John Shepherd - Profile on Academia.edu (original) (raw)

Papers by John Shepherd

Journal of Clinical Pathology, Nov 1, 1994

Aim-To investigate serum placentaltype alkaline phosphatase (PLAP-type) activities in women with ... more Aim-To investigate serum placentaltype alkaline phosphatase (PLAP-type) activities in women with squamous and glandular malignancies of the reproductive tract using an immunoradiometric assay. Methods-PLAP-type immunoreactivity was measured in 180 women with non- ovarian malignancies of the reproductive tract and the values were compared with those from 334 controls. The cases comprised 18 vulval, nine vaginal, 103 cervical, 46 endometrial, and five fal- lopian tube cancers. Results-Serum PLAP-type activities were no different from controls in patients with squamous cell tumours.

Journal of the Royal Society of Medicine, Dec 1, 1991

Ileum has been used to reconstruct the lower urinary tract in 15 patients (10 women, five men) af... more Ileum has been used to reconstruct the lower urinary tract in 15 patients (10 women, five men) after treatment for bladder or gynaecological cancer. Seven patients had previously receivedradical pelvic irradiation. Four methods were.used: group 1 (five patients): bladder patch after partial cystectomy or bladder augmentation after clam ystotomy for bladder contracture; group 2 (four patients): bladder replacement after subtotal (supratglial) cystectomy; group 3 (two patients): uretteric replacement for lower ureteric obstruction or fistula, and group 4 (four patients): complete replacement ofbladder and lower ureters after anterior pelvic exenteration, with creation of neovagina from caecum in the two female patients. Review of the results indicates that ileum provides a versatile and safe material for anterior pelvic reconstruction in cancer patients, even after previous pelvic irradiation.

Hereditary Cancer in Clinical Practice, Nov 23, 2011

Background: We assessed ovarian cancer screening outcomes in women with a positive family history... more Background: We assessed ovarian cancer screening outcomes in women with a positive family history of ovarian cancer divided into a low-, moderate-or high-risk group for development of ovarian cancer. Methods: 545 women with a positive family history of ovarian cancer referred to the Ovarian Screening Service at the Royal Marsden Hospital, London from January 2000-December 2008 were included. They were stratified into three risk-groups according to family history (high-, moderate-and low-risk) of developing ovarian cancer and offered annual serum CA 125 and transvaginal ultrasound screening. The high-risk group was offered genetic testing. The median age at entry was 44 years. The number of women in the high, moderate and low-risk groups was 397, 112, and 36, respectively. During 2266 women years of follow-up two ovarian cancer cases were found: one advanced stage at her fourth annual screening, and one early stage at prophylactic bilateral salpingooophorectomy (BSO). Prophylactic BSO was performed in 138 women (25.3%). Forty-three women had an abnormal CA125, resulting in 59 repeat tests. The re-call rate in the high, moderate and low-risk group was 14%, 3% and 6%. Equivocal transvaginal ultrasound results required 108 recalls in 71 women. The re-call rate in the high, moderate, and low-risk group was 25%, 6% and 17%. No early stage ovarian cancer was picked up at annual screening and a significant number of re-calls for repeat screening tests was identified.

BMJ, Jul 14, 1979

The routine method of induction at Queen Charlotte's Maternity Hospital is now by the use of pros... more The routine method of induction at Queen Charlotte's Maternity Hospital is now by the use of prostaglandin E, pessaries. The first 502 consecutive patients thus induced are presented: the caesarean section rate for a failed induction with an unfavourable cervix has fallen to 2%. The prostaglandin E2 pessary is highly efficient and acceptable for all cases in which a simple amniotomy will not suffice.

The Annals of The Royal College of Surgeons of England, 2009

Annals of The Royal College of Surgeons of England, Apr 1, 2009

INTRODUCTION Cervical cancer is the second commonest cancer to affect women with over half a mill... more INTRODUCTION Cervical cancer is the second commonest cancer to affect women with over half a million cases world-wide yearly. Screening programmes have reduced the incidence and death rate dramatically in Western societies. At the same time, professional and social pressures may delay child bearing such that a significant number of women will present with early stage disease, but be anxious to retain their fertility potential. Standard treatment by radical hysterectomy or radiotherapy has good results, but inevitably renders the women infertile. The rationale for extensive surgery resecting parametrium or destructive radiotherapy treating the whole pelvis in all cases of cervical cancer has been questioned. PATIENTS AND METHODS Lessons learnt from the less radical surgical approach to breast cancer can be applied to cervical cancer whilst still observing Halstead's principles of surgical oncology. Wide, local excision of early stage small tumours by radical vaginal trachelectomy combined with a laparoscopic pelvic lymphadenectomy utilises modern technology with traditional surgery. Radical vaginal trachelectomy comprises the distal half of a radical abdominal (Wertheim's) or vaginal (Schauta's) hysterectomy. An isthmic-vaginal anastomosis restores continuity of the lower genital tract after insertion of a cerclage that is necessary to maintain competence during future pregnancies. RESULTS A total of 142 cases were performed between 1994 and 2006, most (98%) in women with Stage 1B carcinoma of the cervix with a mean follow-up of 57 months. Twelve (9%) had completion treatment, 11 with chemo/radiotherapy and one radical hysterectomy. There were four recurrences (3%) among the women who did not have completion treatment, and two (18%) in those that did. There were 72 pregnancies in 43 women and 33 live births in 24 women. The 5-year accumulative pregnancy rate among women trying to conceive was 53%. Delivery was by classical caesarean section in a high-risk fetomaternal units with 8 babies (25%) born before 32 weeks. CONCLUSIONS Radical vaginal trachelectomy appears safe when performed in centres with appropriate experience of radical vaginal surgery and laparoscopic techniques. The impact of this new approach questions traditional teaching whilst preserving potential fertility in hitherto impossible circumstances. SHEPHERD CHALLENGING DOGMA: RADICAL CONSERVATION SURGERY FOR EARLY STAGE CERVICAL CANCER IN ORDER TO RETAIN FERTILITY

British Journal of Cancer, Feb 1, 1995

S_qy Tumours of the vulva and vagina are rare and there are relatively few studies of circulating... more S_qy Tumours of the vulva and vagina are rare and there are relatively few studies of circulating markers in these conditions. The urinary meas t of the core fragment of the s-subunit of bCG has been proposed as a usefl tumour marker in non-trophoblastic ynaecological malignancies. This study describes the measurement of urinary P-core in 50 paents with vulvovaginal malignancy. In contrast to other studis, corrections were made for both the effect of urie concentration and the age of the patienL Each patint was followed up for at least 24 months, and at this time their status was correlated with their initial level of urinary P-core. The senstnivty of P-core was only 38%, but of those patients with elevated kvels 90% had died within 24 months, while only 32% of those with nomal levels had died. For both patients at initial presentation and those with recurrent disease there was a highly significant difference in the survival curves betwn those with devated P-core kvs and those with normal kves. This is similar to findings in cvical carcmoma, and suggets that for lower genital tract cancer the meaurement of unary P-core may be valuable as a prognostc indicator, allowing a more informed aproac to treatment and folow-up.

BMJ, Feb 2, 1991

Objective-To evaluate whether hormone replacement therapy affects survival in women who have unde... more Objective-To evaluate whether hormone replacement therapy affects survival in women who have undergone bilateral salpingo-oophorectomy because of epithelial ovarian cancer. Design-Retrospective analysis by review of patients' notes and questionnaires completed by general practitioners to compare the overall survival and disease free survival in patients with ovarian cancer who did or did not receive hormone replacement therapy after diagnosis. Data were analysed by Cox regression, with hormone replacement therapy as a time dependent covariate because patients who received hormone replacement did so at different times after diagnosis. Setting-Gynaecological oncology unit of Royal Marsden Hospital. Patients-373 patients aged 50 years or younger who attended the hospital from 1972 to 1988. Ali of the women had undergone bilateral salpingooophorectomy for epithelial ovarian cancer. In ali, 78 had received hormone replacement therapy, starting at a median of four months after diagnosis. Intervention-A questionnaire was sent to the general practitioners of all patients who were not recorded as having received hormone replacement therapy. Main outcome measures-Overall survival and disease free survival. Results-There was no significant difference in survival between women receiving hormone replacement therapy and those not receiving it after accounting for the effects of other known prognostic factors (stage of cancer, differentiation of tumour, histological results, and time to relapse). The relative risk of dying in those who received hormone replacement therapy was 0-73 (95% confidence interval 0-44 to 1-20). In addition, there was no significant difference in disease free survival (relative risk in those receiving hormone replacement therapy was 0-90; 95% confidence interval 0-52 to 1-54). Conclusions-This study shows that hormone replacement therapy is unlikely to have a detrimental effect on the prognosis of patients with ovarian cancer, but this would be shown conclusively only by a randomised controlled trial.

BMJ, 1968

The mothers were quite unselected, and one of the nursing sisters felt that it would be a good id... more The mothers were quite unselected, and one of the nursing sisters felt that it would be a good idea to screen mothers before admission and omit the likely troublemakers. In practice it would be difficult to do this without considerable knowledge of the mother and child; furthermore, 22 out of the 27 mothers in the experimental group who were thought to be emotionally disturbed when the first home visit was made stayed in hospital with their children and caused no trouble whatsoever.

Multi-parameter flow cytometric quantitation of the expression of the tumor-associated antigen SM3 in normal and neoplastic ovarian tissues. A comparison with HMFG1 and HMFG2

Cancer, 1991

A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal gr... more A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein on 85 cryopreserved normal tissues (30 ovary, 29 endometrium, 16 cervix) and 67 carcinomas (31 ovarian, 18 cervical, 15 endometrial, 3 vulvar). Overexpression of the EGFR and c-erbB-2 oncoproteins was found in respectively 3/31 (9%) and 10/31 (32%) ovarian carcinomas, 13/18 (72%) and 7/18 (38%) cervical carcinomas, and 2/15 (13%) and 2/15 (13%) endometrial carcinomas. Oncoprotein expression was significantly higher in the malignant tumors (for all tumor sites) than in the corresponding normal tissues (P less than 0.034 for all combinations). Aneuploid tumors expressed levels of EGFR and c-erbB-2 oncoprotein significantly higher than those of DNA diploid tumors (P = 0.042 and P = 0.048, respectively). Oncoprotein could be detected in nearly all normal tissues: expression was higher in premenopausal than in postmenopausal patients (EGFR, P = 0.07; c-erbB-2, P less than 0.001). The present study supports the idea that EGFR and c-erbB-2 may play an important role in the autocrine, paracrine, and/or endocrine growth control and differentiation of normal tissues. Alteration in the expression of these oncoproteins is probably involved in malignant transformation and tumorigenesis.

Acta Obstetricia et Gynecologica Scandinavica, 2008

The obstetrician & gynaecologist, Apr 1, 2005

Cancer Imaging, 2007

As the overall prognosis for patients with ovarian cancer is poor, the management of this conditi... more As the overall prognosis for patients with ovarian cancer is poor, the management of this condition should be restricted to expert multidisciplinary teams in gynaecological oncology. Apparent early stage ovarian cancer requires accurate and complete staging so that potential sites for metastases are not missed. Omitting adequate staging may have significant consequences including a negative impact on survival rates in young patients. The challenge with advanced ovarian cancer is to obtain a detailed appreciation of the extent of disease. This information allows treatment with primary chemotherapy if the cancer is considered to be inoperable and/or the general condition of the patient renders her unfit for appropriate surgery. Available data would suggest that a 5-year survival rate of 50% is only possible for those patients who have had complete cytoreduction of all tumour. Therefore, the best surgical option for patients with advanced ovarian cancer is a complete primary surgical procedure that achieves complete clearance of the abdominal cavity rather than optimal surgery that leaves tumour nodules up to 1 cm in diameter in situ in the patient.

Radiographics, 2005

Carcinoma of the cervix has a predilection for affecting young women. In recent years, surgical p... more Carcinoma of the cervix has a predilection for affecting young women. In recent years, surgical procedures that combine local radical surgery with maintenance of fertility potential in young women have been investigated. One such procedure is radical trachelectomy with pelvic lymphadenectomy, in which the corpus uteri is preserved, thus maintaining fertility potential. Magnetic resonance (MR) imaging is useful in the selection of suitable patients for trachelectomy and in postsurgical follow-up. The MR imaging findings in 45 patients who underwent trachelectomy at one institution between 1996 and 2004 were retrospectively reviewed. The uterovaginal anastomosis has variable appearances, with an end-to-end anastomotic appearance or a vaginal neofornix seen after surgery; suture artifacts can also occur. Possible changes affecting the vagina include diffuse wall thickening and hematomas, whereas lymphoceles and exaggeration of the pelvic venous plexuses can occur in the pelvis. Adenomyosis and endometriosis may be found incidentally in this patient group. Successful pregnancies after trachelectomy have been reported and should be treated as high-risk pregnancies. Knowledge of these MR imaging appearances will help radiologists distinguish between normal postsurgical variations, benign postsurgical changes, and recurrent disease in patients who have undergone trachelectomy.

Bone Marrow Transplantation, 1999

We report the unusual complication of vaginal stenosis occurring after allogeneic bone marrow tra... more We report the unusual complication of vaginal stenosis occurring after allogeneic bone marrow transplantation (BMT) for leukaemia. This was in all likelihood a manifestation of chronic graft-versus-host disease (cGVHD), although the patient has no other stigmata of this and suffered little acute graft-versus-host disease (aGVHD) after BMT. Other risk factors for vaginal stenosis were considered and appear to be absent in this patient, although the total body irradiation used as part of her conditioning therapy may play a role. We suggest that vaginal stenosis may be under-reported, since female patients suffer a number of gynaecological complications after BMT, and that regular questioning and examination may aid in making an earlier diagnosis, allowing speedier instigation of therapy and thus improving quality of life.

Author response to: A statement for extensive primary cytoreductive surgery in advanced ovarian cancer

Bjog: An International Journal Of Obstetrics And Gynaecology, Dec 1, 2008

Sir, We welcome the comments from Naik et al.1 at Gateshead who share a similar surgical philosop... more Sir, We welcome the comments from Naik et al.1 at Gateshead who share a similar surgical philosophy to ours. The data from surgical studies on the benefit of optimal primary cytoreductive surgery in ovarian cancer are more consistent and convincing, whereas those data on neoadjuvant chemotherapy are less so. Despite massive expenditure on chemotherapeutic agents, optimal primary surgical cytoreduction, not chemotherapy, is the single most important means to give women the best chance of a prolonged disease-free interval. Naik et al.1 suggest reasons to explain the low optimal/ complete primary surgical cytoreductive rate on average in the UK. At a recent British Gynaecological Cancer Society meeting, we presented some results of a questionnaire on advanced epithelial ovarian cancer sent to all UK gynaecological oncologists. One finding was that the mean operating time was about 3 hours, yet many claimed to achieve optimal cytoreduction in that time. This contrasts with our units and other in the USA or Europe, which achieve a high rate of optimal cytoreduction where the mean operating time is 5 hours or more! There are evidently two mindsets or philosophies. Fundamentally, how are the patients’ interests best served? For advanced peritoneal ovarian carcinosis, the surgical challenge is in the upper abdomen and not the pelvis. The argument has been confused by whether a gynaecological oncologist should or should not undertake upper abdominal surgery. Just as one would involve an oncoplastic surgeon for a complicated vulvovaginal reconstruction, there must be careful consideration given to the team approach to advanced ovarian cancer with upper abdominal disease. In experienced hands, this may be the gynaecological oncology team alone or it might involve the upper gastrointestinal or hepatobiliary team. What is key is that the gynaecological oncology team’s philosophy is a priori to aim for compete cytoreduction, involve other surgical colleagues if necessary or not, and plan the operating day appropriately. As pointed out by Naik et al.,1 surgical centres in the UK have been slow to maintain comprehensive data sets and publish data on outcomes, including morbidity, mortality, and survival. Today, it still remains a truism that appropriate radical surgery is the key to the control of the majority of solid malignancies. j

Urinary metabolites of the (3 subunit of human chorionic gonadotropin (hCG(3), particularly the f... more Urinary metabolites of the (3 subunit of human chorionic gonadotropin (hCG(3), particularly the fragment known as (3-core, are potential tumor markers for gynecological cancers (1-6). We have found that an increased concentration (�tg’L) of (3-core in early-morning urine samples is relatively common in gynecological cancers, but the sensitivity (36%) and specificity (90%) of such measurements are low (7). Most clinical studies have reported /3-core concentrations in early-morning or random urine specimens without correction for urine volume or concentration (1-7). For many urinary solutes, however, including proteins, expressing the concentration as a ratio to the urinary creatinine concentration is less variable and may better reflect the true urine output than does concentration per unit volume (8-11). In the present study, we examined the variation of urinary (3-core excretion over a 24-h period, to determine whether expressing (3-core results as a ratio to creatinine or to total...