Functional polymorphism of each of the two HLA-DR beta chain loci demonstrated with antigen-specific DR3- and DRw52-restricted T cell clones.

HLA-DR3- and HLA-DRw52-associated functional polymorphism was investigated with selected tetanus toxoid (TT)-specific T cell clones. We have shown earlier that HLA-DR antigens are encoded by two distinct loci, DR beta I and DR beta III. The alloantigenic determinant(s) defined by the serological HLA-DR3 specificity map to the former, while the supratypic HLA-DRw52 determinants map to DR beta III. Furthermore, we have recently recognized by DNA sequencing three alleles of HLA-DRw52 at locus DR beta III, referred to as 52 a, b, and c. Our objective was to correlate the pattern of T cell restriction with the gene products of individual DR beta chain loci and with the three newly described alleles of locus DR beta III. Among the selected T cell clones, 5 reacted exclusively when TT was presented by HLA-DR3+ APCs (TT-DR3-APC). In contrast, two T cell clones were stimulated by TT-DRw52-APC. More specifically, these two T cell clones (Clones 10 and 16) were stimulated by different subsets of TT-DRw52-APC. Clone 16 responded to some DR3 and TT-DRw6-APC, while clone 10 was stimulated by other TT-DR3 and TT-DRw6, and all TT-DR5-APC. This same pattern of DRw52 restriction was found in panel, as well as in family studies. Because this suggested a correlation with the pattern of DRw52 polymorphism observed earlier by DNA sequencing and oligonucleotide hybridization, the APC used in these experiments were typed for the 52 a, b, and c alleles of locus DR beta III by allele-specific oligonucleotide probes. This distribution overlapped exactly with the stimulation pattern defined by the T cell clones. Clone 16 responded to TT-52a-APC, clone 10 to TT-52b-APC, and both clones to a TT-52c-APC. The response of the T cell clones was inhibited differentially by mAbs to DR. Raising TT concentration, or increasing HLA-class II expression with INF-gamma both affected the magnitude of response of the TT-specific clones but did not modify their specificities. These results demonstrate that a restriction specificity can be attributed to the DR beta III locus and illustrate the functional relevance of the polymorphism observed at this locus. This is of special interest in view of the striking difference in the pattern of structural diversity among alleles of DR beta I and DR beta III.

Anaphylactic shock following castor bean contact: a case report.

BACKGROUND: The castor bean plant, Ricinus communis, is known to have allergenic and toxic properties. Castor bean allergy has been described mainly as an occupational inhalation allergy in laboratory workers, in persons working in oil processing mills or in agricultural industry. So far, only one case of anaphylactic reaction due to castor bean sensitization confirmed by specific IgE has been described in literature. CASE PRESENTATION: A 30-year-old woman presented to the emergency room with severe angioedema followed by urticaria, hypotension and tachycardia. She recovered after treatment with antihistamines, corticosteroids, nebulized adrenaline and intravenous fluids. Food induced anaphylaxis was excluded by allergological investigations. After repeated thorough history, the patient mentioned having bitten into a castor bean just before the reaction. Cutaneous test (prick-to-prick) and specific IgE for castor bean were highly positive. CONCLUSIONS: We report the second case of a severe anaphylactic reaction to castor beans, confirmed by IgE testing, reported in the literature. It underlines the importance of a meticulous history in allergology and highlights the fact, that castor beans may cause potentially fatal anaphylaxis.

Initial experience with hand-assisted laparoscopic distal pancreatectomy.

BACKGROUND: Hand-assisted laparoscopic distal pancreatectomy, with or without splenectomy, is gradually gaining acceptance, although its ultimate benefit is yet to be confirmed. This study aimed to report our initial experience with hand-assisted laparoscopic distal pancreatectomy. METHODS: A retrospective review of a prospectively collected database including 17 patients during the period 2002-2004 was conducted. The median age was 60 years (range, 29-85 years), and the female-to-male ratio was 13:4. The preoperative diagnoses included benign and malignant conditions. Besides two to three ports, a hand port was placed in the upper midline to aid in dissection. The pancreas was divided with a stapler in all the patients, and drains were placed in 10 patients (70%). RESULTS: One patient was found to be unresectable because of celiac artery involvement, and 2 of the remaining 16 patients underwent conversion to an open procedure. The median operating time was 196 min (range, 128-235 min). The mean tumor size was 4 cm (range, 2-7 cm), and the estimated blood loss was 125 ml (range, 50-1,250 ml). The median time to resumption of a regular diet was 3.5 days (range, 2-9 days), and the time to conversion to oral pain medications was 3 days (range, 2-9 days). The length of hospital stay was 5.5 days (range, 4-18 days), with a majority of the patients (11 patients, 78%) staying less than 7 days. There were no mortalities. The overall postoperative morbidity rate was 25%, and the morbidities consisted of pancreatic leak/fistula (2 patients, 14%) and fever (1 patient). The margins were negative in 10 (76%) of the relevant 13 patients. At a median follow-up period of 3.8 months (range, 5-14 months), 11 (84%) of 13 patients had no evidence of disease recurrence. CONCLUSIONS: The minimally invasive approach to pancreatic disease is safe and technically feasible. Further large studies with longer follow-up periods are necessary to determine the role of laparoscopic surgery in the management of pancreatic disease.

Appendectomy. Improving care through quality improvement.

OBJECTIVE: To evaluate the practice of appendectomy in Department of Defense hospitals worldwide in a large-scale quality improvement initiative. DESIGN: Case series study. POPULATION AND SETTING: A total of 4950 consecutive nonincidental appendectomies performed in 147 Department of Defense hospitals worldwide during a 12-month period ending January 31, 1993. RESULTS: The mean age was 25.5 years, with 64% males and 36% females. The patients were assigned a diagnosis of normal appendix (negative appendectomy) in 632 cases (12.8%), acute appendicitis in 3286 cases (66.4%), and perforative appendicitis in 1032 cases (20.9%). The influence of inpatient and outpatient delays on perforation and negative appendectomy rates were studied. In at least 52% of all patients ultimately assigned a diagnosis of perforative appendicitis, the perforation occurred before the first outpatient contact with the health care system, and in at least 68% of all patients ultimately assigned the diagnosis of perforative appendicitis, the perforation occurred before surgical evaluation and admission. Neither outpatient delay in diagnosis nor inpatient delay in diagnosis and treatment was associated with a significant change in the rate of negative appendectomy. CONCLUSIONS: Perforation rates are determined predominantly by patient- and primary care-related factors over which surgeons have little control. Negative appendectomies are predominantly related to the wide overlap in presenting signs and symptoms between appendicitis and the diseases that most often mimic it but do not require operative intervention. Whereas studies of this type are useful for identifying potential problems at the health care system level, the relatively small number of appendectomies performed by each surgeon precludes analysis at the practitioner level.

Diagnosis and management of the autonomously functioning thyroid nodule: the Walter Reed Army Medical Center experience, 1975-1996.

In order to characterize the clinical and laboratory features of autonomously functioning thyroid nodules (AFTNs), and to assess optimal diagnosis and management of patients with this disorder, we performed a retrospective analysis of 49 such patients over a 22-year period encompassing January 1975 to November 1996. The following data were analyzed: thyroid hormone levels, thyroid scintiscan, radioiodine uptake, fine-needle aspiration biopsy, triiodothyronine (T3) suppression testing, thyrotropin-releasing hormone (TRH) stimulation test, and thyroid ultrasound. Clinical outcomes assessed included persistent hyperthyroidism, hypothyroidism, and nodule shrinkage after treatment, or in patients followed without definitive therapy, nodule growth, spontaneous degeneration, and progression to hyperthyroidism. Biochemical hyperthyroidism, often subclinical, was found in 73.5% of patients at presentation and in an additional 24.4% of patients during subsequent follow-up. The introduction of sensitive thyrotropin (TSH) testing during the period of study resulted in a decrease in the use of the T3-suppression test and TRH stimulation test from 100% and 20%, respectively, in the period from 1976-1980, to 4% each in the period from 1991-1996. T3-thyrotoxicosis occurred in 12.2% of patients. Thyrotoxicosis at any time during the course of follow-up was positively correlated with nodule size at diagnosis. Definitive therapy, used in 42.8% of patients, consisted of radioiodine ablation (38.1%) or thyroidectomy (61.9%). No patient had recurrence of thyrotoxicosis after definitive therapy, but 25% became hypothyroid. During follow-up for a mean of 30.9 months, nodules enlarged in 25% of patients overall, or 33% of patients not receiving definitive therapy. Cystic degeneration was documented in 26.5% of patients, although this change rarely reversed subclinical hyperthyroidism. The diagnosis of an AFTN requires a demonstration of TSH-independent nodular hyperfunction. The introduction of sensitive TSH assays has simplified the evaluation of AFTN patients and revealed a high prevalence of subclinical thyroid hyperfunction in this disorder. In view of current increased awareness of adverse consequences associated with subclinical hyperthyroidism and the rarity of spontaneous resolution of hyperthyroidism in AFTN patients (despite a propensity for spontaneous hemorrhage), definitive therapy is recommended. Both radioiodine and hemithyroidectomy have high cure rates and a low posttreatment incidence of hypothyroidism.

Parotid tumors in children.

Most salivary gland tumors, both benign and malignant, develop within the parotid glands. Although an overwhelming majority of tumors are reported in the adult population, the parotid glands are also the most frequently involved salivary glands in the pediatric age group. This study represents a combination of case material from the Armed Forces Institute of Pathology and our personal experiences. Of approximately 10,000 salivary gland lesions accessioned in all ages, only 124 tumors occurred in the parotid gland in children less than fifteen years old. There were ninety benign and thirty-four malignant lesions. The two most common benign masses were mixed tumors and vascular lesions. The most common malignancies were the mucoepidermoid and acinic cell carcinomas. We recommended that all solid tumors be removed by parotidectomy.

Definitive mandibular replacement using reconstruction plates.

Mandibular defects following radical cancer surgery continue to provide challenges to head and neck surgeons. Twenty-seven patients with advanced oral cancer underwent primary mandibular replacement with metal reconstruction plates without the use of bone. Twenty-one patients (78%) had successful reconstruction with primary soft tissue healing. Six patients required removal of the plate in the postoperative period. Two of these patients had their reconstruction plates replaced as a secondary procedure following soft tissue healing. Thus, 23 of 27 patients (85%) had final mandibular reconstruction and were followed for an average of 19 months. Functional and cosmetic results were satisfactory. For patients with advanced disease, this technique compares favorably with microvascular transfer in terms of operating time and donor defect. Despite problems with plate exposure, the initial and overall success rates of 78% and 85%, respectively, make the use of these plates a reasonable choice for immediate reconstructive needs in patients with difficult tumors.

Considering the spinal accessory nerve in head and neck surgery.

Loss of trapezius muscle function represents the single most important source of long-term morbidity from a radical neck dissection. Its preservation has been one of the central features of the conservative or modified neck dissection. We recently undertook an evaluation of 100 consecutive patients who had undergone composite resection for head and neck cancer and examined them with particular emphasis on the function of the trapezius muscle. The mean interval from the time of radical neck dissection to the time of this evaluation was 6.2 years. The operations included radical neck dissection with sacrifice of the spinal accessory nerve, radical neck dissection with preservation of the spinal accessory nerve, and radical neck dissection with interpositioned cable graft reconstruction. The survey showed that 67 percent of the patients who underwent radical neck dissection with sacrifice of the spinal accessory nerve, although they showed profound atrophy of the trapezius muscle, had few symptoms related to this deficit. Similarly, 47 percent of patients who underwent radical neck dissection with preservation of the spinal accessory nerve showed some signs of muscle atrophy, and 20 percent showed little or no function of the muscle. Interpositioned nerve grafts appeared to function well in 66 percent of the patients. The survey showed that a surprising number of patients treated with a standard radical neck dissection and sacrifice of the spinal accessory nerve had few postoperative symptoms related to the loss of trapezius muscle function. Also unexpected was the number of patients with signs of muscle dysfunction despite nerve preservation.

Percutaneous endoscopic gastrostomy in patients with head and neck malignancies.

One hundred thirty-six percutaneous endoscopic gastrostomies (PEGs) were placed in 126 patients with head and neck malignancies. PEG was performed by the "push" technique described by Russell. There were 140 PEG attempts, with 136 successful placements (97%). Seven complications occurred related to tube placement (5% of placements). Complications encountered were prolonged ileus in one patient (1%), local skin wound infection in one patient (1%), and early tube dislodgment in five patients (4%). Three patients required laparotomy (2%). There were no episodes of aspiration and no deaths. Patients were followed up for an average of 11 months, with a mean duration of PEG tube placement of 6 1/2 months. Patients continued PEG feedings throughout the postoperative radiotherapy period and until oral intake was satisfactory. Acceptance of PEG feedings has been high. No patient required rehospitalization for nutritional support.

Value of contralateral supraomohyoid neck dissections.

This study was carried out to determine the merit of contralateral supraomohyoid neck dissection in the clinically negative neck. When performed in conjunction with a standard radical neck dissection on the ipsilateral side, a yield of 2.8 percent pathologically positive nodes (5 of 177) was obtained in the contralateral neck. Little difference was noted in the yield of midline lesions versus unilateral lesions which approached the midline (3 and 2.6 percent, respectively). Similarly, the yield with preoperative radiation was close to that of the nonradiated group (3 and 2.7 percent, respectively). Additionally, in 1.7 percent of patients (3 of 177) with both clinically and pathologically negative nodes, metastases later developed in the contralateral neck, which indicates that the dissection is not necessarily effective in preventing future disease. The contralateral supraomohyoid neck dissection in the treatment of malignancies of the oral cavity, pharynx, and larynx does not appear to be of significant therapeutic value.

Cervical presentation of thymic cysts.

Sixteen cases of cervical thymic cyst are added to the previously reported fifty-six cases. Seventy-five per cent of the patients were less than twenty years old. Eighty per cent complained of a painless mass preoperatively. The histologic diagnosis of cervical thymic cyst was made if thymic epithelial elements could be found adjacent to the cyst cavity; Hassall's corpuscles were usually present. Cholesterol granulomata could usually be identified. The theories of origin of cervical thymic cyst are discussed.

Decision making on surgical palliation based on patient outcome data.

BACKGROUND: Strategies for the effective application of palliative procedures are infrequently standardized and incompletely understood. The effect on patient outcome as determined by elements such as resolution of chief complaints, quality of life, pain control, morbidity of therapy, and resource utilization should predominate decisions regarding surgical palliative care. METHODS: Articles published between 1990 and 1996 on the surgical palliation of cancer were identified by a MEDLINE search and reviewed for designated parameters considered important for good palliative care. RESULTS: A total of 348 citations were included. Entries considered these fundamental elements: cost (2%); pain control (12%); quality of life (17%); need to repeat the intervention (59%); morbidity and mortality (61 %); survival (64%); and physiologic response (69%). Established methods for quality of life and pain assessment were sporadically utilized. CONCLUSIONS: In the current surgical literature, there is uncommon reporting of the range of data required to recommend sound palliative surgical choices.

Metastases to lymph nodes of the head and neck from an unknown primary site.

Sixty-four patients with a metastasis to the head and neck from an unknown primary site were reviewed. Survival as a function of cell type, stage of disease, and mode of treatment was analyzed. Survival correlated best with stage of disease prior to treatment.

Head and neck surgery in the aged.

This study was carried out to determine the perioperative mortality rate of patients over the age of 65 years who are undergoing major head and neck resections under general anesthesia. The total number of patients was 810 and the perioperative mortality rate (death within 30 days of operation) was 3.5 percent (29 of 810). This rate is relatively low when compared with the rate for patients undergoing similar procedures during the same period in the 35 to 65 years age group. Since 1975 reports of other types of surgery in the elderly have given perioperative mortality rates of from 4.8 to 26 percent. Previous studies of head and neck surgery in the elderly have given perioperative mortality rates of from 1.3 to 13.6 percent. Head and neck surgery in the elderly continues to be a safe procedure when compared with other types of surgery. As the portion of patients in the population over the age of 65 continues to increase, advanced age alone should not be a deterrent to performing aggressive surgical therapy for head and neck cancer.

Nasolabial flap in intraoral reconstruction. Review of 55 cases.

The nasolabial skin flap has proved very useful in reconstruction of anterior intraoral defects after ablation for cancer. The technique allows immediate single-stage reconstruction with local tissue. Minimal functional or cosmetic deformity results at the donor site. Fifty-five consecutive patients who underwent anterior intraoral reconstruction with 68 nasolabial flaps were followed up for 1 to 10 years. Only two flaps were total failures. Three flaps had partial tissue loss. Successful reconstruction without complication was obtained with 93 percent of the flaps. Technical refinements and considerations in flap design are presented.

Analysis of prognostic variables and results after vertical partial laryngectomy.

A consecutive series of 197 patients who underwent conservation surgery for squamous cell carcinoma of the glottic larynx was analyzed. The majority of patients were male. One hundred forty-one had stage I disease, 44 had stage II, and 12 had stage III disease at the time of treatment. Partial laryngectomy was performed in 25 patients who had recurrent cancer after previous definitive radiotherapy and in 5 patients who had previously undergone cordectomy. There was no operative mortality and postoperative morbidity was low. Local recurrence developed in 32 patients (17 percent); cervical metastasis developed in 8 patients. The determinate survival rates at 3 and 5 years were 92 percent and 87 percent, respectively. Multivariate analysis showed soft-tissue margins and tumor differentiation as the two significant covariates in predicting survival. Positive surgical margins were also significant covariates affecting local recurrence. These data suggest that conservation surgery is an effective treatment for early vocal cord carcinoma. Adequate surgical margins are essential. Postoperative irradiation should be considered in patients with inadequate margins.

Analysis of prognostic variables and results after supraglottic partial laryngectomy.

A consecutive series of 78 patients who underwent conservation surgery for squamous cell carcinoma of the supraglottic larynx is analyzed. The majority of the patients were middle-aged men who had early-stage disease, with only 18 patients in stage III and 6 in stage IV. The epiglottis was the most frequent site, followed by the aryepiglottic fold and other sites in the supraglottic larynx. There was no operative mortality and the complication rate was low. Univariate analysis showed no influence of tumor stage, tumor differentiation, or involved surgical margins on survival. Determinate survival rates of 85 percent at 3 years and 72 percent at 5 years were observed. Local recurrences took place in 12 patients, 4 of whom were salvaged by total laryngectomy; neck failure occurred in 13 patients, 7 of whom were salvaged after further treatment; and 1 of the 2 patients with distant metastasis was salvaged after further treatment. We believe that every patient with a favorable lesion of the supraglottic larynx should be considered for conservation surgery, specifically, supraglottic partial laryngectomy, adhering to the criteria mentioned. Initial surgical treatment offers excellent local control and 5 year survival. Adjuvant postoperative radiotherapy may be considered in those patients with bulky primary tumors, positive surgical margins, and histologically confirmed cervical lymph node metastases.

Salivary glands.

A review of the more common inflammatory and neoplastic conditions affecting salivary glands has been presented. The use of hydration, massage, antibiotics, and steroids is effective initial treatment for suppurative sialadenitis and usually negates the need for surgical drainage. Total excision of the salivary gland and its duct is necessary in procedures for recurrent infection. Our technique for closure of the floor of the mouth after excision of the submandibular gland and Wharton's duct is described. Salivary neoplasms involving the parotid gland, the submandibular gland, and the minor salivary glands are treated on the basis of their histologic and local findings. Stepwise illustrations of our technique of parotidectomy and surgical considerations, including the counseling of a patient with a parotid mass, are presented to assist surgeons who care for patients with salivary disorders.

Patterns of cervical node metastases from squamous carcinoma of the larynx.

We undertook a retrospective review of 247 previously untreated consecutive patients from 1965 to 1986 with primary squamous cell carcinoma of the supraglottic or glottic larynx to ascertain the prevalence of neck node metastases by neck level. The 247 patients underwent a total of 262 radical neck dissections. Patients were grouped by clinical neck status at the time of neck dissection: elective dissection in the NO neck; immediate therapeutic dissection in the N+ neck; and subsequent therapeutic dissection in the NO neck that over time converted clinically to N+. Detailed analysis revealed a predominance of neck node metastases in levels II, III, and IV for all clinical neck groups. Level V was rarely involved, but always in conjunction with neck node metastases in levels II, III, or IV (ie, N2 disease). Level I was rarely involved; involvement occurred with neck node metastases in levels II, III, or IV 75% of the time. Level I involvement correlated with T3 or T4 primary tumors exhibiting histologic extralaryngeal spread. These data support the trend toward selective limited neck dissection in both NO and N1 patients.

Chylothorax complicating radical neck dissection.

The third reported instance of chylothorax occurring after left radical neck dissection is presented and the literature reviewed. The pathogenesis appears to be lymphatic leakage in the neck with accumulation of chyle in the pleural space in spite of the absence of pneumothorax. The means for entry across an intact pleura is uncertain. The condition can be managed by conservative means consisting of adequate neck drainage and thoracentesis or chest tube drainage. A favorable outcome can be expected.