Functional Assessment of Synoptic Pathology Reporting for Ovarian Cancer.

BACKGROUND: Ovarian cancer has one of the highest death/incidence rates and is commonly diagnosed at an advanced stage. In the recent WHO classification, new histotypes were classified which respond differently to chemotherapy. The e-standardized synoptic cancer pathology reports offer the clinicians essential and reliable information. The aim of our project was to develop an e-template for the standardized synoptic pathology reporting of ovarian carcinoma [based on the checklist of the College of American Pathologists (CAP) and the recent WHO/FIGO classification] to introduce a uniform and improved quality of cancer pathology reports. A functional and qualitative evaluation of the synoptic reporting was performed. METHODS: An indispensable module for e-synoptic reporting was developed and integrated into the Hospital Information System (HIS). The electronic pathology system used a standardized structure with drop-down lists of defined elements to ensure completeness and consistency of reporting practices with the required guidelines. All ovarian cancer pathology reports (partial and final) with the corresponding glass slides selected from a 1-year current workflow were revised for the standard structured reports, and 42 tumors [13 borderline tumors and 29 carcinomas (mainly serous)] were included in the study. RESULTS: Analysis of the reports for completeness against the CAP checklist standard showed a lack of pTNM staging in 80% of the partial or final unstructured reports; ICD-O coding was missing in 83%. Much less frequently missed or unstated data were: ovarian capsule infiltration, angioinvasion and implant evaluation. The e-records of ovarian tumors were supplemented with digital macro- and micro-images and whole-slide images. CONCLUSIONS: The e-module developed for synoptic ovarian cancer pathology reporting was easily incorporated into HIS.CGM CliniNet and facilitated comprehensive reporting; it also provided open access to the database for concerned recipients. The e-synoptic pathology reports appeared more accurate, clear and conclusive than traditional narrative reports. Standardizing structured reporting and electronic tools allows open access and downstream utilization of pathology data for clinicians and tumor registries.

Digital pathology in personalized cancer therapy.

The development of small molecule inhibitors of the growth factor receptors and discovery of somatic mutations of the thyrosine kinase domain resulted in new paradigms for the cancers therapy. Digital microscopy is an important tool for surgical pathologists. The achievements in the digital pathology field have modified the workflow of pathomorphology labs, enhanced the pathologists' role in the diagnostics and increased their contribution to the personalized targeted medicine. Digital image analysis is now available in a variety of platforms to improve quantification performance of diagnostic pathology. The authors describe the state of digital microscopy as it applies to the field of quantitative immunohistochemistry of biomarkers related to the clinical personalized targeted therapy of breast cancer, non-small lung cancer and colorectal cancer: HER-2, EGFR, KRAS and BRAF genes. The information is derived from the experience of the authors and review of the literature.

State of the art in pathology business process analysis, modeling, design and optimization.

For analyzing current workflows and processes, for improving them, for quality management and quality assurance, for integrating hardware and software components, but also for education, training and communication between different domains' experts, modeling business process in a pathology department is inevitable. The authors highlight three main processes in pathology: general diagnostic, cytology diagnostic, and autopsy. In this chapter, those processes are formally modeled and described in detail. Finally, specialized processes such as immunohistochemistry and frozen section have been considered.

Digital pathology in Europe: coordinating patient care and research efforts.

The COST Action IC0604 "Telepathology Network in Europe" (EURO-TELEPATH) is an initiative of the COST (European Cooperation in the field of Scientific and Technical Research) framework, supported by the Seventh Framework Programme for research and technological development (FP7), of the European Union will be running from 2007 to 2011 and is aimed to coordinate research efforts to develop the most adequate technological framework for the management of multimedia electronic healthcare records (data and images) applied to Anatomic Pathology. Sixteen countries are participating in EURO-TELEPATH. Activities are organized in four Working Groups (WGs): WG1 - Pathology Business Modeling, WG2 - Informatics Standards in Pathology, WG3 - Images: Analysis, Processing, Retrieval and Management, and WG4 - Technology and Automation in Pathology. During the first year of work, the collaboration between software engineers, computer scientists, pathologists and other clinicians has been essential to detect three main areas of interest in digital pathology research: virtual microscopy scanning solutions, health informatics standards, and image processing and analysis. Research in these areas is essential to a correct approach to telepathology, including primary diagnosis, and secondary or teleconsultation services. Managing microscopic pathology images (virtual slides) is a challenge to existing information systems, mainly due to its large size, large number, and complex interpretation. Regarding interoperability, the integration of pathology reports and images into eHealth records is an essential objective that research groups should consider. Promoting participation in standards bodies (DICOM, IHE, HL7, IHTSDO) is an essential part of the project work. Understanding the business process of pathology departments in daily practice, including healthcare, education, research, and quality control activities, is the starting point to be sure that standardization efforts converge with user needs. Following a recent IHE proposal, coordination with public health services like national or regional tumor registries must also be supported. Virtual or digital slides are fostering the use of image processing and analysis in pathology not only for research purposes, but also in daily practice. Nowadays, further discussion is needed on the adequacy of current existing technical solutions, including for instance quality of images obtained by scanners, or the efficiency of image analysis applications.

Morphometric and functional abnormalities of kidneys in the progeny of mice fed chocolate during pregnancy and lactation.

Even most commonly consumed beverages like tea, coffee, chocolate and cocoa contain methylxanthines, biogenic amines and polyphenols, among them catechins, that exhibit significant biological activity and might profoundly affect the organism homeostasis. We have previously shown that 400 mg of bitter chocolate or 6 mg of theobromine added to the daily diet of pregnant and afterwards lactating mice affected embryonic angiogenesis and caused bone mineralization disturbances as well as limb shortening in 4-weeks old offspring. The aim of the present study was the morphometric and functional evaluation of kidneys in the 4-weeks old progeny mice fed according to the protocol mentioned above. Progeny from the mice fed chocolate presented considerable morphometric abnormalities in the kidney structure, with the lower number of glomeruli per mm2 and their increased diameter. Moreover, higher serum creatinine concentration was observed in that group of offspring. No morphometric or functional irregularities were found in the progeny of mice fed theobromine. Abnormalities demonstrated in the offspring of mice fed chocolate are not related to its theobromine content. Consequently, identification of active compound(s) responsible for the observed effects is of vital importance.

Extrapulmonary lymphangioleiomyomatosis presented as the asymptomatic retroperitoneal tumours--two cases report.

Lymphangioleiomyomatosis [LAM] is a rare lung disease affecting women and characterized by abnormal smooth muscle cells (LAM cells) proliferation along lung and lymphatic channels. The frequent occurrence of extrapulmonary LAM [e-LAM] has been reported as abdomen pelvic lymph nodes involvement, angiomyolipomas, lymphangioleiomyomas or lymphangiomas in LAM patients. An extrapulmonary manifestation as the initial LAM presentation preceding pulmonary disorders and as asymptomatic extrapulmonary LAM lesions are unusual. We report two women presented with asymptomatic retroperitoneal cystic masses accidentally found on ultrasound examination. The tumours were surgically removed and diagnosed as: 1-malignant mesothelioma and 2-tymphangiomyoma. The microscopical sections were reviewed and re-diagnosed as e-LAM at advanced pulmonary LAM development. Mesotheliosis present in e-LAM morphology is unique and was misleading for malignancy diagnosis. The second case illustrates the hormone dependent growth of lymphangiomyoma and LAM development in young women. It is difficult to prove the presence of pulmonary LAM at the time of tumours excision but both cases demonstrate importance of appropriate LAM diagnosis and being aware of such diagnosis in cases presenting with extrapulmonary extension of the disease.

Hot-spot selection and evaluation methods for whole slice images of meningiomas and oligodendrogliomas.

The paper presents a combined method for an automatic hot-spot areas selection based on penalty factor in the whole slide images to support the pathomorphological diagnostic procedure. The studied slides represent the meningiomas and oligodendrogliomas tumor on the basis of the Ki-67/MIB-1 immunohistochemical reaction. It allows determining the tumor proliferation index as well as gives an indication to the medical treatment and prognosis. The combined method based on mathematical morphology, thresholding, texture analysis and classification is proposed and verified. The presented algorithm includes building a specimen map, elimination of hemorrhages from them, two methods for detection of hot-spot fields with respect to an introduced penalty factor. Furthermore, we propose localization concordance measure to evaluation localization of hot spot selection by the algorithms in respect to the expert's results. Thus, the results of the influence of the penalty factor are presented and discussed. It was found that the best results are obtained for 0.2 value of them. They confirm effectiveness of applied approach.

Comparison of the manual, semiautomatic, and automatic selection and leveling of hot spots in whole slide images for Ki-67 quantification in meningiomas.

Background. This paper presents the study concerning hot-spot selection in the assessment of whole slide images of tissue sections collected from meningioma patients. The samples were immunohistochemically stained to determine the Ki-67/MIB-1 proliferation index used for prognosis and treatment planning. Objective. The observer performance was examined by comparing results of the proposed method of automatic hot-spot selection in whole slide images, results of traditional scoring under a microscope, and results of a pathologist's manual hot-spot selection. Methods. The results of scoring the Ki-67 index using optical scoring under a microscope, software for Ki-67 index quantification based on hot spots selected by two pathologists (resp., once and three times), and the same software but on hot spots selected by proposed automatic methods were compared using Kendall's tau-b statistics. Results. Results show intra- and interobserver agreement. The agreement between Ki-67 scoring with manual and automatic hot-spot selection is high, while agreement between Ki-67 index scoring results in whole slide images and traditional microscopic examination is lower. Conclusions. The agreement observed for the three scoring methods shows that automation of area selection is an effective tool in supporting physicians and in increasing the reliability of Ki-67 scoring in meningioma.

[Diffuse large B-cell lymphoma mimicking Wegener's granulomatosis]. / Rozlany chloniak z duzych komórek B imitujacy ziarniniakowatosc Wegenera.

We report 39 years old man with the history of chronic sinusitis and rhinitis. After tooth extraction he gradually developed unilateral proptosis with ophtalmoplegia and visual loss caused by retroorbital mass which was related to destruction of the adjacent orbital walls, sinuses and base of the skull. During the following month the progressing lung nodules with mediastinal and hilar lymphadenopathy, macular skin lesions, renal insufficiency with proteinuria and anaemia appeared. The diagnosis of Wegener's Granulomatosis (WG) was formed on the base of clinical features and result of pathologic examination of surgical specimen from the paranasal sinuses. The progressive course under the standard immunosuppressive therapy required reevaluation of histologic slides, which resulted with the diagnosis of diffuse large B-cell lymphoma confirmed by the immunohistochemical staining. Administration of CHOP regimen resulted in spectacular regression of all of lesions.

[Neuron-specific enolase (NSE) serum level as a prognostic factor in non-small cell lung cancer]. / Wartosc stezenia neuronoswoistej enolazy (NSE) w surowicy chorych na niedrobnokomórkowego raka pluca w prognozowaniu wyników leczenie cytostatycznego.

The aim of the study was to assess the significance of elevated NSE serum level in NSCLC patients for tumor response to chemotherapy and for survival. The NSE serum level above 12.5 mg/l was regarded as elevated. We found elevated serum level of NSE in 71 of 146 patients (48.6%) at the time of diagnosis of inoperable non-small cell lung cancer, independently to age, sex, performance status and histological type of cancer. All patients were treated using cisplatin based combination chemotherapy. 44 patients were treated with cisplatin/etoposide (group PE), 37 with cisplatin/vinblastine (group PV), 20 with cisplatin/vinorelbine (group PN) and 58 with cisplatin/etoposide/vinblastine (group PEV) combination. In 26.7% partial response and in another 21.2% minimal regression were found after chemotherapy. Partial response was observed in 38% patients with elevated NSE serum level but only in 16% patients with normal NSE serum level and difference was significant (p = 0.0153). Median survival time was 8.5 months for the whole group with no difference according to serum level of NSE. One-year survival rate was 29% and 9 patients survived 24 month or more. We conclude that although the tumor in patients with elevated NSE serum levels regress more frequently than in others it does not influence their survival.

Nucleolus detection in the Fuhrman grading system for application in CCRC.

The paper presents a method for nucleolus detection in images of nuclei in clear-cell renal carcinoma (CCRC). The method is based on the similarity of the nuclei image and the two-dimensional paraboloidal window function. The results of numerical experiments performed on almost 2600 images of CCRC nuclei have confirmed the good accuracy of the method. The developed algorithm will be used to accelerate further research in computer-assisted diagnosis of CCRC.

Computer approach to recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma.

OBJECTIVE: To present a computerized system for recognition of Fuhrman grade of cells in clear-cell renal cell carcinoma on the basis of microscopic images of the neoplasm cells in application of hematoxylin and eosin staining. STUDY DESIGN: The applied methods use combined gradient and mathematical morphology to obtain nuclei and classifiers in the form of support vector machine to estimate their Fuhrman grade. The starting point is a microscopic kidney image, which is subject to the advanced methods of preprocessing, leading finally to estimation of Fuhrman grade of cells and the whole analyzed image. RESULTS: The results of the numerical experiments have shown that the proposed nuclei descriptors based on different principles of generation are well connected with the Fuhrman grade. These descriptors have been used as the diagnostic features forming the inputs to the classifier, which performs the final recognition of the cells. The average discrepancy rate between the score of our system and the human expert results, estimated on the basis of over 3,000 nuclei, is below 10%. CONCLUSION: The obtained results have shown that the system is able to recognize 4 Fuhrman grades of the cells with high statistical accuracy and agreement with different expert scores. This result gives a good perspective to apply the system for supporting and accelerating the research of kidney cancer.

Digital pathology in personalized cancer therapy.

The development of small molecule inhibitors of growth factor receptors, and the discovery of somatic mutations of the tyrosine kinase domain, have resulted in new paradigms for cancer therapy. Digital microscopy is an important tool for surgical pathologists. The achievements in the digital pathology field have modified the workflow of pathomorphology labs, enhanced the pathologist's role in diagnostics, and increased their contribution to personalized targeted medicine. Digital image analysis is now available in a variety of platforms to improve quantification performance of diagnostic pathology. We here describe the state of digital microscopy as it applies to the field of quantitative immunohistochemistry of biomarkers related to the clinical personalized targeted therapy of breast cancer, non-small lung cancer and colorectal cancer: HER-2, EGFR, KRAS and BRAF genes. The information is derived from the experience of the authors and a review of the literature.

Accuracy of a remote quantitative image analysis in the whole slide images.

The rationale for choosing a remote quantitative method supporting a diagnostic decision requires some empirical studies and knowledge on scenarios including valid telepathology standards. The tumours of the central nervous system [CNS] are graded on the base of the morphological features and the Ki-67 labelling Index [Ki-67 LI]. Various methods have been applied for Ki-67 LI estimation. Recently we have introduced the Computerized Analysis of Medical Images [CAMI] software for an automated Ki-67 LI counting in the digital images. Aims of our study was to explore the accuracy and reliability of a remote assessment of Ki-67 LI with CAMI software applied to the whole slide images [WSI]. The WSI representing CNS tumours: 18 meningiomas and 10 oligodendrogliomas were stored on the server of the Warsaw University of Technology. The digital copies of entire glass slides were created automatically by the Aperio ScanScope CS with objective 20x or 40x. Aperio's Image Scope software provided functionality for a remote viewing of WSI. The Ki-67 LI assessment was carried on within 2 out of 20 selected fields of view (objective 40x) representing the highest labelling areas in each WSI. The Ki-67 LI counting was performed by 3 various methods: 1) the manual reading in the light microscope - LM, 2) the automated counting with CAMI software on the digital images - DI , and 3) the remote quantitation on the WSIs - as WSI method. The quality of WSIs and technical efficiency of the on-line system were analysed. The comparative statistical analysis was performed for the results obtained by 3 methods of Ki-67 LI counting. The preliminary analysis showed that in 18% of WSI the results of Ki-67 LI differed from those obtained in other 2 methods of counting when the quality of the glass slides was below the standard range. The results of our investigations indicate that the remote automated Ki-67 LI analysis performed with the CAMI algorithm on the whole slide images of meningiomas and oligodendrogliomas could be successfully used as an alternative method to the manual reading as well as to the digital images quantitation with CAMI software. According to our observation a need of a remote supervision/consultation and training for the effective use of remote quantitative analysis of WSI is necessary.

Study on breast carcinoma Her2/neu and hormonal receptors status assessed by automated images analysis systems: ACIS III (Dako) and ScanScope (Aperio).

UNLABELLED: Her-2/neu is overexpressed in 20-30% of breast cancer patients and is associated with a more aggressive disease. Identification of Her-2/c-erbB-2-neu overexpression is based on immunohistochemical [ihc] detection of protein and/or gene amplification in fluorescence in situ hybridization test (FISH). Also Estrogen receptors [ER] and Progesterone receptors [PR] are the prognostic and predictive biomarkers, recently analysed by ihc methods. Subjective, manual scoring of the ihc Her-2/neu expression and expression of the ER/PR reported as the percentage of immunopositive cells are the most common mode of interpretation among pathologists. Automated microscopy and computerised processing have provided increased accuracy in quantification and standardisation. THE AIMS OF OUR STUDY WERE: to evaluate the scoring reproducibility of Her-2 /neu ihc expression tested by two automated systems: ACIS (Dako) and ScanScope (Aperio); to estimate the ER/PR expression in ihc staining methods with different anti-ER/anti-PR antibodies (the monoclonal and the ER/PR pharmDx TM Kit) by the ACIS system. Her-2/neu ihc expression was measured in 114 primary invasive breast carcinomas by the manual and the automated scoring (ACIS and Aperio system). 106 slides stained ihc with two types of anti-ER/anti-PR antibodies entered the quantisation. The results of our investigations showed very high reproducibility of Her-2/neu scores in intra- and interobserver analysis by ACIS evaluation. The major concordance was present in strong 3+ ihc cases; very small discordance was shown by cases with low expression of Her-2/neu. The accuracy of scoring by the Aperio was little lower in comparison to ACIS but it might result from the smaller and variable series of samples analysed by Aperio. The concordance in scoring of two automated systems was 86.5% (p<0.0001; gamma=0.887); the discordance was referred only to the lower expression of Her-2/neu. The concordance in manual scoring performed by the single observer and the panel was 84.2% (p<0.0001, gamma = 0.99); the discordance comprised a few cases with strong expression (2+ vs 3+). Very high intra- and interobserver reproducibility of the ER/PR ihc measurements was present in the readers results (referred to the percentage of immunoreactive carcinomatous cell population in the breast carcinomas acc. to the ACIS algorithm). No differences were disclosed in the percentage of ER-immunoreactive and PR-immunoreactive carcinomatous cell populations when used 2 different type of antibodies, in the ACIS automated method.

Review of imaging solutions for integrated quantitative immunohistochemistry in the Pathology daily practice.

Immunohistochemistry (IHC) plays an essential role in Pathology. In order to improve reproducibility and standardization of the results interpretation, IHC quantification methods have been developed. IHC interpretation based in whole slide imaging or virtual microscopy is of special interest. The objective of this work is to review the different computer-based programs for automatic immunohistochemistry and Fluorescence In Situ Hybridization (FISH) evaluation. Scanning solutions and image analysis software in immunohistochemistry were studied, focusing especially on systems based in virtual slides. Integrated scanning and image analysis systems are available (Bacus TMAScore, Dako ACIS III, Genetix Ariol, Aperio Image Analysis, 3DHistech Mirax HistoQuant, Bioimagene Pathiam). Other image analysis software systems (Definiens TissueMap, SlidePath Tissue Image Analysis) can be applied to several virtual slide formats. Fluorescence is the preferred approach in HistoRx AQUA, since it allows for a better compartmentalization of signals. Multispectral imaging using CRi Nuance allows multiple antibodies immunohistochemistry, and different stain unmixing. Most current popular automated image analysis solutions are aimed to brightfield immunohistochemistry, but fluorescence and FISH solutions may become more important in the near future. Automated quantitative tissue microarrays (TMA) analysis is essential to provide high-throughput analysis. Medical informatics standards in images (DICOM) and workflow (IHE) under development will foster the use of image analysis in Pathology Departments.

Use of the virtual slide and the dynamic real-time telepathology systems for a consultation and the frozen section intra-operative diagnosis in thoracic/pulmonary pathology.

We report the results of a study designed for assessment of the diagnostic accuracy and usability of internet-based digital microscopy: the dynamic real-time telepathology system (Coolscope) and the Virtual microscopy (Aperio Scan Scope) system, in the context of pulmonary pathology. The systems were implemented to the routine pulmonary pathology workflows and used for the intra-operative frozen-section primary diagnosis as well as for the secondary (consultative) diagnosis. The histological material presented for the teleconsultations included the samples of lung parenchyma, bronchial biopsy and resected lung/bronchi tumours. For the primary diagnosis 4 categories of material can be distinguished (304 samples): 1) the frozen sections of lung tumours, resected bronchial margins and lymph nodes; 2) fine needle aspiration [FNA] biopsies (TBNA; EBUS-TBNA, EUS-FNA; 3) oligobiopsies of bronchus, oesophagus, skin; and 4) exfoliative cytology. The telepathology diagnoses compared with conventional light microscopy diagnoses showed very high concordance for the Coolscope and Aperio Virtual Slide modality: 87.5% and 100%, respectively - within the group of teleconsultations. For the frozen sections, the primary telediagnoses were concordant with the light microscopy paraffin sections diagnoses in 100% for Aperio; and in 97.5% for Coolscope. An excellent agreement (100%) was seen in the telediagnoses and conventional slides diagnoses for FNA, oligobiopsies and cytology - for both telepathology systems. These results provide some encouragement for the implementation of Coolscope and virtual slide-based telepathology (Aperio) system to the routine histopathological diagnostics.

Automated recognition and counting of the immunoreactive neuroendocrine cells in chronic gastritis (the preliminary study).

The paper presents the designed software CAMI (Computerized Analysis of Microscopic Images) for a digital reconstruction of the diversiform glands seen in chronic inflammatory gastric mucosa, and for automated recognition and quantization of the immunoreactive neuroendocrine (NE) cells appearing within mucosal glands. Digital reconstruction of the individual gastric gland is difficult due to variable shapes of the glandular cross-sections. Fifteen gastric biopsy specimens representing chronic gastritis were stained routinely with H+E and immunohistochemically with 3 NE markers: Chromogranin A, Somatostatin and Serotonin. Two expert pathologists counted manually the NE cells with the light microscope in 4 types of glandular cross-sections: round, short- oblique, long- oblique and longitudinal. The automated counting of the NE cells was performed on the digital images presenting the same microscopic areas which were selected for the manual reading. The first step of image analysis was concerned to the cell extraction and recognition of the cytoplasmic immunoreactivity. The unstained nuclei of the NE cells were spotted by the sequential thresholding algorithm combined with the artificial neural network of Support\Vector Machine (SVM) type. The second step of image analysis comprised reconstruction of the glands. The presumed shape of each gastric gland was defined by the cellular lining of viewed glandular cross-section. The designed algorithm for gland reconstruction was based on the cell masks. The third step of analysis dealt the cell counting. Every recognized gland with the face cells was used for the NE cell evaluation. The results of the automated quantization compared with manual counting results for the number of NE cells showed high concordance in 3 types of glandular cross-sections: round, short- and long- oblique. A difference noticed in the results of the longitudinal glands should be verified in the extended study. The designed software CAMI is more adequate for the gland recognition with an discontinuous gland face seen in the immunohistochemical digital images, which appear to be a difficult problem for the accurate automated analysis of the cellular component of glands.

New automated image analysis method for the assessment of Ki-67 labeling index in meningiomas.

Many studies have emphasised the importance of Ki-67 labeling index (LI) as the proliferation marker in meningiomas. Several authors confirmed, that Ki-67 LI has prognostic significance and correlates with likelihood of tumour recurrences. These observations were widely accepted by pathologists, but up till now no standard method for Ki-67 LI assessment was developed and introduced for the diagnostic pathology. In this paper we present a new computerised system for automated Ki-67 LI estimation in meningiomas as an aid for histological grading of meningiomas and potential standard method of Ki-67 LI assessment. We also discuss the concordance of Ki-67 LI results obtained by presented computerized system and expert pathologist, as well as possible pitfalls and mistakes in automated counting of immunopositive or negative cells. For the quantitative evaluation of digital images of meningiomas the designed software uses an algorithm based on mathematical description of cell morphology. This solution acts together with the Support Vector Machine (SVM) used in the classification mode for the recognition of immunoreactivity of cells. The applied sequential thresholding simulated well the human process of cell recognition. The same digital images of randomly selected tumour areas were parallelly analysed by computer and blindly by two expert pathologists. Ki-67 labeling indices were estimated and the results compared. The mean relative discrepancy between the levels of Ki-67 LI by our system and by the human expert did not exceed 14% in all investigated cases. These preliminary results suggest that the designed software could be an useful tool supporting the diagnostic digital pathology. However, more extended studies are needed for approval of this suggestion.