Germline and somatic testing for ovarian Cancer: An SGO clinical practice statement.

Germline and somatic genetic testing have become critical components of care for people with ovarian cancer. The identification of germline and somatic pathogenic variants as well as homologous recombination deficiency can contribute to the prediction of treatment response, prognostic outcome, and suitability for targeted agents (e.g. poly (ADP-ribose) polymerase (PARP) inhibitors). Furthermore, identifying germline pathogenic variants can prompt cascade genetic testing for at-risk relatives. Despite the clinical benefits and consensus recommendations from several organizations calling for universal genetic testing in ovarian cancer, only about one third of patients complete germline or somatic genetic testing. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee have composed this statement to provide an overview of germline and somatic genetic testing for patients with epithelial ovarian cancer, focusing on available testing modalities and options for care delivery.

[Cholecystolithiasis and intestinal bypass procedures]. / Cholezystolithiasis und intestinale Bypassverfahren.

With the increasing number of surgical interventions for obesity, the numbers of associated complications, such as gallstones after bariatric surgery are also increasing. The incidence of postbariatric symptomatic cholecystolithiasis is 5-10%; however, the numbers of severe complications due to gallstones and the probability of a necessary extraction of gallstones are low. For this reason, a simultaneous or preoperative cholecystectomy should only be carried out in symptomatic patients. Treatment with ursodeoxycholic acid reduced the risk of gallstone formation in randomized trials but not the risk of complications related to gallstones in cases of pre-existing gallstones. The most frequently used access route to bile ducts after intestinal bypass procedures is the laparoscopic approach via the stomach remnants. Other possible access routes are the enteroscopic approach as well as the endosonography-guided puncture of the stomach remnants.

Creating work environments where people of all genders in gynecologic oncology can thrive: An SGO evidence-based review.

Equality, equity, and parity in the workplace are necessary to optimize patient care across all aspects of medicine. Gender-based inequities remain an obstacle to quality of care, including within the now majority women subspecialty of gynecologic oncology. The results of the 2020 SGO State of the Society Survey prompted this evidence-based review. Evidence related to relevant aspects of the clinical care model by which women with malignancies are cared for is summarized. Recommendations are made that include ways to create work environments where all members of a gynecologic oncology clinical care team, regardless of gender, can thrive. These recommendations aim to improve equality and equity within the specialty and, in doing so, elevate the care that our patients receive.

An audit of perioperative blood transfusions in a regional hospital to rationalise a maximum surgical blood ordering schedule.

Appropriate preoperative blood typing and cross-matching is an important quality improvement target to minimise costs and rationalise the use of blood bank resources. This can be facilitated using a maximum surgical blood ordering schedule (MSBOS) for specific operations. It is recommended that individual hospitals develop a site-specific MSBOS based on institutional data, but this is challenging in non-tertiary centres without electronic databases. Our aim was to audit our perioperative blood transfusions to develop a site-specific MSBOS. A retrospective audit of blood transfusions in surgical patients in our regional referral hospital was conducted using five years' coded administrative data. Procedures with higher transfusion rates warranting preoperative testing (type and screen with or without subsequent cross-matching) were identified. There were about 15,000 eligible surgical procedures performed in our institution over the audit period. The need for preoperative testing was identified for only a few procedures, namely laparotomy, bowel resection, major amputation, joint arthroplasty, hip/femur fracture and humerus surgery, and procedures for obstetric complications. We observed a reduction in transfusion rates over time for total joint arthroplasty. The use of coding data represents an efficient method by which centres without electronic anaesthesia information management systems can conduct large-scale audits to develop a site-specific MSBOS. This would represent a significant improvement for hospitals that currently base preoperative testing recommendations on expert opinion alone. As many procedures in regional centres have very low transfusion rates, hospitals with a similar case mix to ours could consider selectively auditing higher-risk operations where local data is most likely to alter testing recommendations.

[Infection or metastases? The amoebic abscess]. / Geïnfecteerd of gemetastaseerd?

BACKGROUND: Cases of Entamoeba histolytica infections in the Netherlands are usually imported diseases. The most common extra-intestinal manifestation of E. histolytica is the amoebic abscess. Patients can present with a clinical picture of colitis with pain in the upper right abdomen, accompanied by fever in cases of liver abscess. Diagnostics focus mainly on the detection of E. histolytica with PCR or ELISA. Infections are treated with metronidazole, with clioquinol as follow-up treatment. CASE DESCRIPTION: A 61-year-old, previously healthy man was admitted to hospital with pain in the upper right abdomen and fever. He had no history of travel in the tropics or sub-tropics. CT imaging revealed liver abscesses or liver metastases. Cultures of abscess fluid were negative. After extensive diagnostics the patient was shown to have an amoebic abscess for which he was successfully treated. CONCLUSION: If the bacterial cultures of liver abscess fluid continue to be negative the possibility of an amoebic abscess should be considered, even with a negative history of travel to the tropics or subtropics.

Optimizing the impact of alcohol and drug screening and early intervention in a high-risk population receiving services in New York City sexual health clinics: A process and outcome evaluation of Project Renew.

Unhealthy substance use is associated with increased rates of STDs, including HIV. Within three high-risk New York City (NYC) sexual health clinics between 2008 and 2012 (n = 146,657), 17% of patients screened positive for a current SUD but only 5.3% ever received prior treatment. The goal of Project Renew was to expand the reach of substance use early intervention services within and across sexual health clinics citywide and decrease substance use, poor mental health, and risky sexual behavior. To accomplish this goal, Screening, Brief Intervention, and Referral to Treatment (SBIRT), an evidence-based substance use early intervention model, was implemented in all eight NYC sexual health clinics February 2012-January 2015. Clinic patients were screened for substance misuse using the AUDIT/DAST-10, and those who screened positive were eligible for on-site brief intervention. Overall, 130,597 substance misuse screenings were conducted (66,989, or 51%, positive), and 17,474 on-site brief interventions and 1238 referrals were provided (not unique to individual patients). A 10% sample of 14,709 unique patients who screened positive were interviewed using a federal data collection tool at baseline and six months later to assess changes in substance use, sexual risk behaviors, mental health, and health status (n = 1328). At six-month follow-up, patients reported reduced substance use, less sexual activity, improved overall health, and fewer days of depression and anxiety compared to measures at baseline (p < 0.05). Based on positive results, Project Renew SBIRT services have been sustained, ensuring essential care which may help prevent acquisition of HIV/STDs among a large population of high-risk New Yorkers.

A novel pretherapeutic gene expression-based risk score for treatment guidance in gastric cancer.

Background: Perioperative chemotherapy is an established treatment of advanced gastric cancer patients. Treatment selection is based on clinical staging (cT). We aimed to establish and validate a prognostic score including clinical and molecular factors, to optimize treatment decisions for these patients. Patients and methods: We analyzed 626 carcinomas of the stomach and of the gastro-esophageal junction from two academic centers including primarily resected and pre-/perioperatively treated patients. Patients were divided into a training (N = 269) and validation (N = 357) set. Expression of 11 target genes was measured by quantitative PCR in resected tumors. A risk score to predict overall survival (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by analyzing 50 tumor areas from 10 patients. Results: A risk score including the expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT, tumor localization and histopathologic type suggested two groups with a significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.17-0.52]. The risk score was successfully validated in an independent cohort (HR 0.32; 95% CI 0.21-0.51; P < 0.001) as well as in subgroups of primarily resected (HR 0.30; 95% CI 0.17-0.54; P < 0.001) and pre-/perioperatively treated patients (HR 0.37; 95% CI 0.17-0.81; P = 0.009). A significant difference in OS of high- and low-risk patients was also found in primarily resected patients with intestinal (HR 0.45; 95% CI 0.23-0.90; P = 0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02-0.42; P < 0.001). Intra-tumor heterogeneity analysis indicated a classification reliability of 95% for a supposed analysis of three biopsies. Conclusion: The identified risk score could substantially contribute to an improved management of gastric cancer patients in the context of perioperative chemotherapy.

[Gastric stump carcinoma: frequency, treatment, complications and prognosis]. / Magenstumpfkarzinom: Häufigkeit, Therapie, Komplikationen und Prognose.

BACKGROUND: Gastric stump carcinoma develops in the gastric remnant after partial gastrectomy. While the frequency of gastric cancer is declining, the incidence of gastric stump carcinoma has remained stable due to the long latency period. As the surgical treatment of gastric ulcers by partial gastrectomy has become much less important, more and more gastric stump carcinomas develop after oncological resection. AIM: This study compared the surgical therapy of gastric stump carcinoma with the therapy of primary gastric cancer. MATERIAL AND METHODS: From 2001 to 2014 a total of 24 patients were surgically treated for gastric stump carcinoma in the University Hospital of Heidelberg. In the same time 428 patients underwent resection due to primary gastric cancer. Both groups were analyzed and compared with a focus on preoperative therapy, intraoperative differences, complications and overall survival. RESULTS: Patients with gastric stump carcinoma were older at disease onset (68 years vs. 62 years, p = 0.003). Compared with primary gastric cancer, patients with gastric stump carcinoma were more often suspected of having lymph node (cN+) involvement (51.4 % vs. 41.7 %, p < 0.001) but neoadjuvant therapy was applied less often (48.7 % vs. 14.3 %, p < 0.01). For resection of gastric stump carcinoma, extended resections were more often necessary (54.5 % vs. 28.2 %, p < 0.001). There were no significant differences in mean overall survival between the two patient groups (64.4 months vs. 45.8 months, p = 0.34) CONCLUSION: Despite the differences described, the treatment of gastric stump carcinoma does not essentially differ from that of primary gastric cancer. Carcinomas of the gastric stump are more often locally advanced and in our opinion a neoadjuvant therapy should be applied analogue to gastric cancer even if evidence-based data on this point are limited.

Added sensitivity of component-resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis.

BACKGROUND: Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component-resolved approaches to diagnose this high-risk patient group. To address the component-resolved sIgE sensitization pattern and diagnostic sensitivity in hymenoptera venom-allergic patients with elevated sBT levels and/or mastocytosis, a panel of yellow jacket and honeybee venom allergens was applied on a widely used IgE immunoassay platform. METHODS: Fifty-three patients with mastocytosis and/or elevated sBT tryptase level and systemic reactions to hymenoptera venoms were analyzed for their IgE reactivity to recombinant yellow jacket and honeybee venom allergens by Immulite3 g. RESULTS: sIgE reactivity to Ves v 1, Ves v 5, Api m 1 to Api m 4 and Api m 10 was found at a similar frequency in hymenoptera venom-allergic patients with and without elevated sBT levels and/or mastocytosis. However, the use of the recombinant allergens and a diagnostic cutoff of 0.1 kUA /L allowed the diagnosis of patients with otherwise undetectable IgE to venom extract. The diagnostic sensitivity of yellow jacket venom allergy using the combination of Ves v 1 and Ves v 5 was 100%. CONCLUSIONS: In high-risk patients with elevated sBT levels and/or mastocytosis, the use of molecular components and decreasing the threshold sIgE level to 0.1 kUA /L may be needed to avoid otherwise undetectable IgE to hymenoptera venom extracts in about 8% of such patients.

Surgery in oesophago-gastric cancer with metastatic disease: Treatment, prognosis and preoperative patient selection.

BACKGROUND: The role of surgical resection in metastatic oesophago-gastric adenocarcinomas (EGA) is not defined and regularly discussed in interdisciplinary tumour boards. Primary objective of this retrospective study was the outcome of patients after surgery. We additionally evaluated our preoperative prognostic score (PPS) based on tumour grading, clinical response to chemotherapy and presumed R-status. METHODS: 123 of 811 EGA patients were evaluated as cM1, either confirmed intraoperatively or by imaging. Response evaluation after chemotherapy was performed by endoscopy, CT-scan and histopathologically. The prospectively documented patient and outcome data were analysed retrospectively. RESULTS: 70 patients with adenocarcinoma of the oesophago-gastric junction and 53 patients with gastric cancer were included. The majority had one M1 site (n = 102). 72 received preoperative chemotherapy (CTx) and 51 underwent primary resection. 11 were explored without resection. 49/112 (40%) had multivisceral resections and 63/112 (56%) were completely resected (R0). 26/72 (36%) were clinical responders and 30 patients had a favourable PPS. Median survival was 20.0 months. Survival was significantly prolonged by resection, especially complete resection, and by preoperative CTx (all p = 0.001). Multivisceral resection, type or number of metastases, or primary tumour localization had no impact on survival. In patients undergoing preoperative CTx, clinical response and the PPS influenced survival significantly. In R0 resected patients, preoperative CTx, clinical response and the PPS remained prognostic. CONCLUSION: Primary resection without preoperative CTx is not appropriate for metastatic EGA. Subgroups of patients with a favourable PPS with response to CTx may be good candidates for surgical resection in metastatic oesophago-gastric cancer.

[The use and benefit of the 'children with special health care needs screener' in the paediatric school entrance examinations 2004/2005 in Cologne]. / Einsatz und Nutzen des "Children with Special Health Care Needs-Screener" im Rahmen der Schuleingangsuntersuchung 2004/2005 in Köln.

The aim of this study was to provide an assessment of the usefulness of the questionnaire "Children with Special Health Care Needs Screener" (CSHCN Screener) as a screening instrument to identify children with special needs in the context of paediatric school entrance examinations (SEE).In a retrospective cross-sectional study of the years 2004 and 2005 in Cologne, Germany, the sum variables were derived from the results of the SEE in accordance to the 7 questions of the CSHCN Screener. The correlations of the SEE sum variables and the CSHCN Screener results were analysed and tested for correlations with sociodemographic factors.Of the 18 402 children of the cohorts 2004/2005, corresponding SEE findings and results of the CSHCN Screener were available for 13 076 children. The prevalence of children with special needs was only 6% according to the results of the CSHCN Screener. According to the SEE, however, 26% of the children showed diseases or developmental problems. Out of this group, only one in 8 children was identified by the CSHCN Screener (sensitivity 13%). The sensitivity of the screener was also 13% for children who had been diagnosed to be in need of special support by school physicians. In the case of girls and of children with migration family backgrounds, the sensitivity of the screener was even lower. The CSHCN Screener also could not detect the higher rate of special needs determined by school physicians in children from areas with high quotas of state family support payments.The results of the CSHCN Screener are not convincing, due to his low sensitivity. This is true with regard to its use as a diagnostic tool for the individual child at the beginning of school age as well for its use as an instrument to assess an increased need for support in cohorts of school entry students.

Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas.

BACKGROUND: Recently, histopathological tumour regression, prevalence of signet ring cells, and localisation were reported as prognostic factors in neoadjuvantly treated oesophagogastric (junctional and gastric) cancer. This exploratory retrospective study analyses independent prognostic factors within a large patient cohort after preoperative chemotherapy including clinical and histopathological factors. METHODS: In all, 850 patients presenting with oesophagogastric cancer staged cT3/4 Nany cM0/x were treated with neoadjuvant chemotherapy followed by resection in two academic centres. Patient data were documented in a prospective database and retrospectively analysed. RESULTS: Of all factors prognostic on univariate analysis, only clinical response, complications, ypTNM stage, and R category were independently prognostic (P<0.01) on multivariate analysis. Tumour localisation and signet ring cells were independently prognostic only when investigator-dependent clinical response evaluation was excluded from the multivariate model. Histopathological tumour regression correlates with tumour grading, Laurén classification, clinical response, ypT, ypN, and R categories but was not identified as an independent prognostic factor. Within R0-resected patients only surgical complications and ypTNM stage were independent prognostic factors. CONCLUSIONS: Only established prognostic factors like ypTNM stage, R category, and complications were identified as independent prognostic factors in resected patients after neoadjuvant chemotherapy. In contrast, histopathological tumour regression was not found as an independent prognostic marker.

Outcomes following liver resection and clinical pathologic characteristics of hepatocellular carcinoma occurring in patients with chronic hepatitis B and minimally fibrotic liver.

AIMS: The intent of this analysis is to assess clinico-pathologic and prognostic characteristics of HCC in patients with minimal liver fibrosis (Ishak stage 1-2) after primary surgical liver resection as compared to patients with moderate to severe fibrosis (Ishak stage 3-6) in order to improve screening and treatment of HCC. METHODS: Data were obtained from 200 patients with HBV-related HCC who underwent primary surgical liver resection at a single North American medical institution between 1988 and 2012. A dedicated liver pathologist performed fibrosis staging for each resection specimen using the modified Ishak method. Univariate and multivariate analyses of clinico-pathologic variables were performed to determine those associated with prognosis. RESULTS: Twenty-two percent of patients had minimal fibrosis defined as Ishak stage 1 or 2. Kaplan-Meier analysis of 5-year survival showed a non-significant trend toward better outcome among Ishak 1-2 patients compared to Ishak 3-6 (p = 0.09). Ishak 1-2 was associated with lower hazard of death compared to Ishak 3-6 (adjusted HR = 0.38, 95% CI = 0.15-0.99). Ishak 1-2 retained statistical significance after multivariate analysis for overall survival (p = 0.05), but not recurrence-free survival. CONCLUSIONS: A significant proportion of HBV-HCC cases arise in the minimally fibrotic liver. Patients with Ishak 1-2 fibrosis have better overall survival compared to those with Ishak 3-6, indicating that minimally fibrotic patients should be treated as a separate cohort. There is a need to better understand the mechanisms underlying hepatocarcinogenesis and to formulate unique diagnostic and therapeutic algorithms for minimally fibrotic HCC patients.

Impact of liver fibrosis on prognosis following liver resection for hepatitis B-associated hepatocellular carcinoma.

BACKGROUND: This study aims to evaluate the impact of liver fibrosis severity on prognosis following liver resection among HBV-HCC patients. METHODS: Data were extracted from a prospective database of 189 HBV-HCC patients treated at Mount Sinai between 1995 and 2008. Fibrosis staging of each surgical resection specimen using the modified Ishak method was performed by a single liver pathologist. RESULTS: A wide range of Ishak fibrosis stage was observed among this patient population, with 29% having established cirrhosis (Ishak stage 6). Ishak stage 6 was independently associated with poor overall and recurrence-free survival. In patients with Ishak stage 1-5, Ishak stage did not affect survival; rather, tumour size was associated with poor overall survival, and tumour size, histologic activity index and serum AFP>20 ng ml(-1) were associated with poor recurrence-free survival. In patients with Ishak stage 6, poorly differentiated histology and tumour size were associated with poor overall survival, and tumour size was associated with poor recurrence-free survival. CONCLUSION: HBV-HCC develops with varying degrees of underlying liver fibrosis; however, progressive liver fibrosis does not affect the outcomes following resection until cirrhosis is reached. Established cirrhosis, as defined histologically by Ishak stage 6, is an independent predictor of poor overall and recurrence-free survival among these patients.

A reliable risk score for stage IV esophagogastric cancer.

BACKGROUND: The role of surgery for patients with metastatic esophagogastric adenocarcinoma (EGC) is not defined. The purpose of this study was to define selection criteria for patients who may benefit from resection following systemic chemotherapy. METHODS: From 1987 to 2007, 160 patients presenting with synchronous metastatic EGC (cT3/4 cNany cM0/1 finally pM1) were treated with chemotherapy followed by resection of the primary tumor and metastases. Clinical and histopathological data, site and number of metastases were analyzed. A prognostic score was established and validated in a second cohort from another academic center (n = 32). RESULTS: The median survival (MS) in cohort 1 was 13.6 months. Significant prognostic factors were grading (p = 0.046), ypT- (p = 0.001), ypN- (p = 0.011) and R-category (p = 0.015), lymphangiosis (p = 0.021), clinical (p = 0.004) and histopathological response (p = 0.006), but not localization or number of metastases. The addition of grading (G1/2:0 points; G3/4:1 points), clinical response (responder: 0; nonresponder: 1) and R-category (complete:0; R1:1; R2:2) defines two groups of patients with significantly different survival (p = 0.001) [low risk group (Score 0/1), n = 22: MS 35.3 months, 3-year-survival 47.6%); high risk group (Score 2/3/4) n = 126: MS 12.0 months, 3-year-survival 14.2%]. The score showed a strong trend in the validation cohort (p = 0.063) [low risk group (MS not reached, 3-year-survival 57.1%); high risk group (MS 19.9 months, 3-year-survival 6.7%)]. CONCLUSION: We observed long-term survival after resection of metastatic EGC. A simple clinical score may help to identify a subgroup of patients with a high chance of benefit from resection. However, the accurate estimation of achieving a complete resection, which is an integral element of the score, remains challenging.

Preoperative therapy of esophagogastric cancer: the problem of nonresponding patients.

INTRODUCTION: Preoperative treatment is nowadays standard for locally advanced esophagogastric cancer in Europe. Surprisingly, little attention has been paid to nonresponders so far. The aim of our retrospective exploratory study was the comparison of responder, nonresponder, and primary resected patients in respect of outcome considering the tumor entity. PATIENTS AND METHODS: From 2001-2011, 607 patients with locally advanced esophagogastric carcinoma (adenocarcinoma of the esophagogastric junction (AEG), n = 293; squamous cell cancer (SCC), n = 111; gastric cancer, n = 203) after preoperative treatment (n = 281) or primary resection (n = 326) were included. Histopathological response evaluation (Becker criteria) was available for 263. RESULTS: A total of 76/263 (28.9 %) were responders (<10 % residual tumor). There was an association of response with increased R0 resections (p < 0.001) but also with a higher complication rate (p = 0.008) compared to nonresponse and primary surgery. Mortality was not influenced. Increased R0 resections after response were confirmed in every tumor entity (AEG, p = 0.010; SCC, p = 0.023; gastric cancer, p = 0.006). Median survival was best for responders with 43.5 months [95 % confidence interval (CI), 27.9-59.1], followed by nonresponders with 24.3 months (95 % CI, 21.6-27.0) and primary resected patients with 20.8 months (95 % CI, 17.7-23.9; p = 0.002). AEG (p = 0.012) and gastric cancer (p = 0.017) revealed identical results, but in the subgroup of SCC, the survival of nonresponders (median, 11.6 months; 95 % CI, 6.9-16.3) was even worse than for primary resected patients (median, 23.8 months; 95 % CI, 1.7-46.0; p = 0.012). CONCLUSION: The histopathological response rate was low. Generally, nonresponding patients with AEG or gastric cancer seem not to have a disadvantage compared to primary resected patients, but nonresponders with SCC have a worse prognosis, which strengthens the demand for a critical patient selection in surgery for this tumor entity.

Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer.

BACKGROUND: Suppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer. METHODS: Eligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m(2)). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS). RESULTS: Forty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1-24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2-13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3-37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2-46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1-94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome. CONCLUSION: PLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.