Clinical Usefulness of Endometrial Cytology in Determining the Therapeutic Effect of Fertility Preserving Therapy

<b><i>Introduction:</i></b> The significance of endometrial cytology in determining the therapeutic efficacy of medroxyprogesterone acetate (MPA) therapy is unclear. This study aimed to evaluate the clinical usefulness of endometrial cytology during MPA therapy. <b><i>Methods:</i></b> Overall, 77 patients who underwent dilatation and curettage (D&amp;C) to evaluate the therapeutic efficacy of MPA therapy at our hospital between January 2018 and December 2019 were retrospectively analyzed. The results of D&amp;C, cytological evaluation, and other clinicopathological factors were analyzed based on the patients’ medical records. <b><i>Results:</i></b> The sensitivity and specificity of cytology were 61% and 92%, respectively, with D&amp;C being the gold standard for diagnosis in 142 D&amp;C/cytological examinations. Among patients with no residual disease on D&amp;C, 5 (4%) had suspicious or positive cytology. Although MPA therapy was terminated in 3 of these patients, only 1 patient had early recurrence, and the frequency of recurrence was similar to that of patients who showed negative results in both D&amp;C and cytology. <b><i>Discussion/Conclusion:</i></b> The sensitivity of endometrial cytology in determining the therapeutic effect of MPA therapy is low, and we confirmed that the omission of D&amp;C is unacceptable. Our findings also suggested that the addition of cytological evaluation to D&amp;C during MPA therapy had a low clinical significance.

TP6.2.15 Staging Laparoscopy and Peritoneal Cytology for Gastric and Gastro-oesophageal Junction Malignancy: an Audit from a Single Oesophagogastric Resection Centre

Aims AUGIS recommends staging laparoscopy in all gastric cancers and selected gastro-oesophageal junction (GOJ) cancers. We previously audited our practice of staging laparoscopy and peritoneal cytology and found that in a cohort of 158 consecutive patients, no tumours less than T3 with negative nodes had positive cytology, resulting in change in practice to selectively use peritoneal cytology in patients with a T-stage of 3 and above or N+ disease. Our aim was to assess the impact of this audit on current practice. Methods We retrospectively reviewed the notes of patients undergoing staging laparoscopy and oesophagogastroduodenoscopy (OGD) identified by MDT from January 2019 to December 2019. Patients who underwent resection on the same day were excluded. Results 63 patients underwent staging laparoscopy and OGD, 54 for GOJ and 9 for gastric disease. The majority were staged as T3 or T4a (81%). As a result of staging laparoscopy and OGD, 4 (6%) patients were changed from curative to palliative pathway, 2 (3%) of whom had positive cytology. No patients had positive peritoneal cytology for a T stage of 2 and below with no positive nodes, further demonstrating the safety of the recommendation. Conclusions Peritoneal cytology has a low yield in changing the clinical course of patients but can upstage up to 6% of patients. The re-audit backs up the previous guidance in the safety of using our current threshold for recommending peritoneal cytology and potentially prevents delaying treatment while waiting for cytology results.

Leptomeningeal Carcinomatosis: A Call for Optimizing Diagnostic Sensitivity by the Hematology Laboratory

In the cerebrospinal fluid (CSF), the demonstration of malignant cells by cytological examination is currently the gold standard for the diagnosis of leptomeningeal carcinomatosis (LC). However, a positive cytology is observed in only 50–60% of patients with LC and highly dependent on pre-analytical factors. The hematology laboratory could provide an immediate and accurate diagnosis, but diagnostic sensitivity is not always optimized once the sample is received. We hereby report a 49-year-old woman with a 3-year grade III invasive ductal carcinoma who was admitted to the emergency department due to headaches, nausea, and vomiting. The CSF revealed pleocytosis with suspicious high fluorescent cells on the hematology analyzer concomitantly with biochemical alterations. Cytomorphological examination confirmed tumor cells, thus diagnosing a leptomeningeal metastasis of her breast cancer. The patient was eventually transferred to palliative care. Cytological examination is a valuable tool for a rapid diagnosis of LC if diagnostic performance is optimized. In addition to repeated CSF collections with a sufficient volume (5–10 mL), this could be reached by processing the CSF as soon as possible, taking into account the fluorescence information from the analyzer, proceeding systematically to microscopic examination even with normal CSF white blood cell count, and providing quality improvement of the staff to identify malignant cells.

Necessity for craniospinal irradiation of germinoma with positive cytology without spinal lesion on MR imaging - A controversy

Background Cerebrospinal fluid (CSF) cytology and spinal MR imaging are routinely performed for staging before treatment of intracranial germinoma. However, the interpretation of the results of CSF cytology poses two unresolved clinical questions: 1) Does positive CSF cytology correlate with the presence of spinal lesion before treatment?; and 2) Is craniospinal irradiation (CSI) necessary for patients with positive CSF cytology in the absence of spinal lesion? Methods Multicenter retrospective analyses were performed based on a questionnaire on clinical features, spinal MR imaging finding, results of CSF cytology, treatments, and outcomes which was sent to 86 neurosurgical and 35 pediatrics departments in Japan. Pretreatment frequencies of spinal lesion on MR imaging were compared between the patients with positive and negative cytology. Progression-free survival (PFS) rates were compared between patients with positive CSF cytology without spinal lesion on MR imaging treated with CSI and with whole brain or whole ventricular irradiation (non-CSI). Results A total of 92 germinoma patients from 45 institutes were evaluated by both CSF cytology and spinal MR images, but 26 patients were excluded because of tumor markers, the timing of CSF sampling or incomplete estimation of spinal lesion. Of the remaining 66 germinoma patients, spinal lesions were equally identified in patients with negative CSF cytology and positive cytology (4.9% and 8.0%, respectively). 11 patients treated with non-CSI had excellent PFS comparable to 11 patients treated with CSI. Conclusion CSI is unnecessary for germinoma patients with positive CSF cytology without spinal lesions on MR imaging.

The Impact of Intra-Uterine Manipulators on Outcome and Recurrence Patterns of Endometrial Cancer Patients Undergoing Minimally Invasive Surgery

PurposeTo evaluate the use of an intrauterine manipulator on the oncologic outcome of women who had minimally invasive surgery for endometrial cancer. MethodsRetrospective analysis of consecutive patients who were operated with or without the use of an intrauterine manipulator. Univariate and multivariate analysis were used to adjust for possible confounders. Results699 patients were included, of whom 220 (32.8%) were operated with an intrauterine manipulator. The median follow-up was 44 months (range, 29-67). Disease-free survival was similar between groups. 19 (8.8%) patients had positive cytology in the manipulator group vs. 21 (4.4%) in the comparison group (p=0.02). Total recurrence rate was similar between the groups (12.3% vs. 11.9%; p = 0.8). Vaginal vault recurrence was the most common site of recurrence with higher incidence in the manipulator group (4.5% vs. 1.3%; p=0.007). Sub-group analysis of patients who did not receive adjuvant treatment showed higher recurrence rate (8.3% vs. 3%; p=0.023) and worse disease-free survival (p=0.01) for the manipulator group. After controlling for other variables, the use of a manipulator did not affect the risk of recurrence for the whole cohort (HR, 1.28; 95% CI, 0.7-2.1, p=0.3) and for the sub-group of patients who did not receive adjuvant treatment (HR, 2.47; 95% CI, 0.8-7, p=0.08).ConclusionThe use of a manipulator during surgery for endometrial cancer increases the risk of positive cytology as well as vaginal vault recurrences, but it does not reduce the disease-free and overall survival of patients.

Triaging HPV-positive, cytology-negative cervical cancer screening results with extended HPV genotyping and p16INK4a immunostaining in China

Background Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16INK4a immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women. Methods A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity and specificity for CIN2+/CIN3+ in reference to the comparator, being HPV16/18 + . Results A total of 2731 HPCN women aged 30–64 years were enrolled, 136 (5.0%) CIN2+ and 53 (1.9%) CIN3+ were detected. Five triage strategies met the criteria: p16+; HPV16/33+; ‘HPV16+ or HPV33/58/31/35+&p16+’; ‘HPV16/33+ or HPV58/31/35+&p16+’; HPV16/18/31/33/45/52/58 + & p16+. These strategies required less or similar colposcopy referrals, and less colposcopies to detected one case of CIN2+/CIN3+, achieving favorable false positive (negative) rates to the comparator. Among them, p16 staining detected 83.1% (79.2%) of underlying CIN2 + (CIN3+) in HPCN women. Moreover, three triage strategies were favorable in sensitivity and/or specificity to the ‘HPV16/33+’ strategy: p16+; ‘HPV16+ or HPV33/58/31/35 + &p16+’; HPV16/18/31/33/45/52/58 + &p16 + . Conclusions Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.

Assessing treatment response after intravesical bacillus Calmette–Guerin induction cycle: are routine bladder biopsies necessary?

Purpose To determine the need for routine bladder biopsies (BBs) in assessing response to the induction cycle of intravesical bacillus Calmette–Guérin (BCG) for high-risk non-muscle-invasive bladder cancer (NMIBC). Methods Our prospectively maintained NMIBC database was queried to identify patients with high-risk disease (carcinoma in situ, high-grade Ta/T1) who underwent BBs after BCG induction cycle. Urine cytology, cystoscopy, and BBs findings were evaluated. Results A total of 219 patients met the inclusion criteria. Urine cytology was positive in 20 patients and negative in 199; cystoscopy was positive in 35 patients, suspicious in 32 and normal in 152 patients. BBs yielded bladder cancer (BCa) in 43 (19.6%) patients, with a BCa rate of 9.3% in patients with negative cytology and cystoscopy as opposed to 38.0% in patients whereby one or both exams were suspicious/positive. The diagnostic accuracy of urine cytology, cystoscopy, and combined tests was 0.56, 0.70, and 0.71, respectively. The negative predictive value of combined tests was 90.7%. Performing BBs only in patients with positive cytology and/or positive/suspicious cystoscopy would have spared 140 (64%) patients to undergo this procedure while missing BCa in 13 (9.3%) of them, representing 30% of all BCa cases. Conclusion Performing BBs only in patients with positive cytology and suspicious/positive cystoscopy would spare 64% of un-necessary BBs but miss a non-negligible number of BCas. While no data are available regarding the potential consequences of missing such BCas, such information should be taken into account in patient’s counselling.

Evaluation of Peritoneal Lavage for Gastric Cancer Staging in Patients Without Ascites Based on Cytology and Carcinoembryonic Antigen

Background: Imaging, cytological examination of ascites (if present), laparosco- py, and peritoneal lavage are performed before surgery for gastric cancer staging. Peritoneal lavage aims to diagnose the microscopic presence of tumor cells on the peritoneal surface. Positive cytology may have a prognostic value that classifies the disorder as stage IV, in which the patient is no longer an elective surgical candidate. Thus, our study was designed to assess the ability of peritoneal lavage to stage gastric cancer in non-ascitic patients based on cytological evaluation and carcinoembryonic antigen (CEA) level measurement. Methods: In our prospective study, we examined gastric cancer patients who were candidates for elective surgery. Upon entering the abdominal cavity and before tu- mor manipulation, normal saline (500 ml) was applied, and the abdominal cavity was thoroughly dispersed. After three minutes, the fluid was drained and addressed to cytological analysis and CEA measurement by radioimmunoassay (RIA). Study var- iables including age, sex, family history, tumor position, pathology, staging, grading, the original tumor size, regional lymph node involvement, and distant metastases were recorded during the pre- and postoperative staging. The association between positive peritoneal lavage cytology and various patients’ characteristics was investigated. Results: In this study, 94 patients were screened. Due to lymphoma and gastrointes- tinal stromal tumor (GIST), two patients were excluded. We examined 92 patients, including 63 males (68.5 %) and 29 females (31.5 %). The mean age of patients was 58.52 ± 11.87 years. The most common tumor location was the esophagogastric junction. Moderately differentiated adenocarcinoma was the most frequent micro- scopic diagnosis. T3 was the most prevalent primary tumor size in 51 patients. Sev- enty-two patients (78.26%) were operable, of whom 18 (19.6 %) were positive for peritoneal lavage cytology. Positive cytology of peritoneal lavage was significantly related to tumor size, tumor grade, serosa/adjacent organ invasion (T4), laparoscopic staging findings, locally advanced disease (R0), and stage of the disease (P < 0.05). In the peritoneal lavage fluid, elevated CEA titers were significantly related to the high-grade tumor (P = 0.012). Conclusion: Our study demonstrated that positive cytology and high CEA titers in peritoneal lavage fluid of gastric cancer patients without ascites are significantly correlated to the advanced stages.

Is there a role for urine cytology following BCG therapy for non-muscle-invasive bladder cancer (NMIBC)?

404 Background: Voided urine cytology has been used as an adjunct in the diagnosis of non-muscle invasive bladder cancer (NMIBC), with a sensitivity and specificity ranging between 13-75% and 76-100% respectively. There is limited data on the accuracy and utility of cytology following BCG therapy. We reviewed the results of cytology in patients undergoing induction and maintenance BCG immunotherapy in our institution. Methods: Newly diagnosed patients who had received induction and maintenance intravesical BCG therapy from 2004 - 2019 were identified from a prospective database and their outcomes reviewed retrospectively. Histopathology results of biopsies / resected specimens and voided urine cytology results were examined for 273 patients. Results: A total of 2567 cytology results and 638 biopsy results were recorded. The average age was 73.2 years and median number of BCG treatments was four (induction followed by three maintenance courses). Median follow up was 38 months. 94 patients (34.4%) had recurrence following BCG therapy. Of those 33 patients (12.1%) had progression to muscle invasive disease. The number of cytology samples per patient after BCG therapy ranged from 1-23 (median 7), with several patients having repeated, potentially unnecessary negative urine cytology. Overall accuracy of cytology (n = 526) was sensitivity 44.2%, specificity 84.7%, PPV 38.9%, NPV 87.3%. Patients that had an erythematous bladder or red patch at flexible cystoscopy underwent subgroup analysis; this gave a very high NPV of 95.9%, with additional sensitivity being 65.5%, specificity 85.9% and PPV 33.3%. Number of positive cytology results (Chi2 = 44.30, P = 0.002), any positive cytology (Chi2 = 27.94, P < 0.001) and positive cytology after induction BCG therapy (Chi2 = 30.381, P < 0.001) were all strongly associated with recurrence. Conclusions: Positive urine cytology in patients undergoing intravesical BCG therapy predicts increased risk of recurrence and has good specificity. We would recommend using voided urine cytology in patients who have an erythematous bladder or red patch at flexible cystoscopy. If the cytology is positive then proceed to biopsy, however, if it is negative continue with surveillance. [Table: see text]