Cytology-positive Patients Research Articles

OGC SO20 - Audit of the guidelines for staging laparoscopy in gastro-oesophageal cancers

Abstract Background Staging laparoscopy and peritoneal washings form part of surgical work up of oesopheageal and gastric cancers. Peritoneal washings help to identify microscopic disease, the presence of which drastically alters prognosis. This audit looks at the adherence to staging laparoscopy guidelines introduced, and the intraoperative finding. Method Staging laparoscopy and peritoneal washings form part of surgical work up of oesophageal and gastric cancers. Peritoneal washings help to identify microscopic disease, the presence of which drastically alters prognosis. This audit looks at the adherence to staging laparoscopy guidelines introduced, and the intraoperative finding. Results Two hundred and twenty-seven patients were identified. Two patients did not have washings performed due to the extent of their disease, which was appropriate. The remaining patients had washings performed. Twelve patients had washings performed but not in line with policy. In all cases a clinical reason was found. Overall twelve patients had positive cytology from the washings. Of those that had washings, forty-one patient’s had T1/T2 disease and one hundred and eight-four patients had T3/T4 disease. All cytology positive patients had T3/T4 stage disease. Conclusion Two hundred and twenty-seven patients were identified. Two patients did not have washings performed due to the extent of their disease, which was appropriate. The remaining patients had washings performed. Twelve patients had washings performed but not in line with policy. In all cases a clinical reason was found. Overall twelve patients had positive cytology from the washings. Of those that had washings, forty-one patient’s had T1/T2 disease and one hundred and eight-four patients had T3/T4 disease. All cytology positive patients had T3/T4 stage disease

Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives.

Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects. The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase survival rates in these patients. Despite these advancements, debates persist regarding the magnitude of survival improvement attributed to this treatment modality. The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis, and it took a comparative analysis of patients exhibiting positive and negative cytological findings. To compare the impact of HIPEC on survival in gastric cancer patients with peritoneal metastasis and positive or negative cytology. Between April 2013 and March 2020, 84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts: HIPEC (20 patients with peritoneal metastasis), cytology-positive (23 patients without peritoneal nodules but with positive wash cytology), and cytology-negative (41 patients with advanced gastric cancer, no peritoneal nodules, and negative wash cytology). The HIPEC cohort underwent gastrectomy with HIPEC, while the cytology-positive and cytology-negative groups received gastrectomy alone. The demographic, pathological, and survival data of the groups were compared. The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss. Nevertheless, the complication rates were consistent across all three groups. Median survival in the HIPEC group was 20.00 ± 4.89 months, with 1-year, 2-year, and 3-year overall survival rates of 73.90%, 28.70%, and 9.60%, respectively. These figures paralleled the survival rates of the cytology-positive group (52.20% at 1 year, 28.50% at 2 years, and 19.00% at 3 years). Notably, 47% of patients experienced peritoneal recurrence. HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis, mirroring the outcomes in cytology-positive patients. However, peritoneal recurrence remained high.

Prognostic impact of clinical and radiological factors on leptomeningeal metastasis from solid cancers.

The number of leptomeningeal metastasis (LM) patients has increased in recent years, as the cancer survival rates increased. An optimal prediction of prognosis is essential for selecting an appropriate treatment. The European Association of Neuro-Oncology-European Society for Medical Oncology (EANO-ESMO) guidelines for LM proposed a classification based on the cerebrospinal fluid cytological findings and contrast-enhanced magnetic resonance imaging (MRI) pattern. However, few studies have validated the utility of this classification. This study aimed to investigate the prognostic factors of LM, including the radiological and cytological types. We retrospectively analyzed the data of 240 adult patients with suspected LM who had undergone lumbar puncture between April 2014 and September 2021. The most common primary cancer types were non-small-cell lung cancer (NSCLC) (143 (60%)) and breast cancer (27 (11%)). Positive cytology results and the presence of leptomeningeal lesions on contrast-enhanced MRI correlated with decreased survival in all patients. Nodular lesions detected on contrast-enhanced magnetic resonance were a poor prognostic factor in cytology-negative patients, while contrast-enhanced patterns had no prognostic significance in cytology-positive patients. Systemic therapy using cytotoxic agents and molecular-targeted therapy after LM diagnosis correlated with prolonged survival, regardless of the cytology results. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment and systemic chemotherapy after LM improved the survival of EGFR-mutated and wild-type NSCLC patients with positive cytology results. This study validated the efficacy of prognostication according to the EANO-ESMO guidelines for LM. Systemic therapy after LM diagnosis improves the survival of NSCLC patients.

The Role of Lymphovascular Space Invasion and Cytology in the Prognosis of Endometrial Cancer.

Lymphovascular space invasion (LVSI) and cytology are both independent and strong prognostic factors in endometrial cancer. This study aims to highlight the impact of LVSI and cytology positivity on prognosis, in addition to molecular classification. A retrospective review was conducted on the records of 223 patients with endometrial cancer diagnosed between January 2011 and January 2021. The inclusion criteria stipulated that the patients were diagnosed with endometrial cancer by endometrial biopsy and were operated in the clinic. The exclusion criteria included sarcoma in the postoperative pathology report results or synchronous tumor. Staging was performed according to the Fédération internationale de gynécologie et d'obstétrique (FIGO) 2009 criteria. Cytology (using 50 cc saline) was obtained upon entry into the peritoneal cavity. In 20 patients, saline was not used due to the presence of ascites in the abdomen. The Kaplan-Meier method was employed to evaluate overall survival and progression-free survival. Survival rates were compared in terms of cytology and LVSI. After analyzing the postoperative pathology results, it was found that the mean tumor size was 4.03 ± 2.3 cm. The most common histological type was endometrioid carcinoma, with stage IA being the most common stage. Out of 223 patients with endometrial cancer, the overall survival rate was 82.4%, and the progression-free survival rate was 88.3%. For patients negative for LVSI, the progression-free survival rate was 93%, while for LVSI-positive patients, it was 77.3% (p < 0.001). Additionally, the progression-free survival rate for patients negative for cytology was 90.4%, whereas for cytology-positive patients, it was 77.1% (p < 0.05). In our study, we observed that LVSI positivity and cytology positivity also reduced the overall survival rate. We aimed to highlight that, in addition to molecular classification, cytology positivity and LVSI positivity are still highly significant and independent factors in prognosis.

Gastric Cancer Surgery During the Pandemic: What It Costs?

BackgroundFrom the early days of 2020, the COVID-19 pandemic continues to change whole life all around the world. Oncological patients are the most affected populations since these days. Because of decreasing numbers in surgery and endoscopy, gastric cancer patients had difficulties in treatment and diagnoses. Therefore, the early and long-term results may be affected during the pandemic. In this study, we aimed to evaluate pandemia effects on gastric cancer surgery in a single center.Patients-MethodsPatients were categorized as the COVID group and the Pre-COVID group. Patients who received neoadjuvant chemotherapy were excluded from the study. In the COVID period, 50 patients underwent gastric cancer surgery, while 64 were operated on in the pre-COVID period. Patients’ demographics and clinical and pathological outcomes were evaluated.ResultsThere was no statistically significant difference in both periods among patient characteristics such as age, gender, and body mass index. Pre-operative laboratory results were similar between two groups. Although there was no difference in operation types, an increase was detected in Clavien-Dindo grade 3 and higher complications during the COVID period. During the pandemic, there was a significant difference in the pathological outcomes. Peritoneal cytology-positive patients were hıgher in the COVID group. More lymphovascular invasions were also detected in the COVID period. Finally, it resulted stage differences between two groups.ConclusionBecause of COVID-19’s heavy burden on healthcare system, delays in the diagnosis and treatment of oncological patients may occur. Therefore, this may be affected pathological and survival outcomes of cancer patients. Finally, further investigations are needed.

Comprehensive RNA analysis of CSF reveals a role for CEACAM6 in lung cancer leptomeningeal metastases

Non-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture (n = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM (n = 14) to non-tumor controls (n = 7). The NSCLC-associated gene, CEACAM6, underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6, MUC1) was present in NSCLC LM patients’ CSF, but not in controls (CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

Effect of Intraoperative Imprint Cytology Followed by Frozen Section on Margin Assessment in Breast-Conserving Surgery.

Intraoperative margin assessment can reduce positive margins in patients undergoing breast-conserving surgery. However, reports on intraoperative margin assessment have described only the use of either imprint cytology or frozen section. This study was designed to elucidate the effect of intraoperative margin assessment using imprint cytology followed by frozen section. Overall, 522 patients were enrolled. First, the entire surgical margin was subjected to imprint cytology. Frozen section was performed only in cases with "positive" or "suspicious" imprint cytology results. An additional intraoperative excision was performed in patients with frozen section-positive lesion sites. All margins were evaluated using postoperative permanent sections after excision. Among 522 patients, 136 (26.1%) were imprint cytology-positive, and 386 (73.9%) were imprint cytology-negative. Among the 386 imprint cytology-negative patients not subjected to frozen section, 11 (2.1%) were permanent sections-positive (imprint cytology-false-negative). In 47 of the 136 imprint cytology-positive patients, additional intraoperative excision was unnecessary due to the frozen section-negative diagnosis. Moreover, these patients could avoid reoperation, because they were permanent section-negative. The false-positive rate of imprint cytology alone was 13.4%, but adding frozen section to imprint cytology decreased the overall false-positive rate to 2.5%. After undergoing excision, four patients still had positive margins. The overall positive margin rate in the final pathology based on permanent sections was 2.9% (15/522). Imprint cytology followed by frozen section led to a markedly decreased positive margin rate. This is considered the best method for intraoperative margin assessment, as it can overcome the limitations of cytology and histology performed individually.

Human Trial of a Genetically Modified Herpes Simplex Virus for Rapid Detection of Positive Peritoneal Cytology in the Staging of Pancreatic Cancer

IntroductionPatients with peritoneal dissemination of pancreatic adenocarcinoma do not benefit from surgical resection, but radiologic and cytologic detection of peritoneal cancer lack sensitivity. This trial sought to determine if an oncolytic virus may be used as a diagnostic agent to detect peritoneal cancer. MethodsPeritoneal washings from patients with pancreatic adenocarcinoma were incubated with the enhanced green fluorescent protein (eGFP)-expressing oncolytic herpes simplex virus (HSV) NV1066. eGFP-positive or negative status was recorded for each specimen and compared to results obtained by conventional cytologic evaluation. These results were correlated with recurrence and survival for patients who underwent R0 resection. ResultsOf 82 patients entered in this trial, 12 (15%) had positive cytology and 50 (61%) had virally-mediated eGFP positive cells in peritoneal washings. All cytology-positive patients were also eGFP positive. HSV-mediated fluorescence detection had sensitivities of 94% and 100% for detection of any and peritoneal metastatic disease; respectively. Median recurrence free and disease specific survival were 6.5 and 18.3months for eGFP positive patients, versus 12.2 and 36.2months for eGFP negative patients (P=0.01 and 0.19); respectively. ConclusionsA genetically modified HSV can be used as a highly sensitive diagnostic agent for detection of micro-metastatic disease in patients with pancreatic adenocarcinoma and may improve patient selection for surgery.

Abstract 3412: Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells: a preliminary clinical study as a potential clinical biomarker

Abstract Objectives: In patients with gastric cancer, peritoneal dissemination is the most common metastasis. To predict future peritoneal recurrences, peritoneal lavage cytology is performed during operation. But even cytology-negative patients sometimes develop peritoneal recurrences. Thus an additional method to detect intraperitoneal free gastric cancer cells is necessary. We have developed a genetically engineered adenovirus, TelomeScan, which replicates and expresses GFP only in telomerase-activated cancer cells. Here we detected intraperitoneal free gastric cancer cells using TelomeScan, and investigated the correlation between the number of GFP-positive cells and patient prognosis. Methods: Peritoneal wash was obtained from 69 gastric cancer patients during operation. The cells in the wash were infected with TelomeScan for 24 hours. Finally, GFP-positive cells were counted under a fluorescence microscope. In some GFP-positive cases immunofluorescence assay was added. Clinicopathological data were obtained from medical records. Then we examined different cut-off values (the number of GFP-positive cells which indicates TelomeScan-positive) and estimated survival curves using the Kaplan-Meier method, and compared using the Wilcoxon test. Results: For a cut-off value of 10, 25 of the 69 cases were TelomeScan-positive (10 or more GFP-positive cells). And these 25 cases showed the most significant worse prognosis when compared to the 44 TelomeScan-negative cases (p = 0.0040). In addition, 17 of the 69 cases were conventional cytology-positive. Of these 17 cases, 9 were TelomeScan-positive, and these 9 cases showed significantly worse prognosis than the 8 TelomeScan-negative conventional cytology-positive cases (p = 0.0017, MST 195 days). Under fluorescence microscope we observed that GFP-positive cells sometimes formed cell clusters with GFP-negative cells. Immunofluorescence assay showed that these GFP-negative cells expressed CD45, which means these cells were leukocytes. Conclusion: We have successfully detected cancer cells in peritoneal wash using TelomeScan. The presence of GFP-positive cells in peritoneal wash was associated with worse prognosis. TelomeScan-positive patients, especially in conventional cytology-positive cases, showed remarkably worse prognosis than TelomeScan-negative conventional cytology-positive patients. Our data suggest that TelomeScan-guided cytological detection may have clinical implications as a prognostic biomarker in gastric cancer. Citation Format: Megumi Watanabe, Shunsuke Kagawa, Kazuya Kuwata, Michihiro Ishida, Yuuri Hashimoto, Naoto Hori, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara. Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells: a preliminary clinical study as a potential clinical biomarker. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2015-3412

Preoperative assessment of the axilla by surgeon performed ultrasound and cytology in patients with breast cancer.

BackgroundPreoperative evaluation of the axilla, an important prognostic determinant for patients with invasive breast cancer, is achieved by non- or minimally invasive methods to avoid the potential hazards of operative intervention. The aim of this study was to determine statistical power of axillary ultrasound (US) and US-guided fine needle aspiration cytology (FNAC) for evaluating axillary status.MethodsAxillary lymph nodes were imaged for malignant involvement by high resolution US in 93 breast cancer patients with clinically negative axilla. Cytological samples were obtained by US-guided FNAC from image-suspicious lymph nodes. Cytology-positive patients directly underwent axillary lymph node dissection (ALND). Patients with US and/or cytology-negative axilla underwent sentinel lymph node biopsy (SLNB). Using statistical analysis, US findings and US combined with FNAC were compared with SLNB and final pathology to measure performance.ResultsUS was suspicious for metastasis in 38 patients (41%), of whom 16 (42%) were cytology-positive. Axilla was positive in 36/93 patients (38.7%). Sixteen patients with positive FNAC directly underwent ALND. SLNB and/or final pathology was positive in 13/55 patients (23.7%) with negative US (false negative of US) and in 7/22 patients (31.8%) with positive US but negative cytology (false negative of FNAC). SLNB and/or final pathology was negative in 15/38 patients (39.5%) with positive US (false positive of US). Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of US alone were 63.8%, 73.6%, 69.8%, 60.5% and 76.3%, respectively, and 69.6%,100%, 81.6%, 100% and 68.1%, respectively, for US combined with FNAC.ConclusionStatistical measures of the US alone did not achieve a satisfactory value for excluding operative biopsy. US-negative and US-positive but cytology-negative cases still require SLNB for accurate evaluation of axillary status. On the other hand, US-guided positive cytology can obviate SLNB proceeding directly to ALND and avoiding frozen section of sentinel node(s).

Diagnostic accuracy and effectiveness of the Xpert MTB/RIF assay for the diagnosis of HIV-associated lymph node tuberculosis

Xpert MTB/RIF (Xpert) is recommended for human immunodeficiency virus (HIV)-associated pulmonary tuberculosis but not extrapulmonary tuberculosis. We assessed the performance of Xpert for HIV-associated lymph node tuberculosis (LNTB), the most common type of extrapulmonary tuberculosis. Among HIV-infected adults suspected of LNTB presenting for fine needle aspirate (FNA) at a South African hospital, we assessed the diagnostic accuracy of Xpert using either FNA culture or a composite of microscopy, culture, and cytology as the reference standard, and evaluated the impact of different diagnostics on patient management. Among 344 adults with valid FNA culture and Xpert results, 84 (24 %) were positive on microscopy, 149 (43 %) on culture, 152 (53 %) on Xpert, and 181 (57 %) had a cytology result suggestive of tuberculosis. Using liquid culture as the reference standard, the specificity of a single Xpert was suboptimal (88.2 %) but the sensitivity was high [93.3 %, 95 % confidence interval (CI) 87.6-96.6] and increased with decreasing CD4 count (from 87.0 % for CD4 >250 to 98.6 % for CD4 <100 cells/mm(3)). Using a composite reference standard reduced the sensitivity to 79.2 % but increased the specificity to 98.6 %. All Xpert-positive patients initiated treatment within one day, compared to 70 % of culture-positive but Xpert-negative and 13 % of culture- and Xpert-negative but cytology-positive patients. Xpert is accurate and effective and could be endorsed as the initial diagnostic for HIV-associated LNTB.

Comparison of Lymphedema in Patients With Axillary Lymph Node Dissections to Those With Sentinel Lymph Node Biopsy Followed by Immediate and Delayed ALND

The purpose of the study was to show that delayed axillary lymph node dissection (ALND) has higher rates of lymphedema compared with immediate ALND, using data from NSABP-B32 at Beaumont Hospital. NSABP B-32 at Beaumont had 207 patients with follow-up data on 199 patients, randomizing clinically negative axilla to sentinel lymph node biopsy (SLNB)+ALND (GrA N=98), and SLNB+cytology±ALND (GrB N=101). All patients had preoperative volumetric arm measurements and only node negatives had routine postoperative measurements assessing lymphedema for 36 months. We contacted node-positive patients for postoperative measurements for this study. Twenty-four and 15 cytology-positive patients had SLNB+ALND in GrA and GrB, respectively (SubGrA1 N=24; SubGrB1 N=15). Fourteen hematoxylin and eosin-positive patients had delayed ALND (SubGrB2a N=14). Lymphedema rate for node-positive SLNB+ALND was 10.3% [SubGrA1 (3/24)+SubGrB1 (1/15)=4/39] and node-negative SLNB+ALND was 6.8% (SubGrA2=5/74). Lymphedema was 14.3% for delayed ALND in SubGrB2a (2 of 14) and 0% for 72 SLNBs in SubGrB2b. Our study comparing immediate and delayed ALND lymphedema was not statistically significant (10.3% vs. 14.3%, P=0.65). Comparing node-negative ALND (SubGrA2= 5/74=6.8%) to node-positive ALND (A1+B1+B2a=6/53=11.3%) was not statistically significant (P=0.52). Comparing lymphedema for node-negative ALND (SubGrA2) to SLNB (SubGrB2b) only approached significance (6.8% vs. 0%, P=0.058). The rate of lymphedema was higher in delayed ALND but not statistically significant. Comparison, however, is difficult, given the limited sample size. We urge the other centers of NSABP-B32 to validate this, by contacting the node-positive patients for measurements. The lymphedema rate for SLNB alone was 0% and approached statistical significance when compared with node-negative ALND.

A cyto-epidemiological study on married women in reproductive age group (15-49 years) regarding reproductive tract infection in a rural community of West Bengal

Reproductive tract infection (RTI) represents a major public health problem in India. Women are either not aware of the symptoms of RTI or refuse to seek health care due to economic and time constrains unless suffering from alarming symptoms. To find out the prevalence of women with suggestive symptoms of RTI; to identify clinical and cytological abnormalities among the symptomatic women and to find out association between socio-demographic profile and risk factors with RTI symptomatic and cytology positive patients. A total of 385 married women in reproductive age group residing in Baligori sub-center area in Tarakeswar block of Hooghly district, West Bengal, India, were screened for symptom suggestive of RTI; symptomatic women went through gynecological examination and cancer cervix screening by Pap smear. Analysis of results was done by Odds ratio and multivariate logistic regression. Overall, 23.6% of the study population had symptoms suggestive of RTI. Most of them (68.1%) had abnormal vaginal discharge. Among the symptomatic women, cytology proved that 24.4% were suffering from acute cervicitis, 4.7% from A Squamous Cell of Undetermined Significance (ASCUS) and 2.3% from Low Grade Intra epithelial Lesion (LSIL) Squamous. Statistically significant association was observed for age, number of children, contact history of husband, pond bathing, menstrual hygiene, intra uterine device insertion, non-usage of barrier method, and history of abortion among women symptomatic for RTI and asymptomatic women. Prevalence of suggestive symptoms of RTI in women was found to be high (23.6%), and among them 7% had cervical dysplasia. Therefore, enhancing awareness and organizing screening camps are absolute necessity and must be held at frequent intervals to curb the menace due to cervical cancer.

Pre-Operative Axillary Nodal Staging by Ultrasonography and Fine-Needle Cytology Reduces the Number of Unnecessary Sentinel Node Biopsies in Breast Cancer Patients.

Abstract Aims: The role of pre-operative axillary ultrasound for nodal staging in early breast cancer patients is evolving. In this study, we evaluated the role of axillary ultrasound (AUS) and fine-needle aspiration cytology (FNAC) to stage the axilla pre-operatively in a large series of operable breast cancer patients including its role in the detection of nodal micrometastases. A second objective was to ascertain whether a significant learning curve is associated with this technique.Methods: Between October 2006 and March 2009, all patients diagnosed with invasive breast cancer in our unit had an AUS pre-operatively. Patients with suspicious nodes on ultrasound underwent FNAC. Cytology positive patients proceeded directly to axillary clearance, while others underwent sentinel lymph node biopsy. Data from this retrospective study was analyzed using appropriate statistical techniques to evaluate the efficacy of this technique to detect nodal metastases pre-operatively.Results: 495 patients scheduled to undergo surgery for invasive breast cancer were included in this study. 7 patients had bilateral malignancies and, therefore, a total of 502 axillae were examined using ultrasound. The median age of patients in our study was 61 years (range 32-91). 137 patients (27.3%) had proven nodal metastases on final histology. 39 of 137 (28.5%) node positive patients were accurately identified by pre-operative AUS and FNAC and, therefore, spared an unnecessary sentinel node biopsy. The combined technique of AUS and FNAC had an overall accuracy of 80.5% (95% CI: 76.8-83.7), sensitivity of 28.5% (95% CI: 21.6-36.5), specificity of 100% (95% CI: 99-100), positive predictive value of 100% (95% CI: 91-100), and negative predictive value of 78.8% (95% CI: 74.9-82.3). Pre-operative AUS and FNAC was normal in all patients with nodal micrometastases (n=15) and isolated tumour cells (n=11) on histopathology. No significant learning curve was demonstrated for this technique in our study. Overall, 28.5% of node positive patients and 7.9% of all breast cancer patients avoided an unnecessary sentinel node biopsy due to this procedure.Conclusions: Pre-operative AUS and FNAC is an inexpensive, minimally-invasive outpatient procedure with an accuracy of more than 80% that can avoid unnecessary sentinel lymph node biopsy in 28.7% of node positive patients. It has no role in the detection of nodal micrometastases and there is no demonstrable learning curve seen with this technique. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1018.

Towards rational axillary treatment in relation to neoadjuvant therapy in breast cancer

Aims The purpose of this study is to analyse nodal staging and axillary response in breast cancer patients treated with neoadjuvant chemotherapy (NAC) to explore venues to safely spare patients axillary clearance whenever it could be avoided. Methods In 327 patients we determined the nodal status before NAC by ultrasound-guided cytology and if indicated by sentinel node biopsy (SNB). In patients with proven metastasis we analysed the axillary response after NAC. Results Before NAC, the ultrasound-guided cytology was positive in 252 patients. In the remaining 75 patients SNB was performed prior to NAC. The SNB was negative in 53 patients, thus in these patients axillary clearance could be avoided. All 274 patients with proven axillary metastases at diagnosis underwent axillary clearance after NAC. Twenty percent of the cytology-positive patients (50/252) had an axillary pathological complete remission (pCR) and 68% of the SNB-positive patients (15/22) had no lymph node (LN) metastasis after NAC. Subgroups with a high axillary pCR rate were patients with triple-negative tumours (57%) and human epidermal growth-factor receptor 2 (HER2)-positive tumours (68%) who had a pCR of the primary tumour. Conclusions Twenty percent of the patients with proven metastasis by cytology prior to NAC have an axillary pCR. The axillary pCR rate is very high in certain subgroups. Identification of these patients, could result in more axilla-conserving therapies.

VATS pericardiotomy for patients with known malignancy and pericardial effusion: Survival and prognosis of positive cytology and metastatic involvement of the pericardium: A case control study

Background Pericardiotomy for cancer patients with effusion can alleviate symptoms, but with unclear effect on long term survival. Our experience with VATS technique has produced some long-term survivors. Methods A retrospective review of 62 VATS pericardiotomy for pericardial effusion in patients with known malignancy. Kaplan–Meier survival curves and Log-Rank tests were used for analysis. Results The mean age was 54.8 ± 14.3 years (ranging from 19 to 79). The mean hospital stay was 8.7 ± 5.5 days. The median survival was 6.75 months (range 1 month–10 years). Overall one-year survival was 44.2%, 3-year survival 17.6%, and 5-year survival 10% after drainage of pericardial effusion. The mean survival in cytology negative patients ( n = 21) was 13.4 ± 0.98 months, compared to 4.89 ± 0.9 months in cytology positive patients ( n = 27) ( p = 0.0175). The 5-year survival in cytology negative patients was 19.6%, while none of the patients with positive cytology were alive after 36 months. The mean survival in patients with no evidence of metastatic disease on the pericardium ( n = 28) was 12.8 ± 0.9 months, compared to patients with metastatic disease of the pericardium ( n = 22) 4.66 ± 0.8 months ( p = 0.026). Conclusions VATS Pericardiotomy can provide effective long-term drainage in patients with symptomatic pericardial effusion. Positive cytology and metastatic involvement of the pericardium are predictive of worse survival. Survival greater than 5 years can be expected in 19% and 17% of patients with negative fluid cytology and negative metastatic disease of the pericardium, respectively.

Postoperative cytology for drained fluid from the pancreatic bed after "curative" resection of pancreatic cancers: does it predict both the patient's prognosis and the site of cancer recurrence?

To evaluate the postoperative cytology of drained fluid from the pancreatic bed as a predictive indicator of local recurrence after curative (R0) resection of pancreatic cancer. The pancreatic bed offers a common site of cancer recurrence (local recurrence), even after curative (R0) resection is performed for pancreatic cancer. If local recurrence is thereby predicted precisely, soon after surgery, we have a chance to treat it by adding radiation or some other locoregional therapy before it can grow or spread beyond the pancreatic bed. However, there have been no previous reports of cytology performed on the drained fluid after pancreatectomy. This study includes 94 patients who had shown negative results in the peritoneal washing cytology before resection and subsequently received pancreatectomies for pancreatic tumors. They consisted of 12 benign tumors, 17 noninvasive or minimally invasive carcinomas and 65 invasive ductal carcinomas (R0 = 58; R1/2 = 7). Postoperatively, the drained fluid from the pancreatic bed was collected for 24 hours and used for cytologic examination. The cytologic results were examined in association with the histopathology of the resected tumor, patient's survival, and mode of cancer recurrence, including local recurrence. Patients with benign tumors or noninvasive/minimally invasive carcinomas had negative result in cytology, and none of them have died of local recurrence (limited to the pancreatic bed) to date. However, patients with invasive ductal carcinoma revealed higher cytology-positive rates: 28% (16/58) in curative (R0) resection; and 71% (5/7) in noncurative (R1/2) resection. Among 58 patients with R0 resection, the 3-year survival rate was 14% in 16 cytology-positive patients and 55% in 42 cytology-negative patients (P < 0.05). The 3-year cumulative rate of local recurrence was 85% and 23%, respectively (P < 0.05). Compared with other histopathologic parameters obtained from the resected specimens, the drain cytology was more specific in predicting the subsequent development of local recurrence. Drain-cytology was a quick examination that enabled us to specifically indicate both minute residual cancer and subsequent development of local recurrence even after R0 resection of pancreatic cancer.

Peritoneal lavage cytology findings as prognostic factor for gastric cancer.

The validity of lavage cytology for accurate gastric cancer staging is demonstrated in this study. Between 1988 and 1996, 29 cases (8. 4%) were revealed as positive among 347 patients with resectable gastric cancer in whom peritoneal lavage cytology was performed. The survival rate of cytology-positive patients in each stage was found to be worse than that of all other patients in the same stage. The prognostic factors selected by the univariate analysis were enrolled for multivariate analysis using Cox's proportional hazards model with the backward stepwise procedure. As a result, although cytology finding was selected as an independent prognostic factor, macroscopic finding of dissemination was not selected. Our data indicate that positive cytology findings indicated a poor prognosis, and therefore the results of peritoneal lavage cytology should be included as a factor in gastric cancer staging.

Importance of positive peritoneal lavage cytology findings in the stage grouping of gastric cancer.

Although peritoneal lavage cytology is widely performed during surgery for gastric cancer and the results have been reported to be one of the accurate prognostic factors, the cancer stage is determined independent of the results of lavage cytology according to the First English Edition of Japanese Classification of Gastric Carcinoma. In this study we demonstrated the validity of lavage cytology for accurately staging gastric cancer. Between 1988 and 1996, peritoneal lavage cytology was performed in 347 patients with resectable gastric cancer. Among them, cytology was positive in 29 cases (8.4%). The survival rate of the cytology-positive patients in each stage was worse than that of all patients in the same stage. The prognosis of patients with positive cytology findings and serosa-exposed gastric cancer was significantly worse than that of negative cytology findings and serosa-exposed gastric cancer, and similar to that of negative cytology findings and serosa-infiltrating gastric cancer. Our data indicated that positive cytology findings thus indicated a poor prognosis, and the prognostic difference between positive and negative cytology findings was approximately a one-stage difference in the Japanese stage grouping. Based on our findings, the results of peritoneal lavage cytology should thus be included in the factors for staging gastric cancer.

Relationship between cytomegalovirus cells and survival in acquired immunodeficiency syndrome patients.

To determine whether cytopathic changes due to cytomegalovirus (CMV) in human immunodeficiency virus-infected patients are prognostic. Three-month mortality was compared in three groups: 36 patients with positive CMV cytology, 38 with negative cytology but culture positive, and 40 with no evidence of CMV. Bronchoalveolar lavage, Papanicolaou-stained cytocentrifuge smears were quantitated using an average of two slides per case. Additionally, coinfection with Pneumocystis carinii and Cryptococcus neoformans was evaluated. There was a statistically significant increase in mortality at three months in CMV cytology-positive patients versus those with no evidence of CMV. Ten patients had quantitative CMV counts of less than 2, with a median survival of 3.0 months (range, 0.3-13.0); seven patients had counts of 2 or 3, with a median survival of 5.5 months (0.4-13.5); and 11 patients had CMV counts greater than 3, with a median survival of 7.2 months (0.3-14.0). There was no significant difference between the groups. Coinfection was P Carinii (12) or C neoformans (2) showed no difference from patients without coinfection (chi2 = 0.81). The presence of CMV cytopathic changes is associated with poorer survival, but an increased number of CMV-infected cells is not related to higher mortality.