes (intranasal (i.n.), intraperitoneal (i.p.), intravenous (i.v.), and subcutaneous (s.c.)) without adjuvant 1 to 3 times, and determined time-dependent changes in the total and specific serum IgE levels compared with those in the serum levels of other isotype Igs. After an i.p. or i.n. injection of allergen into the mice, they produced a 1.5-to 1.7-fold increase in total IgE, but none in IgG, IgM, or IgA antibodies in their serum, whereas an i.v. or s.c. injection of allergen was inactive as an inducer of total IgE antibodies. Upon a 2nd (s.c.) injection of the allergen into the i.p. or i.n. sensitized mice, a large amount of allergen-specific IgE antibodies was found in the serum. In the case of i.v. or s.c. sensitized mice, however, they produced total, but not specific, IgE antibodies; and a 3rd (s.c.) injection of the allergen resulted in a large amount of specific IgE antibodies in the serum. These results imply that resident cells at the i.p. or i.n. injection site may play a crucial role in the efficient production of total and specific IgE antibodies toward the allergen.

Differential susceptibility of cells expressing allogeneic MHC or viral antigen to killing by antigen-specific CTL.

CD8(+) cytotoxic T lymphocytes (CTLs) generated by immunization with allogeneic cells or viral infection are able to lyse allogeneic or virally infected in vitro cells (e.g., lymphoma and mastocytoma). In contrast, it is reported that CD8(+) T cells are not essential for allograft rejection (e.g., heart and skin), and that clearance of influenza or the Sendai virus from virus-infected respiratory epithelium is normal or only slightly delayed after a primary viral challenge of CD8-knockout mice. To address this controversy, we generated H-2(d)-specific CD8(+) CTLs by a mixed lymphocyte culture and examined the susceptibility of a panel of H-2(d) cells to CTL lysis. KLN205 squamous cell carcinoma, Meth A fibrosarcoma, and BALB/c skin components were found to be resistant to CTL-mediated lysis. This resistance did not appear to be related to a reduced expression of MHC class I molecules, and all these cells could block the recognition of H-2(d) targets by CTLs in cold target inhibition assays. We extended our observation by persistently infecting the same panel of cell lines with defective-interfering Sendai virus particles. The Meth A and KLN205 lines infected with a variant Sendai virus were resistant to lysis by Sendai virus-specific CTLs. The Sendai virus-infected Meth A and KLN205 lines were able to block the lysis of Sendai virus-infected targets by CTLs in cold target inhibition assays. Taken together, these results suggest that not all in vivo tissues may be sensitive to CTL lysis.

[Diagnosis of lateral cervical lymph node metastasis of papillary carcinoma of the thyroid by ultrasonography].

No consensus for papillary carcinoma of the thyroid exists on the preoperative diagnosis of lateral cervical lymph node metastasis, indications, or range of neck dissection, so we studied the usefulness and limits of ultrasonography and sufficient dissection by comparing preoperative ultrasonographic and postoperative histopathological diagnosis. Subjects were 45 patients (51 affected sides) with lateral cervical lymph node metastasis of papillary carcinoma of the thyroid who underwent modified neck dissection between July 1997 and July 2003. Preoperative ultrasonographic and postoperative histopathological diagnosis were compared. Specimens excised by neck dissection contained 1,325 lymph nodes. Of these, 198 (15%) detected by preoperative ultrasonography were selected for investigation of diagnostic criteria for metastasis-positive lymph nodes. The best criterion for the diagnosis of metastasis-positive lymph node was 0.5 or greater [minor axis/major axis] with 6 mm or greater minor axis at levels III, IV, or V (7 mm or greater at level II), and sensitivity, specificity, and accuracy were 78%, 100%, and 84% respectively. The lateral cervical lymph node metastasis rate obtained by this diagnostic criterion was 41%. Regional histopathological metastasis positivity was investigated in the lateral cervical region, and high positivity rates were obtained: 57% at level II, 71% at level III, and 84% at level IV. Considering these findings and the preoperative ultrasonographic diagnosis rate of 41%, sufficient dissection at levels II-IV may be necessary for patients in whom lateral cervical metastasis is observed before surgery. The metastasis rate was 10% at level V, but dissection should always be done in lateral cervical metastasis-positive patients because: 1) No trend was observed in age, gender, the number of metastatic lymph nodes, or regional metastasis rate; 2) no anatomical boundary is present between levels II, III, IV and level V; 3) no functional disorder due to preservation of the accessory nerve occurred; 4) the prognosis of patients with advancement to the accessory nerve was poor; and 5) improvement of the prognosis of papillary carcinoma of the thyroid by modified radical neck dissection has been reported.

Cellular origin of IFN-gamma essential for hair cycle in normal skin.

Hair growth abnormalities in mice usually are accompanied by histologic abnormalities as well. Recently, however, we reported a mouse model in which an arrest of the hair cycle and diffuse shedding of the hair without pathologic features induced alopecia in interferon-gamma(-/-) (IFN-gamma(-/-)) C57BL/6 (B6) mice. Here, we explored the cellular origin of IFN-gamma. When bone marrow from IFN-gamma(-/-) B6 mice was transplanted into lethally irradiated IFN-gamma(+/+) B6 mice, the level of IFN-gamma mRNA expression in the skin or peripheral blood mononuclear cells (PBMCs) of recipient mouse was markedly reduced, suggesting that IFN-gamma is normally produced by bone marrow-derived cells. Although severe combined immunodeficiency (SCID) mice lack mature T cells and B cells, IFN-gamma-dependent hair regrowth was induced in SCID mice by depilation, which caused alopecia in IFN-gamma(-/-) B6 mice. Consistently, IFN-gamma mRNA expression in the skin or PBMC from SCID mice was comparable to that from their genetic counterpart (BALB/c mice), suggesting IFN-gamma production by non-T cells. RT-PCR analyses after separation of PBMC from SCID mice into eight fractions by a cell sorter revealed that Mac-1(+) cells were the major origin of IFN-gamma.

[A clinical study of ultrasonography for lymph node metastases in head and neck cancer].

Ultrasonography (US) is very useful in evaluating cervical lymph node swelling in head and neck cancers. We studied problems with US in evaluating lymph nodes. Cervical lymph nodes were removed by radical neck dissection or modified radical neck dissection from 79 patients with squamous cell carcinoma in the head and neck. We studied the correlation between preoperative US findings and the histopathological features. Preoperative lymph nodes were measured three-dimensionally. We diagnosed lymph nodes as metastases when they meet two criteria: One is the shortest diameter exceeding 7 mm in level I and II and 6 mm in level III, IV and V. The other is shortest to longest diameter ratio exceeding 0.5. A total of 2004 lymph nodes were removed by neck dissection, and 199 lymph nodes were diagnosed histopathologically as metastases. Of the 199 metastatic lymph nodes, 93 (46%) were diagnosed as metastases by preoperative US findings and 33 (17%) were false negative. Thirty-six cases were diagnosed preoperatively as N0 by US findings, but 15 of these were pN(+) histopathologically. In the 15 cases, 21 lymph nodes were metastases. Of the 21 metastatic lymph nodes, 10 nodes were not detected by US. Thirty-one cases were diagnosed preoperatively as N1 by US findings, but 20 of these were pN2b histopathologically. In the 20 cases, 66 lymph nodes were metastases. Of the 66 metastatic lymph nodes, 46 were not diagnosed as metastases. They often located distant level from the lymph node diagnosed correctly as a metastasis. US is very useful in evaluating cervical lymph node metastasis, but it has the limitations indicated above. If 1 metastatic lymph node is detected by US, there will be multiple metastatic lymph nodes and sometimes they are distant from the original level. Radical neck dissection should be done for positive lymph nodes detected by US findings. If a lymph node is not clearly a metastasis, fine-needle aspiration cytology (FNA) should be done, because it provides more accurate diagnosis for metastatic lymph nodes.