Combined Gland Research Articles

Retrospective comparison of individual risk factors hemithyroidectomy and thyroidectomy in patients with papillary carcinoma of the thyroid gland in combination with autoimmune thyroiditis

Introduction. Papillary thyroid carcinoma is the most common subtype of thyroid cancer as it comprises 95 % of cases. Frequently, this pathology develops in the presence of autoimmune thyroiditis (Hashimoto’s thyroiditis) which is the main cause of hypothyroidism in various rich in iodine regions. Papillary thyroid carcinoma is characterized by good prognosis, however some patients experience recurrence which depends on the volume of surgical intervention.Aim. To compare clinical outcomes and complications after hemithyroidectomy (HE) and thyroidectomy (TE) in patients with papillary thyroid carcinoma secondary to autoimmune thyroiditis.Materials and methods. The retrospective study included 2031 patients with papillary thyroid carcinoma. Considering individual risk factors, 67 patients were excluded from the HE group, and 588 patients were excluded from the TE group. Each group included 688 patients for whom data were matched. Such individual factors as age, sex, primary tumor size, extrathyroidal invasion, multifocal tumor and cervical lymph node metastasis were taken into account.Results. During 10‑year follow-up, recurrence was diagnosed in 26 (3.8 %) patients of the HE group and 11 (1.6 %) patients of the TE group. Relative risk of recurrence was significantly lower after TE than after HE (risk ratio (RR) 0.41; 95 % confidence interval (CI) 0.21–0.81; р = 0.01). In the HE group, for the majority of patients recurrence was observed in the contralateral lobe of the thyroid (84.6 %). In the TE group, there were no recurrences in all patients. There were no significant differences between the groups after exclusion of recurrence in the contralateral thyroid lobe (RR 2.75; 95 % CI 0.08–8.79; р = 0.08). In the TE group, the number of patients with transient and permanent hypothyroidism in the TE group was significantly higher than in the HE group (р <0.001).Conclusion. Hemithyroidectomy is appropriate for the majority of patients with papillary thyroid carcinoma in the absence of extrathyroidal invasion in the neighboring tissues per preoperative examination. For patients after HE, preoperative and postoperative diagnostic examinations are important as most recurrences develop in the contralateral thyroid lobe.

Evolution of the Diagnosis and Treatment of Primary Hyperparathyroidism.

This study aims to present the evolution of our center's approach to treating primary hyperparathyroidism (PHPT) from diagnosis to intraoperative interventions. We have also evaluated the intraoperative localization benefits of indocyanine green fluorescence angiography. This retrospective single-center study involved 296 patients who underwent parathyroidectomy for PHPT between January 2010 and December 2022. The preoperative diagnostic procedure included neck ultrasonography in all patients, [99mTc]Tc-MIBI scintigraphy in 278 patients, and, in 20 doubtful cases, [18F] fluorocholine positron emission tomography (PET) computed tomography (CT) was performed. Intraoperative PTH was measured in all cases. Indocyanine green has been administered intravenously since 2020 to guide surgical navigation using a fluorescence imaging system. The development of high precision diagnostic tools that can localize an abnormal parathyroid gland in combination with intra-operative PTH assay (ioPTH) enables the surgical treatment of PHPT patients with focused approaches and excellent results that are stackable with bilateral neck exploration (98% of surgical success). Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly and with minimal risk, especially when pre-operative localization has failed. When everything else fails, it is only an experienced surgeon who can resolve the situation.

Effect of combined vitamin D and microwave ablation of parathyroid glands on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism

Purpose: To investigate the effect of microwave ablation of parathyroid glands in combination with active vitamin D on blood pressure and cardiac function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism.
 Methods: One hundred and twenty maintenance-hemodialysis patients with uremic secondary hyperparathyroidism admitted to Meizhou People’s Hospital were assigned to 2 groups (A and B) in the order of their admission. Each group had 60 patients. Both groups were treated with active vitamin D, while patients in group A were, in addition, subjected to microwave ablation of parathyroid glands. Blood pressure, and indices for cardiac function, thyroid function s and anemia were determined.
 Results: After treatment, the blood pressure of group A was significantly lower than that of group B (p < 0.05). Moreover, after treatment, there were significant improvements in indices of cardiac function, thyroid function and anemia in group A patients, relative to group B patients.
 Conclusion: Microwave ablation of parathyroid glands, when combined with active vitamin D, improves blood pressure, cardiac function and anemia status. Furthermore, the combined therapy enhances recovery of thyroid function in maintenance-hemodialysis patients with uremic secondary hyperparathyroidism. However, the combined therapy should be subjected to further clinical trials prior to application in clinical practice.
 Keywords: Microwave ablation; Parathyroid glands; Active vitamin D; Hyperparathyroidism

Benign diseases of the breast glands on the background of hyperplastic processes of the endometry (references)

Purpose of the study. To highlight the most substantiated theories that reflect the dependence of benign diseases of the mammary glands in combination with hyperplastic processes of the endometrium.
 Materials and metods. The sources of literature related to the study of combined benign breast diseases on the background of gynecological pathology and thoroughly reflect the modern views of scientists on this pathology are analyzed.
 Results. Given the many unexplained patterns of hormonal diseases of the female reproductive system – the search for new options for combining these diseases continues.
 Conclusion. It is established that in recent years there has been an increase in the number of benign breast diseases in patients with combined gynecological pathology within 60–80%.

Results of simultaneous operations for nodular goiter

In recent years, there has been an increase in patients with thyroid pathology around the world, which is associated with iodine deficiency and often these diseases are combined with other pathologies that require surgical treatment. The aim of our work was to evaluate the effectiveness of simultaneous operations in nodular goiter. Material and methods . The article presents the results of simultaneous operations that were performed in 19 patients with nodular goiter. Echinococcosis of the liver was found in 8 of them, cholelithiasis in 11 (chronic calculous cholecystitis – 7 and recurrent choledocholithiasis – 4). All operations were performed under endotracheal anesthesia from two approaches, and thyroidectomy and resection of the thyroid gland in combination with cholecystectomy (choledochotomy) were performed in 11 and in 8 with echinococcectomy. In addition to conventional examination methods, a fine-needle aspiration biopsy of the thyroid gland was performed in all patients with nodular goiter to exclude proliferative growth and identify the contents of the cyst. Postoperative complications and long-term results were studied (from 3 months to 3.5 years). Results . In the immediate postoperative period, complications arose in 3 cases each (wound suppuration, infiltration and pleurisy). 18 patients were examined up to 3 and 6 months, 15 patients – from one to 2 years, 13 patients – from 2 to 3.5 years; recurrence of goiter and associated diseases (gallstone disease and echinococcosis of the liver) were not found. Conclusion . Simultaneous operations can be performed in cases of nodular goiter combination with echinococcosis and gallstone disease, but under the condition of strict adherence to the rules of the principle of aparasiticity and antiparasiticity in echinococcectomy. When performing simultaneous operations, it is necessary to fully examine the patient, determine the indications and contraindications, the volume of the planned operation, and also pay attention to the preoperative preparation and management of the postoperative period.

Primary sialorrhea and its surgical treatment with denervation of the submandibular glands in combination with sublingual gland excision

ObjectivesThe purpose of this study was to evaluate the effectiveness of ablating postganglionic parasympathetic fibers of the submandibular ganglion in combination with sublingual gland excision in the treatment of primary sialorrhea. Materials and methodsHealthy volunteers were initially chosen to determine a basic saliva flow rate value by saliva collection. Next, unstimulated and stimulated saliva flow rates, and a visual analog scale index for sialorrhea were recorded in all the patients pre- and postoperatively. In addition, the generalized anxiety disorder scale was used to assess preoperative anxiety symptoms. The follow-up durations ranged from 24 to 36 months after surgery. ResultsA total of 10 patients were included in this study. Preoperatively, the mean unstimulated saliva flow rate for the 10 patients was 11.26 ± 4.19 ml/10 min, the stimulated saliva flow rate was 16.76 ± 3.49 ml/6 min, and the visual analog scale index was 66.29 ± 14.86. Postoperatively, the mean unstimulated and stimulated saliva flow rates were significantly reduced to 5.99 ± 1.33 ml/10 min (p = 0.001) and 13.28 ± 1.86 ml/6 min (p = 0.013), respectively, and the visual analog scale index was 25.41 ± 5.6 (p < 0.001). No complications were found after operation. ConclusionThis study demonstrates that ablation of postganglionic parasympathetic fibers of the submandibular ganglion in combination with sublingual gland excision by an intraoral approach is a simple, safe, and efficient approach for treating primary sialorrhea.

Actual Aspects of Pathogenesis of Dysplasia of Mammary Glands and Hysteromyoma at Women of Perimenopause Age

The objective: to study actual aspects of pathogenesis of dysplasia of mammary glands in combination with hysteromyoma at women of perimenopause age.Materials and methods. 50 patients with dysplasia of mammary glands (25 women from diffuse and 25 women with the localized forms) and a hysteromyoma was created. We developed the program of researches providing carrying out: clinical-statistical analysis, complex hormonal researches, X-ray inspection of mammary glands, ehografical of researches of genitalias and mammary glands, cytologic and histological methods with puncture biopsy application that mathematical processing.Results. Highlights of pathogenesis of dysplasia of mammary glands and hysteromyomas are clinical-anamnestic data, and also change of ratio of levels of hypotalamo-hypophysial hormones, the ovarium of hormones in the form of the absolute or relative giperestrogeniya, more expressed at patients with the localized forms. Disturbances of normal menstrual cycle are taped at 76% of patients, disbiotical processes of genitalias – at 46% of women with dysplasia of mammary glands.Conclusion. The received results needs to be used when developing complex of diagnostic and treatment-and-prophylactic actions.

Тактика діагностики та лікування дисплазії грудних залоз та міоми матки у жінок перименопаузального віку

The objective: development and deployment of tactics of diagnostics and treatment of dysplasia of mammary glands in combination with hysteromyoma at women of perimenopause age Materials and methods. Complex clinical-laboratory, ehografical and morphological examination 93 women of perimenopause age with the combined pathology – benign dysplasia of mammary glands and hysteromyoma was conducted. Results. Should be noticed efficiency of the complex developed by us that at women with the combined pathology it was succeeded to carry out to 43.4% of cases prophylaxis of advance and a recedives of dysplasia of mammary glands and to 36.7% – hysteromyomas. The obtained data, in our opinion, convincingly testify that complex conservative treatment of the women suffering from illnesses of mammary glands in combination with hysteromyoma, is preventive action concerning advance and recedives of the combined pathology at this category of patients. Conclusion. The results received by us grant to us the right to recommend an offered complex in practical health care. Key words: dysplasia of mammary glands, hysteromyoma, diagnostics, treatment, perimenopause age.

Incorporation of Dosimetric Gradients and Parotid Gland Migration Into Xerostomia Prediction

Purpose: Due to the sharp gradients of intensity-modulated radiotherapy (IMRT) dose distributions, treatment uncertainties may induce substantial deviations from the planned dose during irradiation. Here, we investigate if the planned mean dose to parotid glands in combination with the dose gradient and information about anatomical changes during the treatment improves xerostomia prediction in head and neck cancer patients.Materials and methods: Eighty eight patients were retrospectively analyzed. Three features of the contralateral parotid gland were studied in terms of their association with the outcome, i.e., grade ≥ 2 (G2) xerostomia between 6 months and 2 years after radiotherapy (RT): planned mean dose (MD), average lateral dose gradient (GRADX), and parotid gland migration toward medial (PGM). PGM was estimated using daily megavoltage computed tomography (MVCT) images. Three logistic regression models where analyzed: based on (1) MD only, (2) MD and GRADX, and (3) MD, GRADX, and PGM. Additionally, the cohort was stratified based on the median value of GRADX, and a univariate analysis was performed to study the association of the MD with the outcome for patients in low- and high-GRADX domains.Results: The planned MD failed to recognize G2 xerostomia patients (AUC = 0.57). By adding the information of GRADX (second model), the model performance increased to AUC = 0.72. The addition of PGM (third model) led to further improvement in the recognition of the outcome (AUC = 0.79). Remarkably, xerostomia patients in the low-GRADX domain were successfully identified (AUC = 0.88) by the MD alone.Conclusions: Our results indicate that GRADX and PGM, which together serve as a proxy of dosimetric changes, provide valuable information for xerostomia prediction.

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low- and intermediate-risk prostate cancer patients (Gleason scores 6–7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach.

Mechanical meibomian gland squeezing combined with eyelid scrubs and warm compresses for the treatment of meibomian gland dysfunction

BackgroundThe aim was to investigate the efficacy of mechanical meibomian gland squeezing combined with eyelid scrubs and warm compresses in participants with moderate and severe meibomian gland dysfunction (MGD).MethodsIn this prospective, uncontrolled, open label, intervention study, 32 eyes of 32 participants with moderate and severe MGD were treated with mechanical squeezing of meibomian glands in combination with eyelid scrubs and warm compresses. We evaluated tear film break‐up time (TBUT), corneal and conjunctival fluorescein staining scores, biomicroscopic examination of lid margins and meibomian glands, Ocular Surface Disease Index (OSDI) questionnaire and tear film lipid layer thickness determined via an interferometer before initiating treatment and after one month of treatment.ResultsThere were significant improvements in TBUT, corneal and conjunctival fluorescein staining scores, lid margin abnormality, meibum quality and expressibility, OSDI and MGD stage after mechanical meibomian gland squeezing combined with eyelid scrubs and warm compresses (p < 0.001 for TBUT, corneal fluorescein staining scores, Dry Eye Workshop score, Oxford staining score, lid margin abnormality, meibum quality, expressibility, OSDI and MGD stage and p = 0.001 for conjunctival fluorescein staining scores). There were no significant differences in lipid layer thickness or interferometer‐derived parameters before treatment and after one month of treatment. Palpebral conjunctival erosion detected after the squeezing treatment resolved spontaneously in all participants.ConclusionsMechanical squeezing of meibomian glands combined with eyelid scrubs and warm compresses can provide clinical benefits without serious adverse events.

Planning of the Autotransplantation of the Liver to the Patients with Advanced Alveococosis Based on the Multidetector Computed Tomography

Aim: to analize computed tomography data while planning autotransplantation of the liver for advanced alveococcosis.Materials and Methods.A retrospective analysis of the results of multidetector computed tomography of the abdomen and retroperitoneal space of 7 patients with advanced liver alveococcosis was made in order to plan autotransplantation. Besides a description of the location and size of parasitic lesion for each patient relationship with main vessels was evaluated - the inferior vena cava, hepatic and portal veins, hepatic arteries, and the presence of extrahepatic component. The vessel assessed as involved in the pathological process not only in case of clear invasion, but also with abutment because of infiltrative growth of alveococcus. The accuracy of the method was estimated by comparison with the intraoperative data.Results.The data of computed tomography while the planning of liver autotransplantation coincided with the intraoperative data in all examined patients. The main criteria indicating the need for this type of surgical intervention was the involvement of the retrohepatic part of the inferior vena cava to the caval gates inclusive and/or hepatic veins. With extrahepatic spread of parasitic masses it is possible to affect not only the surrounding organs, but also the main vessels, for example, with growth in the hepatic-duodenal ligament. Thus, in one patient during the operation, the occlusion of artery hepatica propria was confirmed. In two cases of recurrence of the parasitic process after rightsided hemihepatectomy, the almost identical pattern of involvement of the liver resection surface, inferior cava and portal veins, diaphragm, adrenal gland in combination with a extent adhesive process in the right subdiaphragmal space.Conclusions.CT scan data allowed to correctly plan the volume of operative intervention – autotransplantation of the liver – in all the examined patients. It is of interest to evaluate the accuracy of the method on a larger group of patients.

Postoperative diagnostics clinical case of the patient with kidney canсer metastasis in the thyroid gland in combination with left internal jugular vein thrombosis

Представлено клиническое наблюдение пациентки 68 лет с жалобами на увеличение в размерах шеи, преимущественно с левой стороны, ощущение першения в горле. В ходе обследования по данным УЗИ органов шеи выявлено конгломератное образование левой доли щитовидной железы. Кроме того, в просвете в верхней трети внутренней яремной вены выявлено образование средней эхогенности. По данным последующей тонкоигольной биопсии левой доли – признаки коллоидного зоба. Пациентке проведено оперативное лечение в объеме левосторонней гемитиреоидэктомии: при ревизии левая доля значительно увеличена в размерах за счет узлового образования, доходящего до левого угла нижней челюсти, располагающегося частично загрудинно и за трахеей. По данным послеоперационного гистологического исследования выявлен метастаз светлоклеточного рака почки в левую долю щитовидной железы с признаками прорастания в окружающие сосуды и мышцы.

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of lactating dairy cows

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the mammary gland of the lactating dairy cow is constructed and solved in the steady state. The model contains four intracellular and four extracellular pools and conservation of mass principles are applied to generate the fundamental equations describing the behaviour of the system. The experimental measurements required for model solution are milk secretion and plasma flow rate across the gland in combination with phenylalanine and tyrosine concentrations and plateau isotopic enrichments in arterial and venous plasma and free and protein bound milk during a constant infusion of [1-13C]phenylalanine and [2,3,5,6-2H]tyrosine tracer. If assumptions are made, model solution enables determination of steady state flows for phenylalanine and tyrosine inflow to the gland, outflow from it and bypass, and flows representing the synthesis and degradation of constitutive protein and phenylalanine hydroxylation. The model is effective in providing information about the fates of phenylalanine and tyrosine in the mammary gland and could be used as part of a more complex system describing amino acid metabolism in the whole ruminant.

Calcium Release from Acidic Stores Modulate Fluid and Protein Secretion in the Salivary Gland

Autonomic input to salivary glands controls the rate of salivary flow by regulating the activities of ion channels and transporters that induce fluid and protein secretion. This control is achieved by signaling complexes that generate the complex patterns of cytosolic Ca2+ observed in acinar cells. Most work to date in these cells has focused on canonical intracellular Ca2+ release channels resident on the endoplasmic reticulum. In the current study we identified acidic organelles as an additional releasable Ca2+ store in mouse parotid salivary gland. The large, protein-containing secretory granules were found to be the major subcellular acidic organelle. However, the role that acidic Ca2+ stores play in these cells in the triggering or globalization of receptor mediated Ca2+ signals has not yet been investigated. Treatment with bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, altered the amplitude and kinetics of Ca2+ dynamics evoked by low level muscarinic receptor activation but not by stronger stimulations. In contrast bafilomycin treatment nearly abolished protein exocytosis regardless of stimulation intensity. In addition, using acinar cell clusters prepared from mouse salivary gland in combination with flash photolysis and high-speed fluorescence imaging we demonstrated that caged-nicotinic acid adenine dinucleotide phosphate (NAADP) functions as a highly potent Ca2+ mobilizing messenger that initiates or sensitizes agonist-stimulated Ca2+ signals in these cells. Consistent with a role for NAADP-mediated signaling in acinar cell function, treatment with the NAADP inhibitor BZ194 altered agonist evoked Ca2+ signals similar to bafilomycin treatment. This work implicates neurotransmitter-evoked rises in NAADP as a signaling pathway relevant for salivary gland function and identifies a potential target for augmenting function for patients suffering reduced saliva formation.

Transoraler Zugang bei sublingualer Tauchranula

The case of a 7-year-old boy suffering from progressive submental/submandibular swelling is reported. Following clinical and imaging diagnostics (MRI), the suspected diagnosis of a sublingual-plunging ranula was made. Surgery was performed with transoral excision of the sublingual gland in combination with excision of the ranula. Additional submandibular gland excision should be avoided.

Is Lymphocytic (Hashimoto) Thyroiditis Associated With Suicide?

The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in problematic cases (ie, overdose deaths). This diagnosis is rendered with essentially equal frequency in suicide victims versus controls.

Should We Consider Hypohidrotic Ectodermal Dysplasia as a Possible Risk Factor for Malignant Melanoma?

Hypohidrotic ectodermal dysplasia (HED) is a rare multisystem disorder that typically affects hair, teeth, nails, and sweat glands in combination with abnormalities of ectodermal originated tissues. To raise the issue of whether heightened awareness is required in the follow-up of pigmented lesions in patients with HED. Two patients with HED are reported. The first had a history of two malignant melanomas, whereas the second presented with a novel malignant melanoma. Although a prospective epidemiologic study to determine the incidence of malignant melanoma in patients with HED is virtually impossible and the probable pathogenesis warrants further investigation, these two case reports, in conjunction with other recent reports associating other ectodermal dysplasias with malignant melanoma, suggest that heightened awareness might be prudent in the follow-up of pigmented lesions in patients with HED.

Studies on human minor salivary gland secretions using the periotron ® method

Secretions from minor salivary glands were estimated in 127 individuals by the Periotron ® method of measuring fluid output from different mucosal sites, and outputs were related to different variables. Large intra- and interindividual variations in secretions (expressed as μI/cm 2 2 per min) were observed, with means of 0.9 for the palatal, 4.8 for the labial and 16.0 for the buccal mucosal sites. Age had no influence on the secretion rate, but women had 10–20% lower values from all three sites than men ( p < 0.05). Individuals wearing upper dentures or using tobacco had 300 and 27% increased palatal secretion rates, respectively ( p < 0.001, p < 0.05). In addition, those being treated with diuretics had 15% lower rates of secretion from buccal mucosal glands ( p < 0.05), and those complaining of oral dryness had 21% lower fluid output from the labial mucosa ( p < 0.05). These results support the use of minor salivary glands in combination with the Periotron ® method to study mucosal secretions and functions

Fundamentals of combating cancer metastasis by oxygen multistep immunostimulation processes

Becuase more than 80% of all cancer deaths are caused by metastases, development and evaluation of methods for fighting tumor dissemination should be major tasks of present cancer research. Formation of metastases is favoured by both reduced numbers of immune cells in the bloodstream and impaired oxygen transport into tissues. These closely related signs often emerge concomitantly when the organism is endangered by circulating tumor cells released from the original tumor by therapeutic manipulations. From knowledge of these facts the O 2-multistep immunostimulation technique has been developed as a way of diminishing the risk of tumor spread. The process combines temporary elevation of the number of circulating immune cells with continuous improvement of oxygen transport into tissues. The former is achieved by a peptide mixture isolated from thymus glands in combination with the chemical immunomodulator 2-cyano-ethyl urea; the latter is the outcome of several variants of the O 2-multistep therapy discussed here. The efficiency ranges of the different variants are quantified on the basis of findings that allow assessment of the number of tumor cells which can be destroyed by this treatment. This number may be about 100 times the number of malignant cells that must be killed in terms of an effective metastasis prophylaxis (≈ 3 × 10 5). The estimated efficiency range represents therefore a not yet fully exhausted preventive and possibly even therapeutic potential. — To speed the introduction of the procedures described into practice, all clinical oncologists are encouraged to refer their patients to established facilities for O 2-multistep immunostimulation after termination of any conventional therapy.