[PERSONALIZED MEDICINE IN ONCOLOGY REQUIRES TEAMWORK BETWEEN MEDICAL ONCOLOGISTS AND MOLECULAR PATHOLOGISTS].

INTRODUCTION: The systemic anti-cancer approach is based on medical/pharmaceutical interventions affecting cancer cells at multiple sites, including local and distant regions. Interventions include: cytotoxic chemotherapy agents used for direct extermination of proliferating cells, hormonal interventions altering the tumor environment and affecting its ability to survive and thrive, biological drugs restoring the function defective proteins in mutated tumors, and immunological medications encouraging effective immune recognition of tumor cells and associated immune response. "Personalized medicine in oncology" aims to make anti-cancer treatment more effective and with less side effects. Potential candidates are identified both clinically per indication for therapy and ability to tolerate it, and pathologically-molecularly assessing unique biological changes in the tumor cells and/or their immediate environment. Safe and effective treatment directed to the dominant biological changes is essential as well. The biological changes in the tumor and/or its immediate environment are referred to as "bio-markers", and point to pathological changes accumulated in the tissue during the malignant transformation and tumor progression. The relevant tests for biomarker assessment are performed at the protein level or on genetic material (DNA or RNA); they require high levels of accuracy and reliability and short turnover time for results. Communication between teams assessing the molecular results and a general pathologist may facilitate high quality assessment. Laboratory tests with accurate assessment of biomarkers in over 500 genes are available in the pathology laboratories in Israel since 2020.

Re-Examining Distal Resection in Colon Cancer.

BACKGROUND: In colon cancer, data regarding proximal and distal metastasis to lymph nodes remains scarce. OBJECTIVES: To evaluate lymph node distribution along the longitudinal axis of the colon as related to a tumor to re-examine the common practice of 5 cm proximal and 2 cm distal resection margins. METHODS: We studied 106 patients (53 males and 53 females, mean age 67.9 ± 10 years) who had undergone left hemicolectomy or sigmoidectomy. Colonic cancer specimens were divided into five zones proximally and distally to the tumor. For each zone, overall lymph node evaluation and ratio was performed. RESULTS: The mean number of retrieved lymph nodes per patient was 24.3 ± 12, with 54.9% of the nodes concentrated in zone I, 22.1% in zone II, 9.5% in zone III, 10.3% in zone IV, and 3% in zone V. While most positive nodes were found in zone I, significant numbers were also detected in both directions proximally and distally to the tumor. CONCLUSIONS: It seems that longer colonic segments proximally, and especially distally, should be considered for resection to significantly reduce the chances of finding involved lymph node.

An intraoperative MRI system for margin assessment in breast conserving surgery: Initial results from a novel technique.

BACKGROUND AND OBJECTIVES: One of the major unmet needs in Breast Conserving Surgery (BCS) is a rapid and accurate margin assessment of the lumpectomy specimen. This study evaluates the ability of a novel MRI system (prototype of the ClearSight™ system; Clear-Cut Medical Ltd., Rehovot, Israel) to distinguish malignant and non-malignant tissues in freshly excised breast specimen by comparing MR measurements to histopathology results. METHODS: Seventy-seven samples were obtained from 22 patients undergoing BCS enrolled in the study. A T2* (T2 Star) value in milliseconds (ms) was calculated for each sample and correlated with histopathology results. RESULTS: Of the 77 samples, 35 samples were classified by histopathology as malignant and 42 as non-malignant. T2* values were significantly higher in malignant samples compared to non-malignant samples (15.3 ± 2.72 ms and 10.6 ± 1.47 ms, respectively [P < 0.00001]). Analysis for a determined cutoff of 11.7 ms revealed 91% sensitivity, 93% specificity, and 92% accuracy. ROC curve analysis yielded AUC of 0.97. CONCLUSIONS: This study demonstrates that the system is sensitive and specific in differentiating malignant and non-malignant tissues in freshly excised breast specimen. The system has the potential to be used for breast specimen margin assessment during BCS, with the goal of decreasing the need for re-operation. J. Surg. Oncol. 2016;114:22-26. © 2016 Wiley Periodicals, Inc.

Mapping breast tissue types by miniature radio-frequency near-field spectroscopy sensor in ex-vivo freshly excised specimens.

BACKGROUND: Receiving real-time information on tissue properties while performing biopsy procedures has the potential of improving biopsy accuracy. The study goal was to test the ability of a miniature flexible Radio-Frequency (RF) sensor (Dune Medical Devices), designed to be mounted on the surface of surgical tools, in measuring and mapping the various breast tissue types and abnormalities in terms of electrical properties. METHODS: Between January and October 2012, 102 patients undergoing lumpectomy, open-biopsy or mastectomy, in 3 medical centers, were enrolled in this study. The device was applied to freshly excised specimens, with registration between device measurements and histology analysis. Based on histology, the dielectric properties of the various tissue types were derived. Additionally, the ability of the device to differentiate between malignant and non-malignant tissue was assessed. RESULTS: A total of 4322 measurements from 106 specimens from 102 patients were analyzed. The dielectric properties of 10 tissue types in the low RF-frequency range were measured, showing distinct differences between the various types. Based on the dielectric properties, a score variable was derived, which showed a correlation of 90 % between the RF measurements and the tissue types. Differentiation ability between tissue types was characterized using ROC curve analysis, with AUC of 0.96, and sensitivity and specificity of 90 and 91 % respectively, for tissue feature sizes at or above 0.8 mm. CONCLUSIONS: Using a radio-frequency near-field spectroscopy miniature flexible sensor the dielectric properties of multiple breast tissue types, both normal and abnormal, were evaluated. The results show promise in differentiating between various breast tissue types, and specifically for differentiation between cancer and normal tissues.

Prevalence and correlates of human papillomavirus genotypes among patients with cervical cancer and cervical intraepithelial neoplasia 3 in Israel.

OBJECTIVES: This study aimed to assess the prevalence of human papillomavirus (HPV) in Israeli patients with cervical cancer and cervical intraepithelial neoplasia 3 (CIN3), to describe the distribution of the virus genotypes among positive cases, to characterize patients positive to HPV and, in particular, patients positive to HPV-16 and/or -18, and to evaluate the possible contribution of implementing HPV vaccination in Israel. METHODS: Samples from 84 patients with cervical cancer and 886 patients with CIN3, archived at the Maccabi Institute of Pathology, were screened for HPV. DNA extraction was performed using DNeasy Blood and Tissue Kit/QIAGEN. HPV detection and typing were performed by multiplex polymerase chain reaction with primers E6/E7, using the f-HPV/Genomed kit. RESULTS: Of the samples from 84 patients with cervical cancer, 89.3% were positive for HPV. Among these positive samples, HPV-16 was found in 70.7% and HPV-18 was found in 9.3%. Of the samples from 886 patients with CIN3, 85.0% were positive for HPV. Among these positive samples, HPV-16 was found in 73.8% and HPV-18 was found in 1.1%. In the patients with CIN3, the prevalence of HPV genotypes 16 and/or 18 was higher among young women and decreased across age groups. In addition, age, being born in Israel, being born in Europe, and being born in the former Soviet Union were correlated with a low risk of being infected with genotypes 16 and/or 18. DISCUSSION: The prevalence of HPV-16 and -18 in patients with cervical cancer and CIN3 in Israel is high. It is expected that the implementation of routine vaccination against these types of HPV will significantly reduce the burden of these diseases in Israel.

Adenocarcinoma of the Gallbladder: Incidental Finding in Patients following Laparoscopic Sleeve Gastrectomy and Cholecystectomy.

BACKGROUND: Gallbladder (GB) cancer is rare. Most cases are incidentally found in specimens after a cholecystectomy. Cholelithiasis is almost always present when this diagnosis is made. Obesity is a known risk factor for gallstone formation and thus may be related to GB cancer. OBJECTIVES: To highlight the importance of evaluating the gallbladder before surgery, resecting the gallbladder whenever required, and screening the resected tissue for malignancy. METHODS: We retrospectively searched a prospectively maintained database of all bariatric procedures during the last 8 years for cases of concomitant laparoscopic sleeve gastrectomy (LSG) and laparoscopic cholecystectomy (LC). Pathologic reports of the gallbladders were reviewed. Demographic data and perioperative parameters were documented. RESULTS: Of 2708 patients reviewed, 1721 (63.55%) were females and 987 (36.45%) males. Excluded were 145 (5.35%) who had a previous cholecystectomy. Of the remaining 2563, 180 (7.02%) had symptomatic gallbladder disease and underwent LSG with LC. Of these, two females (BMI 53 kg/m2 and 47 kg/m2, both age 60) were found by histological examination to have adenocarcinoma in their GB specimens (1.11%). Both were reoperated, which included partial hepatectomy of the GB bed, resection of the cystic stump, lymph node dissection, and resection of the port sites. One patient is doing well, with no evidence of disease at a postoperative follow-up of 4 years. The second patient had recurrent disease with peritoneal spread and ascites 20 months post-surgery and died 18 months later. CONCLUSIONS: GB cancer is a rare finding in cholecystectomy specimens. The incidence of this entity might be higher in obese older females owing to the higher incidence of cholelithiasis in these patients.

D1 versus D2 Gastrectomy for Gastric Adenocarcinoma.

BACKGROUND: Despite the ongoing decrease in the incidence of gastric cancer, this disease is still a major cause of death. It is still debatable whether D2 lymphadenectomy improves survival and whether this procedure should be performed routinely or selectively. OBJECTIVES: To compare the pathological and short-term results following radical D2-type gastric resection and lymphadenectomy versus the more limited D1 type resection and lymphadenectomy. METHODS: We conducted a retrospective study on 4 years experience treating 164 patients suffering from gastric cancer. We compared the results between the group of patients who underwent a radical D2 type gastric resection and lymphadenectomy (n = 100) and those of a relatively small group of patients who intentionally underwent the more limited D1 type (n = 34). RESULTS: The overall number of harvested lymph nodes was 9 ± 4 in the D1 group compared to 30 ± 12 (range 16-69) in the D2 group (P = 0.001). Of the 100 patients undergoing a D2 lymphadenectomy, 57% had positive nodes compared to 38% of the 34 patients in the D1 group (P = 0.045). CONCLUSIONS: We showed statistically significant differences between D1 and D2 procedures in the overall number of harvested lymph nodes and the proportion of positive nodes to the overall number. Our results support the fact that D2 resection should be recommended as the standard approach of treatment for gastric cancer patients, ensuring a larger number of retrieved lymph nodes and a comparable rate of complications and mortality.

A novel porcine model for chemically inducible Crohn's-like reaction.

BACKGROUND: New animal models provide insights into the pathogenesis of different types of inflammatory bowel disease as well as novel pathways for new therapeutic options. However, the scarcity of large animal models hinders the research and development of new surgical procedures and technological devices in inflammatory bowel disease surgery. Common small animal inducible models involve chemical agents that result in the development of acute intestinal inflammation. OBJECTIVES: To assess a novel method for the induction of Crohn's-like colitis using intramural injection of sclerosants in a porcine model. METHODS: Seven domestic pigs underwent several experimental protocols to assess the efficacy of intramural colonic injections of two different compounds (lauromacrogol, and phenol in almond oil).Twenty-five different large bowel segments were treated with intramural injections of the compounds. The animals were followed for 6 weeks, and treated colonic segments were resected for histopathological examination. RESULTS: Intramural injection of lauromacrogol resulted in non-specific, mild reactive foreign body changes only. Injection of various dosages of 5% phenol in almond oil caused a range of histopathological changes varying from focal fibrosis to Crohn's-like reactions com rising acute and chronic infiltrates, mucosal ulceration and focal necrosis with enteric and lymphoid non-caseating granulomas. CONCLUSIONS: Intramural colonic phenol in almond oil injection in pigs induces inflammatory reactions that histologically resemble Crohn's disease in humans.

Morbidity and mortality after major pulmonary resections in patients with locally advanced stage IIIA non-small cell lung carcinoma who underwent induction therapy.

BACKGROUND: The optimal treatment for patients with locally advanced stage IIIA non-small cell lung carcinoma (NSCLC) remains controversial, but induction therapy is increasingly used. The aim of this study was to evaluate mortality, morbidity, hospital stay and frequency of postoperative complications in stage IIIA NSCLC patients that underwent major pulmonary resections after neoadjuvant chemotherapy or chemoradiation. METHODS: We conducted a retrospective analysis of all patients who underwent major pulmonary resections after induction therapy for locally advanced NSCLC from October 2009 to February 2014. Forty-one patients were included in the study. RESULTS: Complete resection was achieved in 40 patients (97.5%). A complete pathologic response was seen in 10 patients (24.4%). Mean hospital stay was 17.7 days (ranged 5-129 days). Early (in-hospital) mortality occurred in 2.4% (one patient after bilobectomy), late (six months) mortality in 4.9% (two patients after right pneumonectomy and bilobectomy), and overall morbidity in 58.5% (24 patients). Postoperative complications included: bronchopleural fistula (BPF) with empyema - three patients, empyema without BPF - five patients, air leak - eight patients, atrial fibrillation - eight patients, pneumonia - eight patients, and lobar atelectasis - four patients. CONCLUSION: Following neoadjuvant therapy for stage IIIA NSCLC, pneumonectomy can be performed with low early and late mortality (0% and 5.8%, respectively), bilobectomy is a high risk operation (16.7% early and 16.7% late mortality); and lobectomy a low risk operation (0% early and late mortality). The need for major pulmonary resections should not be a reason to exclude patients from a potentially curative procedure if it can be performed with acceptable morbidity and mortality rates at an experienced medical centre.

Platelet-derived growth factor BB mimics serum-induced dispersal of pancreatic epithelial cell clusters.

We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic ß-catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BB--and serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway.

Cervical Pap screening among Israeli women, 2005-2010.

PURPOSE: This study describes the distribution and the trends of cervical abnormalities in Israel, based on Pap smear results. METHODS: A retrospective analysis of cervical smears received by the Central Pathology Laboratory of Maccabi Healthcare Services between January 2005 and December 2010. RESULTS: In total, 711,541 Pap smears were screened in the study period. Cytological abnormalities were observed in 4.78% of the total smears screened. An increase was observed in the rate of positive results from 2.63% in 2005 to 6.78% in 2010 (p = 0.0026). The cervical abnormalities in the study period distributed as follows: atypical squamous cell (ASC)-2.72%, low-grade squamous intraepithelial lesion (LSIL)-1.54%, high-grade squamous intraepithelial lesion (HSIL)-0.34%, squamous cell carcinoma-0.01%, atypical glandular cells (AGC)-0.10%, adenocarcinoma in situ (AIS)-0.06% and invasive adenocarcinoma-0.01%. The increase was statistically significant for ASC (p = 0.0028), LSIL (p = 0.0069) and for HSIL (p = 0.0260). The mean ages at diagnosis of women with ASCUS, LSIL, HSIL, squamous cell carcinoma, AGC, AIS and adenocarcinoma were 37.8, 33.2, 38.6, 55.4, 41.1, 49.9 and 57.1 years, respectively. CONCLUSIONS: The increase in the rate of squamous cell abnormalities demonstrated in this study emphasizes the need of implementing an education and a screening program among Israeli women. HPV vaccine, sexual behavior, cytology performance and HPV test are primary and secondary prevention tools which may reduce morbidity and mortality in the future. In addition, based on the age at diagnosis of the different pathologies, the age group in which Pap test is performed in Israel should be expanded from 35-54 to 25-65 years.

Knock-down of plasminogen-activator inhibitor-1 enhances expression of E-cadherin and promotes epithelial differentiation of human pancreatic adenocarcinoma cells.

High levels of plasminogen activator inhibitor-1 (PAI-1), which is produced by stromal, endothelial, and cancer cells and has multiple complex effects on cancers, correlate with poor cancer prognosis. To more definitively study the role of endogenously produced PAI-1 in human pancreatic adenocarcinoma (PAC) PANC-1 cell line biology, we used anti-PAI-1 shRNA to create stable PAI-1 deficient cells (PD-PANC-1s). PD-PANC-1s exhibited a heterogeneous morphology. While the majority of cells exhibited a cuboidal shape similar to the parental PANC-1 or the vector-infected control cells, numerous large cells with long filopodia and a neuronal-like appearance were observed. Although both Vector-control cells and PD-PANC-1s expressed mRNAs that are characteristic of mesenchymal, neural, and epithelial phenotypes, epithelial marker RNAs were up-regulated (e.g., E-cadherin, 32-fold) whereas mesenchymal marker RNAs were down-regulated (e.g., Thy1, ninefold) in PD-PANC-1s, suggesting mesenchymal-to-epithelial transition. Neural markers exhibited both up- and down-regulation. Immunocytochemistry indicated that epithelial-like PD-PANC-1s expressed E-cadherin and ß-catenin in significantly more cells, while neural-like cells exhibited robust expression of organized ß-3-tubulin. PAI-1 and E-cadherin were rarely co-expressed in the same cells. Indeed, examination of PAI-1 and E-cadherin mRNAs expression in additional cell lines yielded clear inverse correlation. Indeed, infection of Colo357 PAC cells (that exhibit high expression of E-cadherin) with PAI-1-expressing adenovirus led to a marked decrease in E-cadherin expression and to enhanced migration of cells from clusters. Our results suggest that endogenous PAI-1 suppresses expression of E-cadherin and differentiation in PAC cells in vitro, supporting its negative impact on tumor prognosis.

Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients.

Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR and high resolution melting," we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.

Indication for relumpectomy--a useful scoring system in cases of invasive breast cancer.

BACKGROUND AND OBJECTIVES: In two-thirds of breast cancer patients undergoing reoperation no residual tumor will be found. A scoring system for selection of patients who might benefit from relumpectomy is proposed. METHODS: This study is based on 293 patients with invasive breast cancer undergoing reoperation due to margins of <2 mm. Eighteen parameters were evaluated by univariate and multivariate stepwise logistic regression. RESULTS: Univariate analysis identified nine parameters associated with a residual invasive tumor: surgical margins; lobular histological type; grade 3; multifocality; positive lymph modes; non-fine needle localization (FNL) versus FNL lumpectomy; vascular/lymphatic invasion; age <50 years; and tumor size ≥3 cm. Multivariate stepwise logistic regression study identified six out of nine parameters associated with a higher probability of finding a residual invasive tumor: margins <1 mm, multifocality, tumor size ≥3 cm, positive lymph nodes, age <50 years, and lumpectomy without previous FNL. Odds of these factors were used for scoring. CONCLUSIONS: For patients with surgical margins <2 mm and a score of <4, the probability of finding a residual invasive tumor is 0%, while the probability of finding a microfocus of <2 mm of invasive carcinoma is 3.2% and of finding residual DCIS is up to 10%.

Biplanar Lipoabdominoplasty: Introducing the Subscarpal Lipo Aponeurotic System.

Preservation of Scarpa's fascia in abdominoplasty has been previously presented. Herein we introduce the subscarpal lipo aponeurotic system (SLAS) and the technique of preserving the SLAS and its tightening in lipoabdominoplasty. METHODS: A retrospective cohort study of patients who underwent lipoabdominoplasty performed by a single plastic surgeon (YW) between 2014 and 2019 was conducted. We compared postoperative complications, aesthetic outcomes, and procedure lengths between standard and biplanar lipoabdominoplasty with SLAS tightening. Supra-scarpal fat and SLAS tissue specimens were obtained for histological analysis. RESULTS: In total, 179 patients underwent biplanar lipoabdominoplasty with SLAS tightening and were compared with a control group of 65 patients who underwent standard lipoabdominoplasty. Fifty-four patients (29.9%) underwent concomitant umbilical, epigastric, or postoperative ventral hernia (POVH) repair. No major complications were encountered other than one skin necrosis in a standard lipoabdominoplasty. Moderate complication rate was 10.05% in the biplanar group, compared with 16.92% in the standard lipoabdominoplasty. The average length of the procedure and overall aesthetic results were equivalent. CONCLUSIONS: The SLAS can be individually dissected and used during abdominoplasty. No statistically significant differences were found in complication rates, length of procedure, or aesthetic outcomes between standard and biplanar lipoabdominoplasty with SLAS tightening. Further investigation is needed. Nonetheless, we postulate that patients who would benefit the most from this procedure are those with weakening of the abdominal wall, and with some fullness of the hip line, as this technique adds reinforcement to the lower abdomen and "pulls in" the flanks.

Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies.

Breast cancer is the most common malignant disease worldwide, with over 2.26 million new cases in 2020. Its diagnosis is determined by a histological review of breast biopsy specimens, which can be labor-intensive, subjective, and error-prone. Artificial Intelligence (AI)-based tools can support cancer detection and classification in breast biopsies ensuring rapid, accurate, and objective diagnosis. We present here the development, external clinical validation, and deployment in routine use of an AI-based quality control solution for breast biopsy review. The underlying AI algorithm is trained to identify 51 different types of clinical and morphological features, and it achieves very high accuracy in a large, multi-site validation study. Specifically, the area under the receiver operating characteristic curves (AUC) for the detection of invasive carcinoma and of ductal carcinoma in situ (DCIS) are 0.99 (specificity and sensitivity of 93.57 and 95.51%, respectively) and 0.98 (specificity and sensitivity of 93.79 and 93.20% respectively), respectively. The AI algorithm differentiates well between subtypes of invasive and different grades of in situ carcinomas with an AUC of 0.97 for invasive ductal carcinoma (IDC) vs. invasive lobular carcinoma (ILC) and AUC of 0.92 for DCIS high grade vs. low grade/atypical ductal hyperplasia, respectively, as well as accurately identifies stromal tumor-infiltrating lymphocytes (TILs) with an AUC of 0.965. Deployment of this AI solution as a real-time quality control solution in clinical routine leads to the identification of cancers initially missed by the reviewing pathologist, demonstrating both clinical utility and accuracy in real-world clinical application.

Epithelioid hemangioendothelioma as a rare cause of blue toe syndrome.

Blue toe syndrome (BTS), is a well-known entity of toe gangrene and rest pain secondary to micro emboli lodged within the digital arteries. BTS among young patients should alert physicians to look for causes such as trauma, connective tissue disease, hypercoagulability state, and others. We hereby describe a 32-year-old female with right BTS. A mass obstructing 80% of the right popliteal artery lumen was the source of emboli. The histologic results of the replaced arterial segment revealed a thrombus on top of epithelioid hemangioendothelioma. This is the first description of the association between primary vascular tumor and BTS.

Comparative study of the pathological characteristics of gastric stump carcinoma and carcinoma of the upper third of the stomach.

BACKGROUND: Gastric stump cancer is often described as a tumor with a poor prognosis and low resectability rates. OBJECTIVES: To compare the pathological characteristics of gastric stump cancer patients with those of patients with proximal gastric cancer. METHODS: This retrospective study was based on the demographic and pathological data of patients diagnosed with gastric cancer and treated at Assaf Harofeh Medical Center during an 11 year period. The patients were divided into two groups: those undergoing proximal gastrectomy for proximal gastric cancer and those undergoing total gastrectomy for gastric stump cancer. RESULTS: Patients with gastric stump cancer were predominantly male, older (P = 0.202, not significant), and had a lower T stage with less signet-ring type histology, fewer harvested and fewer involved lymph nodes (P = 0.03, statistically significant) and less vascular/lymphatic involvement than patients with proximal gastric cancer. CONCLUSIONS: The lower incidence of involved lymph nodes and lymphovascular invasion in gastric stump cancer as compared to proximal gastric cancer in this study may imply that the prognosis of gastric stump cancer may be better than that of proximal gastric cancer. However, to verify this assumption a study comparing patient survival is required.

HPV Screening Test for the Detection of Precancerous Cervical Lesions and Cervical Cancer in Israeli Women.

OBJECTIVES: This work is aimed to summarize the first year of the high-risk human papillomavirus (hrHPV) screening test and compare it to the cytology screening test, regarding positivity rates and premalignant lesions diagnosed in the Israeli population. A specific consideration is for the age group 25-30 that is not considered mandatory for the HPV primary screening testing. METHODS: A retrospective study was performed in women who were screened for prevention of cervical cancer in Maccabi HealthCare HMO from March 2017 to March 2019. Screening methods included hrHPV typing for types 16, 18, and the other 12 hrHPV types and the PAP LBC test. RESULTS: A total of 115,807 cervical samples were tested for HPV presence and 91% (105,225) were found negative for hrHPV. The other 9% (10,582) were positive for one or more of the 14 hrHPV types tested, and 37% (3,916) of them showed abnormal PAP LBC results. In the age group of 25-30, 3,104 (17.5%) women were found positive for hr-HPV (825 had hrHPV types 16 and/or 18), of which 42% (1,293) of them showed abnormal PAP LBC results. During the hrHPV versus PAP LBC screening era, 258 more women were diagnosed with precancerous cervical lesions (CIN2/3), 70% increased detection versus cytology screening. CONCLUSIONS: The hrHPV screening test is currently the best method for the detection of precancerous cervical lesions and cervical cancer, and it is better started at age 25.

Diagnostic performance of a novel device for real-time margin assessment in lumpectomy specimens.

BACKGROUND: Margin status in breast lumpectomy procedures is a prognostic factor for local recurrence and the need to obtain clear margins is often a cause for repeated surgical procedures. A recently developed device for real-time intraoperative margin assessment (MarginProbe; Dune Medical Devices, Caesarea, Israel), was clinically tested. The work presented here looks at the diagnostic performance of the device. METHODS: The device was applied to freshly excised lumpectomy and mastectomy specimens at specific tissue measurement sites. These measurement sites were accurately marked, cut out, and sent for histopathologic analysis. Device readings (positive or negative) were compared with histology findings (namely malignant, containing any microscopically detected tumor, or nonmalignant) on a per measurement site basis. The sensitivity and specificity of the device was computed for the full dataset and for additional relevant subgroups. RESULTS: A total of 869 tissue measurement sites were obtained from 76 patients, 753 were analyzed, of which 165 were cancerous and 588 were nonmalignant. Device performance on relatively homogeneous sites was: sensitivity 1.00 (95% CI: 0.85-1), specificity 0.87 (95% CI: 0.83-0.90). Performance for the full dataset was: sensitivity 0.70 (95% CI: 0.63-0.77), specificity 0.70 (95% CI: 0.67-0.74). Device sensitivity was estimated to change from 56% to 97% as the cancer feature size increased from 0.7 mm to 6.6 mm. Detection rate of samples containing pure DCIS clusters was not different from rates of samples containing IDC. CONCLUSIONS: The device has high sensitivity and specificity in distinguishing between normal and cancer tissue even down to small cancer features.