Towards clinical adherence monitoring of oral endocrine breast cancer therapies by LC-HRMS-method development, validation, comparison of four sample matrices, and proof of concept.

Oral endocrine therapies (OET) for breast cancer treatment need to be taken over a long period of time and are associated with considerable side effects. Therefore, adherence to OET is an important issue and of high clinical significance for breast cancer patients' caregivers. We hypothesized that a new bioanalytical strategy based on liquid chromatography and high-resolution mass spectrometry might be suitable for unbiased adherence monitoring (AM) of OET. Four different biomatrices (plasma, urine, finger prick blood by volumetric absorptive microsampling (VAMS), oral fluid (OF)) were evaluated regarding their suitability for AM of the OET abemaciclib, anastrozole, exemestane, letrozole, palbociclib, ribociclib, tamoxifen, and endoxifen. An analytical method was developed and validated according to international recommendations. The analytical procedures were successfully validated in all sample matrices for most analytes, even meeting requirements for therapeutic drug monitoring. Chromatographic separation of analytes was achieved in less than 10 min and limits of quantification ranged from 1 to 1000 ng/mL. The analysis of 25 matching patient samples showed that AM of OET is possible using all four matrices with the exception of, e.g., letrozole and exemestane in OF. We were able to show that unbiased bioanalytical AM of OET was possible using different biomatrices with distinct restrictions. Sample collection of VAMS was difficult in most cases due to circulatory restraints and peripheral neuropathy in fingers and OF sampling was hampered by dry mouth syndrome in some cases. Although parent compounds could be detected in most of the urine samples, metabolites should be included when analyzing urine or OF. Plasma is currently the most suitable matrix due to available reference concentrations.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

PURPOSE: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations. METHODS: Statements and voting results from the 18th St. Gallen International Breast Cancer Consensus Conference were collected and analyzed according to their relevance for the radiation oncology community. The voting results were discussed in two hybrid meetings among the authors of this manuscript on March 18 and 19, 2023, in light of the German S3 guideline and the 2023 version of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) guidelines. RESULTS AND CONCLUSION: There was a high level of agreement between the radiotherapy-related statements of the 18th St. Gallen International Breast Cancer Consensus Conference and the German S3 and AGO guidelines. Discrepancies include the impact of number of lymph node metastases for the indication for postmastectomy radiotherapy.

Dkk1 as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Breast Cancer Patients.

PURPOSE: To investigate the role of Dkk1 as a predictor of response to NACT in BC patients. METHODS: This retrospective monocentric study included 145 women who had undergone NACT followed by breast surgery. Dkk1 protein expression was assessed using immunohistochemistry staining in core needle biopsies and mammary carcinoma specimens. RESULTS: Dkk1 levels were lower in treated BC tumours than in untreated tumours. The outcomes of 68 matched pre- and post-therapy tissues showed that Dkk1 levels in mammary carcinoma tissues were significantly predicted by levels in core needle biopsies and that Dkk1 expression was reduced in 83% of cases. Smaller cT stage, positive Her2 expression, and decreased Dkk1-IRS in core needle biopsy tissues were all independent predictors of regression grade (R4), according to Sinn. However, the percentage of Dkk1 expression differences prior to and following NACT had no effect on PFS or OS. CONCLUSIONS: In this study, we demonstrated for the first time that Dkk1 could be identified as an independent predictor of NACT response in BC patients, particularly those with TNBC. Further research with a multicentric expanded (pre-/post-therapy) sample set and better-defined populations in terms of molecular subtypes, therapy modality, and long-term follow-up is recommended to obtain more solid evidence.

Laparoscopic Fertility-Sparing Surgery for Early Ovarian Malignancies.

The demand for fertility-sparing surgery (FSS) has increased in the last decade due to increased maternal age, increased incidence of ovarian malignancies in younger patients, and technical advances in surgery. Data on oncological safety and fertility outcomes of patients with ovarian cancer after laparoscopic FSS are sparse, but some retrospective studies have shown that open FSS may be offered to selected patients. We assessed the role of minimally invasive FSS in comparison with radical surgery (RS) in terms of oncological safety and reproductive outcomes after FSS in this multicenter study. Eighty patients with FIGO stage I/II ovarian cancer treated with laparoscopic FSS or RS between 01/2000 and 10/2018 at the participating centers (comprehensive gynecological cancer centers with minimally invasive surgical expertise) were included in this retrospective analysis of prospectively kept data. Case-control (n = 40 each) matching according to the FIGO stage was performed. Progression-free survival [150 (3-150) and 150 (5-150) months; p = 0.61] and overall survival [36 (3-150) and 50 (1-275) months; p = 0.65] did not differ between the FSS and RS groups. Eight (25.8%) women became pregnant after FSS, resulting in seven (22.5%) deliveries; three (37.5%) patients conceived after in vitro fertilization, and five (62.5%) conceived spontaneously. Laparoscopic FSS seems to be applicable and oncologically safe for patients with early-stage ovarian cancer, with adequate fertility outcomes.

Treatment of Early Breast Cancer: The 18th St. Gallen International Breast Cancer Consensus Conference against the Background of Current German Treatment Recommendations.

This year's 18th St. Gallen (SG) consensus conference on the treatment of early breast cancer (SGBCC: St. Gallen International Breast Cancer Conference) focused on practice-oriented questions. The individual situation and risk-benefit assessment were discussed in great detail. As in previous years, a German working group of leading breast cancer experts presented the results of the international SGBCC 2023 against the background of German treatment recommendations - especially the updated treatment recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie e. V. (AGO) - for everyday clinical practice in Germany. The German treatment recommendations of AGO are based on the current evidence. The comparison with the clinical approach in Germany has proven useful, as the SGBCC panel consists of experts from different countries and disciplines. That is why country-specific characteristics can be incorporated into the SGBCC recommendations.

The 3q Oncogene SEC62 Predicts Response to Neoadjuvant Chemotherapy and Regulates Tumor Cell Migration in Triple Negative Breast Cancer.

In the absence of targeted treatment options, neoadjuvant chemotherapy (NACT) is applied widely for triple-negative breast cancer (TNBC). Response to NACT is an important parameter predictive of oncological outcomes (progression-free and overall survival). An approach to the evaluation of predictive markers enabling therapy individualization is the identification of tumor driver genetic mutations. This study was conducted to investigate the role of SEC62, harbored at 3q26 and identified as a driver of breast cancer pathogenesis, in TNBC. We analyzed SEC62 expression in The Cancer Genome Atlas database, and immunohistologically investigated SEC62 expression in pre- and post-NACT tissue samples from 64 patients with TNBC treated at the Department of Gynecology and Obstetrics/Saarland University Hospital/Homburg between January 2010 and December 2018 and compared the effect of SEC62 on tumor cell migration and proliferation in functional assays. SEC62 expression dynamics correlated positively with the response to NACT (p ≤ 0.01) and oncological outcomes (p ≤ 0.01). SEC62 expression stimulated tumor cell migration (p ≤ 0.01). The study findings indicate that SEC62 is overexpressed in TNBC and serves as a predictive marker for the response to NACT, a prognostic marker for oncological outcomes, and a migration-stimulating oncogene in TNBC.

Neurologic Consultations and Headache during Pregnancy and in Puerperium: A Retrospective Chart Review.

Headache is a common symptom during pregnancy and in puerperium that requires careful consideration, as it may be caused by a life-threatening condition. Headaches in pregnant women and women in puerperium are classified as primary or secondary; acute, severe and newly diagnosed headaches should prompt further investigation. We aimed to further characterise the demographic features, symptoms, examination findings, and neuroimaging results of cases of headache during pregnancy and in puerperium. All pregnant women or women in postpartum conditions who attended neurological consultations at the emergency department of the clinic for Gynaecology, Obstetrics and Reproductive Medicine of Saarland University/Germany between 2001/2015 and 2012/2019 were enrolled in this retrospective chart review. Data collected from the charts included demographic/pregnancy characteristics, clinical features and imaging findings. Descriptive statistics as well as binary logistic regression were performed. More than 50% of 97 patients had abnormal findings in their neurological examination. Magnetic resonance imaging findings were pathological for almost 20% of patients-indicating conditions such as cerebral venous thrombosis, reversible posterior leukoencephalopathy, brain tumour and intracranial bleeding. The odds of abnormal neuroimaging results were 2.2-times greater among women with abnormal neurological examination findings than among those with normal examination results. In cases of headache during pregnancy and in puerperium, neuroimaging should be indicated early on. Further research is needed to determine which conditions indicate a need for immediate neuroimaging.

Quality of life and sexual function in patients aged 35 years or younger undergoing hysterectomy for benign gynecologic conditions: A prospective cohort study.

OBJECTIVE: To evaluate how hysterectomy performed for benign gynecologic pathologies affects the quality of life and sexual function of patients aged 35 years or younger, and if outcomes differ according to the surgical technique. METHODS: Seventy-three patients who underwent total laparoscopic hysterectomy (TLH), supracervical laparoscopic hysterectomy (SLH), or vaginal hysterectomy (VH) for benign uterine disorders between April 2014 and June 2020 at the Department of Gynecology and Obstetrics, Saarland University Hospital, Homburg, Germany, were enrolled in this prospective observational cohort study. Quality of life and sexual function were assessed preoperatively and 6 months postoperatively using standardized validated questionnaires: the European Quality of Life Five-Dimension Scale (EQ-5D) and the Female Sexual Function Index (FSFI). RESULTS: Thirty-three (45%) patients underwent TLH, 25 (34%) underwent SLH, and 15 (21%) patients underwent VH. The median preoperative EQ-5D score, FSFI score, and EQ-5D visual analog scale were 0.9 (range 0.62-1), 19.25 (range 2.4-27.4), and 50 (range 0-100); postoperative scores were 1 (range 0.61-1), 24.15 (range 3.9-29.3), and 90 (range 30-100), respectively (P ≤ 0.001). Postoperative scores were significantly higher than preoperative scores, with no significant difference according to the surgical technique. CONCLUSION: Hysterectomy for benign indication in women aged 35 years or less significantly improved the patients' quality of life and sexual function with no differences regarding the surgical technique. CLINICAL TRIAL REGISTRATION: The study was registered in the German trial registry (no. DRKS00005622).

The endoplasmic reticulum membrane protein Sec62 as potential therapeutic target in SEC62 overexpressing tumors.

The human SEC62 gene is located on chromosome 3q, was characterized as a tumor driver gene and is found to be overexpressed in an ever-growing number of tumors, particularly those with 3q26 amplification. Where analyzed, SEC62 overexpression was associated with poor prognosis. Sec62 protein is a membrane protein of the endoplasmic reticulum (ER) and has functions in endoplasmic reticulum protein import, endoplasmic reticulum-phagy and -in cooperation with the cytosolic protein calmodulin- the maintenance of cellular calcium homeostasis. Various human tumors show SEC62 overexpression in immunohistochemistry and corresponding cell lines confirm this phenomenon in western blots and immunofluorescence. Furthermore, these tumor cells are characterized by increased stress tolerance and migratory as well as invasive potential, three hallmarks of cancer cells. Strikingly, plasmid-driven overexpression of SEC62 in non-SEC62 overexpressing cells introduces the same three hallmarks of cancer into the transfected cells. Depletion of Sec62 from either type of SEC62 overexpressing tumor cells by treatment with SEC62-targeting siRNAs leads to reduced stress tolerance and reduced migratory as well as invasive potential. Where tested, treatment of SEC62 overexpressing tumor cells with the small molecule/calmodulin antagonist trifluoperazine (TFP) phenocopied the effect of SEC62-targeting siRNAs. Recently, first phase II clinical trials with the prodrug mipsagargin/G202, which targets cellular calcium homeostasis in prostate cells as well as neovascular tissue in various tumors were started. According to experiments with tumor cell lines, however, SEC62 overexpressing tumor cells may be less responsive or resistant against such treatment. Therefore, murine tumor models for tumor growth or metastasis were evaluated with respect to their responsiveness to treatment with a mipsagargin analog (thapsigargin), or trifluoperazine, which had previously been in clinical use for the treatment of schizophrenia, or with the combination of both drugs. So far, no additive effect of the two drugs was observed but trifluoperazine had an inhibitory effect on tumor growth and metastatic potential in the models. Here, we review the state of affairs.

Effect of the 3q26-coding oncogene SEC62 as a potential prognostic marker in patients with ovarian neoplasia.

With approximately 220,000 newly diagnosed cases per year, ovarian cancer is among the most frequently occurring cancers among women and the second leading cause of death from gynecological malignancies worldwide. About 70% of these cancers are diagnosed in advanced stages (FIGO IIB-IV), with a 5-year survival rate of 20-30%. Due to the poor prognosis of this disease, research has focused on its pathogenesis and the identification of prognostic factors. One possible approach for the identification of biological markers is the identification of tumor entity-specific genetic "driver mutations". One such mutation is 3q26 amplification in the tumor driver SEC62, which has been identified as relevant to the pathogenesis of ovarian cancer. This study was conducted to investigate the role of SEC62 in ovarian malignancies. Patients with ovarian neoplasias (borderline tumors of the ovary and ovarian cancer) who were treated between January 2007 and April 2019 at the Department of Gynecology and Obstetrics, Saarland University Hospital, were included in this retrospective study. SEC62 expression in tumor tissue samples taken during clinical treatment was assessed immunohistochemically, with the calculation of immunoreactivity scores according to Remmele and Stegner, Pathologe, 1987, 8, 138-140. Correlations of SEC62 expression with the TNM stage, histological subtype, tumor entity, and oncological outcomes (progression-free and overall survival) were examined. The sample comprised 167 patients (123 with ovarian cancer and 44 with borderline tumors of the ovary) with a median age of 60 (range, 15-87) years. At the time of diagnosis, 77 (46%) cases were FIGO stage III. All tissue slides showed SEC62 overexpression in tumor cells and no SEC62 expression in other cells. Median immunoreactivity scores were 8 (range, 2-12) for ovarian cancer and 9 (range, 4-12) for borderline tumors of the ovary. Patients with borderline tumors of the ovary as well as patients with ovarian cancer and an immunoreactive score (IRS) ≤ 9 showed an improved overall survival compared to those presenting with an IRS score >9 (p = 0.03). SEC62 seems to be a prognostic biomarker for the overall survival of patients with ovarian malignancies.

Augmented reality-enhanced navigation in endoscopic sinus surgery: A prospective, randomized, controlled clinical trial.

OBJECTIVE: Endoscopic sinus surgery represents the gold standard for surgical treatment of chronic sinus diseases. Thereby, navigation systems can be of distinct use. In our study, we tested the recently developed KARL STORZ NAV1 SinusTracker navigation software that incorporates elements of augmented reality (AR) to provide a better preoperative planning and guidance during the surgical procedure. METHODS: One hundred patients with chronic sinus disease were operated on using either a conventional navigation software (n = 52, non-AR, control group) or a navigation software incorporating AR elements (n = 48, AR, intervention group). Incidence of postoperative complications, duration of surgery, surgeon-reported benefit from the navigation system and patient-reported postoperative rehabilitation were assessed. RESULTS: The surgeons reported a higher benefit during surgery, used the navigation system for more surgical steps and spent longer time with preoperative image analysis when using the AR system as compared with the non-AR system. No significant differences were seen in terms of postoperative complications, target registration error, operation time and postoperative rehabilitation. CONCLUSION: The AR enhanced navigation software shows a high acceptance by sinus surgeons in different stages of surgical training and offers potential benefits during surgery without affecting the duration of the operation or the incidence of postoperative complications. LEVEL OF EVIDENCE: 1b.

Treatment algorithm for women with endometriosis in a certified Endometriosis Unit.

INTRODUCTION: Endometriosis is a chronic hormone-dependent disease affecting approximately 25-30% of women in the third and fourth decade. Despite its frequency, it is often detected late. The aim of this overview article was to present a standardized treatment algorithm for an interdisciplinary endometriosis consultation considering conservative and surgical approaches. EVIDENCE ACQUISITION: Despite the frequency of endometriosis and a high number of publications dealing with the disease there is a lack of evidence in literature for standardized treatment algorithms allowing a rational diagnostic and therapeutic approach. In May 2019 we did a literature search in Medline. While finding 26702 publications under the term "endometriosis" there was only one publication for the search term "endometriosis consultation treatment algorithm." After screening the abstracts 144 publications in English, French or German language had been assessed as relevant for the diagnosis and therapy of endometriosis (143 overview articles and one guideline). EVIDENCE SYNTHESIS: Based on clinical evidence, we have developed a treatment algorithm for women with suspected endometriosis. The diagnosis includes a structured medical history with the identification of endometriosis-typical symptoms and a gynecological examination, if necessary additional examinations. The treatment algorithm is essentially divided into the phase of diagnosis and the phase of therapy as well as the prevention of recurrence or long-term treatment. A multi-professional team of visceral surgery, urology, nutritional medicine, physiotherapy and psychology can be consulted for support. CONCLUSIONS: The treatment of endometriosis should be multiprofessional, standardized and reproducible during specialized consultations at certified centers. So far, there are few publications on a standardized and clinically proven treatment algorithm for women with suspected endometriosis. The presented treatment algorithm could be helpful in the diagnosis and treatment of endometriosis patients, even at other centers.

Risk of loco-regional recurrence and distant metastases of patients with invasive breast cancer up to ten years after diagnosis - results from a registry-based study from Germany.

BACKGROUND: Population-based estimates of the long-term risk of loco-regional recurrence and distant metastases of breast cancer (BRC) patients are scant, as most published studies used hospital-based cohorts or participants of clinical trials. This work aims to extend available knowledge by providing population-based long-term estimates of the cumulative risk of BRC recurrence up to 10 years after diagnosis. METHODS: Data from the population-based Saarland Cancer Registry were used and included 9359 female patients with primary invasive BRC diagnosed between 1999 and 2009. Estimates of the cumulative incidence (CI) of BRC recurrence were derived for patients who had received local surgery with free resection margins by type of recurrence and stratified by age, tumor characteristics and major treatment options, taking into account mortality from any cause as a competing risk. RESULTS: The 10-year CI of BRC recurrence was 16%. For loco-regional recurrence and distant metastases alone it was 8 and 11%, respectively. The estimates showed substantial variation and were particularly increased if tumors were advanced (T1/2N+ 23%, T3/4N0 24%, T3/4N+ 34%), of high grade (23%), or of 'HER2/neu positive' (28%) or 'triple negative' subtype (23%), respectively. CONCLUSIONS: The derived estimates reflect the risk of 'real world' patients and may therefore extend available knowledge. These data are thus of great relevance for clinicians, their patients and researchers. The study likewise demonstrated the usefulness of cancer registries for a population-based monitoring of the effectiveness of cancer care in terms of disease recurrence as a major treatment related outcome measure.

Fertility preservation in female cancer patients: current knowledge and future perspectives.

INTRODUCTION: Protecting fertility in the presence of cancer has become highly significant, as the desire to give birth to a child is increasingly postponed to later in life, and long-term survival with cancer has increased. A variety of fertility-preserving methods have been developed. EVIDENCE ACQUISITION: To find them, we performed a literature search in Medline using the key words "female fertility preservation in cancer" in December 2017. A total of 2381 different publications were found. EVIDENCE SYNTHESIS: After screening the abstracts 78 publications in English, French, or German language had been assessed as relevant (17 dealing with medical approaches, six with surgical approaches, 15 with oocyte cryopreservation, 11 with ovarian tissue cryopreservation and 29 were review articles). In general, there are medical (non-surgical) and surgical approaches. Medical approaches comprise administration of GnRH-analogues during gonad toxic oncologic treatment, and cryopreservation of oocytes after ovarian stimulation. Surgical approaches comprise traditional methods of organ-saving surgery and ovarian transposition outside of the radiation portal as well as ovary cryopreservation as standard. CONCLUSIONS: It is important to inquire about a prospective desire to have children with premenopausal women with cancer and comprehensively explain the fertility conserving methods available. Every premenopausal woman with cancer should be counseled about the methods of fertility protection currently available at a multiprofessional center.

Holmium-166 Radioembolization in Hepatocellular Carcinoma: Feasibility and Safety of a New Treatment Option in Clinical Practice.

PURPOSE: To investigate clinical feasibility, technical success and toxicity of 166Ho-radioembolization (166Ho-RE) as new approach for treatment of hepatocellular carcinomas (HCC) and to assess postinterventional calculation of exact dosimetry through quantitative analysis of MR images. MATERIALS AND METHODS: From March 2017 to April 2018, nine patients suffering from HCC were treated with 166Ho-RE. To calculate mean doses on healthy liver/tumor tissue, MR was performed within the first day after treatment. For evaluation of hepatotoxicity and to rule out radioembolization-induced liver disease (REILD), the Model for End-Stage Liver Disease (MELD) Score, the Common Terminology Criteria for Adverse Events and specific laboratory parameters were used 1-day pre- and posttreatment and after 60 days. After 6 months, MR/CT follow-up was performed. RESULTS: In five patients the right liver lobe, in one patient the left liver lobe and in three patients both liver lobes were treated. Median administered activity was 3.7 GBq (range 1.7-5.9 GBq). Median dose on healthy liver tissue was 41 Gy (21-55 Gy) and on tumor tissue 112 Gy (61-172 Gy). Four patients suffered from mild postradioembolization syndrome. No significant differences in median MELD-Score were observed pre-, posttherapeutic and 60 days after 166Ho-RE. No deterioration of liver function and no indicators of REILD were observed. One patient showed a complete response, four a partial response, three a stable disease and one a progressive disease at the 6 months follow-up. CONCLUSION: 166Ho-RE seems to be a feasible and safe treatment option with no significant hepatotoxicity for treatment of HCC.

Instrument usage in laparoscopic gynecologic surgery: a prospective clinical trial.

PURPOSE: To evaluate instrumental usage in laparoscopic gynecological surgeries and to develop key timesets of a laparoscopic operation, which allows categorization of the operation time into different sections. METHODS: In this prospective clinical observational study, frequency of instrument usage, time for instrument switches, and instrument utilization time were recorded in a standardized manner for laparoscopic surgeries in 103 endoscopic surgeries. RESULTS: A standard equipment (including atraumatic grasping forceps, irrigation and suction device, bipolar clamp, and laparoscopic scissors) was used for nearly all interventions. Bipolar clamps and scissors were changed most frequently. The tool used for the longest amount of time was the atraumatic grasping forceps. Laparoscopic instruments were switched 51 times per surgery (range 2-250 times). One instrument switch lasted for a median of 0.13 min (0.08-1.2 min). Median time for instrument switch for a single surgery added up to 6.83 min. Instrument switches required 10.5% of the overall operation time. CONCLUSION: We analyzed the current instrument usage in laparoscopic gynecological surgeries. The results of our standardized investigation suggest ways to reduce the time required for surgery and provide starting points for the standardization of the work routine.

Evaluation of Local and Distant Recurrence Patterns in Patients with Triple-Negative Breast Cancer According to Age.

BACKGROUND: Triple-negative breast cancer (TNBC) subtype and young patient age are both associated with an increased risk of local recurrence (LR) and distant recurrence (DR). In young women with TNBC, it is unclear whether subtype or patient age is driving prognosis. METHODS: Patients treated for primary TNBC from 1998 to 2011 were identified from the breast surgery database. Clinicopathologic characteristics, treatment, and outcomes were compared between patients <40 and ≥40 years of age at diagnosis. Multivariate models were used to identify factors independently associated with LR and DR. RESULTS: Among 1930 patients with TNBC, 289 (15 %) were <40 and 1641 (85 %) were ≥40 years of age at diagnosis. Younger patients were more likely to present with higher stage disease and more likely to receive mastectomy (p < 0.01), axillary node dissection (p < 0.01), and chemotherapy (p < 0.01). At a median follow-up of 74 (0-201.1) months, there was no difference in LR or disease-free survival (DFS) by age group [5-year LR = 3.9 % (95 % confidence interval (CI) 1.5-6.2) vs. 4.5 % (95 % CI 3.5-5.6) and 5-year DFS = 75.3 % (95 % CI 70.2-80.7) vs. 77.7 % (95 % CI 75.6-79.8), p = 0.94] in patients aged <40 and ≥40 years, respectively. On multivariate analysis, larger tumor size, lymphovascular invasion, and nodal positivity were associated with increased risk of DR. Age and type of surgery were not significantly associated with either outcome. CONCLUSIONS: Young age at diagnosis is not an independent risk factor for LR or DR in patients with TNBC.

Learning curves for laparoscopic hysterectomy after implementation of minimally invasive surgery.

OBJECTIVE: To evaluate the learning process for total laparoscopic hysterectomy (TLH) and laparoscopic supracervical hysterectomy (LSH) for benign uterine pathologies among surgeons inexperienced in laparoscopy. METHODS: A retrospective comparative study was conducted of all hysterectomies performed by four attending surgeons and three resident surgeons at a tertiary university center in Homburg/Saar, Germany. Laparoscopic procedures were assessed between October 1, 2009, and October 31, 2010 (period A); November 1, 2010, and March 31, 2012 (period B); and April 1, 2012, and June 30, 2013 (period C). Data were obtained by medical chart review. RESULTS: Overall, 269 patients underwent TLH and 165 underwent LSH. Duration of surgery for all surgeons decreased from 136 ± 60 minutes in period A to 118 ± 44 minutes in period B (P=0.013), but increased to 122 ± 56 minutes in period C (A vs C: P=0.067). Among attending surgeons, the duration of surgery seemed to decrease after 20 TLH procedures and after 10 LSH procedures. Among resident surgeons, duration decreased after 10 LSH procedures; no fall was apparent for TLH. CONCLUSION: Both TLH and LSH were readily adopted among a group of surgeons inexperienced in laparoscopy, although LSH might be easier to learn. Experienced surgeons have a steeper learning curve than do their inexperienced counterparts.

Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel Lymph Node Mapping After Periareolar Nuclide Injection.

BACKGROUND: To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients. METHODS AND FINDINGS: 767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5). CONCLUSIONS: Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed.

Five minutes of extended assisted ventilation with an open umbilical trocar valve significantly reduces postoperative abdominal and shoulder pain in patients undergoing laparoscopic hysterectomy.

OBJECTIVE: Residual carbon dioxide contributes substantially to pain following laparoscopic surgery. We evaluated the effects of extended assisted ventilation (EAV) with an open umbilical trocar valve for five additional minutes following laparoscopic hysterectomy on postoperative abdominal and shoulder pain levels. We also examined whether a combination of EAV and trocar site infiltration (TSI) with lidocaine could further reduce postoperative pain levels. STUDY DESIGN: In this prospective randomized trial, the effectiveness of EAV and EAV/TSI in reducing postoperative abdominal and shoulder pain were compared with that of a standard treatment regime in 283 patients undergoing laparoscopic hysterectomy (total or supracervical). Pain levels were evaluated by self-assessment questionnaire using a numeric rating scale (NRS) and by postoperative piritramid requirement, a surrogate parameter for postoperative analgesic drug requirement. The incidence of nausea and vomiting was also assessed. RESULTS: Compared with the standard treatment regime, EAV reduced abdominal pain levels significantly at 3h (NRS score, 3.21 ± 1.56 vs. 4.73 ± 1.71) and 24h (3.82 ± 1.49 vs. 4.95 ± 1.68) postoperatively (both p < 0.01). EAV also significantly reduced shoulder pain at 24h (EAV vs. control, 4.28 ± 1.51 vs. 5.14 ± 1.49) and 48 h (3.64 ± 1.66 vs. 4.22 ± 1.43) postoperatively (both p < 0.01). Patients in the EAV group had significantly lower piritramid requirements compared with standard treatment at 3h post-operatively (4.28 ± 2.09 mg vs. 6.31 ± 2.21 mg; p<0.01). EAV/TSI showed no additional benefit in terms of pain reduction compared with EAV alone. Incidences of postoperative nausea and vomiting were not reduced by EAV or EAV/TSI. CONCLUSION: EAV was found to be an effective and safe method to reduce postoperative pain levels in patients undergoing laparoscopic hysterectomy.