Human Papilloma Virus-Independent/p53abnormal Keratinizing Squamous Cell Carcinoma of the Uterine Cervix Associated With Uterine Prolapse.

Knowledge about the morphologic and molecular characteristics of cervical squamous cell carcinomas (CSCCs) associated with uterine prolapse is very limited. Detailed histopathological and immunohistochemical (p16, p53, and cytokeratin 17), as well as molecular evaluation for human papillomavirus (HPV)-DNA and p53-mutational analyses in 4 consecutive CSCCs associated with uterine prolapse with definition of a hitherto not well-described HPV-independent/p53abnormal precursor lesion (HPV-independent cervical intraepithelial neoplasia [CIN; differentiated CIN]) and molecular tumorigenetic pathway. Cases diagnosed within 7 years with a mean age of 75 (range: 69-83) years and a mean tumor size of 7.3 cm (range: 5.2-9.4 cm). All patients presented with locally advanced disease, and 1 woman died of the disease within 4, and another within 14 months of follow-up. All CSCCs and their adjacent precursor lesions were negative for p16, with aberrant p53-expression and diffuse and strong staining for cytokeratin 17. Both the CSCCs and their precursors were negative for HPV-DNA but harbored a TP53 mutation. The precursor lesions were characterized by epithelial thickening with superficial keratinization, and the presence of basal and parabasal keratinocytes with mitotic figures beyond the basal layer, thus showing features similar to those seen in differentiated types of vulvar intraepithelial lesions (vulvar intraepithelial neoplasia [VIN] syn. HPV-independent/p53abn VIN), suggesting the terminology of differentiated CIN or HPV-independent/p53abn CIN. An HPV-independent pathogenetic pathway with a p53-alteration was identified for these cases. CSCC associated with uterine prolapse represents HPV-independent tumors harboring a TP53 mutation. For the first time, a precursor lesion of HPV-independent CSCC of the uterine cervix is described with a differentiated VIN-like morphology, and a separate tumorigenic pathway defined.

Effects of stepped psychooncological care on referral to psychosocial services and emotional well-being in cancer patients: A cluster-randomized phase III trial.

OBJECTIVE: Emotional distress in cancer patients often goes unnoticed in daily routine; therefore, distress screening is now recommended in many national guidelines. However, screening alone does not necessarily translate into better well-being. We examined whether stepped psychooncological care improves referral to consultation-liaison (CL) services and improves well-being. METHODS: In a cluster-randomized trial, wards were randomly allocated to stepped versus standard care. Stepped care comprised screening for distress, consultation between doctor and patient about the patient's need for CL services, and provision of CL service. Primary outcomes were referral to psychosocial services and emotional well-being half a year after baseline, measured with the Hospital Anxiety and Depression Scale. A secondary endpoint was uptake of outpatient health care. Analysis employed mixed-effects multivariate regression modeling. RESULTS: Thirteen wards were randomized; 1012 patients participated. With stepped care (N = 570; 7 wards), 22% of the patients were referred to CL services and 3% with standard care (N = 442; 6 wards; odds ratio [OR] 10.0; P < .001). Well-being 6 months after baseline was 9.5 after stepped care (N = 341) and 9.4 after standard care (N = 234, ß -0.3; P = .71). After stepped care, patients with psychiatric comorbidity went more often to psychotherapists (OR 4.0, P = .05) and to psychiatrists (OR 2.3, P = .12), whereas patients without comorbidity used psychiatrists less often (OR 0.4, P = .04) than in standard care. CONCLUSIONS: Stepped care resulted in better referral to CL services. The patients' emotional well-being was not improved, but uptake of outpatient psychiatric help was increased in patients with psychiatric comorbidity and decreased in patients without.

Optimism, pessimism and self-efficacy in female cancer patients.

OBJECTIVE: The aim of this examination was to study whether psychological resource variables (optimism and self-efficacy) decrease when cancer is present and to test the predictive power of these variables for anxiety, depression and quality of life (QoL). METHODS: The patient sample was comprised of 354 German women suffering from breast cancer or gynecological cancer. Participants filled in the resource assessment tools Life Orientation Test-Revised and the General Self-Efficacy Scale as well as the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-4 and the QoL instrument EORTC QLQ-C30 at two time points: (t1) during patients' hospital stay and (t2) 3 months later. RESULTS: The mean scores for optimism (total score: M = 16.2) and self-efficacy (M = 29.8) were even somewhat higher than the corresponding means of the general population. Optimism and self-efficacy were positively correlated with QoL (r between 0.15 and 0.17, P < 0.01) and negatively associated with anxiety and depression (r between -0.17 and -0.36, P < 0.01). However, only optimism was predictive of the t2 anxiety, depression and QoL scores when statistically taking into account the baseline levels of the outcome variables. CONCLUSIONS: Having cancer does not generally reduce optimism and self-efficacy on the level of patients' mean scores. Cancer patients with a high level of habitual optimism will adapt to their disease better than pessimistic patients, even if the baseline levels of the outcome variables have been accounted for.

Socio-economic disparities in long-term cancer survival-10 year follow-up with individual patient data.

PURPOSE: Reasons for the social gradient in cancer survival are not fully understood yet. Previous studies were often only able to determine the socio-economic status of the patients from the area they live in, not from their individual socio-economic characteristics. METHODS: In a multi-centre cohort study with 1633 cancer patients and 10-year follow-up, individual socio-economic position was measured using the indicators: education, job grade, job type, and equivalence income. The effect on survival was measured for each indicator individually, adjusting for age, gender, and medical characteristics. The mediating effect of health behaviour (alcohol and tobacco consumption) was analysed in separate models. RESULTS: Patients without vocational training were at increased risk of dying (rate ratio (RR) 1.5, 95% confidence interval (CI) 1.1-2.2) compared to patients with the highest vocational training; patients with blue collar jobs were at increased risk (RR 1.2; 95% CI 1.0-1.5) compared to patients with white collar jobs; income had a gradual effect (RR for the lowest income compared to highest was 2.7, 95% CI 1.9-3.8). Adding health behaviour to the models did not change the effect estimates considerably. There was no evidence for an effect of school education and job grade on cancer survival. CONCLUSIONS: Patients with higher income, better vocational training, and white collar jobs survived longer, regardless of disease stage at baseline and of tobacco and alcohol consumption.

Management of Primary Retroperitoneal Mucinous Tumors: A Retrospective Meta-Analysis.

OBJECTIVE: Primary retroperitoneal mucinous tumors (PRMTs) are rare epithelial neoplasms arising in the retroperitoneal space whose pathogenesis is poorly understood. To date, only single-case reports and small case series on diagnosis and management of these tumors exist. The aim of this first-time meta-analysis was to provide more reliable data to inform the management of PRMTs. METHODS: Database searches were conducted to identify case reports and case series between the years of 1975 and 2015. Two cases of patients treated at our institution were also included. Diagnostic, radiographic, surgical, and follow-up data were gathered. Regression modeling was used to identify factors aiding preoperative diagnosis and affecting treatment. Survival analysis including Cox regression modeling was performed to provide insights into treatment effects on the prognosis of female patients with PRMTs. RESULTS: One hundred forty-four cases of PRMTs were included in this analysis. Eighty-nine percent occurred in women. Most of the PRMTs were found to be malignant (53%). No preoperative factors predicting tumor dignity were identified by multiple regression analysis. Five-year disease specific survival of patients with benign and borderline tumors was excellent, reaching 100%, whereas it was only 68% for patients with malignant disease. Adjuvant surgical treatments including hysterectomy, salpingoophorectomy, and lymph node dissection were not associated with a statistically significant survival advantage. However, there was a nonsignificant association of hysterectomy with improved survival (hazard ratio, 0.42; 95% confidence interval, 0.09-2.07; P = 0.285). Adjuvant chemotherapy was associated with reduced survival (hazard ratio 3.791; 95% confidence interval, 1.509-9.526; P = 0.0046). CONCLUSIONS: A reliable diagnosis of a PRMT can only be made by pathological examination of the tumor. Surgical excision is thus necessary to facilitate diagnosis while it also remains the mainstay of treatment. There is no conclusive evidence supporting the role of adjuvant surgical procedures or chemotherapy.

A cut-off value of 2 cm in tumor size is of prognostic value in surgically treated FIGO stage IB cervical cancer.

OBJECTIVES: Limited knowledge exists about the value of tumor size in surgically treated cervical cancer (CX) using a tumor size of 2 cm as cut-off value. METHODS: A total of 366 cases of CX FIGO stage IB who received upfront surgery were evaluated regarding tumor size, the prediction of pelvic lymph node involvement, and recurrence-free and overall survival during a median follow-up time of 94 months. Tumors ≤2.0 cm were defined as small, tumors 2.1-4.0 cm as medium sized and those larger than 4 cm as bulky disease. RESULTS: Small tumors were seen in 28.7%, medium sized in 52.5% and bulky tumors in 18.9%. There was a significant higher frequency of pelvic lymph node involvement with increasing tumor size (13.3% vs. 23.4% vs. 43.5%, respectively; p<0.001) and an increase of recurrent disease (6.7% vs. 18.8% vs. 29.4%, respectively; p<0.001). The 5-year overall survival rate was significantly reduced with increasing tumor size (94.0% vs. 85.1% vs. 69.9%, respectively; p<0.001). Pelvic lymph node involvement and maximal tumor size were independent prognostic factors for both recurrence-free and overall survival in multivariate analysis. CONCLUSIONS: The results support that tumor size is of prognostic impact in FIGO stage IB cervical carcinomas. A further substaging is suggested for tumors up to 4.0 cm maximum dimension using a cut-off value of 2.0 cm as discriminator. Patients with tumors ≤2.0 cm may represent low risk disease.

Monoclonal origin of peritoneal implants and lymph node deposits in serous borderline ovarian tumors (s-BOT) with high intratumoral homogeneity.

Molecular studies have shown that the most prevalent mutations in serous ovarian borderline tumors (s-BOT) are BRAF and/or KRAS alterations. About one third of s-BOT represent peritoneal implants and/or lymph node involvement. These extraovarian deposits may be monoclonal or polyclonal in origin. To test both the hypotheses, mutational analyses using pyrosequencing for BRAF codon 600 and KRAS codon 12/13 and 61 of microdissected tissue was performed in 15 s-BOT and their invasive and noninvasive peritoneal implants. Two to 6 implants from different peritoneal sites were examined in 13 cases. Lymph node deposits were available for the analysis in 3 cases. Six s-BOT showed mutation in exon 2 codon 12 of the KRAS proto-oncogen. Five additional cases showed BRAF p.V600E mutation representing an overall mutation rate of 73.3%. Multiple (2-6) peritoneal implants were analyzed after microdissection in 13 of 15 cases. All showed identical mutational results when compared with the ovarian site of the disease. All lymph node deposits, including those with multiple deposits in different nodes, showed identical results, suggesting high intratumoral mutational homogeneity. The evidence presented in this study and the majority of data reported in the literature support the hypothesis that s-BOT with their peritoneal implants and lymph node deposits show identical mutational status of BRAF and KRAS suggesting a monoclonal rather than a polyclonal disease regarding these both tested genetic loci. In addition, a high intratumoral genetic homogeneity can be suggested. In conclusion, the results of the present study support the monoclonal origin of s-BOT and their peritoneal implants and lymph node deposits.

Serous tubal in situ carcinoma (STIC) in primary peritoneal serous carcinomas.

Recent new data in the pathogenesis of serous pelvic cancer and the introduction of serous tubal in situ carcinoma (STIC) and its precursors have raised the question that whether all primary peritoneal cancers (PPC) are in fact of tubal origin. Therefore, the present study evaluates the frequency of STIC and its precursor lesions in cases that were diagnosed as PPC using the morphologic criteria of the most recent WHO classification. The present study evaluates immunohistochemically (Ki-67 and p53 staining) the presence of STIC and its precursor lesions (p53 signature, serous tubal intraepithelial lesion [STIL]) in the completely processed Fallopian tubes of 46 consecutive PPCs. STIC was detected in 10 patients (21.7%) and p53 signature in 9 cases (19.6%). No STIL was observed. All except 1 STIC occurred at the fimbriated end of the Fallopian tube, and a bilateral involvement was detected in 2 cases. These precursor lesions were missed during the initial routine screening. Repeated staining for p53 was negative in STIC in 2 cases. STIC and p53 signature as precursor lesions of pelvic serous cancer are detected in some but not all the cases of primary serous peritoneal cancer. There might be the 2 different carcinogenetic pathways within PPC, and further studies are required to identify the source of serous cancer in cases without an STIC lesion.

CD34(low) and SMA(high) represent stromal signature in uterine cervical cancer and are markers for peritumoral stromal remodeling.

Peritumoral desmoplastic stromal reaction (DSR) with myofibroblastic phenotype may be of prognostic impact in uterine cervical carcinoma. The present study evaluates the immunostaining (CD34 and smooth muscle actin; SMA) of 97 squamous cell cancers. Staining was scored as low/negative (<5% stroma positive), moderate (patchy/focal expression, 5%-50%), or high (diffuse expression throughout peritumoral stroma, >50%) and DSR as negative/weak and moderate/strong. The staining results were correlated to patient survival. Of the cases, 78.3% showed a decreased of CD34 (<5% stromal positivity) and 71.9% an increased SMA staining with more than 50% SMA positive stromal cells. Tumors representing moderate/strong DSR showed a significant decreased CD34 (P=.001) and an increased but not statistically significant SMA staining (P=0.345). Cases with low CD34 and high SMA staining showed reduced 5-year overall survival when compared to cases with high CD34 and low SMA positivity (59.9 vs 81.0%; P=0.025 and 64.6 vs 81.1%; P=0.243). Peritumoral stromal response in cervical carcinoma is immunohistochemically characterized by CD34(low)/SMA(high) and associated reduced overall survival.

Gestational and Non-gestational Trophoblastic Neoplasia. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 032/049, April 2022).

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Suitability of infrared microspectroscopic imaging for histopathology of the uterine cervix.

AIMS: Infrared microspectroscopy (IR-MSP) has been proposed for automated histological tissue differentiation of unstained specimens based on chemical analysis of cell and extracellular constituents. This study aimed to determine the accuracy of IR-MSP-based histopathology of cervical carcinoma sections with complex tissue architecture under practically relevant testing conditions. METHODS AND RESULTS: In total, 46 regions of interest, covering an area of almost 50 mm(2) on sections derived from paraffin-embedded tissue of radical hysterectomy specimens, were analysed by IR-MSP (nominal resolution ~4.2 µm). More than 2.8 million pixel spectra that were processed using fuzzy c-means clustering followed by hierarchical cluster analysis permitted image segmentation regarding different biochemical properties. Linear image registration was applied to compare these segmentation results with manual labelling on haematoxylin and eosin-stained references (resolution ~0.7 µm). For recognition of nine tissue types, sensitivities were 42-91% and specificities were 79-100%, mostly being affected by peritumoral inflammatory responses. Algorithmic variation of the outline of dysplasia and carcinoma revealed a spatial preference of false values in tissue transition areas. CONCLUSIONS: This imaging technique has potential as a new method for tissue characterization; however, the recognition accuracy does not justify a pathologist-independent tissue analysis, and the application is only possible in combination with concomitant conventional histopathology.

Pattern analysis of regional spread and therapeutic lymph node dissection in cervical cancer based on ontogenetic anatomy.

OBJECTIVE: In cervical cancer lymph node dissection is applied for regional tumor staging. Up to now, the use of (chemo)radiation in the nodal positive patient has prevented the exact pattern analysis of regional tumor spread and the evaluation of the therapeutic role of lymph node dissection. New surgical techniques founded on ontogenetic instead of functional anatomy for the treatment of cervical cancer dispensing with adjuvant radiotherapy offer the possibility to accurately determine the topography of regional lymph node metastases which is the prerequisite for optimized diagnostic and therapeutic lymph node dissection. METHODS: Patients with cervical cancer FIGO stages IB-IIB were treated with total mesometrial resection (TMMR) and lymph node dissection after exposing the ontogenetic visceroparietal compartments of the female pelvis. Resected lymph nodes were allocated to regions topographically defined by the embryonic development of the iliac, lumbar and mesenteric lymph systems prior to histopathological assessment. RESULTS: 71 of 305 treated patients had lymph node metastases. Topographic distribution of these metastases at primary surgery and analysis of pelvic failures showed a spatial pattern related to the ontogenesis of the abdominopelvic lymphatic system. Five-year locoregional tumor control probability was 96% (95% CI: 94-98) for the whole group and 87% (95% CI: 77-97) for nodal positive patients. CONCLUSIONS: The pattern of regional spread in cervical cancer can be comprehended and predicted from ontogenetic lymphatic compartments. In patients with early cervical cancer lymph node dissection based on ontogenetic anatomy achieves high regional tumor control without adjuvant radiation.

(Laterally) extended endopelvic resection: surgical treatment of locally advanced and recurrent cancer of the uterine cervix and vagina based on ontogenetic anatomy.

OBJECTIVE: Pelvic exenteration is mainly applied as a salvage operation for a subset of patients with persistent and recurrent cervicovaginal cancer. The procedure can also cure locally advanced primary disease not suitable for radiotherapy. However, high operative abortion and intralesional tumor resection rates significantly limit its clinical benefit. To improve locoregional tumor control we have proposed to establish cancer surgery on ontogenetic anatomy and, consequently, we have developed the (Laterally) Extended Endopelvic Resection ((L)EER). METHODS: (L)EER is clinically and histopathologically evaluated with a monocentric prospective observational study. Patients with advanced and recurrent cervicovaginal cancer are treatment candidates if distant metastases and tumor fixation at the region of the sciatic foramen can be excluded. RESULTS: 91 patients with locally advanced primary (n=30) and recurrent or persistent (n=61) carcinoma of the cervix and vagina were treated with (L)EER. 74% of the tumors were fixed to the pelvic wall. No (L)EER treatment was aborted, R0 resection was histopathologically confirmed in all cases. (L)EER definitively controlled the locoregional cancer in 92% (95% CI: 85-99) of the patients. Five year overall survival probability was 61% (95% CI: 49-72). CONCLUSIONS: The results of (L)EER treatment confirm the concept of cancer surgery based on ontogenetic anatomy. In patients with locally advanced and recurrent cervicovaginal cancer (L)EER achieves locoregional tumor control both with central disease and with tumors fixed to the pelvic side wall except at the region of the sciatic foramen.

Clinico-pathologic characteristics and prognostic factors of ovarian carcinoma with different histologic subtypes - A benchmark analysis of 482 cases.

PURPOSE: Ovarian carcinomas (OCX) have traditionally been thought to arise from the ovarian surface epithelium. However, recent (immuno-) histopathological and molecular analyses suggest that OCX consist of morphological subtypes with different epidemiologic features and a varying prognosis. METHODS: The data of 482 OCX from the Clinical Cancer Registry of Leipzig who were surgically treated between 2000 and 2019 and were evaluated regarding incidence, clinico-pathologic characteristics and prognostic factors. Cases were separated into high-grade and non-high-grade serous tumors. Both groups were analyzed regarding the tumor stage, lymph node involvement, site of origin and prognosis. RESULTS: The overall incidence for OCX was 17.9. The most common histological subtype was high-grade serous OCX (57.9%; 279/482). Patients with high-grade were significantly older than those with a non-high-grade serous OCX (63.9 versus 58.5 years; p < 0.001), more frequently diagnosed at an advanced stage >pT3 (78.5% (219/279) versus 42.8% (87/203); p < 0.001) and showed a 2.4-fold higher frequency of lymph node metastases (53.4% vs. 21.2%; p < 0.02) with a 4.6-fold higher rate of > 1 cm metastatic deposits (pN1b) within the lymph nodes (14.8% vs. 4.6%; p < 0.02). Irrespective of tumor stage and morphological subtype, the 1- and 5-year overall survival (OAS) was 72.9% and 40.8%, respectively. Patients with high-grade serous OCX showed a shorter 5-year OAS compared to non-high-grade serous OCX (34.1% vs. 57.0%; p 0.001). This association was reproducible in patients with an advanced tumor stage irrespective of the histopathologic tumor type serous OCX (pT3: 32.4% vs. pT1: 75.1%; p 0.001) as well as within high-grade (pT3: 28.7% vs. pT1: 55.5%; p = 0.003) and non-high-grade serous OCX (pT3: 43.0% vs. 80.0%; p 0.001). There were no differences in OAS depending on the site of origin (fallopian tube, ovary, peritoneum) within the two histologic subgroups. CONCLUSION: OCX cases from a single institution with uniform surgical treatment and a standardized histopathological workup were evaluated. The poor prognostic outcome of patients with high-grade serous compared non-high-grade serous OCX as well as an advanced stage of the disease was confirmed. This study demonstrates for the first time that the histopathological distinction into high-grade serous and non-high-grade serous tumors may be much more prognostically relevant than the site of origin.

p53 signature and serous tubal in-situ carcinoma in cases of primary tubal and peritoneal carcinomas and serous borderline tumors of the ovary.

The objective of this study was to evaluate the role of the fimbriated end and nonfimbriated epithelium of fallopian tubes with regard to p53 signature, tubal intraepithelial lesions in transition (TILT), and serous tubal in-situ carcinoma (STIC) in cases of different kinds of serous pelvic cancer. This study immunohistochemically evaluated (by Ki-67 and p53 staining) the presence of p53 signature, TILT lesions, and STIC in 14 consecutive cases of prophylactic salpingo-oophorectomy in women with BRCA-1/2 mutation (bilateral salpingo-oophorectomy), 11 cases of macroscopically inconspicuous adnexae of patients with primary contralateral tubal cancer (TC), 9 cases of primary peritoneal cancer (PPC), and 10 cases of serous ovarian borderline tumors, evaluating the fallopian tubes (using the Sectioning and Extensively Examining the FIMbria protocol), ovarian surface epithelium, and ovarian cortical inclusion cysts. The frequencies of p53 signature, TILT, and STIC were 35.7%, 7.1%, and 0% in cases of prophylactic surgery, 18.2%, 9.1%, and 18.2% in TC, and 11.1%, 0%, and 33.3% in PPC. These precursor lesions were missed during the initial routine screening and were found in the fimbriated end of the fallopian tubes in 94%. In 1 case of PPC, staining for p53 was negative in STIC. The studied adnexal tissue of serous ovarian borderline tumor and ovarian cortical inclusion cysts of all cases showed no alterations according to p53 signature, TILT, or STIC. STIC and p53 signature as precursor lesions of pelvic serous cancer were seen in macroscopically inconspicuous contralateral fallopian tubes in unilateral TC, in patients with elective bilateral salpingo-oophorectomy, and in patients affected by PPC. Therefore, we propose the complete processing of adnexal tissue and the use of step sectioning to establish the correct diagnosis. Immunohistochemistry for p53 and ki-67 may aid in the diagnosis, but is not necessary for routine investigation.

Identifying tumor patients' depression.

PURPOSE: The aim of this study was to compare the precision of two different methods in detecting clinical depression in tumor patients: the use of a screening questionnaire versus the assessment by health care providers (nurses and doctors). METHODS: During their first days of inpatient cancer treatment, tumor patients were interviewed using the Structured Clinical Interview for DSM (SCID). Their physicians and nurses were asked to assess the mental health of the patients and their need for professional psychosocial support. Additionally, every patient completed the Hospital Anxiety and Depression Scale (HADS). RESULTS: Out of 329 patients, 28 were diagnosed with either a major or a minor depression according to the SCID. Physicians assessed 15 of the depressed patients as being depressed (sensitivity, 0.54; specificity, 0.38). Nurses identified 19 (sensitivity, 0.68; specificity, 0.45) and the HADS 27 (sensitivity, 0.96; specificity, 0.50) of the depressed patients. CONCLUSION: The HADS performed well in detecting depressed cancer patients in acute oncological care, whereas physicians and nurses often were unable to recognize depressed patients.

Increase of fallopian tube and decrease of ovarian carcinoma: fact or fake?

PURPOSE: Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. METHODS: Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. RESULTS: The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. CONCLUSION: The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

Patients' acceptance and psychometric properties of the EORTC QLQ-CX24 after surgery.

OBJECTIVE: The aim of this study was to evaluate patients' acceptance and the reliability and validity of a recently developed instrument to assess quality of life among cervical cancer patients, the European Organization for Research and Treatment of Cancer Cervical Cancer Module (EORTC QLQ-CX24), in surgically treated patients after primary surgery. METHODS: The EORTC QLQ-CX24 was administered to 134 cervical cancer patients who had undergone pelvic surgery. Additional questionnaires completed were the EORTC QLQ-C30, and the Hospital Anxiety and Depression Scale. Sociodemographic and medical data were recorded. RESULTS: Missing values occurred in 4.5% of all non-optional items. Internal consistencies (Cronbach's alpha coefficients) for the three multi-item scales ranged from 0.70 to 0.87 (Symptom Experience 0.70, Body Image 0.87, Sexual/Vaginal Functioning 0.76), whereas scaling errors occurred in 6.8%, 0.0%, and 6.3% of the cases. In all domains, the entire range of the scale was used by patients. The scales were able to discriminate between different subgroups of patients. CONCLUSION: These psychometric analyses confirm that the EORTC QLQ-CX24 is a useful tool for the assessment of quality of life in cervical cancer patients after surgery.

Local spread of cervical cancer revisited: a clinical and pathological pattern analysis.

BACKGROUND: Local tumor spread of cervical cancer is currently considered as radial progressive intra- and extracervical permeation. For radical tumor resection or radiation the inclusion of a wide envelope of tumor-free tissue is demanded. However, this concept may lead to considerable treatment-related morbidity and does not prevent local relapse. We propose an alternative model of local tumor propagation involving permissive compartments related to embryonic development. METHODS: We analyzed local tumor spread macroscopically and microscopically in consecutive patients with advanced cervical cancer and post-irradiation recurrences. RESULTS: Macroscopically, all 33 stage I B (>2cm) tumors, 40 of 42 stage II tumors and 32 of 44 stage III B tumors were confined to the embryologically defined uterovaginal (Müllerian) compartment. Local tumor permeation deformed the uterovaginal compartment mirroring the mesenchyme distribution of the Müllerian anlage at the corresponding pelvic level in cases of symmetrical tumor growth. Tumor transgression into adjacent compartments mainly involved the embryologically related lower urinary tract. Compartmental transgression was associated with larger tumor size, paradox improvement in oxygenation and an increase in microvessel density. Post-irradiation pelvic relapse landscapes were congruent with the inflated Müllerian compartment. Microscopically, all locally advanced primary cancers and post-irradiation recurrences were confined to the uterovaginal and lower urinary tract compartments. CONCLUSION: Cervical cancer spreads locally within the uterovaginal compartment derived from the Müllerian anlage. Compartment transgression is a relatively late event in the natural disease course associated with distinct phenotypic changes of the tumor. Compartmental tumor permeation suggests a new definition of local treatment radicality.

Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: a prospective analysis.

BACKGROUND: Radical hysterectomy based on empirical surgical anatomy to achieve a wide tumour resection is currently applied to treat early cervical cancer. Total mesometrial resection (TMMR) removes the embryologically defined uterovaginal (Müllerian) compartment except its distal part. Non-Müllerian paracervical and paravaginal tissues may remain in situ despite their possible close proximity to the tumour. We propose that in patients with early cervical cancer, the resection of the Müllerian compartment will lead to maximum local tumour control with low morbidity. We also propose that the relatively high rate of pelvic failure after conventional radical hysterectomy, despite adjuvant radiation, might be a consequence of the incomplete removal of the Müllerian compartment. The aim of our study was to test these hypotheses. METHODS: We did a prospective trial to assess the effectiveness of TMMR without adjuvant radiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA, and selected IIB cervical cancer. We also generated MRI-based pelvic relapse landscapes from patients who had experienced pelvic failure after conventional radical hysterectomy. FINDINGS: 212 consecutive patients underwent TMMR without adjuvant radiation. 134 patients (63%) had high-risk histopathological factors. At a median follow-up of 41 months (5-110), three patients developed pelvic recurrences, two patients developed pelvic and distant recurrences, and five patients developed distant recurrences. Recurrence-free and overall 5-year survival probabilities were 94% (95% CI 91-98) and 96% (93-99), respectively. Treatment-related grade 2 morbidity was detected in 20 (9%) patients, the most common being vascular complications. Resection of the Müllerian compartment resulted in local tumour control irrespective of the metric extension of the resection margins. The pelvic topography of the peak relapse probability after conventional radical hysterectomy indicates an incomplete resection of the posterior subperitoneal and retroperitoneal extension of the Müllerian compartment. INTERPRETATION: Resection of the embryologically defined uterovaginal compartment seems to be pivotal for pelvic control in patients with cervical cancer. TMMR without adjuvant radiation has great potential to improve the effectiveness of surgical treatment of early-stage cervical cancer. FUNDING: University of Leipzig, Leipzig, Germany.