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Biomedical subjects

Jonathan Carter

Publications and source records attributed to Jonathan Carter.

14 recordsLinked to original sources
PubMed2006

A new prognostic model for FIGO stage 1 epithelial ovarian cancer.

BACKGROUND: No consensus exists which patients with surgical stage 1 epithelial ovarian should receive postoperative chemotherapy. The purpose of this study was to evaluate the prognostic impact of preoperative CA-125 and to establish a prognostic index to identify patients in different risk categories. METHODS: Data of 600 surgically staged patients with FIGO stage 1 EOC treated in eleven gynecological cancer centers in Australia, the USA and Europe were analyzed. Eligible patients include those with invasive EOC where a preoperative CA-125 was obtained and standard surgical staging performed. Overall survival (OS) was chosen as study endpoint. Preoperative CA-125 values were compared with other prognostic factors, and univariate and multivariate Cox models were calculated. RESULTS: Two hundred and one patients (33.5%) had preoperative CA-125 < or =30 U/ml and CA-125 levels < or =30 U/ml were associated with lower grade, sub-stage 1A and mucinous histologic cell type. Patients with elevated CA-125 levels were more likely to receive chemotherapy. OS probability was 95% and 85% for patients with pretreatment CA-125 < or =30 U/ml and >30 U/ml, respectively (p 0.003). Multivariate analysis confirmed preoperative serum CA-125 >30 U/ml (OR 2.7) and age at diagnosis >70 years (OR 2.6) as the only independent predictors for overall survival. CONCLUSION: Pretreatment of CA-125 < or =30 U/ml dominates over histologic cell type, sub-stage and grade to identify a subgroup of FIGO stage 1 patients with a genuinely good prognosis with extremely good survival and who could possibly be spared with adjuvant chemotherapy.

Adult↗
PubMed2006

Steroid-responsive encephalopathy associated with autoimmune thyroiditis.

BACKGROUND: Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), often termed Hashimoto encephalopathy, is a poorly understood and often misdiagnosed entity. OBJECTIVE: To characterize the clinical, laboratory, and radiologic findings in patients with SREAT to potentially improve recognition of this treatable entity. DESIGN: Retrospective analysis of clinical features and diagnostic test data. SETTING: Two affiliated tertiary care referral institutions. PATIENTS: Twenty consecutive (6 male) patients diagnosed as having SREAT from 1995 to 2003. MAIN OUTCOME MEASURES: Clinical features and ancillary test findings associated with SREAT. RESULTS: The median age at disease onset was 56 years (range, 27-84 years). The most frequent clinical features were tremor in 16 (80%), transient aphasia in 16 (80%), myoclonus in 13 (65%), gait ataxia in 13 (65%), seizures in 12 (60%), and sleep abnormalities in 11 (55%). All patients were assigned an alternative misdiagnosis at presentation, most commonly viral encephalitis (n = 5), Creutzfeldt-Jakob disease (n = 3), or a degenerative dementia (n = 4). The most frequent laboratory abnormalities were increased liver enzyme levels in 11, increased serum sensitive thyroid-stimulating hormone levels in 11, and increased erythrocyte sedimentation rate in 5. In only 5 patients (25%) did cerebrospinal fluid abnormalities suggest an inflammatory process. Magnetic resonance imaging abnormalities believed to be related to the encephalopathy were present in 5 patients (26%). CONCLUSIONS: The clinical, laboratory, and radiologic findings associated with SREAT are more varied than previously reported. Misdiagnosis at presentation is common. This treatable syndrome should be considered even if the serum sensitive thyroid-stimulating hormone level and erythrocyte sedimentation rate are normal, the cerebrospinal fluid profile does not suggest an inflammatory process, and neuroimaging results are normal. Until the pathophysiologic mechanism of this and other autoimmune encephalopathies is better characterized, we believe that descriptive terms that reflect an association rather than causation are most appropriate for this syndrome.

Adult↗
PubMed2006

Recurrence after treatment for high-grade dysplasia: should we modify our post-treatment surveillance protocols?

A cohort of women, having undergone an excisional procedure for high-grade cervical dysplasia, was studied to identify those patients who developed recurrent high-grade cervical dysplasia post-treatment. We have confirmed that recurrent histologically confirmed high-grade cervical dysplasia is uncommon after complete excision and appears not to occur within the first 6 months post-treatment. Post-treatment surveillance protocols should incorporate these findings.

Adult↗
PubMed2006

Not all ovarian cysts in young woman are benign: a case series and review of the management of complex adnexal masses in young women.

While ovarian cancer is a disease that predominately affects postmenopausal women, up to 13% of affected patients are indeed less than 45 years of age. The diagnosis is often delayed because of the non-specific nature of symptoms and a lack of specific and accurate diagnostic tests, that is, CA125 and ultrasound. In premenopausal women these issues are compounded, further reducing the likelihood of an accurate and early diagnosis. It is important for gynaecologists to have a high index of suspicion and appropriately investigate symptomatic patients and interpret test results critically. Not all ovarian cysts in young women are benign, and a low threshold for surgical evaluation is warranted.

Adenocarcinoma, Clear Cell↗
PubMed2006

An overview of uterine cancer and its management.

Endometrial cancer is increasingly common in affluent Western countries, largely owing to the growing obesity of those populations. There are two recognized types of endometrial cancer: Type I is more common and is associated with obese postmenopausal women and comprises approximately 80% of all endometrial cancers; Type II describes a woman who is often younger and thinner with a more aggressive histologic type that is nonestrogen dependent, of either serous or clear cell histology, and consists of a more aggressive clinical course and results in poorer prognosis. As the majority of patients with endometrial cancer present with symptoms and have early disease, screening is unlikely to be cost effective or reduce the mortality rate. However, surveillance of high-risk populations is a different proposition. Patients who may benefit from routine surveillance include those with a family history of endometrial cancer, a history of hormone replacement therapy with less than 12-14 days of progestogens, long-term use of tamoxifen, hereditary nonpolyposis colorectal cancer family syndrome, Cowden's syndrome, Peutz-Jeghers syndrome, a history of breast cancer and obesity. Most patients with endometrial cancer are offered surgery as first-line therapy. The standard surgical procedure should be an extrafascial total hysterectomy with bilateral salpingo-oophorectomy. Adnexal removal is also recommended, even if the adnexa appear normal, as they may contain micrometastases. The safety of a laparoscopic approach in the surgical management of uterine cancer has not yet been demonstrated in prospective randomized trials, therefore, the field awaits the Gynaecologic Oncology Group's prospective Lap-2 study. While post-treatment follow-up guidelines vary between institutions and countries, in general, patients at high risk of recurrence are followed closely every 3-4 months for the first year or two, then every 6 months to complete 5 years of follow-up.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Prognostic importance of preoperative CA-125 in International Federation of Gynecology and Obstetrics stage I epithelial ovarian cancer: an Australian multicenter study.

PURPOSE: To evaluate the prognostic significance of preoperative CA-125 levels on overall survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage I epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Data from 518 patients with FIGO stage I EOC treated in seven gynecologic oncology centers throughout Australia between 1990 and 2002 were analyzed. Patients with borderline tumors and nonepithelial ovarian carcinomas were excluded, as were women in whom CA-125 had not been determined preoperatively. Preoperative CA-125 levels were studied in surgically staged and incompletely staged patients and compared with prognostic factors, such as substage, grade, and histologic type. Multivariate Cox models were calculated. RESULTS: CA-125 levels more than 30 U/mL were associated with higher grade, substage 1B and 1C, nonmucinous histologic type, and older age. In univariate analysis, higher histologic grade, the absence of surgical staging, and preoperative CA-125 levels more than 30 U/mL were associated with impaired survival. Multivariate analysis identified histologic grade, preoperative CA-125, and surgical staging as independent predictors for survival. In the subgroup of completely surgically staged patients, the 5-year overall survival rate was 82% (95% CI, 76% to 88%) for patients with CA-125 levels more than 30 U/mL and 95% (95% CI, 90% to 99%) for patients with CA-125 levels of 30 U/mL or less (P = .028). In the group of incompletely staged patients, the 5-year survival rates were similar for patients with elevated and normal serum CA-125 levels. CONCLUSION: Complete surgical staging, histologic grade, and preoperative serum CA-125 levels are independent prognostic factors and should be included in the decision making for chemotherapy.

Adult↗
PubMed2005

p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: Experience with squamous lesions in 189 consecutive cervical biopsies.

AIM: To test the usefulness of p16(INK4a) immunostaining for improving the diagnostic accuracy of cervical punch biopsies referred to a routine laboratory setting during the investigation of women with abnormal Papanicolaou smears. METHODS: A total of 188 consecutive and unselected colposcopically directed cervical biopsies and a single contemporaneous cervical polyp were accessioned prospectively over a 3-month period, step-serially sectioned and examined by H&E and immunostained for p16(INK4a). The clinical context, results of concurrent Papanicolaou smears/ThinPrep slides and Digene hybrid capture tests for high-risk human papillomavirus (HPV) subtypes, as well as follow-up cervical smears/ThinPrep, biopsies and loop excisions of transformation zones or cone biopsies were all correlated with the morphological and immunohistochemical findings. RESULTS: Seventy-seven biopsies (40.7%) displayed a high-grade squamous intraepithelial lesion (HGSIL; cervical intraepithelial neoplasia [CIN] 2-3), 27 (14.3%) showed a low grade squamous intraepithelial lesion (HPV +/- CIN1) and 85 (45%) showed a range of non-dysplastic (inflammatory or reactive) changes. Diffuse strong parabasal immunostaining for p16(INK4a), suggestive of integrated high-risk HPV DNA into the host genome, was observed in 81 biopsies (42.9%, including the cervical polyp) and correlated (>90%) with HGSIL in the H&E sections. Only one case revealed irreconcilable discordance between the histological features and this strong parabasal immunostaining pattern. Focal and weaker midzonal or superficial p16(INK4a) immunostaining, suggestive of episomal HPV infection, was noted in 19 biopsies (10%) and these biopsies exhibited a range of histological changes but predominantly low grade squamous intraepithelial lesion (LGSIL). No staining of the squamous epithelium was seen in 89 biopsies (47.1%). Again, only one case revealed irreconcilable discordance between the histological features and this negative immunostaining pattern. On review of all cases where discordant results were noted between the H&E appearances and expected p16(INK4a) immunostaining, we found 26 cases (13.7%) in which this discordance prompted justifiable modification of the original diagnosis. CONCLUSIONS: Thus, within a routine diagnostic laboratory, p16(INK4a) immunostaining appears to be a very useful adjunctive test in the examination of colposcopically directed cervical biopsies, in the diagnostic cascade of women investigated for abnormal Papanicolaou smears. It is possible, as further data accumulate concerning the importance of integration of high-risk HPV DNA into the host cell genome and the reliability with which this can be identified by p16(INK4a) immunostaining, that this will become the diagnostic 'lesion of interest', replacing the subjective histological grading of cervical dysplasia, in the management of such patients; i.e., the discriminatory watershed between continued surveillance and active intervention.

Biomarkers, Tumor↗
PubMed2004

Comparative analysis of characteristics of women with cervical cancer in high- versus low-incidence regions.

OBJECTIVE: To identify particular characteristics that might help explain the markedly higher rate of invasive cervical cancer in southern China as compared with Australia. METHODS: One hundred eighty-five women with cervical cancer were recruited between 1999 and 2001: 106 from Guangzhou and Changsha (southern China), and 79 from Sydney (southeast Australia). Demographic and risk factor information was obtained by questionnaire; clinicopathologic data were extracted from hospital records. The human papillomavirus (HPV) status of cancer biopsies was ascertained by consensus PCR assays, direct sequencing and/or Amplicor trade mark hybridisation. RESULTS: The mean age of the Chinese was significantly lower than the Australians (44 versus 53 years), although mean age at first sexual intercourse was similar. Australian women were more likely to smoke, to report multiple sexual partners and to have a history of sexually transmitted diseases (but not of genital warts). However, they were better educated, were more frequent users of barrier contraception and were far more likely to report regular Pap smears before diagnosis. The HPV positivity rate of Chinese cancers (83%) was less than Australian tumours (90%); but HPV 16 and 18 were the most common genotypes in both populations (59% and 77%), and predominated in cancers from younger women. HPV types 58 or 59 were amplified from 12 (14%) of the Chinese but from only one Australian cancer. CONCLUSIONS: Cervical cancer is not only more common in China but also develops at a younger age than in Australia. While significant differences in some risk factors were observed, the much lower participation in cervical screening in southern China is likely to be of greatest consequence.

Adult↗
PubMed2004

Management of upper gastrointestinal obstruction in advanced ovarian cancer with intraluminal stents.

BACKGROUND: The course of many patients with end-stage gynecologic malignancy will be complicated by malignant bowel obstruction. Intraluminal stents are a novel alternative to standard surgical intervention which can involve considerable patient risk. CASES: Two cases are presented of patients with upper gastrointestinal obstruction due to recurrent ovarian cancer. In the first case, a stent was utilised to provide relief from nocturnal vomiting secondary to duodenal obstruction. In the second case, stent insertion for subtotal gastric outlet obstruction provided initial relief from vomiting. However, recurrence of symptoms occurred due to stent occlusion from tumour ingrowth. CONCLUSIONS: In patients with upper gastrointestinal obstruction due to recurrent gynecologic malignancy, intraluminal stents can provide useful palliation.

Adult↗
PubMed2003

Malignant mixed mullerian tumour of the ovary: prognostic factor and response of adjuvant platinum-based chemotherapy.

OBJECTIVES: The purpose of the present study was to analyse retrospectively the data of a series of patients presenting to our unit with malignant mixed mullerian tumour (MMMT) of the ovary to identify the prognostic factors and relate them to survival. The role of platinum-based chemotherapy in the adjuvant treatment of this tumour was also evaluated. METHODS: All patients diagnosed with MMMT of the ovary from 1987 to 2000 were identified from the gynaecological tumour registry of King George V Hospital, Australia. The effect of clinical and histopathological variables on survival was analysed. The response of platinum-based adjuvant chemotherapy after surgery was also evaluated. RESULTS: Twenty patients with MMMT of the ovary were identified. Of the six patients with measurable disease, two (33%) had complete response after adjuvant platinum-based chemotherapy. The median survival of all patients was 8 months, while that of the patients receiving adjuvant platinum-based chemotherapy was 23 months. Women who were older (> 65 years) had a significantly worse survival rate than those who were younger (P = 0.02). The patients with optimal debulking had a better median survival than those with suboptimal debulking, but this difference was not statistically significant (P = 0.21). Sarcomatous component (homologous vs heterologous) was not found to be a significant prognostic factor for predicting survival. CONCLUSIONS: Malignant mixed mullerian tumour of the ovary is a rare and aggressive gynaecological tumour. The current study indicates that patient age was a significant prognostic factor for survival and surgical cytoreduction combined with platinum-based chemotherapy is the most effective management regimen identified to date to treat MMMT of the ovary.

Age Factors↗
PubMed2002

Management of large bowel obstruction in advanced ovarian cancer with intraluminal stents.

BACKGROUND: While most patients with advanced ovarian cancer can achieve prolonged remission with surgery and chemotherapy, eventually most will recur. Commonly bowel obstruction will complicate their recurrence, usually heralding the terminal phase of their disease. Standard management of bowel obstruction has involved surgical intervention after a period of conservative medical management. Unfortunately, many patients submitted for surgery do not derive benefit from such an approach, spending the majority of their remaining life in the hospital or recovering from the surgery. CASES: Two cases of patients with large bowel obstruction resulting from advanced and recurrent ovarian cancer are presented. In the first case, a rectal stent was decided upon as the appropriate management as she was failing first-line therapy, with little likelihood of recovering from a laparotomy. In the second case a large recurrent infected tumor mass had already been debulked, but was continuing to cause obstructive symptoms. In both cases immediate relief of their gastrointestinal symptoms was achieved. CONCLUSIONS: In patients with large bowel obstruction secondary to extrinsic compression, useful palliation can be achieved with a colonoscopically placed endoluminal stent.

Colonic Diseases↗