Minor H antigen matches and mismatches are equally distributed among recipients with or without complications after HLA identical sibling renal transplantation.

Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.

Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT.

Although the feasibility of using HLA-mismatched unrelated donors as an alternate graft source for haematopoietic SCT (HSCT) has been shown, little is known about the safety of HLA-mismatched DLI for the treatment of relapse. We examined the outcome of 58 consecutive leukaemia patients who received escalating-dose DLI for treatment of relapse after alemtuzumab-conditioned myeloablative unrelated donor HSCT at our institution. High-resolution HLA typing on stored DNA samples revealed mismatches in 28/58 patients who were considered HLA-matched at the time of transplantation. Following DLI from HLA-matched (10/10) (n=30) or -mismatched (7-9/10) (n=28) unrelated donors, we found no significant difference in the incidence of acute GVHD (17.2% versus 23.1%, P=0.59), probability of remission at 3 years (62.1% versus 63.9%, P=0.89) or 5-year OS (89.8% versus 77.7%, P=0.22). We conclude that escalating-dose DLI can be safely given to HLA-mismatched recipients following T-depleted myeloablative HSCT.

KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly diagnosed chronic myeloid leukemia patients treated with imatinib.

Natural killer (NK) cells are expanded in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors (TKI) and exert cytotoxicity. The inherited repertoire of killer immunoglobulin-like receptors (KIR) may influence response to TKI. We investigated the impact of KIR-genotype on outcome in 166 chronic phase CML patients on first-line imatinib treatment. We validated our findings in an independent patient group. On multivariate analysis, KIR2DS1 genotype (RR=1.51, P=0.03) and Sokal risk score (low-risk RR=1, intermediate-risk RR=1.53, P=0.04, high-risk RR=1.69, P=0.034) were the only independent predictors for failure to achieve complete cytogenetic response (CCyR). Furthermore, KIR2DS1 was the only factor predicting shorter progression-free (PFS) (RR=3.1, P=0.03) and overall survival (OS) (RR=2.6, P=0.04). The association between KIR2DS1 and CCyR, PFS and OS was validated by KIR genotyping in 174 CML patients on first-line imatinib in the UK multi-center SPIRIT-1 trial; in this cohort, KIR2DS1(+) patients had significantly lower 2-year probabilities of achieving CCyR (76.9 vs 87.9%, P=0.003), PFS (85.3 vs 98.1%, P=0.007) and OS (94.4 vs 100%, P=0.015) than KIR2DS1(-) patients. The impact of KIR2DS1 on CCyR was greatest when the ligand for the corresponding inhibitory receptor, KIR2DL1, was absent (P=0.00006). Our data suggest a novel role for KIR-HLA immunogenetics in CML patients on TKI.

The long-term effect of unilateral t-tube insertion in patients undergoing cleft palate repair: 20-year follow-up of a randomised controlled trial.

OBJECTIVES: Between July 1984 and March 1987, all children that underwent repair for primary cleft palate at the Queen Victoria Hospital were enrolled in a clinical trial. Those found to have otitis media with effusion at time of surgery had a t-tube inserted into one randomised ear, whilst the other ear received no treatment. The object of the study was to reassess the patients from the original trial to discover the impact of the unilateral t-tube, twenty years later analysed on an intention to treat basis. DESIGN: Children that underwent primary palatal closure during the study dates were identified from the cleft palate database. Patients that were involved in the original trial were identified, contacted and invited to take part in the follow-up study. SETTING: Tertiary referral Specialist unit. PARTICIPANTS: Twenty-two patients were identified as potential study participants. Of this group, fourteen were contactable and seven participants agreed to take part in our follow-up study. MAIN OUTCOME MEASURES: Persistent symptomatology, otoscopy, pure tone audiometry and tympanometry. RESULTS: Follow-up results were compared within the original treatment groups from the primary study, on an intention to treat basis. Otoscopically the ears were normal in 2 of the 7 treated ears compared with four of the seven non-treated ears. All the other ear ears had various types of chronic otitis media. Four of the seven had hearing of >10 dB in the treated ear compared with the non-treated ear. CONCLUSIONS: These findings would indicate need for caution in the use of t-tubes in the cleft population and raises the question of long-term follow-up to assess for secondary cholesteatoma.

Myxoid chondrosarcoma of the external auditory meatus.

Extraskeletal myxoid chondrosarcoma presenting in the head and neck is extremely rare. Histological diagnosis is difficult and requires close co-operation between clinician, radiologist and pathologist. The tumour has a good prognosis in comparison to myxoid chondrosarcoma of the bone but surgical resection may be difficult due to its gelatinous nature. We present a case of extraskeletal myxoid chondrosarcoma originating in the external auditory meatus of a 42-year-old man. This is the first report of this tumour in this site.

Pyoderma gangrenosum producing saddle nose deformity.

Pyoderma gangrenosum affecting the nose is rare and this may lead to diagnostic confusion because of the large differential diagnosis. As diagnosis is made, largely, on the basis of exclusion the treatment of pyoderma gangrenosum may be unduly delayed. The condition is often disfiguring, particularly following inappropriate surgical intervention, and early diagnosis is therefore important. We present a case of pyoderma gangrenosum managed initially in the community with minor surgery and resulting in the rare complication of saddle nose deformity.

Long-term results of the use of cultured autologous epithelial cell grafting to mastoid cavities.

Thirty-nine patients (42 ears) who have had a cultured autologous epithelial cell graft technique to a continuously discharging mastoid cavity have been evaluated to determine the continued effectiveness of this procedure. A postal questionnaire indicated a 58% improvement in both the smell and quantity of discharge, and our conclusion is that this is a very effective measure to provide extended symptomatic improvement in this troublesome condition.

Extra-pharyngeal neck pathology complicating pharyngeal pouch surgery.

One case each of: (1) low grade thyroid lymphoma; (2) supraclavicular and para-oesophageal metastasis of a uterine adenocarcinoma; and (3) recurrent multinodular goitre have been encountered in very intimate relationship with the neck of a pharyngeal pouch within the tracheo-oesophageal gutter raising the possibility that the two conditions were interrelated. The practical importance of these cases is that a surgeon excising a pouch from the neck ought to be able to resect a thyroid lobe should it prove necessary, and occasionally endoscopic diverticulotomy is the only reasonable option.

Long-term results of mastoid cavities grafted with cultured epithelium prepared from autologus epidermal cells to prevent chronic otorrhea.

Chronic otorrhea and recurrent infection from open mastoid cavities are common and troublesome clinical problems for which there is no very satisfactory treatment. The authors have previously described a simple procedure to solve this problem, using autologous cultured keratinocyte layers grafted onto the unepithelialized open mastoid cavities. All procedures are carried out on an outpatient basis without anesthesia, except for local anesthesia for the skin biopsy. Twenty-six patients with 28 "difficult" mastoids, in which otorrhea had been present from 2 to 32 years, have been grafted with a follow-up period varying from 10 to 18 months. Seventeen mastoid cavities became symptom-free as a result of this technique. There were 4 failures, and partial success was shown in 7 cavities as judged by both the patient and by clinical examination.

Lateral temporal bone resection for extensive pinnal malignancy. Has anything changed in forty years?

This paper offers an account of the contemporary surgical approach to advanced tumours of the external ear based on a series of 11 patients. There were eight squamous, two basal cell carcinomas and one mucoepidermoid tumour. The traditional method of excision was slightly modified by performing microsurgical dissection of the lateral part of the temporal bone rather than chisel osteotomies, and then including it en bloc with the involved soft tissues. The defect was then closed using a scalp or myocutaneous flap and this combination of otological and reconstructive expertise has proved satisfactory. Four patients are alive with no evidence of disease a mean of 4.2 (range 1.0-7.0) years from surgery: two patients who remained free of disease have subsequently died of unrelated conditions 12 and 24 months post-operatively, and in three cases death from recurrent disease occurred a mean of 1.4 (range 0.9-2.1) years after our surgery. There were two post-operative deaths. Based on the actuarial survival of 36 per cent and a successful disease clearance rate of 54 per cent, our conclusion is that the outlook of this condition has not dramatically improved since the original descriptions of the management of this problem first appeared, although intervention remains justifiable because of the potential curability and relief of symptoms.

A new technique using cultured epithelial sheets for the management of epistaxis associated with hereditary haemorrhagic telangiectasia.

A new technique for the treatment of severe epistaxis associated with hereditary haemorrhagic telangiectasia is described. The nasal septum and inferior turbinates, surgically denuded of respiratory epithelium, were grafted using autografts of cultured epithelial sheets derived from buccal epithelium. All patients upon whom this technique has been used have shown considerable lessening in the frequency and severity of their epistaxes although two patients received grafts on two occasions, in each case approximately three months apart. It is postulated that a nasal lining of stratified squamous epithelium is likely to be more resistant to trauma than the normal respiratory type, and this is supported by the observation that bleeds very seldom occur from the oral cavity in this syndrome.

Dominant maxillary artery as a cause of failure in maxillary artery ligation for posterior epistaxis.

Ligation of the maxillary artery is a logical and effective method for the arrest of severe uncontrollable posterior epistaxis. The failure rates for arrest of haemorrhage are given in the literature as 10-13%. In our centre, over the last 9 years, 23 patients have undergone maxillary artery ligation to control epistaxis without a failure. Bilateral maxillary artery ligation was carried out whenever the maxillary artery of the bleeding side was found to be of small diameter. To investigate whether there is an asymmetry in the size of the maxillary arteries we performed 13 cadaveric dissections. In 6 of the cadavers one maxillary artery was significantly larger than the other. This fact has hitherto not been observed by otolaryngologists or anatomists. Failure to arrest haemorrhage may have resulted from ligation of the non-dominant maxillary artery with consequent opening of cross-anastomoses from the dominant side.

Treatment of chronic mastoiditis by grafting of mastoid cavities with autologous epithelial layers generated by in vitro culture of buccal epithelium.

Autologous cultured epithelial layers were established from biopsies from the mucosa of the cheek, a non-keratinizing region of the oral cavity. These were grafted to the unepithelialized mastoid cavities of nine patients with chronic mastoiditis and severe otorrhoea varying from two to 30 years' duration. All procedures were performed on an out-patient basis, with no anaesthesia except for topical anaesthesia for the mucosal biopsy. In seven of the patients the grafts took well, with complete resolution of the otorrhoea for a minimum follow-up period of eight months. In one patient there was a partial take of the graft with substantial improvement in the rate of discharge. The mastoid cavities of two patients were biopsied five months after grafting, and demonstrated a stratified squamous epithelium, with keratinization of the epithelium clearly evident.

Treatment of postoperative otorrhoea by grafting of mastoid cavities with cultured autologous epidermal cells.

Autologous cultured keratinocyte layers were grafted onto the unepithelialised open mastoid cavities in 8 patients with otorrhoea for 2 to 32 years. All procedures were done on an outpatient basis without anaesthesia, except for local anaesthesia for skin biopsy. The cultured keratinocyte layers adhered well to the bed of granulation tissue lining the mastoid cavity and formed an excellent protective covering of stratified squamous epithelium. All 8 patients have been free from otorrhoea for the 2 to 6 months since grafting.

A preliminary report on the combination of initial chemotherapy and radiotherapy for advanced head and neck cancer.

A RETROSPECTIVE review of 45 patients with advanced squamous cell carcinoma of the head and neck treated by a combination of initial chemotherpy (Price and Hill Schedule A) followed by radiotherapy is presented. The regime produced excellent immediate palliation with a tumour control of 50 per cent, and a disease-free survival of 33 per cent at one year and 27 per cent at two years. Treatment morbidity was minimal in an aged patient group.

Second ear stapedectomy.

A long-term follow up of a personal series of 79 second ear stapedectomies indicates that the procedure can be undertaken with minimal complications. No bilateral dead ears or vestibular disasters have occurred. The results were satisfactory in 87.5% of ears, and bilaterally symmetrical hearing with an air-bone gap of 30 dB or less was achieved in 24% of patients. Whilst the established dictum that only one ear should be operated upon should not be abandoned, the results reported in this paper may encourage the more experienced to operate on the second ear at a later date in carefully selected cases.