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Cryosurgery re-visited for the removal and destruction of brain, spinal and orbital tumours.

Advances in neuroimaging and cryosurgical techniques have prompted us to re-evaluate the potential of cryosurgical techniques for the removal and the destruction of various neoplasms. We have used cryosurgical instrumentation to remove tumours in the brain, spine and orbit in 71 patients without complications. Cryosurgery was used to facilitate removal and extraction in 64 and to destroy residual neoplasms when removal was incomplete in 7. Intraoperative real time ultrasonic imaging permitted precise delimitation of tumours from surrounding tissues and allowed monitoring during the production of cryosurgical lesions thus permitting heretofore unavailable visualization of the production of cryogenic lesions in the central nervous system. New cryosurgical instrumentation was used to produce lesions up to three times larger than similar sized probes previously available. Our results reconfirm that cryosurgery facilitates the removal of tumours in the brain, spinal cord and orbit, reduces blood loss in vascular tumours, and is effective in ablating residual neoplasms involving the superior sagittal sinus, torcula and parasagittal areas. A Doppler flowmeter proved useful for monitoring sagittal sinus blood flow during the production of cryosurgical ablation of residual tumour attached to the walls of the sagittal sinus. Recent advances in ultrasonic and neuroimaging coupled with stereotactic techniques and improvements in cryosurgical instrumentation may prove useful in the future percutaneous destruction of selective intracranial neoplasms.

Adult

Cytology of metastatic neuroendocrine (Merkel-cell) carcinoma in pleural fluid. A case report.

A case of Merkel-cell (neuroendocrine) carcinoma of the skin with extensive metastases, including pleural effusion, occurring over 20 years after primary resection and treatment, is reported. The histologic appearance of the primary neoplasm was identical to that seen in the biopsy specimens of the metastatic carcinoma involving the great toe and inguinal lymph nodes and to that of the residual neoplasm tissue found at necropsy. Electron microscopic examination of a lymph node metastasis demonstrated cytoplasmic microfilaments and numerous dense-core, peripheral, neurosecretory granules, as previously described in Merkel-cell carcinoma. Cytologic examination of a pleural fluid specimen demonstrated numerous small malignant cells closely resembling the cells seen in the histopathologic sections from the surgical and necropsy tissues involved by metastatic carcinoma. This is the first report of the cytologic findings in a patient with Merkel-cell carcinoma metastatic to the pleural cavity.

Carcinoma, Small Cell

The value of mammography after limited breast surgery and before definitive radiation therapy.

One hundred twenty consecutive patients who had breast-conserving surgery for cancer and were referred for definitive radiation therapy (RT) had a mammogram performed before starting RT. This was done to determine the presence of residual neoplasm or other abnormalities that may alter or delay the planned RT and are undetected by other means. It also was performed to provide a baseline for the diagnosis of postoperative changes and recurrence of disease on follow-up studies. In six (5%) patients, calcifications or masses were found that proved to be residual tumors. This led to reexcision in two, mastectomies in two, and a higher radiation booster dose to the tumor bed in two. Eight (6.6%) patients had postoperative hematomas larger than 4 cm in diameter, which delayed the start of RT by 2 to 3 weeks. In 39 (32%) patients, the pre-RT mammogram provided information considered to be helpful for the interpretation of post-RT mammograms. Such information may lead to a decrease in the number of diagnostic biopsies based on indeterminate mammographic findings. Therefore, a routine mammogram is recommended before RT is started.

Adult

Snare cautery debridement prior to Nd:YAG photoablation improves treatment efficiency of broad-based adenomas of the colorectum.

Forty-six patients who underwent piecemeal resection of large, sessile villous adenomas followed by immediate laser photoablative therapy are presented. In contrast to previously published series utilizing laser alone, prior snare resection of such lesions provides copious tissue for histologic analysis, decreases the amount of residual neoplasm requiring laser treatment, and has the potential to improve treatment efficacy.

Adenoma

Bilateral simultaneously-occurring adenocarcinoma of the kidney.

Our 3 patients with simultaneously-occurring hypernephromas treated with simultaneously-directed surgical therapy on both kidneys are described. One patient died with residual neoplasm 2 1/2 years postoperatively, while the other 2 patients are alive and presumably free of tumor 60 and 22 months postoperatively.

Adenocarcinoma

Malignant lymphoepithelial lesion of the salivary gland.

Eight cases of malignant lymphoepithelial lesion (MLEL) of major salivary glands, seven of which occurred in Southern Chinese patients, are reported. All but two of the patients were older than 40 years of age; there were five male and three female patients. The parotid and submandibular glands were the sites of origin in equal numbers of cases. Six patients had elevated titers of serum IgA against Epstein-Barr virus capsid antigen. Seven remained well after surgery and local radiation therapy, and one died of miliary tuberculosis without evidence of residual neoplasm. Histologically, MLELs were characterized by syncytial clumps of large cells with vesicular nuclei and prominent nucleoli, admixed with abundant small lymphocytes and plasma cells. Two features not emphasized previously in the literature were the presence of reactive histiocytes in some epithelial islands, producing a starry sky pattern, and perineural invasion, which was identified in four cases. The tumor cells showed strong immunostaining for cytokeratin. The literature concerning this rare tumor is reviewed, and the differential diagnosis between MLEL and benign lymphoepithelial lesion, metastatic undifferentiated carcinoma, and malignant lymphoma is discussed.

Adolescent

Adult intramedullary astrocytomas of the spinal cord.

In this series, 25 adult patients with intramedullary astrocytomas were treated by radical excision alone. Six patients proved to have anaplastic astrocytoma; five of them died within approximately 2 years and the sixth has demonstrated disease progression. The other 19 patients were diagnosed as having low-grade astrocytoma (16 cases) or ganglioglioma (three cases); two of these had advanced preoperative neurological disability and died of medical complications. Fifteen of the remaining 17 patients have no clinical evidence of tumor recurrence after a mean follow-up period of 50.2 months; the other two have a small residual neoplasm that demonstrates no progression. Of these 17 patients, seven had previously received radiation therapy, but had clear evidence of tumor growth subsequently. This experience suggests that surgery is not beneficial for anaplastic spinal astrocytoma. However, in cases of low-grade tumor, radical excision is associated with minimal morbidity and an excellent long-term prognosis when carried out before significant disability occurs.

Adolescent

[The use of intra-arterial lipiodol in assessing hepatocarcinomas treated by percutaneous alcoholization. The initial experience].

Eight patients with inoperable hepatocellular carcinoma were treated by means of percutaneous alcoholization of the malignancy (11 nodular lesions less than 5 cm O). Upon treatment completion they were all given intraarterial injection of lipiodol, which was followed, a week later, by a CT scan. At angiography, during the parenchymal phase, 7 of 11 nodules appeared as avascular areas, whereas in the remaining 4 cases an intense parenchymal effect was seen within the previously treated areas. Lipiodol CT scans revealed intense uptake of oily material in the 4 hypervascular lesions as well as in 1 of those with avascular appearance. In 4 lesions, pathology of bioptic specimens obtained from the areas with contrast pooling was consistent with the persistence of viable neoplastic tissue. In these patients alcoholization had therefore to be continued. Lipiodol accumulation within previously treated nodules has proved to be related to the presence of residual neoplasm. Moreover, in 2 cases, focal retention of lipiodol was very helpful for biopsy under CT guidance. According to our experience, we believe lipiodol administration followed by CT to be very useful in evaluating and staging HCCs. We nevertheless believe that the procedure should be performed only after alcoholization has been completed: this would inform us of treatment effectiveness and subsequently enable us to decide whether treatment can be discontinued.

Angiography, Digital Subtraction

Antrectomy for multicentric, argyrophil gastric carcinoids: a preliminary report.

Multicentric gastric carcinoids develop infrequently in association with atrophic gastritis, achlorhydria, and hypergastrinemia. These unusual tumors, thought to arise from proliferation of enterochromaffin-like (ECL) cells, have not been shown to secrete any measurable biogenic amines and usually grow slowly. Hypergastrinemia, which results from antral G cell stimulation secondary to atrophic gastritis, is believed to be the trophic stimulus, but alternative explanations include production of gastrin-releasing factor (GRF) or gastrin per se by the tumor. We recently encountered two patients with pentagastrin-resistant achlorhydria and multiple gastric carcinoids. Neither had symptoms of carcinoid syndrome. Urinary 5-hydroxyindoleacetic acid and serum human pancreatic polypeptide, vasoactive intestinal peptide, and motilin values were normal. Fasting gastrin values were nearly 1800 pg/ml. Antrectomy and regional lymphadenectomy was performed in each patient. The tumors were locally invasive with penetration through the submucosa. One patient had regional lymph node involvement, and one had an isolated hepatic metastasis. Immunohistochemical stain tests were positive in both patients for neuron-specific enolase and chromogranin, with focal positive staining for gastrin and serotonin. Serum gastrin levels decreased to less than 25 pg/ml after antrectomy. Evaluation with upper gastrointestinal endoscopy and biopsy examination 4 to 6 months after antrectomy showed complete regression of disease in one patient and residual neoplasm in one patient, despite normal serum gastrin levels. Additional studies with careful long-term follow-up will be needed to determine whether antrectomy eliminates the hypergastrinemia associated with enterochromaffin-like hyperplasia and leads to regression of disease.

Adult

[Minimal residual disease in hematological neoplasms].

The existence of neoplastic cells with low or no sensibility to antiblastic drugs represents the most important cause of relapse in hematological malignancies. The amount of leukemic cells that remains after antiblastic chemotherapy represents the minimal residual disease. These cells can re-expand at any moment, even after months or years, causing short-term or long-term relapse. The minimal residual disease is not always detectable with morphological examination. The recent utilization of techniques such as cell culture by stimulation with growth factors and genetic amplification have made it possible to reach resolutions of more than 1-10(5) cells. The therapeutic strategies for total eradication of residual neoplastic cells are currently under investigation. The combined use of biological responder modifiers with chemotherapy or the use of immunotherapy with Interleukin-2 or LAK cells has provided one possible solution to this problem.

Antineoplastic Agents

ctDNA can detect minimal residual disease in curative treated non-small cell lung cancer patients using a tumor agnostic approach.

BACKGROUND: Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits. METHODS: We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment). RESULTS: Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1. CONCLUSION: These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

Humans

Meningioma with sarcomatous change and hepatic metastasis.

A 72-year-old patient had a meningotheliomatous meningioma that invaded through the skull and into temporalis muscle. One year following craniotomy for removal of the neoplasm, he developed headaches, diplopia, and proptosis of the left eye. Biopsy of the orbital contents revealed a malignant supporting tissue neoplasm having a resemblance to the previous meningioma. No curative therapy was possible and the patient died 33 months after diagnosis. Autopsy examination showed extensive residual intracranial neoplasm and a 3-cm metastasis in the liver. The metastatic tumor appeared similar to the meningioma and did not appear malignant histologically. The case illustrates the distinct histologic variations in meningiomas and the difficulties in predicting their biologic activity. Aggressive local behavior may indicate possible malignant areas in the neoplasm. Therefore, examination of the neoplasm should be thorough. Such a correlation may suggest malignant biologic potential.

Aged

Modulation of carbohydrate residues in regenerative nodules and neoplasms of canine and feline pancreas.

The glycoconjugates of regenerative acinar cells, acinic cell carcinomas, islet cell tumors, and normal canine and feline pancreas were studied. The authors used biotinylated lectins as probes and avidin-biotin-peroxidase complex as visualant to identify and to compare the distribution of carbohydrate residues on paraffin sections from 74 cases. The findings demonstrate a difference in the staining pattern between normal acinar, islet, and ductal cells in each species and small differences in the staining pattern between the species. It is shown that in nodules of regenerative acinar cells and acinic cell carcinomas there is an increased staining intensity with Concanavalia ensiformis agglutinin, Ricinus communis agglutinin-I, and wheat germ agglutinin. The pattern of lectin staining in regenerative cells and malignant acinar cells reflects the degree of cellular differentiation. Intensive apical staining characterizes a higher degree of differentiation, while dispersed staining is a major feature of poor differentiation. These findings suggest that malignant transformation of pancreatic acinar cells is associated with enhanced expression of glycoconjugates, which resembles that seen in a normal immature acinar cells.

Animals

Prognostic Value of Circulating Tumor DNA-Based Minimal Residual Disease for Recurrence-Free Survival in Resectable Gastric Cancer: A Systematic Review and Meta-Analysis with Serial Monitoring Analysis.

BACKGROUND: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) is an emerging biomarker, but its utility in resectable gastric cancer remains incompletely characterized. METHODS: We conducted a systematic review and meta-analysis of eight studies (520 patients) to evaluate the prognostic value of ctDNA-based MRD for recurrence-free survival (RFS) and overall survival (OS) in resectable gastric cancer. RESULTS: In localized resectable gastric cancer (Stage I-III), the setting in which postoperative ctDNA most coherently represents true molecular residual disease after curative-intent surgery, postoperative ctDNA positivity was associated with diminished recurrence-free survival (RFS: HR 12.26, 95% CI 3.30-45.52) and overall survival (OS: HR 8.57, 95% CI 3.06-23.98). The test for subgroup differences between localized and mixed-stage cohorts was not statistically significant (P = 0.57), and the numerically higher HR in the localized subgroup should therefore not be interpreted as evidence of a quantitatively stronger prognostic effect. Postoperative ctDNA detection demonstrated substantially stronger prognostic value (overall RFS: HR 10.00, 95% CI 4.53-22.10) compared to preoperative assessment (HR 2.17, 95% CI 1.10-4.28). Both tumor-informed and tumor-agnostic strategies effectively stratified high-risk patients. However, these effect sizes should be interpreted cautiously given the small number of studies and substantial heterogeneity (I2 = 65-72%). Results from mixed-stage cohorts including Stage IV disease are supportive but should not be considered equivalent to localized-disease findings, as ctDNA in metastatic disease reflects persistent systemic burden rather than minimal residual disease in the postoperative sense. CONCLUSIONS: Postoperative ctDNA-based MRD shows a consistent adverse prognostic association in resectable gastric cancer, with localized disease (Stage I-III) representing the most biologically and clinically coherent setting for interpretation. However, the large pooled hazard ratios (HR 10.00-12.26) should be interpreted as a directionally consistent signal rather than precise quantitative estimates, given the small number of studies, wide confidence intervals, and substantial heterogeneity (I2 = 65-73%). This heterogeneity is largely driven by substantial variation in postoperative sampling timing (4 days to 16 weeks) and ctDNA assay characteristics (platform, sensitivity, coverage, variant filtering, and positivity thresholds), which require standardization in future studies. While ctDNA is prognostically valuable, its clinical utility remains unestablished. Prospective randomized trials are needed to determine whether ctDNA-guided strategies improve patient outcomes before routine clinical implementation can be recommended.

Humans

Molecular Residual Disease and Recurrence in Rectal Cancer Patients Undergoing Upfront Surgery: A Prospective Cohort Study.

OBJECTIVE: To evaluate the prognostic utility of postoperative circulating tumor DNA (ctDNA) for recurrence and treatment response in patients with rectal cancer undergoing upfront surgery. BACKGROUND: ctDNA-based molecular residual disease (MRD) testing shows promise in colorectal cancer, but its role in patients with rectal cancer not receiving neoadjuvant therapy is unclear. This study evaluates whether postoperative ctDNA predicts disease-free survival (DFS) and guides adjuvant chemotherapy (ACT) decisions. METHODS: We analyzed ctDNA from patients with stage II to III rectal cancer (N=250) enrolled in the GALAXY study, a multicenter registry in Japan. A clinically validated, personalized, tumor-informed 16-plex PCR next-generation sequencing assay (Signatera) was used to detect and quantify ctDNA. The primary outcome was DFS, defined as the time from landmark to recurrence, death, or the latest radiologic assessment. RESULTS: In the MRD window (2-10&#xa0;wk postsurgery, before ACT), 14.2% (35/246) of patients were ctDNA-positive and had significantly shorter DFS (HR: 9.96, 95% CI: 5.76-17.2, P <0.0001). Among patients who were ctDNA-positive in the MRD window, a significant benefit from ACT was observed (HR: 0.28, 95% CI: 0.09-0.89, P =0.031), whereas no benefit was seen in ctDNA-negative patients (HR: 0.59, 95% CI: 0.26-1.35, P =0.211). When analyzing ctDNA dynamics from the MRD window to 6 months postsurgery, recurrence risk was higher in patients who converted from ctDNA-negative to positive (HR: 8.22, 95% CI: 1.86-36.32, P =0.0055) and who remained ctDNA-positive (HR: 45.48, 95% CI: 14.31-144.57, P <0.0001) compared with serially ctDNA-negative patients. CONCLUSIONS: Postoperative ctDNA status is a robust biomarker predicting recurrence risk and ACT benefit in patients with rectal cancer undergoing upfront surgery.

Humans

Treatment Decisions in Multiple Myeloma.

Revolutions in transplantation and targeted and immune therapies have transformed multiple myeloma from a disease with an associated survival of a few years into one for which functional cure is an emerging goal. This abundance of effective therapies has created clinical complexity. Here we provide a practical framework, anchored in trial evidence and informed by emerging biologic discoveries, for the navigation of treatment decisions across the disease spectrum. We outline how cytogenetic and genomic risk stratification, functional fitness, and measurable residual disease status individualize therapy in newly diagnosed disease, in which quadruplet induction therapy is now standard and the role of autologous transplantation is being reevaluated. Regarding relapse, we address the sequencing of B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates, emphasizing T-cell fitness and multiantigen targeting to counter exhaustion and antigen escape. We also consider early interception in high-risk smoldering myeloma. Throughout, we underscore that enrollment of patients in clinical trials should be considered in order to ensure continued progress.

Humans

Defining and managing high-risk acute myeloid leukemia (AML) in 2026.

Acute myeloid leukemia (AML) remains a highly heterogeneous malignancy in which outcomes are particularly poor for patients classified as having high-risk disease. Traditionally, high-risk AML has been defined by adverse baseline genetic features, including complex cytogenetics, TP53 alterations, and mutations associated with secondary or therapy-related disease. However, this static, genetics-centered definition is increasingly insufficient in the modern therapeutic era. Emerging evidence supports a more dynamic and context-dependent model in which risk is shaped not only by molecular architecture but also by treatment intensity, patient fitness, measurable residual disease (MRD), and evolving resistance mechanisms. Advances in genomic profiling have refined risk stratification frameworks, including ELN 2022 for intensively treated patients and the ELN 2024 classification for those receiving less-intensive therapies. In parallel, MRD has emerged as a powerful biomarker that reclassifies patients during treatment, identifying those with persistent, therapy-resistant disease despite morphologic remission. Biologically, high-risk AML is driven by the interplay of clonal evolution, epigenetic plasticity, leukemic stem cell persistence, and protective microenvironmental and immune interactions, all of which contribute to relapse. Therapeutically, the landscape has expanded to include targeted agents, venetoclax-based combinations, and transplantation strategies, yet outcomes remain limited in key high-risk subsets, particularly TP53-mutated disease and post-venetoclax relapse. Accordingly, current strategies emphasize rational combination therapies, MRD-guided treatment adaptation, and approaches targeting both leukemic cells and their supportive niches. In 2026, high-risk AML is best understood as a dynamic, treatment-context-dependent state. Improving outcomes will require integration of precision diagnostics, biologically informed therapy, and adaptive strategies designed to anticipate and overcome resistance.

Humans

The Natural History of Residual and Recurrent Disease in Advanced Juvenile Nasopharyngeal Angiofibroma: A Systematic Review.

OBJECTIVE: This systematic review explores the natural history of residual and recurrent juvenile nasopharyngeal angiofibromas (JNAs) to inform clinical decision-making. DATA SOURCES: PubMed, Embase, Scopus, and Web of Science. REVIEW METHODS: A systematic literature review was conducted according to PRISMA guidelines across PubMed, Embase, Scopus, and Web of Science from inception to February 20, 2025 and was re-run on September 21, 2025. Studies included patients with advanced JNA and documented follow-up of residual or recurrent disease. Descriptive statistics, chi-squared analysis, and analysis of variance were used to evaluate treatment outcomes across different modalities including surgery, radiotherapy, gamma knife surgery, and medical therapies. RESULTS: Twenty-one studies encompassing 131 male patients (mean age 16.3&#x2009;years) were included. Residual or recurrent disease demonstrated complete involution in 41%, stable disease in 29%, and reduction in size in 25% of cases. Only 2% of patients had progressive disease. A statistically significant association was observed between treatment modality and outcome (p&#x2009;=&#x2009;0.015), with radiotherapy, either alone, or as part of a multimodal approach, showing the highest rates of spontaneous involution. CONCLUSION: Residual and recurrent JNAs often remain stable or regress without further intervention. Close surveillance with imaging is a safe and effective strategy for asymptomatic patients, minimizing the risks of additional treatment in a young patient population with disease near critical anatomical structures.

Humans