Marked Differences In Prognosis Research Articles

New HCC Subtypes Based on CD8 Tex-Related lncRNA Signature Could Predict Prognosis, Immunological and Drug Sensitivity Characteristics of Hepatocellular Carcinoma.

Hepatocellular carcinoma has become one of the severe diseases threatening human health. T cell exhaustion is deemed as a reason for immunotherapy resistance. However, little is known about the roles of CD8 Tex-related lncRNAs in HCC. We processed single-cell RNA sequencing to identify CD8 Tex-related genes. CD8 Tex-related lncRNAs were identified based on their correlations with mRNAs. Unsupervised clustering approach was used to identify molecular clusters of CD8 Tex-related lncRNAs. Differences in prognosis and immune infiltration between the clusters were explored. Machine learning algorithms were used to construct a prognostic signature. Samples were classified as low- and high-risk groups based on their risk scores. We identified prognosis-related lncRNAs and constructed a ceRNA network. In vitro experiments were conducted to investigate the impacts of CD8 Tex-related lncRNAs on proliferation and apoptosis of HCC cells. We clarified cell types within two HCC single-cell datasets. We identified specific markers of CD8 Tex cells and analyzed their potential functions. Twenty-eight lncRNAs were identified as CD8 Tex-related. Based on CD8 Tex-related lncRNAs, samples were categorized into two distinct clusters, which exhibited significant differences in survival rates and immune infiltration. Ninety-six algorithm combinations were employed to establish a prognostic signature. RSF emerged as the one with the highest C-index. Patients in high- and low-risk groups exhibited marked differences in prognosis, enriched pathways, mutations and drug sensitivities. MCM3AP-AS1, MAPKAPK5-AS1 and PART1 were regarded as prognosis-related lncRNAs. A ceRNA network was constructed based on CD8 Tex-related lncRNAs and mRNAs. Experiments on cell lines and organoids indicated that downregulation of MCM3AP-AS1, MAPKAPK5-AS1 and PART1 suppressed cell proliferation and induced apoptosis. CD8 Tex-related lncRNAs played crucial roles in HCC progression. Our findings provided new insights into the regulatory mechanisms of CD8 Tex-related lncRNAs in HCC.

Assessing the Role of Different Heterogeneous Regions in DCE-MRI for Predicting Molecular Subtypes of Breast Cancer based on Network Architecture Search and Vision Transformer.

Breast cancer, the most common female malignancy, is highly heterogeneous, manifesting as different molecular subtypes. It is clinically important to distinguish between these molecular subtypes due to marked differences in prognosis, treatment and survival outcomes. In this study, we first performed convex analysis of mixtures (CAM) analysis on both intratumoral and peritumoral regions in DCE-MRI to generate multiple heterogeneous regions. Then, we developed a vision transformer (ViT)-based DL model and performed network architecture search (NAS) to evaluate all the combination of different heterogeneous regions for predicting molecular subtypes of breast cancer. Experimental results showed that the input plasma from both peritumoral and intratumoral regions, and the fast-flow kinetics from intratumoral regions were critical for predicting different molecular subtypes, achieving an area under receiver operating characteristic curve (AUROC) value of 0.66-0.68.Clinical Relevance- This study reduces the redundancy in multiple heterogeneous subregions and supports the precise prediction of molecular subtypes, which is of potential importance for the medicine care and treatment planning of patients with breast cancer.

Ferroptosis-Related Genes Are Potential Therapeutic Targets and the Model of These Genes Influences Overall Survival of NSCLC Patients.

Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSCC) are two of the most common subtypes of non-small cell lung cancer (NSCLC), with high mortality rates and rising incidence worldwide. Ferroptosis is a mode of programmed cell death caused by lipid peroxidation, the accumulation of reactive oxygen species, and is dependent on iron. The recent discovery of ferroptosis has provided new insights into tumor development, and the clinical relevance of ferroptosis for tumor therapy is being increasingly appreciated. However, its role in NSCLC remains to be explored. Methods: The clinical and molecular data for 1727 LUAD and LUSCC patients and 73 control individuals were obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Gene expression profiles, copy number variations and somatic mutations of 57 ferroptosis-related genes in 1727 tumor samples from the four datasets were used in a univariate Cox analysis and consensus clustering analysis. The biological signatures of each pattern were identified. A ferroptosis score was generated by combining the univariate Cox regression analysis and random forest algorithm followed by principal component analysis (PCA) and further investigated for its predictive and therapeutic value in LUAD and LUSCC. Results: The expression of 57 ferroptosis-related genes in NSCLC patients differed significantly from that of normal subjects. Based on unsupervised clustering of ferroptosis-related genes, we divided all patients into three ferroptosis expression pattern groups, which showed differences in ferroptosis-associated gene expression patterns, immune cell infiltration levels, prognostic characteristics and enriched pathways. Using the differentially expressed genes in the three ferroptosis expression patterns, a set of 17 ferroptosis-related gene prognostic models was established, which clustered all patients in the cohort into a low score group and a high score group, with marked differences in prognosis (p < 0.001). The high ferroptosis score was significantly associated with positive response to radiotherapy (p < 0.001), high T stage (p < 0.001), high N stage (p < 0.001) and high-grade tumor (p < 0.001) characteristics. Conclusions: The 17 ferroptosis-associated genes show great potential for stratifying LUAD and LUSCC patients into high and low risk groups. Interestingly, a high ferroptosis score in LUAD patients was associated with a good prognosis, whereas a similar high ferroptosis score in LUSCC patients was associated with a poor prognosis. Familiarity with the mechanisms underlying ferroptosis and its implications for the treatment of NSCLC, as well as its effect on OS and PFS, may provide guidance and insights in developing new therapeutic targets for NSCLC.

Cutaneous soft tissue tumors: diagnostically disorienting epithelioid tumors that are not epithelial, and other perplexing mesenchymal lesions.

Cutaneous soft tissue tumors with epithelioid features present a diagnostic challenge given that many entities in this category are rare, and they show morphologic overlap with significantly more common cutaneous epithelial and melanocytic neoplasms. The challenge is compounded by overlapping expression of epithelial or melanocytic markers in some of these entities. A broad spectrum of primary cutaneous epithelioid soft tissue tumors exists, including benign and malignant counterparts of tumors with various differentiation including melanocytic, peripheral nerve sheath, angiomatous, fibrohistiocytic, and myoid or myoepithelial, in addition to translocation-associated tumors lacking a derivative tissue type. Given this spectrum, an initial targeted immunohistochemical panel for epithelioid dermal and subcutaneous neoplasms is recommended, covering a broad spectrum of differentiation. In diagnostically challenging cases, select molecular studies can be employed to make critical distinctions between entities sharing morphologic and immunohistochemical properties. Due to sometimes marked differences in prognosis and treatment, knowledge and familiarity with epithelioid soft tissue tumors is key for any surgical pathologist who evaluates skin and subcutaneous biopsies and excision specimens. This concise review provides brief descriptions, key diagnostic features, and important modern ancillary studies for the diagnosis of non-epithelial, non-melanocytic cutaneous tumors that can exhibit a prominent degree of epithelioid morphology.

Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium.

Colorectal cancer is the second most common cause of cancer‐related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I–IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography‐mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I–IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p FDR < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl‐alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p FDR < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.

Comparison of clinical findings between dogs with suspected anaphylaxis and dogs with confirmed sepsis

OBJECTIVE To compare clinical signs, laboratory test results, and imaging findings between dogs with suspected anaphylaxis and dogs with sepsis. DESIGN Retrospective case-case study. ANIMALS 10 dogs with suspected anaphylaxis and 22 dogs with confirmed sepsis that met the criteria for systemic inflammatory response syndrome. PROCEDURES Medical records for dogs in each group were reviewed and data extracted regarding signalment; reason for hospital admission; physical examination findings; results of CBC, serum biochemical analysis, coagulation testing, cytologic examination, and microbial culture; and imaging reports. RESULTS All dogs in the anaphylaxis group fulfilled the criteria for systemic inflammatory response syndrome. Dogs in both groups had gastrointestinal signs, lethargy, mentation change, and bleeding abnormalities. Dogs with suspected anaphylaxis had a significantly higher eosinophil count and serum alanine aminotransferase activity and lower blood pH than dogs with sepsis. Dogs with sepsis had a significantly higher band neutrophil count, serum globulins concentration, and serum alkaline phosphatase activity and lower serum glucose concentration. Dogs in both groups had intracavitary free fluid and ultrasonographic findings of thickened intestines, gas or fluid-filled intestines, and a thickened gallbladder wall. CONCLUSIONS AND CLINICAL RELEVANCE Clinical signs, laboratory values, and imaging findings may be similar in dogs with sepsis or anaphylaxis. Given the marked difference in prognosis and treatment, early differentiation is important. Anaphylaxis should be considered if a septic nidus cannot be identified, and supportive care should be considered for such patients.

Abstract B2-51: SpEeCH: Quantifying Spatial Expression of Clonal Heterogeneity in breast cancer

Abstract In routine breast cancer clinical practice, multiple serial sections are stained for guiding therapy. These include the most widely used hematoxylin &amp; eosin (H&amp;E) as well as established immunohistochemical biomarkers such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and increasingly so, Ki67, collectively known as the IHC4. Analysis of these sections involves visual assessment which is labor intensive and inefficient. More importantly, it ignores the wealth of spatial information in histological samples that can be used to better understand clonal heterogeneity, which may potentially be responsible for mixed response to treatment and drug resistance. Material and Methods: We have developed an automated image registration algorithm that aligns H&amp;E and IHC4 serial section images from the same tumor by employing a combination of rigid and non-rigid registration. This automated image registration algorithm subsequently enables us to develop SpEeCH (spatial expression of clonal heterogeneity), a novel method to identify spatial clusters with differential expression. At the core of SpEeCH is a clustering method that exploits spatial cellular characteristics of tumor regions to identify spatial clonal clusters. Gaussian mixture Model (GMM) is used in combination with the Bayesian information criterion and resampling to identify the optimal number of stable clusters. As GMM ignores local spatial dependency which is an important tumor characteristic, we are also comparing GMM with conditional random fields that are undirected graphical models to account for local dependencies instead of full joint distribution. To discover spatial clusters, we applied SpEeCH to a set of 13 high-grade surgically resected breast tumors with serial sections of H&amp;E and IHC4. Tumor regions were defined as 5 μm x 5 μm squares, resulting in &amp;gt;10,000 regions for clustering in each tumor. Clinical implications of the spatial clusters were verified in an independent dataset (METABRIC) that consists of gene expression whole-tumor profiles and disease-specific survival data of 2,000 breast cancer tumors. Results: By employing SpEeCH, we identified five stable spatial clusters based on histological section of H&amp;E and IHC4 in the discovery set, with significantly different disease-specific survival validated in METABRIC gene expression data (p=0, log-rank test). This analysis revealed a group of poor prognosis ER-/HER2+/Ki67+ patients (p=0, hazard ratio = 4.4, 95% confidence interval = 3.0-6.3, log-rank test compared to a good prognosis group ER+/HER2-/Ki67-). Marked differences in prognosis among these groups highlight the significance of identified spatial clusters. For example, one of the tumors in the discovery set contains both ER-/HER2+/Ki67+ and ER+/HER2-/Ki67- clones. Therefore, such clonal heterogeneity, which is ignored during diagnosis, may help explain treatment resistance. To this end, our observation confirmed the clinical relevance of spatial clusters by leveraging a large-scale dataset under the assumption that such data represents signal from major clones. We propose that the number of clonal clusters and their spatial relationship within a tumor can be used as measures of intra-tumor heterogeneity. Their efficacy is currently being evaluated on independent clinical datasets. Conclusion: Large numbers of histology samples are available from clinical diagnostics and research laboratories, yet there is a lack of tools that facilitate objective analysis of tumor heterogeneity in these samples. Compared to high-cost multimarker immunofluorescence approaches, our automated image and statistical analysis pipeline enables efficient and effective analysis of available histology samples, which is critical for understanding cancers as highly heterogeneous diseases. Citation Format: Andreas Heindl, Adnan Mujahid Khan, Yinyin Yuan. SpEeCH: Quantifying Spatial Expression of Clonal Heterogeneity in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-51.

Uterine sarcomas.

Uterine sarcomas.

Gliosis Versus Glioma?

A major challenge in the routine practice of surgical neuropathology is the distinction between reactive astrocytosis, which may be because of non-neoplastic and neoplastic conditions, and a low-grade infiltrating diffuse astrocytoma [World Health Organization (WHO) grade II]. This can be particularly challenging with small biopsies that often yield limited amounts of tissue for pathologic study, especially considering the marked differences in prognosis and therapy after a pathologic diagnosis. This paper will review some basic principles of gliosis as an astrocytic reaction to a wide range of central nervous system insults and focus on some common diagnostic pitfalls such as (1) gliosis associated with brain tumor mimics, including demyelinating disease and infections, (2) gliosis associated with nonglial tumors such as craniopharyngioma, hemangioblastoma, metastases, and central nervous system lymphoma. New diagnostic methods have facilitated the differentiation between reactive astrocytosis and the diffuse gliomas. Of these, the use of mutated isocitrate dehydrogenase-1 (IDH-1) as a marker of diffuse infiltrating astroctomas, oligodendrogliomas, and a subset of glioblastomas (secondary glioblastomas) is particularly exciting for tissue diagnosis and patient prognosis. In addition IDH-1 may be useful to distinguish a diffuse infiltrating glioma from low-grade "focal" neoplasms such as the pilocytic astocytoma in histologically ambiguous cases. The discovery of BRAF mutations as molecular signatures of some pilocytic astrocytomas, gangliogliomas, and pleomorphic xanthoastrocytomas has provided another diagnostic tool for the pathologist. Only after a definitive diagnosis of a diffuse infiltrating glioma or a focal glioma is made should a tumor grade be applied and some practical issues in current glioma grading are provided.

Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients

To determine the frequency and survival of the various types of uterine sarcoma in the total population of Norway and evaluate histopathological prognostic factors in order to identify risk groups. Histopathological review of all uterine sarcoma cases reported to the Norwegian Cancer Registry during 1970-2000 was undertaken. Survival dates were provided by The Cancer Registry. Kaplan-Meier survival curves were generated. The log rank test was used for univariate analysis and a Cox proportional hazards regression model for multivariate evaluation of survival. Stage of disease was the most important prognostic factor for all tumour types. Tumour size and the mitotic index (MI) were significant prognostic factors (P < 0.0001) in leiomyosarcomas confined to the uterus and allowed for separation into three risk groups with marked differences in prognosis. The prognosis of endometrial stromal sarcomas confined to the uterus was related to MI (P < 0.0001) and tumour cell necrosis (P < 0.004). Combining these parameters allowed for separation into three risk groups with marked difference in prognosis. In adenosarcomas, tumour cell necrosis was the only significant prognostic factor. There are marked differences in survival between uterine sarcoma types. Leiomyosarcomas and endometrial stromal sarcomas can be divided into different groups.

Does Stage T3a Renal Cell Carcinoma Embrace a Homogeneous Group of Patients?

Renal cell carcinoma invading the perinephric fat is classified as a stage T3a tumor in the 2002 TNM version. Based on long-term followup we examined the prognostic significance of this definition. We evaluated the outcome in 237 consecutive patients with localized renal cell carcinoma operated on between January 1985 and December 1997. Median followup was 8 years. Disease-free survival was analyzed using univariate and multivariate analyses. Based on this we proposed and tested a new TNM system against the 2002 TNM version. Tumor recurrence was diagnosed in 48 patients (20.2%) at a median of 21.5 months. Diameter based analysis of stage T3a revealed that this was an inhomogeneous group that included patients with small tumors and an excellent prognosis along with patients with large tumors and a poor prognosis. Based on this information we initiated a modified TNM staging system that ignores perinephric fat invasion. In the proposed staging system stage T1a includes tumors 4 cm or less and stage T1b includes tumors more than 4 but 7 cm or less. Stage T2 is divided into T2a-tumors greater than 7 but 10 cm or less and T2b-tumors greater than 10 cm. Stage T3a is reserved for renal vein tumor invasion. The proposed TNM performed better than the 2002 version using the Nagelkerke R(2) test (0.439 vs 0.359), and the Hosmer and Lemeshow test (0.335 vs 0.191). The current definition of stage T3a renal cell carcinoma embraces an inhomogeneous group of patients with marked differences in prognosis. We believe that tumor invasion into the perinephric fat does not necessarily predict aggressive biological behavior.

Turbulence of glomerular hemodynamics involved in progressive glomerulosclerosis

There is increasing evidence that changes of glomerular hemodynamics or glomerular growth responses may promote the development of glomerulosclerosis. Major problems retarding research progress include lack of suitable experimental animal models, with the exception of the ablation model, and the need for in vivo real-time analysis of glomerular hemodynamics. This study examined the sequence of pathological changes from the viewpoints of microcirculation and histopathology, from the acute stage to the chronic course and the final stage of glomerulosclerosis, using the confocal laser scanning microscope system. There is a marked difference in prognosis between sham-operated (two-kidney) and nephrectomized (one-kidney) rats after injection with anti-Thy-1 antibody. The former reversibly returns to normal and the latter irreversibly go to progressive sclerosis, respectively. The turning point determining the progression of glomerulosclerosis in both groups seemed to be the period from 7 to 14 days after disease induction, when disturbance of local intraglomerular blood flow continued in the one-kidney groups. In conclusion, this study provides the first hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulosclerosis.

Multimodal therapy of colon carcinoma

A large variety of immunological and cytotoxic adjuvant treatment concepts and application routes have been observed to be effective in colon cancer by randomized trials during the past three decades. Presently adjuvant 5-fluorouracil based chemotherapy is favoured for patients with lymph node metastases (UICC stage III), since this treatment was associated with a 5-10% increase in 5-year survival. Uncertainty persists regarding the optimal use of adjuvant treatment, since marked differences in prognosis have been recognized within stage III and because the impact of surgical treatment on long-term survival has not been thoroughly controlled for in past trials. Current and future studies will have to determine precisely which patients will benefit most from adjuvant treatment and which combination of surgical and adjuvant treatment will be most effective.

Renal Oncocytoma and its Congeners

Although the morphologic criteria for separating renal oncocytomas from renal carcinomas with overlapping features are not established completely, the distinction is crucial because of the marked difference in prognosis. Of the 247 renal carcinomas observed at our hospital since 1947, six had sufficient morphologic features of oncocytoma to pose potential difficulty in diagnosis. We term this group the “congeners of renal oncocytoma.” Both the congeners and our 10 oncocytomas were well-circumscribed tumors, varied considerably in size, and were composed of cells with granular, pink-red cytoplasm. The congeners lacked the diffuse organoid packeting of cells, characteristic of oncocytoma. Additional features that helped separate individual congeners from oncocytomas included yellow-tan rather than brown-red gross color, necrosis, pleomorphism, ballooned cytoplasm, or clear cells. Our studies indicate that some renal carcinomas have fields identical to oncocytoma, and frozen section, needle biopsy, or aspiration cytology from such an area could lead to a misdiagnosis.

Renal oncocytoma and its congeners.

Although the morphologic criteria for separating renal oncocytomas from renal carcinomas with overlapping features are not established completely, the distinction is crucial because of the marked difference in prognosis. Of the 247 renal carcinomas observed at our hospital since 1947, six had sufficient morphologic features of oncocytoma to pose potential difficulty in diagnosis. We term this group the "congeners of renal oncocytoma." Both the congeners and our 10 oncocytomas were well-circumscribed tumors, varied considerably in size, and were composed of cells with granular, pink-red cytoplasm. The congeners lacked the diffuse organoid packeting of cells, characteristic of oncocytoma. Additional features that helped separate individual congeners from oncocytomas included yellow-tan rather than brown-red gross color, necrosis, pleomorphism, ballooned cytoplasm, or clear cells. Our studies indicate that some renal carcinomas have fields identical to oncocytoma, and frozen section, needle biopsy, or aspiration cytology from such an area could lead to a misdiagnosis.

Survival from invasive cutaneous malignant melanoma in western australia and the oxford region: A comparative histological study of high and low incidence populations

A detailed histological review of 196 cases of invasive cutaneous malignant melanoma diagnosed in Western Australia, a high incidence area, during 1975-76 and of 226 cases during the period 1972-76 from the Oxford Region, a low incidence area, was made by one pathologist using the same parameters for each series. Five-year survival rates were analysed with respect to histological features, sex and site, with and without correction for tumour thickness. The results showed higher overall survival rates in Western Australia, with marked differences in prognosis between males and females in the Oxford Region, and between Oxford males and patients of both sexes in Western Australia. These findings were in accord with the corresponding differences in tumour thickness, and they support the theory that survival rates from cutaneous malignant melanoma are higher in areas of high incidence because they are diagnosed and treated earlier.

Acute Mitral Insufficiency Secondary to Ruptured Chordae Tendineae

A patient had acute mitral insufficiency secondary to ruptured chordae tendineae. Recognition of acute mitral insufficiency and of its differentiation from chronic mitral insufficiency is important because of marked differences in prognosis and management. We emphasize the pathophysiology of acute and chronic mitral insufficiency to provide a firm basis for understanding the clinical and laboratory manifestations of these two entities as well as their differential diagnosis. We consider this differential diagnosis in detail, comparing and contrasting pathophysiologic mechanisms and clinical and laboratory manifestations.

Pseudomyxoma peritonei: failure of activated trypsin to modify the course of the disease.

PSEUDOMYXOMA peritonei is an uncommon disease with wide variability in degree of malignancy, marked differences in prognosis, and unpredictable response to therapy. Definitive surgery in itself is usually unsuccessful in arresting the disease. As adjuncts to surgery, a variety of therapeutic agents have been tried, including radiotherapy, radioactive gold, and nitrogen mustard. None has proved especially efficient. Part of the therapeutic problem obviously lies in the rarity of the condition and, therefore, in the paucity of reports concerning its management. Another part of the problem is related to the chronicity of the disease and the difficulty of being able to assess the value of therapy. A recent publication by Saegesser1made a therapeutic claim for the intraperitoneal use of activated pancreatic extract in the treatment of pseudomyxoma peritonei. This report prompted us to try this form of treatment on one of our patients with a long, well-documented history of pseudomyxoma

The roentgen spectrum in persistent common atrioventricular canal.

With the advent of corrective surgery in congenital heart disease, the differential diagnosis of cardiac abnormalities has become a matter of vital importance to the clinician and the radiologist. The group of lesions classified as persistent common atrioventricular canal defects or endocardial cushion defects represent a broad spectrum of clinical and anatomic abnormalities. In addition, especially with respect to the surgical results, the prognosis depends upon the actual anatomic and functional severity of the anomaly. A brief survey of the literature indicates a marked difference in prognosis between patients with an ostium primum defect in association with a cleft mitral valve and those with an ostium primum defect, a common atrioventricular canal, and a significant ventricular septal defect (Table I). Operative mortality in the first group varies between 7.5 and 22 per cent in several reported series (3–5, 8). If patients in the second group are subjected to primary corrective surgery, however, operative mortality may be as high as 67 per cent. It thus becomes extremely important to determine as accurately as possible the exact anatomic abnormality prior to surgical intervention. Classification We have subdivided our cases in a manner corresponding to the classification of Wakaiand Edwards (10), as follows (Table II): I. Partial form: An ostium primum type of interatrial septal defect in association with a cleft in the anterior leaflet of the mitral valve. Slight shortening of the septal leaflet of the tricuspid valve may be present. Usually there is no ventricular septal defect, although occasionally one which is small and functionally insignificant may be encountered. II. Intermediate form: An ostium primum interatrial septal defect with cleft mitral and tricuspid valves. Small interventricular septal defects are usual, but their size is much smaller than in the complete form. III. Complete form: A continuous cleft through both the anterior mitral and septal tricuspid leaflets in association with an ostium primum interatrial septal defect and a functionally significant ventricular septal defect. IV. Complete or partial forms: Associated pulmonic stenosis. Clinical Material We have seen 43 patients with persistent common atrioventricular canal defects, and in 33 of these, roentgen examinations were adequate. The patients ranged in age from two weeks to fifty-four years (Table III). Plain and Findings The diagnosis of persistent atrioventricular canal is ordinarily made at the time of the clinical examination, including electrocardiography. The electrocardiogram is usually quite characteristic, demonstrating evidence of left axis deviation in association with an rSR or right ventricular hypertrophy pattern in the right precordial leads (2, 7).