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IgM-mediated, T cell-independent suppression of humoral immunity.

The immunological unreactive state occurring in (T,G)-A-L nonresponder mice after secondary antigen challenge was investigated. Syngeneic IgM anti-(T,G)-A-L antibody-containing plasma, transferred at the time of the time of primary challenge, induced persistent suppression of autologous specific antibody production. Removal of plasma IgM with goat anti-mu antisera removed the ability of the plasma to supress. The induction and maintenance of the suppressed state were not different in thymectomized or sham-thymectomized animals. Primed animals subjected to graft-vs-host reaction (GVHR) at the time of secondary challenge switched over to IgG production. Animals suppressed by passive antibody transfer reacted to GVHR, at the time of secondary challenge, with specific IgM but not IgG antibody production. Transfused normal spleen cells partially abrogated suppression only when (suppressed) hosts had been lethally irradiated. Spleen cells from antigen-plus-antibody suppressed donors, upon transfer to previously normal, syngeneic hosts, were less immunocompetent than spleen cells from untreated donors. These data are consistent with a model of IgM mediated, T cell-independent persistent suppression of humoral immunity.

Animals↗

Transplantation of allogeneic bone marrow without graft-versus-host disease using total lymphoid irradiation.

Bone marrow (BM) and skin allografts from C57BL/Ka (H-2b/b) mice were transplanted to BALB/c (H-2d/d) recipients treated with total lymphoid irradiation (TLI), whole-body irradiation (WBI), or fractionated thymic irradiation TLI prolonged skin allograft survival about five times as long as that in untreated controls, and allowed for permanent engraftment of BM cells in approximately equal to 90% of recipients. None of the BM recipients showed clinical signs of graft-versus-host disease (GVHD) (diarrhea, weight loss, hunched back, etc.). On the other hand, recipients given WBI and allogeneic BM cells developed severe clinical GVHD. The majority of the latter recipients died within 12 days after BM transplantation, and 95% died within 61 days. Although TLI protected BALB/c mice against GVHD induced by BM cells, all recipients given TLI and allogeneic spleen cells developed lethal GVHD. Thymic irradiation alone marginally prolonged skin allograft survival, and did not allow for allogeneic BM engraftment. These results suggest that TLI may be a useful regimen in clinical BM transplantation, since this form of radiotherapy is used extensively in humans and has few severe side effects.

Animals↗

[Pulmonary embolism in the elderly patient (author's transl)].

Pulmonary embolism has a high incidence in old patients and is often not recognized. In most cases the embolism is of unknown origin, although the deep venous system of the lower extremities is involved in almost 95%. The diagnostic procedure consists of evaluation of clinical symptoms and findings. ECG and chest X-ray are often not conclusive. Confirmation of the diagnosis is possible by ventilation-perfusion scanning of the lung. Pulmonary angiography is of no value in the elderly patient, because of the lack of consequences. Besides local therapy of a thrombosis, therapy consists of administration of heparin, while oral anticoagulation should be used only with precaution. The efficacy of platelet aggregation inhibiting substances remains to be determined. The main point are prophylactic measures in patients with risk factors or in high risk situation.

Aged↗

The effectiveness and cost of acute respiratory illness medical care provided by physicians and algorithm-assisted physicians' assistants.

The medical management of patients with acute respiratory illnesses was analyzed at two different clinics during a 14- to 21-month period. Patients received care from either physicians or physician-supervised physician's assistants (PA). The PAs used respiratory illness clinical algorithms to guide their choice of diagnostic tests and treatment. Illness outcome, patient satisfaction, and medical care cost data were obtained for all patients approximately two weeks after the index illness. Despite significant differences in patient population characteristics, illness outcomes were similar, regardless of the provider's educational background. Medical care costs, however, were highest for the physician's patients. For all patients, diagnostic tests contributed about one-third of the total direct costs, mainly because of chest x-ray and throat culture use. Sixty to eighty per cent of medication costs were due to nonprescription drugs used principally for symptom relief. The data demonstrate that the medical care delivered by these physician's assistants was as effective and less costly than the care provided by physicians. Reducing chest x-ray and throat culture use would have a significant economic impact, without adversely affecting medical care effectiveness.

Acute Disease↗

Advancing cancer detection and treatment using longitudinal routine clinical data.

Cancer management remains fragmented across its continuum, from late-stage diagnosis and salvage therapies to non-personalized surveillance. Here, we present Oncoformer, a unified multimodal transformer model trained on the China Oncology Multimodal Prediction and Surveillance Study (COMPASS) cohort (3.67 million individuals, 17.7 million clinical visits) and validated on independent external cohorts, including the UK Biobank. Oncoformer integrates longitudinal electronic health records with chest X-ray imaging to address multiple clinical tasks: pan-cancer diagnosis (area under the receiver operating characteristic curve [AUROC] = 0.956), future cancer prediction up to 1 year before diagnosis (AUROC = 0.869), tumor stage inference (mean AUROC > 0.90), patient-specific treatment-response forecasting, and recurrence-free survival stratification across ten cancer types (all p < 0.01). Staging predictions were independently validated against postoperative pathological endpoints and shown to converge on core cancer genomic pathways. By translating routine clinical data into a dynamic view of cancer evolution, Oncoformer provides a framework for risk-informed cancer prediction and treatment stratification using routine clinical data.

Humans↗

Generation of cytotoxic T lymphocytes in vitro. VII. Suppressive effect of irradiated MLC cells on CTL response.

Irradiated cells obtained from MLC at the peak of the CTL response caused profound suppression of generation of CTL when added in small numbers at the initiation of primary MLC prepared with normal spleen cells. The inhibitory activity of the MLC cells was not affected by irradiation (1000 rads) but was abolished by treatment with anti-theta serum and complement. The suppression was immunologically specific. The response of A (H-2a) spleen cells toward C3H (H-2k) alloantigens was suppressed by irradiated MLC cells obtained from MLC prepared with A spleen cells and irradiated C3H-stimulating cells, whereas the response of A spleen cells toward DBA/2 (H-2d) alloantigens was affected relatively little. However, if irradiated C3H X DBA/2 F1 hybrid spleen cells were used to stimulate A spleen cells in MLC, addition of irradiated MLC cells having cytotoxic activity toward C3H antigens abolished the response to both C3H and DBA/2 antigens. The response to DBA/2 antigens was much less affected when a mixture of irradiated C3H and DBA/2 spleen cells was used as stimulating cells. Thus, the presence of MLC cells having cytotoxic activity toward one alloantigen abolished the response to another non-cross reacting antigen only when both antigens were present on the same F1 hybrid-stimulating cells. This suppression of generation of CTL by irradiated MLC cells apparently involves inactivation of alloantigen-bearing stimulating cells as a result of residual cytotoxic activity of the irradiated MLC cells. This mechanism may be active during the decline in CTL activity noted in the normal immune response in vivo and in vitro.

Animals↗

[The problem of early diagnosis of brain tumours causing seizures only (author's transl)].

The diagnosis of brain tumour could not be made in 91 cases at the first investigation in a group of 1155 brain tumours. Slowly growing gliomas causing only epileptic fits and no other symptoms are especially difficult to diagnose. Of 21 personal observations of tumour seizures, in which the diagnosis of the neoplasm was missed at the first investigation in hospital, 9 were oligodendrogliomas, 5 astrocytomas, 3 glioblastomas, 2 spongioblastomas, 1 gangliocytoma and 1 a metastasis. They were all located in the frontal or centroparietal region. In most cases the seizures appeared during the third or fourth decade. The average interval between the first epileptic fit and the tumour diagnosis was 8.2 years in cases of oligodendrogliomas and 2.2 years in astrocytomas. 5 patients had major seizures, 2 had psychomotor attacks and all the others suffered from partial epilepsy. Anticonvulsive therapy was often successfull; either the frequency of the fits diminished or, in 2 cases, the character of the seizures changed. 18 patients had a normal neurostatus at time of the first investigation. Only 3 patients had a slight difference of physiological reflexes, but no other pathological signs. In none of the patients did investigation of the CSF, skull X-rays, brain scanning, pneumencephalography or cerebral angiography first lead to the diagnosis of a brain tumour. The EEG alone showed focal signs corresponding to the location of the tumour in about 50% of the cases.

Adolescent↗

Computed tomography-guided precision biopsy combined with metagenomic next-generation sequencing for etiological diagnosis in patients with blood culture-negative systemic infections.

ObjectiveTo evaluate the diagnostic efficacy of computed tomography-guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy.MethodsThis single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography-guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (&#x3b1;&#x2009;=&#x2009;0.05, &#x3b2;&#x2009;=&#x2009;0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled.ResultsComputed tomography-guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p&#x2009;<&#x2009;0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9-98.5), specificity of 100.0% (95% confidence interval: 29.2-100.0), positive predictive value of 100.0% (95% confidence interval: 94.9-100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9-81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients.ConclusionsThe integration of computed tomography-guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.

Humans↗

Severe Phenotype in an Indian Family With Progressive Pseudorheumatoid Arthropathy of Childhood.

Progressive pseudorheumatoid arthropathy of childhood (PPAC) is a rare autosomal recessive progressive condition that affects the cartilage of joints and bones. The symptoms of PPAC include stiffness of the joints, bony swelling of the toes and fingers, short stature, kyphosis, and muscle weakness. The radiologic manifestations are often mistaken for juvenile rheumatoid arthritis and include platyspondyly, widened metaphyses, flattened epiphyses, and large femoral heads. The disease is caused by variants in the WISP3 (also known as CCN6) gene, which encodes a member of the WNT1 inducible signaling pathway (WISP) protein subfamily, which belongs to the connective tissue growth factor (CTGF) family. We describe three affected female siblings in an Indian family with PPAC, all of whom manifest a severe phenotype of the disease. The girls all walked with a crouching gait from severe joint contractures. Radiographic findings included generalized periarticular osteopenia and widened metaphyses. The radiographs of the hands and feet showed similar changes with narrow joint spaces, widened metaphyses, and flattened epiphyses. Elbows and knees revealed gracile bones, and contractures with severe muscle atrophy. Spine films were significant for marked beaking, lumbar vertebrae anterior narrowing, irregular end plates and rotational scoliosis. X-rays of the hips revealed deformed femurs, coxa vara, and large flat epiphyses. All affected individuals were compound heterozygotes for two pathogenic variants in the WISP3/CCN6 gene, a novel nonsense variant (c.172A>T [p.Lys58*]) and a 2-base pair deletion (c.740_741delGT [p.Cys247Leufs*31]). This combination of a nonsense and frameshift variant has not previously been reported and may be the explanation for the severe clinical manifestation of PPAC in this family. Further investigation into the mechanism of the disease may provide promising therapies to modify disease progression.

WISP3↗

Functional characterization of DPP4 and FcRn as receptor and coreceptor for classical human astroviruses in Caco-2 cells.

Classical human astroviruses (HAstV) are a global cause of viral gastroenteritis, particularly in children and immunocompromised individuals. Despite their clinical significance, the biology of HAstV remains poorly understood. In particular, the identification of cellular receptors and coreceptors has been elusive. Recent studies have identified the human neonatal Fc receptor (FcRn) as a functional receptor and dipeptidyl peptidase IV (DPP4) as an entry factor for HAstV. However, the precise roles of FcRn and DPP4 during HAstV infection are unknown. To learn about their function, we used FcRn-knockout (KO), DPP4-KO, and FcRn/DPP4 double-KO Caco-2 cells generated via CRISPR/Cas9. Our results showed that DPP4 serves as the receptor for classical HAstV. In contrast, infectious virus assays and confocal fluorescence microscopy revealed that FcRn acts as a coreceptor, facilitating viral internalization and the release of the RNA genome. The half-time for HAstV-1 genome uncoating was delayed threefold in FcRn-KO Caco-2 cells compared to WT cells. Additionally, the characterization of HAstV-8 variants with reduced FcRn binding capacity allowed the identification of two amino acids in the viral capsid spike protein, D471 and N512, critical for the spike-FcRn interaction. These amino acid residues are part of the epitope footprint of neutralizing monoclonal antibodies (Nt-MAbs) to HAstV previously mapped by X-ray crystallography. Further experiments using virus infectivity and attachment assays, along with Nt-MAbs targeting HAstV-1, suggest that the binding sites for FcRn and DPP4 are spatially proximal on the viral spike, defining a functional domain for cell infection. Notably, the infectivity of the divergent HAstV-VA1 was independent of these two proteins, highlighting the receptor variability across HAstV clades. These findings provide new insights into the mechanism of HAstV infection, offering relevant implications for the development of antiviral therapies and vaccines targeting this significant human pathogen.

Humans↗

[New possibilities in diagnosis and therapy of renal carcinoma (author's transl)].

A brief discussion of the aetiology and epidemiology of renal carcinomas is followed by a description of the clinical features. Attention is drawn to the significance of symptoms emphasizing the importance of early diagnosis. Intravenous urography still remains as the most important diagnostic procedure. It is pointed out that sonography and computer-tomography are now established as newer diagnostic methods, i.e. in distinguishing between cyst and tumor, in renal masses. Therapy, is still based upon surgical treatment. Transperitoneal, radical tumornephrectomy as compared with simple lumbar nephrectomy, has improved 5-year survival rate up to 16% especially in stage III tumors. Extracorporeal surgery for single kidney patients as hyperthermic surgery constitute new surgical methods, but only for specifically equiped urologic clinics. Embolisation of renal cell carcinoma is also used as therapeutic management in largely progressed tumors, and also used, as a preoperative measure, for the reducement of tumor size. Irradiation, before and after surgical treatment, as well as cytostatic therapy, revealed no significant improvement. We have reason to hope that progress in the research of hormonal- and immunotherapy will improve 5-year survival rate, in renal cell carcinoma.

Adolescent↗

Development and Validation an Integrated Deep Learning Model to Assist Eosinophilic Chronic Rhinosinusitis Diagnosis: A Multicenter Study.

BACKGROUND: The assessment of eosinophilic chronic rhinosinusitis (eCRS) lacks accurate non-invasive preoperative prediction methods, relying primarily on invasive histopathological sections. This study aims to use computed tomography (CT) images and clinical parameters to develop an integrated deep learning model for the preoperative identification of eCRS and further explore the biological basis of its predictions. METHODS: A total of 1098 patients with sinus CT images were included from two hospitals and were divided into training, internal, and external test sets. The region of interest of sinus lesions was manually outlined by an experienced radiologist. We utilized three deep learning models (3D-ResNet, 3D-Xception, and HR-Net) to extract features from CT images and calculate deep learning scores. The clinical signature and deep learning score were inputted into a support vector machine for classification. The receiver operating characteristic curve, sensitivity, specificity, and accuracy were used to evaluate the integrated deep learning model. Additionally, proteomic analysis was performed on 34 patients to explore the biological basis of the model's predictions. RESULTS: The area under the curve of the integrated deep learning model to predict eCRS was 0.851 (95% confidence interval [CI]: 0.77-0.93) and 0.821 (95% CI: 0.78-0.86) in the internal and external test sets. Proteomic analysis revealed that in patients predicted to be eCRS, 594 genes were dysregulated, and some of them were associated with pathways and biological processes such as chemokine signaling pathway. CONCLUSIONS: The proposed integrated deep learning model could effectively predict eCRS patients. This study provided a non-invasive way of identifying eCRS to facilitate personalized therapy, which will pave the way toward precision medicine for CRS.

Humans↗

[Pulmonary edemas due to acute heroin poisoning].

Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.

Acute Disease↗

Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn's disease.

In a prospective multicentre study, 97 patients with Crohn's disease and operated on by a radical excision of the Crohn-involved bowel were randomly divided into two groups, one treated 33 weeks postoperatively by corticosteroids and Salazopyrin and the other without any medical treatment postoperatively. The patients in the two groups were followed up during three years after the operation and an X-ray of the bowel was yearly performed. Thirteen patients were excluded for different reasons, which means that 84 patients were left for the study. There was no statistically significant difference in the number of recurrences after one, two, or three years of observation time in the two groups of patients. There was a statistically significantly longer time between diagnosis and operation in the group of patients with recurrences than in patients with no recurrences. This might mean that patients with Crohn's disease undergoing an early operation have a better chance of escaping recurrences.

Adult↗

Longitudinal In Vivo Imaging at Single-Lesion Resolution Identifies Allele-Associated Response and Resistance Dynamics in EGFR-Mutant Lung Cancer.

Acquired resistance to targeted therapies is inevitable in EGFR-mutant non-small cell lung cancer (NSCLC), yet the principles governing its emergence in vivo remain incompletely understood. In particular, how lesion-level response patterns vary across distinct EGFR allele contexts during therapy has not been systematically examined at single-lesion resolution. Here, we establish a longitudinal in vivo imaging platform enabling single-lesion resolution tracking of tumor behavior during therapy in genetically engineered mouse models representing clinically relevant EGFR alleles. Using high-resolution micro-computed tomography (micro-CT) and three-dimensional reconstruction, we monitor tumor growth, therapeutic response, and resistance during osimertinib treatment. EGFR genotype is associated with distinct patterns of tumor growth, response kinetics, and resistance timing. Therapeutic response is spatially heterogeneous, with coexisting lesions undergoing complete regression, persistence, or progression within the same lung. During treatment, spatially distinct lesion-level behaviors included persistent growth during therapy and initial regression followed by regrowth. These findings demonstrate the utility of longitudinal micro-CT imaging to investigate allele-associated differences in treatment response and resistance timing at single-lesion resolution in vivo.

Animals↗

The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span. II. Cell-mediated immune activity.

The late effects of various immunosuppressive insults on cell-mediated immunity in mice were studied in an attempt to assess the role of immune surveillance in the aging process. Results were obtained using susceptibility to allogeneic tumor cell challenge, graft-versus-host reaction (GVHR), blastogenic response to PHA, a thymus derived T cell-specific plant mitogen, and cytolytic activity against allogeneic tumor cells as measures of immunologic activity. In vivo studies late in life show that resistance to allogeneic tumor cells is significantly decreased in thymectomized mice, whereas those treated with cortisone, cyclophosphamide and sublethal X-ray remain unchanged. Spleen cells from only the thymectomized and the sublethally irradiated mice show reduced activity in the GVHR. No difference is seen in the activity of bone marrow cells. Results consistent with these findings were obtained in in vitro studies. Thus spleen cells from thymectomized or sublethally irradiated mice show decreased activity is response to PHA, whereas no change is seen in spleen cells from other treated groups. Hence, surgical and physical insults are more likely to induce long-lasting immunosuppression in those immunocompetent tissues whose activity normally diminishes with advancing age. Furthermore, the degree of immunosuppression seen in this study is not of the order of magnitude that one could reasonably predict a significant decrease in mean life-span.

Age Factors↗

An Aspergillus luchuensis isolated from a patient with hemoptysis insights from a comprehensive genome-based analysis: Case report.

RATIONALE: Asp luchuensis, a member of the A niger group, is widely used in food fermentation and rarely causes invasive pulmonary aspergillosis (IPA) in humans. Clinical cases of IPA induced by this strain are extremely scarce, and its genomic characteristics, virulence profiles, and pathogenic mechanisms remain poorly understood, resulting in insufficient clinical recognition of its invasive infection potential. PATIENT CONCERNS: A 57-year-old immunocompetent non-neutropenic male patient with a long-term smoking and drinking history presented with unexplained severe cough and massive hemoptysis (approximately100&#x2009;mL) without other typical infectious symptoms. DIAGNOSES: Combined with chest computed tomography (CT) inflammatory lesions, positive galactomannan test, fungal PCR and metagenomic next-generation sequencing results, the patient was definitively diagnosed with probable A luchuensis-induced IPA. Genomic and transcriptomic analyses confirmed the pathogen as a variant A luchuensis strain with 3 key hypervirulence genes, highly active mitochondrial energy metabolism, and no specific antifungal resistance genes. INTERVENTIONS: The patient received standardized intravenous antifungal combination therapy with voriconazole and amphotericin B after confirmed diagnosis. OUTCOMES: The patient's cough and hemoptysis were significantly relieved after 10 days of treatment, with stable vital signs and no adverse drug reactions or disease progression. LESSONS: A luchuensis possesses strong invasive pathogenicity and can trigger IPA even in non-neutropenic immunocompetent individuals. Negative conventional microbial tests cannot exclude its infection, and mNGS is a reliable diagnostic tool. This strain is susceptible to routine antifungal drugs, and clinicians should raise awareness of atypical Asp species-induced invasive pulmonary infections.

Humans↗

Liver tumors in children in the particular reference to hepatoblastoma and hepatocellular carcinoma: American Academy of Pediatrics Surgical Section Survey--1974.

A review of 227 cases of hepatoblastoma, hepatic cell carcinoma in children seen in the United States over a 10-yr period is presented. Both tumors were seen most commonly in infancy, but the hepatocellular carcinoma shows a second peak of incidence around puberty. Males predominated in both diseases more so in hepatoblastoma. Presenting symptoms in both diseases were very similar, most commonly an upper abdominal mass or abdominal enlargement associated with anorexia and weight loss. In the preoperative evaluation the presence of alpha-feto protein was one of the most helpful diagnostic tests. Disturbances of liver function were usually mild but were more marked in those children with hepatocellular carcinoma. Preoperative x-rays were abnormal in a large percentage of cases with the hepatic arteriogram and vena cavagram being the most useful diagnostic x-rays for liver tumors. Liver scans were positive for liver tumor in 95% of the children when this test was carried out. The follow-up for these patients ranged from 2 to 10 yr. The size of the primary tumor did not appear to correlate with survival but bilateral location of the tumor, 33% in hepatoblastoma and 45% in hepatocellular carcinoma, made many of these tumors inoperable. Multicentric tumors were also found in a large number of patients, being more common in hepatocellular carcinoma. There was a high rate of local recurrence or local extension after operation in both diseases, and metastatic spread was similar being most common to the lungs and abdomen. A wide variety of surgical procedures were carried out in these patients from biopsy only to extended hepatic lobectomy. When incomplete excision or biopsy only was carried out no patient survived in either group. Among the hepatoblastoma patients, 45 of 78 patients who had complete excision are surviving. In the hepatocellular carcinoma patients where the operability rate was much lower 12 of 33 patients are surviving when tumor was completely excised. Complications were frequent, the most common being excessive blood loss at operation. There were eight operative deaths and 17 postoperative deaths in the combined group. There was no evidence that radiation therapy or chemotherapy controlled disease which could not be completely excised surgically. The only direct evidence of a favorable effect of radiation and chemotherapy were three cases of hepatoblastoma in which the tumor changed from inoperable to operable by a combination of radiation therapy and multiple drug chemotherapy. Both tumors are highly malignant, and 90% of the children who died of hepatoblastoma died within 12 mo of diagnosis. In the hepatocellular carcinoma 80% of the deaths occurred within 1 yr of diagnosis. At this time it seems that operative excision offers the only chance of cure in children with these tumors and cure rates of 60% can be expected with hepatoblastoma and 33% in hepatocellular carcinoma if the tumor can be completely excised.

Adolescent↗