Intraoperative Histopathological Diagnosis Research Articles

Automated Ovarian Cancer Identification Using End-to-End Deep Learning and Second Harmonic Generation Imaging

Surgery is one of the most important methods for the treatment of ovarian cancer. During this procedure, a biopsy is usually required to evaluate the suspicious lesions and provide guidance for the size of the surgical resection. However, the conventional biopsy for intraoperative histopathological diagnosis performed by trained pathologists is labor-intensive, time-consuming, and carries the risk of bias. Therefore, we present a novel optical biopsy method to assist physicians in accurately and rapidly diagnosing ovarian cancer during surgery. We demonstrate that second harmonic generation (SHG) images of unstained, freshly resected ovarian tissues can be accurately characterized by deep learning techniques. Using 13,563 SHG images obtained from freshly resected human ovarian tissues of 74 patients, we fine-trained a convolutional neural network (CNN) based on pretrained ResNet50 framework to distinguish normal, benign, and malignant ovarian tissue with an average accuracy of 99.7%. These results suggest that optical biopsies based on label-free SHG imaging and deep learning technology have great potential for rapid and accurate characterizations of ovarian lesions in surgery.

Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis.

With the advent of the molecular era, the diagnosis and treatment systems of glioma have also changed. A single histological type cannot be used for prognosis grade. Only by combining molecular diagnosis can precision medicine be realized. To develop an automatic integrated gene detection system (AIGS) for intraoperative detection in glioma and to explore its positive role in intraoperative diagnosis and treatment. We analyzed the isocitrate dehydrogenase 1 (IDH1) mutation status of 105 glioma samples and evaluated the product's potential value for diagnosis; 37 glioma samples were detected intraoperatively to evaluate the feasibility of using the product in an actual situation. A blinding method was used to evaluate the effect of the detection technology on the accuracy of intraoperative histopathological diagnosis by pathologists. We also reviewed the current research status in the field of intraoperative molecular diagnosis. Compared with next-generation sequencing, the accuracy of AIGS in detecting IDH1 was 100% for 105 samples and 37 intraoperative samples. The blind diagnostic results were compared between the 2 groups, and the molecular information provided by AIGS increased the intraoperative diagnostic accuracy of glioma by 16.2%. Using the technical advantages of multipoint synchronous detection, we determined the tumor molecular margins for 5 IDH-positive patients and achieved accurate resection at the molecular level. AIGS can quickly and accurately provide molecular information during surgery. This methodology not only improves the accuracy of intraoperative pathological diagnosis but also provides an important molecular basis for determining tumor margins to facilitate precision surgery.

INNV-28. A PILOT STUDY EVALUATING THE FEASIBILITY OF USING AN ULTRA-FAST DIGITAL CONFOCAL MICROSCOPY SCANNER FOR REAL-TIME INTRA-OPERATIVE BRAIN TUMOUR DIAGNOSIS

Abstract INTRODUCTION Real-time intra-operative brain tumour tissue analysis in the operating room (OR) can shorten turnaround times and facilitate repeated sampling; the latter can improve diagnostic accuracy and guide resection to maximise extent. We evaluated the feasibility of using an ultra-fast confocal microscopy scanner (Histolog®, SamanTree Medical SA) in the OR for real-time intra-operative brain tumour tissue diagnosis. This study is the first use of Histolog® on primary human brain tissue globally. METHODS An observational pilot study with varying brain tumour types was conducted in a tertiary UK brain tumour centre. Multiple, freshly excised tissue samples were stained with Acridine Orange, and images captured within 60 seconds on Histolog® in the OR in parallel to current diagnostic pathways. A Consultant Neuropathologist performed a blinded correspondence assessment between Histolog® and current gold standard histopathology. Qualitative logging of diagnostic features was performed. RESULTS Cases studied (n=12) included glioma, metastasis, meningioma, schwannoma, and pituitary adenoma. Concordance between Histolog® and traditional (frozen section) intra-operative histopathological diagnosis was 83% (10/12 cases). One Histolog® case demonstrated superior diagnostic accuracy to frozen section. Histolog® images demonstrated specific diagnostic features such as clusters of cohesive epithelioid cells (metastatic carcinoma), sheet-like variably cellular and pleomorphic cells (gliomas), diffuse sheet-like monomorphic round nuclei (pituitary adenoma), elongated spindle cells (schwannoma), and nodular architecture and oval nuclei (meningioma). DISCUSSION Ultra-fast confocal microscopy scanning with Histolog® is feasible in the OR and Histolog® image resolution is adequate to identify histopathological features necessary for intra-operative brain tumour diagnosis. Training and clinico-radiological details are important in minimising discordance. A larger study with greater numbers and tumour types will now be performed to define an optimal scanning protocol and determine the strengths and limitations of the technology. Future studies should investigate the effect of real-time margin zone analysis on extending resection.

Structural and Functional Imaging in Glioma Management.

The goal of glioma surgery is maximal safe resection in order to provide optimal tumor control and survival benefit to the patient. There are multiple imaging modalities beyond traditional contrast-enhanced magnetic resonance imaging (MRI) that have been incorporated into the preoperative workup of patients presenting with gliomas. The aim of these imaging modalities is to identify cortical and subcortical areas of eloquence, and their relationship to the lesion. In this article, multiple modalities are described with an emphasis on the underlying technology, clinical utilization, advantages, and disadvantages of each. functional MRI and its role in identifying hemispheric dominance and areas of language and motor are discussed. The nuances of magnetoencephalography and transcranial magnetic stimulation in localization of eloquent cortex are examined, as well as the role of diffusion tensor imaging in defining normal white matter tracts in glioma surgery. Lastly, we highlight the role of stimulated Raman spectroscopy in intraoperative histopathological diagnosis of tissue to guide tumor resection. Tumors may shift the normal arrangement of functional anatomy in the brain; thus, utilization of multiple modalities may be helpful in operative planning and patient counseling for successful surgery.

Prospective evaluation of sentinel node navigation surgery in Japanese patients with low-risk endometrial cancer-safety and occurrence of lymphedema.

The present study aimed to clarify the occurrence rate of lymphedema and prognosis in patients with endometrial cancer according to sentinel lymph node biopsy alone with intraoperative histopathological examination. The study included 45 consecutive patients with endometrial cancer treated at Tohoku University Hospital between October 2014 and August 2017. All patients had endometrial carcinoma with endometrioid histology Grade 1 or Grade 2 confirmed by biopsy and stage I on magnetic resonance imaging and/or computed tomography at their preoperative evaluation. Sentinel lymph node detection was performed by radioisotope and dye. Patients who were diagnosed intraoperatively as negative for sentinel lymph node metastasis did not undergo further systematic pelvic lymphadenectomy. The occurrence rate of lymphedema and prognosis was evaluated. Bilateral sentinel lymph nodes were detected in 44 of 45 patients (97%). Forty-three patients underwent sentinel lymph node biopsy alone, and only two patients underwent systematic lymphadenectomy. Sentinel lymph node metastases were detected in one patient intraoperatively and two patients postoperatively as ITCs. No patients experienced recurrence. New symptomatic lower-extremity lymphedema was identified in one of 43 patients (2.3%) who underwent sentinel lymph node biopsy alone. Sentinel lymph node biopsy alone with intraoperative histopathological diagnosis appears to be a safe and effective strategy to detect lymph node metastasis and to reduce the number of patients with lower-extremity lymphedema among patients with endometrial cancer.

Visualization of the human enteric nervous system by confocal laser endomicroscopy in Hirschsprung's disease: An alternative to intraoperative histopathological diagnosis?

Hirschsprung's disease is a congenital abnormality of the enteric nervous system (ENS) presenting severe constipation soon after birth due to the lack of ganglion cells in the distal gut. Surgery for Hirschsprung's disease requires an intraoperative histopathological diagnosis to assess the extent of aganglionosis. Confocal laser endomicroscopy (CLE) is a novel endoscopic technique allowing real-time, in vivo analysis of cellular details during ongoing endoscopy. In this study, we evaluated the possibility of a new application of CLE to provide real-time observations of the ENS in patients with Hirschsprung's disease. In this preclinical feasibility study, we assessed the visualization of the ENS by CLE using surgically resected intestines. The subjects were nine patients who underwent pull-through surgery for Hirschsprung's disease between September 2014 and March 2016. The colon specimens were stained with 0.1% cresyl violet and evaluated using CLE. We compared the CLE findings with those of the histopathological examination. The ENS was clearly visualized as a ladder-like structure in the ganglionic segment but was not observed in the aganglionic segment. Of the 69 samples, corresponding positive and negative results for both CLE and the histopathology were obtained in 61 (88%). In addition, CLE was able to visualize unique, wavy structures comprising thick nerve bundles characteristic of the aganglionic/transition zone in Hirschsprung's disease. As a novel tool for visualizing the human ENS, CLE has the potential to revolutionize how pediatric surgeons identify the level of ganglionosis during surgery for Hirschsprung's disease and may be a superior alternative to intraoperative histopathological diagnosis.

Radioguided Surgery in Primary Hyperparathyroidism: Results and Correlation With Intraoperative Histopathologic Diagnosis

Introduction and objectivesRadioguided surgery is a minimally invasive surgical technique for the treatment of primary hyperparathyroidism. The goals of our study were to evaluate the rate of success and compare the results with intraoperative histological analysis. MethodsWe retrospectively studied 84 patients with primary parathyroidism who had undergone radioguided surgery. All the patients had a positive parathyroid scintigraphy prior to surgery. An intravenous injection of Tc-99m sestamibi was administered before surgery, and radioguided location of the pathologic parathyroid tissue was performed using an intraoperative gamma probe, applying the “20% rule”. All resected specimens underwent intraoperative histologic analysis. All patients were followed up for at least 6 months. Positive predictive values of both parathyroid scintigraphy and cervical ultrasonography were also compared. ResultsRadioguided surgery success rate was 99%. Sensitivity, specificity, positive and negative predictive values for gamma probe were 99%, 73%, 97% and 89%, respectively. After surgery, 83 of 84 patients were eucalcaemic (99%) and parathyroid hormone normalised in 77 of 84 patients (92%). Ultrasonography showed low positive predictive value (41%) when compared with scintigraphy. ConclusionsRadioguided surgery is a minimally invasive surgical technique with excellent results for the treatment of primary hyperparathyroidism and could replace both intraoperative histological analysis and intraoperative parathyroid hormone assay. Further studies are needed to confirm these findings.

Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.

Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room by using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients. We also introduce an image-processing method – stimulated Raman histology (SRH) – which leverages SRS images to create virtual haematoxylin-and-eosin-stained slides, revealing essential diagnostic features. In a simulation of intraoperative pathologic consultation in 30 patients, we found a remarkable concordance of SRH and conventional histology for predicting diagnosis (Cohen's kappa, κ > 0.89), with accuracy exceeding 92%. We also built and validated a multilayer perceptron based on quantified SRH image attributes that predicts brain-tumour subtype with 90% accuracy. Our findings provide insight into how SRH can now be used to improve the surgical care of brain tumour patients.

INFORMATION-GUIDED SURGERY USING INTRAOPERATIVE MRI AND FUNCTIONAL MAPPING FOR GLIOMAS.

BACKGROUND: Contemporary technological developments revolutionized surgical management of intraaxial brain tumors. The intraoperative MRI (iMRI) and updated neuronavigation permitted for neurosurgeons to perform tumor resection under precise guidance. Neurophysiological monitoring and brain mapping allows precise localization of the cerebral functions and preservation of the important function during removal of the tumor. Intraoperative histopathological diagnosis allows fast direct investigation for identification of the neoplastic cells. Incorporation of these adjuncts provides for the surgeon an opportunity to perform aggressive glioma resection with minimal risk of neurological morbidity. The present report highlights our experience with information-guided surgical management of gliomas using low magnetic field strength iMRI in the intelligent operating theater with an emphasis on tumor resection rate and outcome. METHODS: From 2000 to 2013, 1234 surgeries for intracranial lesions were performed with the use of intraoperative MRI (iMRI) with low magnetic field strength of 0.3 Tesla, updated neuronavigation, serial intraoperative histopathological investigations, and neurophysiological monitoring (1000 gliomas, 45 cavernous malformations, 34 pituitary tumors, and other tumors). Newly-diagnostic gliomas followed more than one year were 533 cases (8 biopsies, 525 craniotomy) and WHO grade-II, -III, and -IV gliomas resected were 197, 150, and 170 cases, respectively (8 not specified). Adjuvant therapy for grade-II, -III, and IV patients was radiation (RT) and/or ACNU chemotherapy if resection rate were less than 90%, RT + ACNU, and RT + TMZ, respectively. RESULTS: Mean resection rates (RR) of grade-II, -III, and -IV were 87.7%, 89.5%, and 93.7%, respectively (P = 0.0004). Five-year and 10-year- survival rates of grade-II patients were 91.7% and 78.3%, those of grade-III patients were 76.9% and 71.9%, and 5-year survival of grade-IV patients were 19% (P = 0.042). RR of all-grade patients underwent awake craniotomy with functional mapping (AC: n = 174) and general anesthesia without functional mapping (GA: n = 351) were 86% and 93% (P 0.05). RR of patients with iMRI and without iMRI were significantly different in grade IV (94% vs. 78%: P 0.05)). Overall survival of Grade-IV patients with iMRI and without MRI were 21 months and 11 months (P = 0.037). CONCLUSIONS: Information-guided management of gliomas using functional mapping and low-field-strength iMRI provides a good opportunity for maximal possible tumor resection, and may result in survival advantage. SECONDARY CATEGORY: Imaging.

劇症型Ａ群β溶連菌感染症の救命にＭＲＩと術中迅速病理診断を用いた１症例

A 33-year-old man was admitted to our emergency room with tachycardia and hypotension. Diffuse swelling, extensive blistering were noted in the body region extending from the left thigh to the left scrotum. Laboratory data revealed severe metabolic acidosis with an elevated anion gap and high lactate level, leukocytosis and renal dysfunction. Bacteriological examination of the exudate obtained from the blisters revealed numerous Gram-positive cocci. Although computed tomography revealed only swelling of the left thigh and scrotum, MRI, which was performed when the patient was clinically stable at the previous hospital, clearly suggested extensive myofascitis of the left thigh. An emergency debridement of the infected wounds was carried out, and intraoperative histopathological diagnosis guided the area of debridment. The resected tissues from the left thigh and scrotum revealed widespread necrosis and large numbers of Gram-positive cocci, which were identified as Group A β-hemolytic streptococci. In this case report, we show that MRI and intraoperative histopathological examination are more effective than computed tomography for the early diagnosis of TSLS.

喉頭腫ようとの鑑別を要した喉頭真菌症例

A case of fungal infection of the larynx requiring differential diagnosis from laryngeal carcinoma is reported. A 75-year-old male was referred to our clinic with a complaint of hoarseness, and a mass lesion was detected on the left vocal cord. Biopsy under laryngeal fiberscopy was performed on suspicion of laryngeal carcinoma. Resection and vaporization of the lesion was carried out using a KTP laser, because the intraoperative histopathological diagnosis was dysplasia. The final histopathological diagnosis was revised to dysplasia with an infection of Aspergillus. Additional therapy for the fungal infection was not performed, but no reccurence was seen for 3 years after surgery. The post-vaporization lesion on the vocal cord was covered with intact mucosa. KTP laser was found to be effective in this case.

Reliability of telepathology for frozen section service.

One of the most promising applications of telepathology (pathology at a distance by electronic transmission of images in pathology) is frozen section diagnosis, especially because by means of this tool operations requiring an intraoperative histopathological diagnosis are feasible at hospitals without a pathologist on‐site. For the introduction of this diagnostic tool into pathologist's daily practice the evidence of its diagnostic accuracy comparable to that of the conventional frozen section diagnosis is crucial.For this purpose the literature on the diagnostic accuracy of telepathological frozen section diagnosis was reviewed. In a metaanalysis these studies and reports, in which a total of more than 1290 cases had been examined, showed a slightly lower overall diagnostic accuracy (of the telepathological frozen section diagnosis) of about 0.91 than the conventional frozen section diagnosis with an average accuracy of about 0.98 found in an analysis of several studies (on frozen section diagnosis of different organs). This difference is at least predominantly caused by a higher rate of deferred and false negative frozen section diagnoses in the telepathological method, while the specificity of both methods, each more than 0.99 was not significantly different.In conclusion, the introduction of a telepathological frozen section diagnosis for hospitals without an acceptable access to a pathologist is justifiable already at the current state of the technological development especially when considering the advantages (time saving, reduction in costs) compared to the alternative of surgical interventions without access to an intraoperative diagnosis.