Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid.

BACKGROUND: The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated. METHODS: PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT. Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes. RESULTS: Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings. CONCLUSION: Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.

Is laparoscopically assisted radical vaginal hysterectomy for cervical carcinoma safe? A case control study with follow up.

OBJECTIVE: To compare a new surgical approach, laparoscopically assisted radical vaginal hysterectomy (LARVH) with open radical hysterectomy in women with cervical cancer. Can selected women benefit from the minimally invasive approach without compromising safety (recurrence rate) and morbidity (complications)? DESIGN: Retrospective case control study. SETTING: A tertiary referral unit for gynaecological malignancies. POPULATION: Thirty women undergoing LARVH were included and compared with 30 women undergoing open radical surgery. The control group was matched for age, body mass index and disease stage. METHODS: Retrospective collection of data from patient files and follow up. MAIN OUTCOME MEASURES: Recurrence rate, complication rate, hospital stay, nodal counts, blood loss, operating time. RESULTS: Recurrence rates were equal (6.7%). There was one death, in the LARVH group. Follow up was mean 31 months in the LARVH group and 30.9 months in the open group. Blood loss as measured by mean drop in haemoglobin was greater in the open group (2.03 versus 3.01 g/dl, P = 0.02). Transfusions were given in 40% of women in the open group and 16.7% in the LARVH group. Hospital stay was significantly less in the LARVH group (5.9 versus 7.8 nights, P = 0.003). Mean operating time was longer in the LARVH group (131 versus 187 minutes P = 0.0001). Mean nodal counts did not differ significantly (17.4 in open vs 14.8 in LARVH, P > 0.05). There were seven perioperative complications in the open group and four in the LARVH group. There have been two recurrences in each group (6.67%) at mean follow up of 31 (LARVH) and 30.9 (open) months. CONCLUSIONS: The first 30 LARVH procedures performed in this unit are comparable in terms of safety (recurrence rate and complication rate) and economic factors (shorter hospital stay mitigating longer operating time). Further development of this technique is warranted.

the management of vulval intraepithelial neoplasia in Northern Ireland.

In this study, we present the findings of a regional retrospective audit of all cases of vulval intraepithelial neoplasia (VIN) diagnosed in Northern Ireland (NI) over an 11-year period (1989-1999). During the period of the study, there were 97 cases of VIN. Cases of VIN were treated by many different clinicians at 14 hospitals. The commonest symptom at presentation was pruritus vulvae. The most common histopathologic diagnosis was VIN III (73%). In 52% of the cases, there was multifocal VIN, and in 43%, there was involvement of other sites such as the cervix, vagina, or anal region. The most common initial treatment was surgical excision, but a multitude of different treatments were performed initially. During the study period, 18 of 90 patients (20%) for whom follow-up was available developed invasive vulval squamous carcinoma. Most of the vulval cancers were superficially invasive, but three patients died of vulval cancer during the study period. This study illustrates that in NI, VIN is treated at many institutions by a multitude of clinicians. Management seems largely dependent on personal clinician preference and has been haphazard with little central coordination and organized strategy. VIN should be managed by clinicians with expertise in this field and who are treating significant numbers of patients according to evidence-based protocols.

The large loop excision of the transformation zone cut or blend thermal artefact study: a randomized controlled trial.

The objective of this randomized controlled trial was to determine whether the pure cut setting results in less thermal artefact than the traditional blend setting when performing a large loop excision of the transformation zone (LLETZ). Forty-nine consenting women were randomized to undergo an LLETZ procedure using either the pure cut or the blend setting. Two histopathologists, who were blind to the randomization, examined the specimens and then graded and measured the degree of thermal artefact. No significant difference was noted at the epithelial margin. At the deep stromal margins, in the blend group, the mean thickness of thermal artefact was 0.382 mm (95% CI, 0.350-0.414) and in the cut group 0.325 mm (95% CI, 0.297-0.353). This was statistically significant. No significant difference was detected in terms of grading of thermal artefact, the presence of dysplasia at the specimen margins, or in positive follow-up smears. Although there was less thermal artefact at the deep stromal margin, cautery at this margin does not generally interfere with pathological assessment of the specimen and the pure cut setting does not produce a clinically significant decrease in the degree of thermal artefact.

Efficacy of cervical intrarepithelial neoplasia (CIN) treatment by cold coagulation.

Our objective was to evaluate the efficacy of cold coagulation in the treatment of cervical intraepithelial neoplasia. The study design consisted of a retrospective review of case records of all women treated with cold coagulation from the colposcopy clinics inception in 1980 to 1994. A total of 725 women received treatment with cold coagulation. All grades of CIN were treated. 632 (87.1%) had long term negative follow up. 93 (12.6%) of patients had abnormal cytological follow up, but only 45 (6.2%) required re-treatment. Within the first year after treatment 52 (7.1%) patients presented with persistent cytological abnormalities, 32 (4.4%) required repeated treatment for persistent dyskaryosis. 41 (5.6%) of patients had recurrent cytological abnormalities, 13 (1.8%) required repeated treatment. Recurrence developed between two and 12 years from initial treatment. One case of cervical carcinoma following treatment with cold coagulation was recorded. Our data suggest that cold coagulation appears to be safe, efficient treatment for cervical intraepithelial neoplasia.

Serous carcinoma arising in an adenofibroma of the endometrium.

A serous carcinoma and endometrial intraepithelial carcinoma were encountered in an endometrial adenofibroma in a 61-year-old woman. The carcinoma involved the myometrium and cervix (stage IIa). To our knowledge, this is the third documented case of an adenocarcinoma and the first serous carcinoma involving a uterine adenofibroma.

Rhabdomyosarcoma of the uterus: report of two cases, including one of the spindle cell variant.

Most uterine sarcomas fall into the category of leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma. Pure rhabdomyosarcomas are extremely rare, although a rhabdomyosarcomatous element may be present as a component of an adenosarcoma or carcinosarcoma (malignant mixed müllerian tumor). This report describes two uterine rhabdomyosarcomas in 28- and 67-year-old women. These were of spindle cell and pleomorphic types, respectively. At presentation the pleomorphic rhabdomyosaroma was stage IV, exhibiting massive pelvic and abdominal dissemination that mimicked an ovarian neoplasm. The spindle cell rhabdomyosarcoma was stage I, being confined to the uterus. Grossly, both uterine tumors had a polypoid appearance. Immunohistochemically, tumor cells were positive with the skeletal muscle markers sarcomeric actin, myoglobin, and myoD1. The patient with stage IV disease died within a short time of diagnosis and the other patient is alive and well at 2 years' follow-up. This report adds to the published literature on uterine rhabdomyosarcomas. This is the first reported uterine case of the spindle cell variant of embryonal rhabdomyosarcoma. Based on these cases and the published literature, rhabdomyosarcoma, especially the pleomorphic variant, appears to be a very aggressive neoplasm with an extremely poor prognosis. Immunohistochemical demonstration of skeletal muscle differentiation is necessary for a definitive diagnosis.

Morphological effects of chemotherapy on ovarian carcinoma.

AIMS: Traditionally, advanced stage ovarian carcinoma is treated by debulking surgery followed by chemotherapy. However, in some circumstances preoperative chemotherapy may be given before optimal surgical debulking. This study aims to describe the morphological features found in ovarian carcinoma after chemotherapy because these have not been detailed previously. METHODS: Histological sections were examined from 18 cases of ovarian carcinoma that had been treated by preoperative chemotherapy. The morphology was compared with any pre-chemotherapy biopsies that had been performed. Tumours were classified as showing morphological features suggesting a good response to chemotherapy (n = 14) or as showing little or no response (n = 4). Serum CA125 values before and after chemotherapy were compared. In all cases, the mitotic activity index (MAI), volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour cells were calculated. RESULTS: The preoperative biopsies were all typical ovarian serous or endometrioid adenocarcinomas. Morphological features present in the group responding to chemotherapy included the presence of small groups or single tumour cells in a densely fibrotic stroma. Tumour cells were characterised by both nuclear and cytoplasmic alteration, making accurate tumour typing and grading impossible. Nuclear features included the presence of bizarre enlargement with hyperchromatism, irregularity of outline, and chromatin clumping or smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or foam cell change. There were pronounced stromal changes of fibrosis, inflammation, collections of foamy histiocytes, cholesterol cleft formation, haemosiderin deposition, fat necrosis, and dystrophic calcification, including the presence of many free psammoma bodies. There was no correlation between morphological response and biochemical response, as determined by serum CA125 values. In all nine cases in which pre-chemotherapy and post-chemotherapy biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093). CONCLUSIONS: Because preoperative chemotherapy is being used increasingly in the management of ovarian cancer, pathologists should be aware of the resultant morphological effects. Accurate tumour typing and grading is impossible. In some cases, it may be difficult to confirm the presence of residual tumour, making it imperative that pre-chemotherapy tissue biopsies are obtained. Definite confirmation of residual tumour may require the examination of multiple histological sections from areas showing pronounced stromal changes, sometimes with multiple levels and immunohistochemistry. In the absence of definite residual tumour, the report should state that the features are consistent with the prior presence of tumour.

Massive abdominal and pelvic myxoma in Carney's syndrome.

This report describes a massive abdominal and pelvic myxoma in a patient with Carney's syndrome. A 38 year old woman presented with abdominal distension and a palpable mass, and at operation a large pelvic and abdominal tumour was identified and resected. The surgical specimen consisted of a lobulated mass, which on cut section had a uniform gelatinous consistency. The mass surrounded both ovaries, the appendix, and the upper part of the uterus, but macroscopically did not appear to involve these organs. Histological examination showed plump stellate and spindle shaped cells set in an abundant myxoid stroma, in keeping with a myxoma. Immunohistochemical staining revealed positivity of tumour cells for vimentin, but no reactivity to desmin, alpha-smooth muscle actin, S-100 protein, CD34, or AE1/AE3. This is the first documented case of massive adominal and pelvic myxoma in a patient with Carney's syndrome. Clinicians and pathologists should be aware that myxomas in Carney's syndrome can rarely involve unusual sites other than the skin and heart.

Trans-cervical resection of the endometrium: the first four years' experience at the Belfast City Hospital.

We have evaluated the quality of service provided in performing trans cervical resection of the endometrium (TCRE) in the treatment of women presenting with menstrual dysfunction. Of the 78 patients who underwent TCRE, ten had, at the time of writing, subsequently undergone hysterectomy. A chart review was carried out on those patients. Two others were on the waiting list for hysterectomy. Sixty-one of 68 (90%) patients responded to the postal questionnaires. Of these, 50 (82%) were satisfied with the result of the procedure. Twenty-three (38%) were rendered amenorrhoeic. Thirty-eight still had bleeding, but of these, 19 (31%) had very light regular periods and 13 (21%) had only an occasional stain. Overall, 90% of women felt that there had been an improvement in their bleeding. Six (10%) women claimed that there had been no improvement. TCRE is a safe and effective alternative to hysterectomy or medical treatment for the treatment of menstrual dysfunction.

Saved by a hernia: an unusual presentation of ovarian cancer.

A lump in the groin of a 75-year-old woman co-existed with a single ovarian cyst. It was eventually diagnosed as a solitary necrotic omental metastasis from a cystadenocarcinoma of the ovary which had herniated through the femoral canal.

Hysteroscopic metroplasty.

Four patients with reproductive failure associated with uterine septa had transvaginal hysteroscopic metroplasty performed. Two successful pregnancies have occurred and a third patient is now in the second trimester of pregnancy. This method of treatment should replace the traditional open method of surgical repair of these malformations.

Shrinkage of uterine fibroids by preoperative LHRH analogue injection.

Six patients with large uterine fibroids were given a single subcutaneous implant of an LHRH analogue (goserelin 3.5 mg) prior to elective hysterectomy. Overall fibroid volume decreased by 30-47% within six weeks of implantation. All patients reported improvement in their symptoms of pressure and pain, and were rendered amenorrhoeic prior to surgery.