First Trimester Ultrasound Detection of Fetal Central Nervous System Anomalies.

OBJECTIVE: To evaluate the potential of the first-trimester ultrasound (US) features for the detection of central nervous system (CNS) anomalies. Methods/Methodology: This is a prospective one-center three-year study. Unselected singleton pregnant women were examined using an extended first-trimester anomaly scan (FTAS) that included the CNS assessment: the calvaria shape, the septum (falx cerebri), the aspect of the lateral ventricles, the presence of the third ventricle and aqueduct of Sylvius (AS) and the posterior brain morphometry: the fourth ventricle, namely intracranial translucency (IT), brain stem/brain stem-occipital bone ratio (BS/BSOB) and cisterna magna (CM). The spine and underlying skin were also evaluated. The cases were also followed during the second and third trimesters of pregnancy and at delivery. FTAS efficiency to detect major CNS abnormalities was calculated. RESULTS: We detected 17 cases with CNS major abnormalities in a population of 1943 first-trimester (FT) fetuses, including spina bifida with myelomeningocele, exencephaly-anencephaly, holoprosencephaly, hydrocephaly, cephalocele and Dandy-Walker malformation. The CNS features in the abnormal group are presented. In the second trimester (ST), we further diagnosed cases of corpus callosum agenesis, cerebellar hypoplasia, vein of Galen aneurysm and fetal infection features (ventriculomegaly, intraventricular bands, intraventricular cyst and hyperechoic foci), all declared normal at the FTAS. During the third trimester (TT) scan we identified a massive fetal cerebral haemorrhage absent at previous investigations. We report a detection rate of 72.7% of fetal brain anomalies in the FT using the proposed CNS parameters. The sensitivity of the examination protocol was 72.7%, and the specificity was 100%. CONCLUSION: A detailed FT CNS scan is feasible and efficient. The majority of cases of major CNS abnormalities can be detected early in pregnancy. The visualization rates of the CNS parameters in the FT are great with short, if any, additional investigation time. FT cerebral disorders such as haemorrhage or infections were missed in the FT even when an extended evaluation protocol was used.

Uterine Perforation as a Complication of the Intrauterine Procedures Causing Omentum Incarceration: A Review.

OBJECTIVE: Omentum involvement resulting from uterine perforation is a rare complication following intrauterine procedures that might require immediate intervention due to severe ischemic consequences. This review examines the prevalence of this complication, risk factors, the mode and timing of diagnosis, the proper management and the outcome. METHODS: A systematic literature search was conducted on PubMed, PubMed Central and Scopus using uterine perforation, D&C, abortion and omentum as keywords. The exclusion criteria included the presence of the uterus or placenta's malignancy and uterine perforation following delivery or caused by an intrauterine device. RESULTS: The review included 11 articles from 133 screened papers. We identified 12 cases that three evaluators further analysed. We also present the case of a 32-year-old woman diagnosed with uterine perforation and omentum involvement. The patient underwent a hysteroscopic procedure with resectioning the protruding omentum into the uterine cavity, followed by intrauterine device insertion. CONCLUSION: This paper highlights the importance of a comprehensive gynaecological evaluation following a D&C procedure that includes a thorough clinical examination and a detailed ultrasound assessment. Healthcare providers should not overlook the diagnosis of omentum involvement in the presence of a history of intrauterine procedures.

Open Spina Bifida: The Role of Ultrasound Markers in the First Trimester and Morphopathology Correlation.

Objectives-To evaluate ultrasound markers during a first-trimester (FT) routine ultrasound examination for an early detection of open spina bifida (OSB) and to correlate the sonographic findings with the morpho-histological ones. MATERIALS AND METHODS: This retrospective research was performed using data from foetuses that underwent FT anatomy scans (FTAS) with a gestational age between 11 weeks and 13 weeks and 6 days in the Prenatal Diagnostic Unit of the Clinical Emergency County Hospital Craiova from October 2022 until September 2023. RESULTS: The study included 648 FT singleton pregnancies and 5 OSB cases were detected. In the OSB group, we found abnormal aspects of the fourth ventricle, also named intracranial translucency (IT) in 4 out of 5 cases of OSB (80%), a brain stem anteroposterior diameter, and brain stem to occipital bone ratio abnormal in all 5 cases (greater than 1) (100%), the crash sign was present in 80% (4 out of 5 cases) and the spinal defect was visualized in 4 out of 5 patients (80%). Medical termination of pregnancy (MTOP) was the preferred option in all cases of OSB. This allowed us to include an extended histological study to confirm the ultrasound diagnosis. CONCLUSIONS: A combined detailed FTAS that includes both cranial ultrasound markers of the posterior fossa and also a good visualization of the foetal spine offers an early optimal detection rate of spine abnormalities.

The influence of SARS-CoV-2 on the immune system elements and on the placental structure. Clinical, histological and immunohistochemical study.

BACKGROUND: The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy remain relatively unknown. AIM: We present this original paper where we analyzed 60 parturients, at term, 30 without associated infection (C-) and 30 with associated infection (C+), present at birth. METHODS: We analyzed the blood count and placental microscopic structure through classical and immunohistochemical staining and observed the placental areas affected by the presence of SARS-CoV-2. RESULTS: SARS-CoV-2 infection was accompanied by a decrease in the number of lymphocytes, the number of platelets and the presence of placental structural changes, identifying extensive areas of amyloid deposits, placental infarcts, vascular thrombosis, syncytial knots, with a decrease in placental vascular density and the presence of infection in the cells located at decidual level, at syncytiotrophoblast level and at the level of the cells of the chorionic plate, still without overcoming this barrier and without causing any fetal infection in the analyzed cases. CONCLUSIONS: This study shows that the invasion of SARS-CoV-2 in the placenta can produce significant structural changes, with a decrease in placental vascular density that can have significant implications on proper fetal perfusion. Also, the presence of immunoreactivity at the level of decidua, the placental villi, as well as the chorionic plate proves that the virus can overcome the maternal-fetal barrier. However, in the analyzed cases there were no fetal infections at birth, which may show that local placental factors can be a protective filter for the fetus.

Correlations between periodontal indices and osteoporosis.

In the pathogenesis of chronic periodontitis, there are general systemic factors which play a major role, such as osteoporosis, with menopause as the most common etiological factor, and other pathological determining conditions for osteoporosis as well (ovary, thyroid and malignant tumors). The aim of the present study was to assess the correlations between periodontal indices and osteoporosis. The study was performed on 35 patients with periodontal disease aged between 45 and 79 years. These patients were divided into two groups: a study group with osteoporosis and periodontal disease (n=25) and a control group with periodontal disease (n=10) only. The periodontal assessment included community periodontal index (CPI), gingival inflammation index (GI), plaque index (PI), body mass index (BMI), bone mineral density (BMD), tooth mobility and tooth loss. Osteoporosis was assessed by dual-energy X-ray absorptiometry. Results were statistically analyzed with Microsoft Excel software and XLSTAT. The results showed that patients in the study group had higher values of periodontal indices, and a highly significant inverse correlation was observed between the CPI and the tooth loss. Inverse correlations between BMI and tooth mobility, as well as BMI and CPI were determined for the study group. In conclusion, the positive association between BMD and GI shows that the gingival index can be a predictive factor in the occurrence of osteoporosis.

Triple immunohistochemistry for assessing the inflammatory, vascular and progression of adenomyosis.

Adenomyosis is a benign pathology, common to both women at reproductive age as well as later during menopause. This condition is accompanied by a strong symptomatology, which has induced intense research on this topic. From a morphological point of view, it is represented by the existence of endometrial glands and, sometimes, of the periglandular stroma (endometriosis) in the structure of the myometrium, at a significant distance from the normal endometrium. Various inflammatory, vascular and mechanical factors accentuate the symptoms and evolution of this pathology. Our study included a total number of 32 patients, eight cases for each of the following histopathological subtypes: endometrium - proliferative phase, endometrium - secretory phase, myometrium with endometrial glands (adenomyosis), and myometrium with hyperplastic transformation of endometrial glands (hyperplastic adenomyosis), respectively. We have conducted clinical, morphological and morphopathological studies of the structures in question. Using the classical histological technique (Hematoxylin-Eosin), we identified the glandular structures; utilizing immunohistochemistry, we have labeled the endometrial epithelium with the anti-cytokeratin 7 (CK7) antibody and we analyzed the periglandular cell types of the immune system: T-lymphocytes using anti-cluster of differentiation (CD) 3 antibody, macrophages using anti-CD68 antibody, mast cells using anti-tryptase antibody, periglandular vascularization with the reaction using anti-CD34∕anti-CD31 antibodies, thus demonstrating their involvement in the development of adenomyosis. The interesting aspect of this study is the technique of simultaneously labeling of the inflammatory, vascular and epithelial elements.

Corrigendum to "Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes".

[This corrects the article DOI: 10.1155/2015/604208.].

A morpho-functional study using PEP/LVET ratio and global longitudinal strain in patients with dilated cardiomyopathy.

AIM: To assess left ventricular (LV) systolic function and morphology in patients with severe dilated cardiomyopathy (DCM), using both conventional and a complex technique, speckle-tracking echocardiography, and evaluate the correlation between pre-ejection period and left ventricular ejection period (PEP/LVET) ratio, global longitudinal strain (GLS), and severity of the condition. PATIENTS, MATERIALS AND METHODS: Seventeen patients were enrolled after rigorous criteria. Echocardiography was performed in conventional and speckle-tracking mode, in all patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction (LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and was defined as the time between QRS onset and LV ejection reported to LV ejection period. Speckle-tracking imaging was performed in offline mode and GLS was obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging longitudinal peak systolic strain of all 17 LV-segments. RESULTS: New York Heart Association (NYHA) functional class correlated significantly with LVEF (-0.82; p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable correlations were between mitral regurgitation (MR) severity and LVEF (-0.65; p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS (0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014, respectively). As opposed to the parameters in conventional echocardiography, GLS correlated with DCM etiology (p=0.0046) and with the gender (p=0.048). CONCLUSIONS: This study demonstrates that, in patients with DCM, assessment of cardiac dyssynchrony can be accurately accomplished by combining parameters in conventional and in speckle-tracking echocardiography.

Mutational status of KRAS and MMR genes in a series of colorectal carcinoma cases.

BACKGROUND: The KRAS gene mutation is the most common somatic change in colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of all CRCs, more frequent in early stages. CRCs with MSI present better prognosis, a distinct histopathological aspect and a different response to chemotherapy. Patients with both KRAS wild type and MSI have a reduced risk of dissemination and recurrence. MATERIALS AND METHODS: Our study included formalin-fixed paraffin-embedded tissue samples from 40 patients with metastatic CRCs, aged between 40 and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were analyzed using an indirect bistadial immunohistochemical (IHC) technique with monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Of the 40 tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13. IHC expression of MMR proteins revealed a microsatellite stable status in 35 cases, including 15 cases with mutated KRAS. MSI status was identified in five cases (four with KRAS wild type). All MSI tumors had a poorer histological differentiation and four cases revealed a mucinous phenotype. Eighty percent of the patients with MSI status were older women. CONCLUSIONS: Our study demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS mutations being inversely correlated with MSI status in these tumors. MMR protein deficient CRCs tend to occur in older females, have a poorer differentiation and are frequently associated with KRAS wild type.

The Herlyn-Werner-Wunderlich triad (OHVIRA syndrome) with good pregnancy outcome - two cases and literature review.

The Herlyn-Werner-Wunderlich syndrome (HWWS) is a complex congenital malformation, originally described as a triad of symptoms: didelphys uterus, low genital obstruction and unilateral renal anomaly. The term OHVIRA is an acronym (obstructed hemivagina/hemicervix with ipsilateral renal anomaly) and refers to the same syndrome. It gained acceptance in recent years, due to reports of cases having a non-didelphys uterus (normal, septated or having other abnormalities). In the following, we report two cases with good pregnancy outcome and we provide a short discussion on published literature. We highlight differences and complications in these two cases, confirming the extreme variability of anatomic structures involved in the syndrome. Though rare, the condition allows successful pregnancies. We describe the sixth case of didelphys uterus with unique (anatomically normal) vagina and unilateral isolated hemicervix hypoplasia∕atresia. Imaging has a paramount importance in the diagnosis of HWWS∕OHVIRA, with magnetic resonance (MR) usually superseding the ultrasound (US) method, and providing other viscera details. US, MR and laparoscopy∕laparotomy complement each other, and for describing the anatomy of the obstruction a thorough clinical examination is required. The clinical course of the pathology is not standard and the management must be tailored, but term∕near-term pregnancies resulting in healthy newborns are possible in HWWS. We advocate an appropriate maternal and fetal prenatal care and long-term follow-up.

The importance of perinatal autopsy. Review of the literature and series of cases.

Perinatal autopsy remains the gold-standard procedure used to establish the fetal, neonatal or infant abnormalities. Progressively, perinatal pathology has become a specialized field with important roles of audit for fetal prenatal diagnostic tools, in parents counseling regarding future pregnancies, in scientific research, for epidemiology of congenital abnormalities and teaching. The differences between prenatal ultrasound and autopsy reports represent a strong argument for the autopsy examination following termination of pregnancy. The reasons for such discrepancies are related to the ultrasonographic or pathological examination conditions, the type of the anomalies, the expertise and availability of the operators. Several facts led to an undesirable increase of refusals from parents to consent to a conventional invasive autopsy: the centralization of pathology services, the poor counseling provided by non-experts in fetal medicine and the clinicians' over-appreciation of the importance of the ultrasound diagnostic investigation. Although non-invasive alternatives have been tested with promising results, conventional autopsy remains the gold standard technique for the prenatal diagnosis audit. We report and analyze several cases of prenatally diagnosed malformed fetuses with different particularities that underline the necessity of perinatal autopsy. We discuss the antenatal findings and management and post-mortem autopsies in the respective pregnancies.

The impact of liver steatosis on early and sustained treatment response in chronic hepatitis C patients.

Steatosis is a frequent feature of hepatitis C virus (HCV) infection. Steatosis may be an important cofactor in both accelerating fibrosis and increasing liver necroinflammatory activity in chronic hepatitis C. The main objective of this study was the evaluation of biological response rates, early viral response, sustained viral response in patients with chronic hepatitis C treated with Interferon-alpha (IFN-α), Pegylated (PEG)-IFN-α2a or -α2b plus Ribavirin and to relate it to the presence of hepatic steatosis. There were selected to take part to the research 210 patients with chronic hepatitis C who have fulfilled all inclusion and exclusion criteria and were treated with PEG-IFN plus Ribavirin. Patients' progress has been monitored by determining next parameters: age, gender; biochemical tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays - detect antibody to hepatitis C virus (anti-HCV); molecular assays - detect, quantify and/or characterize HCV-RNA; liver histopathological examination. Steatosis was graded using the Brunt system. These parameters were included in an area under curve (AUC) analysis. Purpose is to estimate their degree of influence on getting early viral response (EVR) and sustained viral response (SVR). Based on the obtained results, it appears that initial value of HCV-RNA, dVL parameter value (low relative percentage of viral load during the first 12 weeks of treatment), histological scores steatosis may be predictive in the viral response in chronic hepatitis C. Our research demonstrates that a high degree of liver steatosis impairs both EVR and SVR in chronic hepatitis C treated with standard PEG-IFN and Ribavirin for 48 weeks and that a steatosis score of ≤3 predicts EVR with a sensibility of 91.03% with specificity of 21.54%.

Neuro-neoplastic interrelationships in colorectal level - immunohistochemical aspect in three cases and review of the literature.

Colorectal cancer represents a severe public health issue. Recent studies have shown the essential role played by nerves and their neurotransmitters in tumor initiation and progression. The aim of this study is to asses the expression of beta 2-adrenergic receptors (ß2A) for adrenaline and noradrenaline, and the expression of M3 muscarinic receptors (M3R) for acetylcholine (neurotransmitters produced and released by sympathetic and parasympathetic afferents of the digestive tract and also by the enteric nervous system) in different tumor gradings of colorectal adenocarcinoma, and also the tropomyosin receptor kinase A (TrkA) for the nerve growth factor produced by the cells of colorectal adenocarcinoma. Beta 2-adrenergic receptors were expressed both in normal colic tissue and in the tumor tissues, from the three patients included in the study. It was observed that both area and integrated optical density (IOD) are more elevated for this type of receptor in tumor tissues than in normal colic tissue. For the M3 muscarinic receptors, similarly to beta 2-adrenergic receptors, it was observed a growth both of the area and of the IOD with the tumor grading. The presence of TrkA receptors was also observed both in the normal colic mucosa and in the tumor tissues examined, but with a significant reduction of the signal in the poorly differentiated tumor tissue. Understanding the neurobiology of cancer in this context becomes necessary for establishing much more complex and targeted molecular targeted therapies.

Histological factors that predict the liver fibrosis in patients with chronic hepatitis C.

In chronic hepatitis, pathologies reveal a prominent inflammatory infiltrate portal consisting mostly of lymphocytes and plasma cells invading the portal spaces, although one can also identify macrophages, neutrophils or eosinophils. In all the forms of chronic hepatitis, fibrosis starts in the portal area, namely periportally, subsequently extends towards the lobules to the central veins, causing septa, followed by fibrosis. We studied 52 patients with chronic hepatitis C, who underwent a hematological, biochemical, virological and histopathological investigation. We found that the severity degree of the portal inflammation was in direct relation to the hepatitis activity index (HAI) and to the degree of fibrosis. The portal inflammation is dependent to the degree of fibrosis. The degree of inflammation significantly changes the distribution of cases with different degrees of fibrosis (chi-square p=0.00011 <0.001). Periportal inflammation, periportal necrosis and focal necrosis are the morphological aspects of the necroinflammatory process best correlated to the occurrence and development of fibrosis.

Non-alcoholic fatty liver disease - clinical and histopathological aspects.

INTRODUCTION: We conducted a retrospective study on patients who were hospitalized in the Emergency County Hospital of Craiova, Romania, between 2009-2014. We selected 75 patients out of 248 cases of fatty liver disease who underwent liver biopsies performed during surgical procedures for various diagnoses. PATIENTS AND METHODS: We analyzed the patients' data recorded in examination charts: anthropometric parameters [height, weight, body mass index (BMI), abdominal circumference], metabolic lab tests (blood glucose, lipid profile), liver destruction enzymes, imaging examinations (abdominal ultrasound). The pathological study was performed on specimens directly after sampling as well as after staining. RESULTS: After analyzing the results of the histological examination, we grouped our studied patients according to the degree of the liver steatosis: 21 (28%) cases with mild steatosis, 46 (61.33%) cases with moderate disease and eight (10.66%) cases with severe steatosis. The necrotic-inflammatory activity was mild in 28 (37.33%) cases, moderate in 36 (48%) cases and severe in 11 (14.66%) cases. Most of the studied patients exhibited septal fibrosis (45 cases - 60%) and porto-portal and porto-central bridging fibrosis (21 cases - 28%). Septal fibrosis and cirrhosis were recorded in four (5.33%) and five (6.66%) cases, respectively. There was a significant correlation between the degree of the hepatic steatosis, the degree of obesity (as expressed by BMI) and the waist circumference (as a measure of central obesity) - p<0.001. CONCLUSIONS: The non-alcoholic fatty liver disease (NAFLD) was found to be significantly associated with waist circumference, BMI, triglycerides. The liver enzymes are not considered to be sensitive or specific for diagnosing NAFLD. Concerning the association between the steatosis and fibrosis, in our study the septal fibrosis was associate with mild steatosis in most of the cases. Moderate steatosis was mostly associated with septal fibrosis as well as porto-portal and porto-central fibrosis. Severe steatosis was correlated with both porto-portal and porto-central fibrosis and cirrhosis in the majority of cases.

Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery setting - preliminary preclinical study.

Iron oxide nanoparticles are promising candidates for theranostics in cancer, that aims to achieve in one-step precise tumor imaging by magnetic resonance, and targeted therapy through surface attached anti-cancer drugs. The aim of this study was to investigate in preclinical setting the biocompatibility of new iron oxide-based nanoparticles that were coated with L-DOPA for improved dispersion in biological media. These nanostructures (NPs) were designed for biomedical applications as contrast agents and/or drug carriers. We investigated the effect exerted in vitro by NPs and L-DOPA on the viability and proliferation of normal mouse L929 fibroblasts. NPs exhibited good biocompatibility against these cells. Moreover, L-DOPA contained in NPs sustained fibroblasts proliferation and/or limited anti-proliferative effects of naked nanoparticles. In the animal study, C57BL/6 mice were injected intraperitoneally with a single dose of NPs (approximately 125 mg/kg body weight). We followed up hematological and histological parameters for one, three and seven days after NPs administration. Results indicated that NPs possibly induced local inflammation and consequent recruitment of peripheral lymphocytes, whilst the decrease of platelet counts may reflect tissue lesions caused by NPs. The histopathological study showed mild to moderate alterations in the hepatocytes, splenic and renal cells, while the brain parenchyma only presented nonspecific congestive changes. Taken altogether, the preclinical study indicated that the new iron oxide nanoparticles coated with L-DOPA were biocompatible against fibroblasts and had a convenient toxicological profile when administered intraperitoneally in a single dose to C57BL/6 mice. Accordingly, the proposed nanostructure is a promising candidate for imaging and treating dispersed peritoneal tumors.

Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes.

This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

The redox biology network in cancer pathophysiology and therapeutics.

The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1) and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic), greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular heterogeneity and the hypoxia map in the tumor niche, along with the adjoining and systemic effects of oxidative stress-based therapies.