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Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC. [Display omitted] [ABSTRACT FROM AUTHOR]

Unexpected vaginal bleeding, whilst responsible for much anxiety amongst women, is rarely associated with any serious underlying pathology. Nevertheless, bleeding which occurs spontaneously in between menses or after intercourse is recognised as a ‘red flag’ symptom for gynaecological cancer. Infection, hormonal fluctuations, benign cervical and endometrial conditions are, however, more common causes of abnormal bleeding. The role of the generalist clinician is to diagnose and treat uncomplicated conditions, whilst also determining the likelihood of malignancy and referring for further investigations appropriately. [ABSTRACT FROM AUTHOR]

Abstract: Body mass index (BMI) is a major risk factor for endometrial cancer incidence but its impact on post-treatment survival is unclear. We investigated the relationships of BMI (categorised using the WHO definitions) with clinico-pathological characteristics and outcome in women treated within the MRC ASTEC randomised trial, which provides data from patients who received standardised allocated treatments and therefore reduces biases. The impact of BMI on both recurrence-free survival (RFS) and overall survival (OS) was analysed using the Cox regression models. An a priori framework of evaluating potential biases was explored. From 1408 participants, there were 1070 women with determinable BMI (median=29.1kg/m2). Histological types were endometrioid (type 1) in 893 and non-endometrioid (type 2) in 146 women; the proportion of the latter decreasing with increasing BMI (8% versus 19% for obese III WHO category versus normal weight, p trend =0.003). For type 1 carcinomas, increasing BMI was associated with less aggressive histopathological features (depth of invasion, p =0.006; tumour grade, p =0.015). With a median follow-up of 34.3months, there was no influence of BMI on RFS - adjusted HRs per 5kg/m2 were 0.98 (95% CI 0.86, 1.13) and 0.95 (0.74, 1.24), for type 1 and 2 carcinomas; and no influence on OS – adjusted HRs per 5kg/m2 were 0.96 (0.81, 1.14) and 0.92 (0.70, 1.23), respectively. These findings demonstrate an important principle: that an established link between an exposure (here, obesity) and increased incident cancer risk, does not necessarily translate into an inferior outcome following treatment for that cancer. [Copyright &y& Elsevier]

Abstract: Objective: To describe the surgical rectus sheath block for post-operative pain relief following major gynaecological surgery. Technique: Local anaesthetic (20ml 0.25% bupivacaine bilaterally) is administered under direct vision to the rectus sheath space at the time of closure of the anterior abdominal wall. Study design: We conducted a retrospective case note review of 98 consecutive patients undergoing major gynaecological surgery for benign or malignant disease who received either standard subcutaneous infiltration of the wound with local anaesthetic (LA, n =51) or the surgical rectus sheath block (n =47) for post-operative pain relief. Main outcome measures: (1) Pain scores on waking, (2) duration of morphine-based patient controlled analgesia (PCA), (3) quantity of morphine used during the first 48 post-operative hours and (4) length of post-operative stay. Results: The groups were similar in age, the range of procedures performed and the type of pathology observed. Patients who received the surgical rectus sheath block had lower pain scores on waking [0 (0–1) vs. 2 (1–3), p <0.001], required less morphine post-operatively [12mg (9–26) vs. 36mg (30–48), p <0.001], had their PCAs discontinued earlier [24h (18–34) vs. 37h (28–48), p <0.001] and went home earlier [4 days (3–4) vs. 5 days post-op (4–8), p <0.001] [median (interquartile range)] than patients receiving standard subcutaneous local anaesthetic into the wound. Conclusions: The surgical rectus sheath block appears to provide effective post-operative analgesia for patients undergoing major gynaecological surgery. A randomised controlled clinical trial is required to assess its efficacy further. [Copyright &y& Elsevier]

Summary: Referral of women with vulval carcinoma to tertiary centres is now established practise in the UK. The centralisation of care for these women promotes the development of specialist teams of gynaecological oncologists, clinical oncologists, pathologists and clinical nurse specialists with expertise in the management of this relatively rare tumour. The primary care physician plays an essential role in the early detection and subsequent urgent referral of women with suspicious vulval lesions. Improved education and awareness campaigns may encourage women to report vulval symptoms early. Where vulval carcinoma is diagnosed at an early stage, surgical excision is likely to be curative. There is, however, a move away from radical surgery for all patients irrespective of stage of disease towards an individualised approach, which takes into account the size and position of the tumour. The challenge is to reduce morbidity associated with treatment without compromising on cure rates. Restricting groin lymphadenectomy to women with lymph node metastases may be possible with the advent of sentinel node technology and it is anticipated that expertise in this area will show significant advances over the coming years. There is still a place for radical surgery, often in combination with other treatment modalities, in the management of advanced or recurrent disease. This article will review the evidence for the current management of vulval carcinoma. [Copyright &y& Elsevier]

This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants. The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30–69 years. Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery. Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes. • Premenopausal oophorectomies in patients not at increased risk of ovarian cancer. • Uptake of risk-reducing surgery (RRS) in Lynch syndrome aligns poorly with cancer risk and mortality. • Uptake of RRS does not correspond well with current clinical guidelines. • There is an unmet need for multidisciplinary planning to avoid repeated surgery. [ABSTRACT FROM AUTHOR]

Abstract: Background: The surgical management of morbidly (BMI >40) and super obese (BMI >50) women with endometrial cancer is challenging. The aim of this study was to describe the short and long term outcomes of apronectomy combined with laparotomy for endometrial cancer staging and tumour debulking. Methods: A retrospective case note review of morbidly obese patients undergoing combined apronectomy and laparotomy for suspected endometrial cancer between 2007 and 2009 was performed. Short term (operating time, estimated blood loss, complication rates, duration of hospital stay) and long term outcomes (weight profile over 24-month follow up period) were evaluated. Results: Twenty-one patients were identified with a median age of 58 years and a median BMI of 49 (range 37–64). Apronectomy combined with laparotomy took 192 min on average to complete, with a mean estimated blood loss of 497 ml. There were no intra-operative complications. Postoperative complications included anaemia (14% required a blood transfusion), urinary tract infection (5%) and wound complications (wound infection in 29% and partial wound dehiscence in 5%). The median post-operative stay was 9 days. At twenty-four months, one-third of patients were heavier (mean 5 kg, range 2–8 kg) but almost two-thirds of patients were considerably lighter than they had been pre-operatively (mean 13 kg lighter, range 9–17 kg). Conclusions: Apronectomy combined with laparotomy was safe and well tolerated in this group of patients. Sustained weight loss by two-thirds of the patients over the two-year follow up period may reflect lifestyle changes instigated by individual patients following surgery. Combined apronectomy and laparotomy may provide an alternative to standard surgery for this challenging group of patients. [Copyright &y& Elsevier]

Abstract: Introduction: Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. Methods: Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of 99mTechnetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. Results: Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. Conclusions: The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation. [Copyright &y& Elsevier]

An association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit. Data from a large, prospective cohort will be informative. Data on UK BRCA pathogenic variant carriers were interrogated for endometrial cancer diagnoses. Standardised incidence ratios (SIRs) were calculated in four distinct cohorts using national endometrial cancer rates; either from 1/1/1980 or age 20, prospectively from date of personal pathogenic variant report, date of family pathogenic variant report or date of risk-reducing salpingo-oophorectomy. Somatic BRCA sequencing of 15 serous endometrial cancers was performed to detect pathogenic variants. Fourteen cases of endometrial cancer were identified in 2609 women (1350 BRCA1 and 1259 BRCA2), of which two were prospectively diagnosed. No significant increase in either overall or serous-like endometrial cancer risk was identified in any of the cohorts examined (SIR = 1.70, 95% confidence interval = 0.74–3.33; no cases of serous endometrial cancer diagnosed). Results were unaffected by the BRCA gene affected, previous breast cancer or tamoxifen use. No BRCA pathogenic variants were detected in any of the serous endometrial cancers tested. Women with a BRCA pathogenic variant do not appear to have a significant increased risk of all-type or serous-like endometrial cancer compared with the general population. These data provide some reassurance that hysterectomy is unlikely to be of significant benefit if performed solely as a preventive measure. • Endometrial cancer risk was not increased in BRCA1/2 pathogenic variant carriers. • Results were unaffected by BRCA gene, previous breast cancer or tamoxifen use. • No specific increase in serous-like endometrial cancer risk was identified. • Sequencing of 15 serous endometrial tumours revealed no pathogenic BRCA1/2 variants. [ABSTRACT FROM AUTHOR]

Abstract: Background: As HPV testing is used increasingly for cervical disease management, there is a demand to optimise the performance of HPV tests, particularly with respect to specificity. Objectives: To compare the clinical performance of an HPV DNA and a RNA based test in women with cytological abnormalities. The influence of age and assay cut off on test performance was also assessed. Study design: A prospective comparison of the Hybrid Capture 2 test (HC2) and the Aptima HPV assay (AHPV) was performed within a colposcopy setting. Clinical sensitivity and specificity were determined for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse. Results: Both assays were >90% sensitive for the detection of CIN2+. AHPV was slightly more specific than HC2 [49.9% (46.8–53.1) vs 45.9% (42.8, 49.1), p <0.0001]. Raising HC2 cut off to 2 RLU did not improve specificity. A cut-off of 10 RLU increased specificity by approximately 10% – although this led to a reduction in sensitivity of 6.3% which equated to 24 missed cases of CIN2+. Both assays were more specific in women over 30 years of age, compared to women under 30 (p <0.001). Conclusion: Although AHPV was more specific than HC2 in the total cohort (p <0.001), we found this difference to be smaller than other studies. This could be attributed to different indications for colposcopic referral across different settings. This study also confirms the relatively poor specificity of commercial HPV assays in women under 30. [Copyright &y& Elsevier]