Immunotherapy with cytokines or cytokine-activated effector cells is a promising therapeutic approach, which has not been extensively evaluated in patients with head and neck cancer (HNC). Preclinical data obtained with human effector cells, both MHCrestricted cytolytic T lymphocytes (CTL) and MHC-nonrestricted natural killer (NK) cells, indicate that it is feasible to generate such cytokine-activated effector cells in patients with advanced HNC. Technology for separation of human effector cells and their culture on a therapeutic scale is available. Purified subsets of lymphocytes derived from autologous peripheral blood, lymph node lymphocytes or tumor-infiltrating cells can be consistently prepared by immunoselection in patients with HNC, evaluated for antitumor efficacy in vitro, using ⁵¹Cr-release assays, monolayer cultures or tumor spheroids and used for adoptive transfers. Locoregional transfer of such immune cells plus cytokine (s) can effectively inhibit growth of squamous cell carcinoma of the head and neck (SCCHN) xenografts established in nude mice. Human IL2-activated NK cells (A-NK) have been shown to preferentially enter SCCHN spheroids and kill or inhibit growth of tumor cells in spheroids or in SCCHN xenografts established in nude mice. A-NK cells can be armed in vitro with chimeric monoclonal antibodies selectively reactive with squamous epithelia (e. g., cMAbs E48 or U36) to optimize their targeting to the tumor. In vivo arming with these cMAbs is likely to increase anti-SCCHN responses. Supernatants of A-NK cells cultured in the presence of IL2 have been shown to arrest SCCHN cells in the G₀/G₁ phase of the cell cycle and to inhibit growth of SCCHN xenografts in nude mice. Efforts to transduce A-NK cells with cytokine genes are in progress. An urgent need exists in head and neck oncology for effective adjuvant therapy, and immunotherapy with immune effector cells should be considered as a feasible therapeutic modality in the adjuvant setting in HNC.

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Broncho-esophageal foreign bodies have been seen throughout human history. This paper presents foreign body cases from Japanese ancient writings particularly after 10th AD. and the correct location of trachea and esophagus, and future problems for foreign body treatments.
1) There were several interesting removal methods. For example, a laryngeal rice-cake foreign body was removed by drinking vinegar, and an esophageal fish bone was removed with a hemp stick, and a pin using an array of beads with a string in the esophagus.
2) T. Yamawaki pointed out the correct position of the trachea and esophagus in his book titled“Zohshi” (1759). Before this book, people had thought that the position of the esophagus was in front of the trachea.
3) Two hundred modern Japanese people were asked where the location of trachea and esophagus were. Thirty-two percent of them believed that the esophagus was in front of the trachea. The author reported 7 reasons why they misunderstood the relative locations of the trachea and esophagus.
4) Future problems regarding the broncho-esophageal foreign bodies and their diagnosis, anesthesiology and removal were discussed. Improvement in the flexible broncho-fiber scope, X-ray diagnosis and methods of anesthesia, and new removal methods for the bronchoesophageal foreign bodies are required.

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Psyco-oncology is a comprehensive approach to cancer treatment that aims at increasing the quality of life of cancer patients.
Psycho-oncology's first field of enquiry is the psychological effects of cancer on patients, families and medical personnel, and how to deal with those effects. Another important focus of research is the way society perceives and treats cancer patients and their families.
Psyco-oncology's second field of enquiry is the scientific explication of psychosocial factors in the cause and treatment of cancer, with related research being carried out from the perspective of psycho-neuro-immunology, a subject marked by recent advances.
In other words, psycho-oncology is a discipline based on a clinical treatment of cancer which incorporates physical, psychological and social factors at all stages of treatment-from initial examination to death.

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This paper deals with advances and problems related to anesthesia of the bronchoesophageal region, including various anesthetic agents and discussion of some of the peculiar difficulties entailed.
Regarding inhalational agents, although halothane's effectiveness is recognized, the risks associated with halothane induced hepatitis and malignant hyperthermia have also been long-recognized. Various alternative inhalational agents, and their relative merits, are discussed. Among the various intravenous agents, of particular interest for its effectiveness, as well as unique attributes such as rapid induction and quick recovery, is propofol, developed over ten years ago and expected to come into use in Japan in 1995. These properties have made propofol a more well-controlled and safe method available for total intravenous anesthesia (TIVA). As to muscle relaxants, vecuronium is noteworthy for its relative lack of effect on the circulatory system, and for its short duration.
Operations in the bronchoesophageal region necessarily find the surgeon and anesthesiologist placing competing demands on the area, and resolution of the various priorities continues to pose challenges. The use of vasoconstrictors (epinephrine) during surgery also poses risks, and the guidelines espoused by Katz are discussed in this paper. The incidence of intubation difficulties is addressed, as are minitracheostomies.
The advantages in this regard of Brain's laryngeal airway mask (LAM) are stressed. In particular, the LAM provides for an unobstructed view during the use of optic fibroscopy in larygeal microsurgery. Finally, the importance of monitoring, especially with respect to the measurement of end-tidal CO₂ (monitoring the capnometer) is emphasized.

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One established mechanism of multi-drug resistance is the elevated expression of P-glycoprotein (Pgp). The expression of Pgp by immunohistochemistry was examined in head and neck cancers using a monoclonal antibody C219. Pgp was detected in 64% of squamous cell carcinomas derived from surgical specimens. Positive Pgp staining correlated with a chemoresistance to adriamycin, which was determined by using a cellular ATP analysis (P<0.05).
For the purpose of achieving individually effective thermotherapy, we also examined thermosensitivity for head and neck cancers by ATP assay, compared with the colony assay. The ATP assay showed a closer correlation with the colony assay and was also quicker than the colony assay in evaluating cell viability after heating. Therefore, the ATP assay is to be recommended as a thermosensitivity test for head and neck cancers.

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Genetic alterations were analyzed in esophageal cancer. Amplification of c-erbB, which codes the epidermal growth factor receptor, was detected in about one-eighth of our cases. The survival rate for patients with c-erbB amplification was significantly lower than the rate for patients without such amplification. There was a significant relation between c-erbB amplification and regional lymph node metastasis at surgery. Amplification of cyclinD1, which codes the G1-regulating protein of the eukaryotic cell cycle, was detected in about one-fourth of our cases. The survival rate for patients with cyclinD1 amplification was also significantly lower than the rate for patients without such amplification. There was a significant relation between cyclinD1 amplification and eventual metastasis to distant organs. As these genetic alterations can be determined by an endoscopic biopsy preoperatively, the biological characteristics of each case should be taken into account for an optimum treatment strategy.

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We determined the DNA ploidy and the centrometric copy number of chromosomes 1, 7, 11, 17, X and Y in head and neck cancers using DNA flow cytometry and fluorescence in situhybridization (FISH) with chromosome-specific alpha-satellite DNA probes. To evaluate the prognostic and therapeutic significance of tumor DNA content was determined by flow cytometory in 279 patients with head and neck squamous cell carcinoma. A better 5-year survival and local control rate were observed in patients with diploid tumor than in patients with aneuploid tumor (P<0.01). These results indicate that DNA ploidy analysis is useful for the evaluation of clinical prognosis. The FISH analysis demonstrated three or four copies of chromosomes 1, 7, 11, 17 and two or three copies of chromosome X in most aneuploid tumors. Over-representation of chromosomes 1, 7, 17, X and Y was detected in deploid tumors (11-3%). Our data suggest that chromosomal aneuploidy can be observed even in tumors with DNA diploidy.

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Human cytotoxic T-lymphocyte (CTL) lines with specificity restricted for autologous squamous cell carcinoma of the head and neck (SCCHN) were established from peripheral blood lymphocytes (PBL) obtained from a patient with cancer of the tongue. The CTL lines were CD3⁺CD8⁺CD11b^-HLA^-DR⁺T cell receptors (TCR) α /β⁺. They were tested in 4 h ⁵¹Cr-release assays against SCCHN cell lines (n=11) and a variety of non-squamous human tumors (n=9) and normal (n=5) cell targets. They were found to lyse only autologous rumor (AuTu, PCI-50) and seven allogeneic SCCHN cell lines. Of these tumor cell lines, three cell lines shared a HLA-A2 locus with the AuTu, while the other two lines shared HLA-B44 with AuTu. Lysis of AuTu and the allogeneic SCCHN targets of the established CTL lines appeared to be MHC-class I restricted. The CTL lines proliferated in vitro in response to autologous PCI-50 or an allogeneic SCCHN cell line. Analysis of the TCRβ chain genes for the CTL and CTL clones indicated that two different CTL populations (Vβ6 and Vβ2) are able to recognize SCCHN-associated antigen (s) and that Vβ6 T cells are HLA-A2-restricted, while Vβ2 T cells may be HLA-B44-restricted.
While the growth of PCI-50 cells in culture was significantly inhibited by the supernatants of A-NK cells, those of the CTL line were not growth inhibitory. On the other hand, the lysis of AuTu targets by the CTL line was increased by preincubation of tumor cells with TNFα or IFNγ. These cytokines augmented the expression of HLA-class I, HLA-class II and intercellular adhesion molecule I (ICAM-I) on PCI-50 cells. The CTL incubated in the presence of HLA-A2 SCCHNs but not HLA-A2 gastric carcinoma produced TNFα, IFNγ and GMCSF.

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Human solid tumors are capable of producing factors that suppress the host immune system and facilitate tumor growth. On the other hand, squamous cell carcinomas of the head and neck (SCCHN) cell lines (PCI-1) have been reported capable of activating human NK cells upon short co-incubation in vitro and expression of mRNA for cytokines.
The purposes of this study were to test the supernatants (SN) of human squamous cell carcinomas of the head and neck cell lines (PCI-50) for the presence of soluble factors capable of inducing activation and proliferation of human immune cells.
The SN of PCI-50 induced and significantly sustained proliferation of human PBL as well as NK and CD4⁺T cells in culture. Purified human NK or CD4⁺T cells cultured in the presence of SN plus IL2 (120 IU/ml) had significantly higher anti-tumor cytotoxicity than that mediated by NK or CD4⁺T cells culture in AIM-V medium plus IL2. SN promoted expression of the following activations on NK and CD4⁺T cells: CD25, HLA-DR, CD54, CD71, and CD69. When SN was fractionated by Amicon filtration into >30 kDa and <30 kDa fractions, the growth and cytotoxicity-promoting activities were consistently detectable in the>30 kDa fraction.
Our results indicate that cultured SN of SCCHN cell lines contain a soluble factor (s) capable of activating NK and CD4⁺T cells and of promoting the growth and anti-tumor cytotoxicity of these lymphocyte subsets in vitro.

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