Improvement of endometrial biopsy over transvaginal ultrasound alone for endometrial surveillance in women with Lynch syndrome

In women with hereditary non polyposis colorectal carcinoma (HNPCC) an annual gynaecological surveillance has been recommended because of an increased lifetime risk of developing endometrial and ovarian carcinoma. The aim of this study was to assess the efficacy of gynaecological surveillance with regard to endometrial and ovarian carcinoma. Included were women from families that fulfilled the revised Amsterdam criteria for HNPCC or who showed a proven mutation in one of the mismatch repair genes. An annual gynaecological surveillance was performed (transvaginal ultrasound (TVU) and CA 125 assessment). From January 2006 on, routine endometrial sampling was included. In a total number of 100 women 285 surveillance visits were performed. Among these, in 64 visits routine endometrial samplings were performed: three atypical hyperplasias and one endometrial carcinoma were diagnosed. This was significantly more than the atypical hyperplasia and two endometrial carcinomas that were detected after 28 samples performed because of abnormal surveillance results in 221 visits. There were no interval carcinomas. One invasive ovarian carcinoma stage IIIC was diagnosed at ovarian surveillance. Endometrial surveillance with routine endometrial sampling in women with HNPCC is more efficient in diagnosing endometrial (pre)malignancies than TVU only. Ovarian surveillance is not capable of diagnosing early stage ovarian carcinoma. Prophylactic hysterectomy in HNPCC should be restricted to women in whom abdominal surgery for other reasons is performed and to those with particularly increased risk such as MSH6 mutation carriers and/or women with multiple relatives with endometrial carcinoma.     

Value of upper gastrointestinal endoscopy for gastric cancer surveillance in patients with Lynch syndrome

In our study, we evaluated the effectiveness of upper gastrointestinal (GI) endoscopy as an instrument for early gastric cancer (GC) detection in Lynch syndrome (LS) patients by analyzing data from the registry of the German Consortium for Familial Intestinal Cancer. In a prospective, multicenter cohort study, 1128 out of 2009 registered individuals with confirmed LS underwent 5176 upper GI endoscopies. Compliance was good since 77.6% of upper GI endoscopies were completed within the recommended interval of 1 to 3 years. Forty‐nine GC events were observed in 47 patients. MLH1 (n = 21) and MSH2 (n = 24) mutations were the most prevalent. GCs in patients undergoing regular surveillance were diagnosed significantly more often in an early‐stage disease (UICC I) than GCs detected through symptoms (83% vs 25%; P = .0231). Thirty‐two (68%) patients had a negative family history of GC. The median age at diagnosis was 51 years (range 28‐66). Of all GC patients, 13 were diagnosed at an age younger than 45. Our study supports the recommendation of regular upper GI endoscopy surveillance for LS patients beginning no later than at the age of 30.     

Chemoprevention in Lynch syndrome

CAPP1 tested aspirin 600 mg/day and/or resistant starch 30 g/day in 200 adolescent FAP carriers. Aspirin treatment resulted in a non-significant reduction in polyp number and a significant reduction in polyp size among patients treated with aspirin for more than 1 year. CAPP2 RCT used the same interventions in 937 Lynch syndrome patients, the first RCT to have cancer prevention as the primary endpoint. Aspirin did not reduce the risk of colorectal neoplasia in a mean treatment period of 29 months but double blind post intervention follow-up has revealed 48 participants developed 53 CRCs. Per protocol analysis showed 63 % fewer colon cancers with aspirin (p = 0.008) apparent from 4 years, with a similar effect on other LS cancers. Resistant starch was not beneficial at long term followup. CAPP3 will involve a double blind dose non-inferiority trial comparing 100, 300 or 600 mg daily in 3,000 gene carriers. We can now recommend aspirin in people at high risk of colorectal cancer.     

Endometrial cancer in Lynch syndrome

Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline pathogenic variants (PVs) in mismatch repair (MMR) genes. LS-associated endometrial cancer (LS-EC) is the most common extraintestinal sentinel cancer caused by germline PVs in MMR genes, including MLH1, MSH2, MSH6 and PMS2. The clinicopathologic features of LS-EC include early age of onset, lower body mass index (BMI), endometrioid carcinoma and lower uterine segment involvement. There has been significant progress in screening, diagnosis, surveillance, prevention and treatment of LS-EC. Many studies support universal screening for LS among patients with EC. Screening mainly involves a combination of traditional clinical criteria and molecular techniques, including MMR-immunohistochemistry (MMR-IHC), microsatellite instability (MSI) testing, MLH1 promoter methylation testing and gene sequencing. The effectiveness of endometrial biopsy and transvaginal ultrasound (TVS) for clinical monitoring of asymptomatic women with LS are uncertain yet. Preventive strategies include hysterectomy and bilateral salpingo-oophorectomy (BSO) as well as chemoprophylaxis using exogenous progestin or aspirin. Recent research has revealed the benefits of immunotherapy for LS-EC. The NCCN guidelines recommend pembrolizumab and nivolumab for treating patients with advanced or recurrent microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) EC.     

Progress Report: New insights into the prevention of CRC by colonoscopic surveillance in Lynch syndrome

Familial Cancer - Lynch syndrome is the most frequent hereditary colorectal cancer (CRC) syndrome, affecting approximately 1 in 300 in the Western population. It is caused by pathogenic variants in...     

Improving outcomes for older women with gynaecological malignancies

The incidence of most gynaecological malignancies rises significantly with increasing age. With an ageing population, the proportion of women over the age of 65 with cancer is expected to rise substantially over the next decade. Unfortunately, survival outcomes are much poorer in older patients and evidence suggests that older women with gynaecological cancers are less likely to receive current standard of care treatment options. Despite this, older women are under-represented in practice changing clinical studies. The evidence for efficacy and tolerability is therefore extrapolated from a younger; often more fit population and applied to in every day clinical practice to older patients with co-morbidities. There has been significant progress in the development of geriatric assessment in oncology to predict treatment outcomes and tolerability however there is still no clear evidence that undertaking a geriatric assessment improves patient outcomes. Clinical trials focusing on treating older patients are urgently required. In this review, we discuss the evidence for treatment of gynaecological cancers as well as methods of assessing older patients for therapy. Potential biomarkers of ageing are also summarised.     

Gynecologic cancers associated with Lynch syndrome/HNPCC

Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited cancer susceptibility syndrome caused by a germline mutation in one of the deoxyribonucleic acid (DNA) mismatch repair genes. It is associated with early onset of cancer (age younger than 50 years) and the development of multiple cancer types, particularly colon and endometrial cancer. Women with Lynch syndrome have a 40-60% risk of endometrial cancer, which equals or exceeds their risk of colorectal cancer. In addition, they have a 12% risk of ovarian cancer. Despite limited information on the efficacy of surveillance in reducing endometrial and ovarian cancer risk in women with Lynch syndrome, the current gynecologic cancer screening guidelines include annual endometrial sampling and transvaginal ultrasonography beginning at age 30-35 years. In addition, risk-reducing surgery consisting of prophylactic hysterectomy and bilateral salpingooophorectomy should be offered to women aged 35 years or older who do not wish to preserve their fertility.     

Lynch syndrome in colorectal cancer patients

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer. It is characterized by early onset of colorectal cancer and other extracolonic-associated malignancies. This disorder is inherited in an autosomal dominant pattern and is due to a mutation in one of the DNA mismatch repair genes. Although clinical and molecular understanding of the syndrome has progressed dramatically in the last decade, diagnosis of the syndrome is still a clinical challenge. This review summarizes the main features of the syndrome and provides an update of its management.     

Survival of European women with gynaecological tumours, during the period 1978–1989

This study concerns the survival of European patients diagnosed between 1978 and 1989 with cancer of corpus and cervix uteri and ovary. Variations in survival in relation to age, country and period of diagnosis were examined. Data from the EUROCARE study were supplied by population-based cancer registries in 17 countries to a common protocol. Five years after diagnosis, relative survival rates were 75, 62 and 35% for cancers of the endometrium, cervix and ovary, respectively. Survival decreased markedly with age. The decrease was especially evident for ovarian cancer, which declined from 65% (15–45 years) to 18% (75+ years). In 1985–1989 there were important inter-country differences in survival for European women with gynaecological cancers: Eastern European countries were characterised by low 5-year relative survival whilst in Sweden, Austria, The Netherlands and Switzerland survival was generally higher than for other European countries. From 1978–1989, 5-year relative survival improved slightly for cervical cancer and improved more among the oldest patients. Prognosis also improved slightly for patients with ovarian tumours and this increase (around 20%) was concentrated among patients between 15 and 64 years of age. Intercountry differences in survival did not in general reduce over time, although for ovarian cancer survival differences narrowed probably in relation to the more widespread use of more effective chemotherapy. Intercountry and time differences in survival for cervical cancer are almost certainly related to variations in the effectiveness of cervical screening programmes. For corpus uteri cancer there was no improvement in survival over the period of this study and intercountry survival differences for this cancer are probably related to differences in patient management.     

Complementary medicine use by Australian women with gynaecological cancer

AIMS AND OBJECTIVES: Social and cultural factors are identified that impact on complementary therapy use among Australia-born and immigrant women diagnosed with gynaecological cancer. METHODS: A qualitative study design including in-depth interviews with women diagnosed with gynaecological cancer (N=53) and participant observation was conducted. RESULTS: Approximately one-third of women utilized complementary and alternative medicine, with this being determined by current health concerns and health beliefs related to the efficacy of different modalities. Four types of complementary therapy users emerged: consequential, therapeutic, informed and exploratory. CONCLUSION: There was a relatively low uptake of complementary treatments. Choice was influenced by women's socio-demographic background, clinical and personal history, lack of personal experiences of gynaecological cancer among study participants' kin and friends, and lack of popular alternative literature on such cancer.     

New phenotypic aspects in a family with Lynch syndrome II

Increasing attention has been given to hereditary nonpolyposis colorectal cancer (HNPCC). This report provides medical genetic/pathologic findings on an HNPCC kindred from southern Italy that shows criteria consistent with Lynch syndrome II. An international collaborative effort led to extension of this kindred with disclosure of a potentially new spectrum of phenotypic findings: an excess of gastric carcinoma; complete intestinal metaplasia and chronic atrophic gastritis restricted to the antrum; an apparent excess of colonic mucosal macrophagia, which by special stain appeared to be positive for mucin, with a constant content of both sialo and sulfomucin, a lack of iron, and an inconstant positivity for lysozyme obtained by immunoperoxidase technique; and findings of crypt atrophy of the colonic mucosa. During the relatively short period of investigation of this family, an intensive educational and surveillance program has been mounted in the interest of improving cancer control through direct application of knowledge of natural history and the risk factor evidence through pedigree assessment.