Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.

OBJECTIVE: In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well. PATIENTS AND METHODS: In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS). RESULTS: A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy. CONCLUSIONS: The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.

Lung cancer and COVID-19: problems and perspectives.

COVID-19 pandemic generated concerns about the healthcare of patients with cancer, not simply because of the formidable impact of COVID-19 patients in the public healthcare system, but also due to the overlapping pathognomonic signs of many forms of lung cancer with lung injuries associated with COVID-19. This report tries to shed light on the issue. We evaluated the great concern of people suffering from lung cancer and also infected with SARS-CoV-2 by discussing evidence and data from current literature. Lung cancer in Italy has represented more than 1 case/4 (27%) in the latest ten years and nevertheless, even due to the concurrence of many complex interplays between COVID-19 and cancer even at the immune level, a consensus protocol and expert guidelines to diagnose and treat lung cancer upon SARS-CoV-2 infection are yet lacking. New insights and consensus panels should be therefore proposed, even at the simplistic level about if priority must be either given to COVID-19 or to cancer therapy.

Fibromyalgia treated with oxygen-ozone auto-haemotherapy (O2-O3-AHT): a case study on 200 patients with a modified 10-PI-NRS evaluation.

OBJECTIVE: Fibromyalgia (FM) is a concerning chronic disease showing as widespread pain, muscle stiffness, sleep disturbances, chronic fatigue, and depressed mood, for which no sound therapy is yet available to date. In this article we assessed a wider patients' cohort the efficacy of oxygen-ozone autohemotherapy (O2-O3-AHT) previously reported. PATIENTS AND METHODS: A number of 200 FM-patients accessed the study and were treated with 3-4 runs of O2-O3-AHT, following their signed consent. A modified 10 points-PI-NRS were used to evaluate pain intensity before and after the conclusion of the complete ozone-treatment cycle (1 month). Kruskall-Wallis' test and other statistics were used at p<0.05 level of significance. RESULTS: A quite complete rehabilitation of the musculoskeletal function and of the overall arthralgia was observed in 76% of the patients at one month of follow-up. The number of patients having a reduction in the PI-NRS score from 10 (the maximal observed) to 3 (including 10-1 and 10-2) following only two runs of O2-O3-AHT was 23.5%, whereas only 17.5% did not show any significant improvement (ΔPI-NRS = 0 or 1), so assessing that the efficacy of O2-O3-AHT, independently from ages, encompassed at least 41% in a moderate way and 64.5% of the treated patients, as a whole. CONCLUSIONS: Oxygen-ozone autohemotherapy represents a formidable therapeutic approach for FM, deserving further studies to be made in order to fully elucidate ozone effect of this pathology.

Fatigue in post-acute sequelae of SARS-CoV2 (PASC) treated with oxygen-ozone autohemotherapy - preliminary results on 100 patients.

OBJECTIVE: Post-acute sequelae of SARS-CoV2 infection (PASC) are a novel terminology used to describe post-COVID persistent symptoms, mimicking somehow the previously described chronic fatigue syndrome (CFS). In this manuscript, we evaluated a therapeutical approach to address PASC-derived fatigue in a cohort of past-COVID-19 positive patients. PATIENTS AND METHODS: A number of 100 patients, previously diagnosed as COVID-19 positive subjects and meeting our eligibility criteria, was diagnosed having PASC-related fatigue. They were recruited in the study and treated with oxygen-ozone autohemotherapy (O2-O3-AHT), according to the SIOOT protocol. Patients' response to O2-O3-AHT and changes in fatigue were measured with the 7-scoring Fatigue Severity Scale (FSS), according to previously published protocols. RESULTS: Statistics assessed that the effects of O2-O3-AHT on fatigue reduced PASC symptoms by 67%, as a mean, in all the investigated cohort of patients (H = 148.4786 p < 0.0001) (Figure 1). Patients following O2-O3-AHT therapy, quite completely recovered for PASC-associated fatigue, a quote amounting to about two fifths (around 40%) of the whole cohort undergoing ozone treatment and despite most of patients were female subjects, the effect was not influenced by sex distribution (H = 0.7353, p = 0.39117). CONCLUSIONS: Ozone therapy is able to recover normal functionality and to relief pain and discomfort in the form of PASC-associated fatigue in at least 67% of patients suffering from post-COVID sequelae, aside from sex and age distribution.

Ozone Exerts Cytoprotective and Anti-Inflammatory Effects in Cardiomyocytes and Skin Fibroblasts after Incubation with Doxorubicin.

INTRODUCTION: Skin reactions and cardiotoxicity are one of the most common side effects of doxorubicin in cancer patients. The main mechanisms based on the etiopathogenesis of these reactions are mediated by the overproduction of proinflammatory cytokines, metalloproteases, and the disruption of mitochondrial homeostasis. Ozone therapy demonstrated anti-inflammatory effects in several preclinical and clinical studies. The aim of this research is based on the evaluation of cardioprotective and dermatoprotective effects of ozone during incubation with doxorubicin, giving preliminary evidences for further studies in the field of cardio-oncology. METHODS: Human skin fibroblast cells and human fetal cardiomyocytes were exposed to doxorubicin at subclinical concentration (100 nM) alone or combined with ozone concentrated from 10 up to 50 µg/mL. Cell viability and multiple anti-inflammatory studies were performed in both cell lines, with particular attention on the quantification of interleukins, leukotriene B4, NF-κB, and Nrf2 expressions during treatments. RESULTS: Ozone decreased significantly the cytotoxicity of doxorubicin in skin fibroblasts and cardiomyocytes after 24 h of incubation. The best cytoprotective effect of ozone was reached to 30 µg/mL with a plateau phase at higher concentration. Ozone also demonstrated anti-inflammatory effects decreasing significantly the interleukins and proinflammatory mediators in both cells. CONCLUSION: Ozone exerts cardioprotective and dermatoprotective effects during incubation with doxorubicin, and the involved mechanisms are mediated by its anti-inflammatory effects. The overall picture described herein is a pilot study for preclinical studies in oncology.

[Preliminary study to evaluate the meaning of GGT fractions analysis in a population of workers previously exposed to asbestos]. / Studio preliminare volto all'inquadramento del significato preventive del dosaggio di frazioni di GGT in una popolazione di lavoratori ex-esposti ad Amianto.

The GGT enzyme, considered for years only as a marker of liver disease and alcohol abuse, has now revealed a risk of death for many causes. Through a molecular exclusion chromatography on FPLC system (Fast Protein Liquid Chromatography), it is possible to discriminate four fractions of GGT, defined according to the molecular weight: big-GGT, medium-GGT, small-GGT and free-GGT. The objective was to study the preventing meaning of GGT fractions for asbestos-related diseases. This study was conducted on 129 workers previously exposed to asbestos, 22 patients affected by Malignant Pleural Mesothelioma and 107 healthy workers. Our data demonstrated a statistical significant correlation between the fraction free-GGT with the presence of MPM, suggesting a possible role for this molecule as a biomarker for MPM diagnosis. However, being a preliminary study, further studies are warranted to confirm our results.

Transanal haemorrhoidal dearterialisation: nonexcisional surgery for the treatment of haemorrhoidal disease.

BACKGROUND: Transanal haemorrhoidal dearterialisation (THD) is a nonexcisional surgical technique for the treatment of piles, consisting in the ligation of the distal branches of the superior rectal artery, resulting in a reduction of blood flow and decongestion of the haemorrhoidal plexus. The aim of this study was to assess the long-term efficacy of this treatment. METHODS: The procedure was carried out using a proctoscope with a Doppler probe. The terminal branches were located with Doppler and then sutured. RESULTS: From January 2000 to May 2006, we performed THD in 330 patients (180 men; mean age, 52.4 years), including 138 second-degree, 162 third-degree and 30 fourth-degree haemorrhoids. There were 23 postoperative complications (7 cases of bleeding, 5 thrombosed piles, 4 rectal haematomas, 2 anal fissures, 2 cases of dysuria, 1 of haematuria and 2 needle ruptures). The mean postoperative pain score was 1.32 on a visual analog scale. 219 patients were followed for a mean of 46 months (range, 22-79), including 100 patients with second-degree, 104 with third-degree and 15 with fourth-degree haemorrhoids. The operation completely resolved the symptoms in 132 patients (92.5%) with preoperative bleeding and in 110 patients (92%) with preoperative prolapse. CONCLUSIONS: The efficacy and relapse rate of this procedure appears to be similar to that of traditional surgery and stapled haemorrhoidopexy. The technique was effective and safe for all degrees of haemorrhoids because of the excellent results, low complication rate and minor postoperative pain.

gamma-Glutamyl transpeptidase catalyses the extracellular detoxification of cisplatin in a human cell line derived from the proximal convoluted tubule of the kidney.

Nephrotoxicity is a side-effect and the main factor limiting the clinical use of cisplatin. In vivo, the administration of the cysteine-containing tripeptide glutathione (GSH) has been found to reduce nephrotoxicity, but the biochemical mechanism of this protective action is not fully understood. The present study was designed to gain insights into the mechanism by which GSH prevents cisplatin nephrotoxicity. We also wanted to verify the hypothesis of whether the protective action of GSH is mediated by products of the extracellular breakdown of GSH catalysed by gamma-glutamyl transpeptidase (GGT), an enzyme that is highly expressed in kidney tubular cells. The study was performed in HK-2 cells, derived from the immortalisation of human kidney proximal tubule cells. We investigated the influence of modulators of GGT activity and/or thiols on the antiproliferative activity of cisplatin and on the intracellular GSH content. We determined the antiproliferative activity of cisplatin, platinum cellular accumulation and DNA platination following precomplexing of the drug with thiols. The antiproliferative effect of cisplatin was minimally affected by the addition of GSH. However, when the antiproliferative assay was performed in the presence of glycyl-glycine (GlyGly), to serve as a transpeptidation acceptor and thus to stimulate GGT-mediated GSH catabolism, cisplatin-induced growth inhibition was largely prevented. This effect was not mediated through an increase of intracellular GSH levels, which were not affected by the GlyGly supplementation. The thiol dipeptide cysteinyl-glycine, i.e. the GSH catabolite generated by GGT activity, showed a higher reactivity against cisplatin in vitro than GSH, as was shown by the more rapid oxidation of its -SH groups. The cisplatin/GSH or cisplatin/cysteinyl-glycine adducts did not display an antiproliferative effect. However, 2 h precomplexing with GSH in the presence of GGT, or directly with the GSH catabolite cysteinyl-glycine, decreased the antiproliferative effect of cisplatin and drug-induced DNA platination to a greater extent than precomplexing with GSH alone. The results of the present study show that, in HK-2 cells, extracellular GSH decreases the antiproliferative effects of cisplatin only upon its hydrolysis by GGT, thereby supporting the hypothesis that the extracellular metabolism of GSH by GGT plays a role in modulating cisplatin nephrotoxicity. A primary role in the protection of HK-2 cells appears to be played by cysteinyl-glycine, the proximal product of the GGT-mediated hydrolysis of GSH, which shows a high reactivity against CDDP resulting in the rapid inactivation of the drug.

Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer.

BACKGROUND: Currently outer quadrant breast tumors are not felt to have significant drainage to the internal mammary nodal chain. We evaluated the incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy for all breast quadrants. METHODS: Eighty women were prospectively studied by technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative gamma probe identification of sentinel nodes. IMSN detected were surgically removed. RESULTS: Ten of 80 ( 12%) patients had IMSN identified in addition to axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients with positive IMSN also had positive AXSN. CONCLUSIONS: Patients undergoing lymphatic mapping for the management of breast cancer should have radiolabelled tracer and gamma probe sentinel node identification regardless of tumor location in the breast.

[Sclerosing peritonitis. A complication of LeVeen peritoneovenous shunt]. / Peritonite incapsulante. Una complicanza dello shunt peritoneo-venoso di LeVeen.

Sclerosing peritonitis (abdominal cocoon syndrome) is a rare chronic affection of the peritoneum; its etiology is multifactorial and it affects all ages. Capsulating membranes seem to grow from a poorly cellular connective deposition in many layers on the intestinal peritoneum and are casually detected by surgery or autopsy. The placement of the peritoneovenous shunt can favour the deposition of fibrin on the visceral peritoneum, determining the formation of sclerosing membranes. When mechanical occlusion occurs, surgery is the choice therapy in order to remove the obstacle and, if possible, the membranes as well.

[Bilateral renal oncocytoma. A clinical case and review of the literature]. / Oncocitoma renale bilaterale. Caso clinico e revisione della letteratura.

Renal oncocytoma is an epithelial tumour of the kidney, originally considered benign neoplasm, but now it is thought have a limited but real malignant or metastatic potential. Usually monolateral, in 6% of cases it is bilateral in a synchronous or metachronous way. A case of bilateral renal oncocytoma in a 56-year-old woman, observed by chance during a follow-up carried out after breast cancer is described. The etiopathogenic and clinical-therapeutic aspects of this neoplasm are examined, and the conclusion is drawn that the most correct therapeutic approach must aim at both the protection of kidney function and complete removal of the tumour.

[Acute obstruction of the abdominal aorta]. / L'ostruzione acuta dell'aorta addominale.

The acute occlusion of abdominal aorta is a rare event that may have severe clinical results. Personal experience in three cases of acute thrombosis treated in emergency surgery are presented. Aorto-iliac thromboendarterectomy, aorto-bifemoral bypass and thrombectomy with Fogarty catheter were performed. In the first case, after the operation, a renal ischemia occurred. The second and the third patient died after seven days and twenty-four hours respectively.

[Cholangiojejunostomy of the duct of the 3d segment. Palliative treatment of cholestatic jaundice caused by neoplastic obstruction of the hepatic hilus]. / Derivazione bilio-digiunale sul dotto del III segmento. Trattamento palliativo dell'ittero colostatico da ostruzione neoplastica dell'ilo epatico.

Cholangiojejunostomy of the duct of the III segment in the palliative treatment of mechanical jaundice from neoplastic obstruction of the hepatic hilus. The neoplastic obstruction of the liver hilus has an almost total absence of forewarning clinical signs and therefore results in surgery at a late stage when the patient is not susceptible to radical treatment. It is therefore necessary to use palliative treatment in order to resolve the serious jaundice, the main cause of a quick death. Among the palliative treatment the Authors report their experience of intrahepatic cholangiojejunostomy of the duct of the III segment that they consider the most suitable technique for its ease of execution, its constant anatomical situation and the peripheral position of the anastomoses in relation to the neoplastic lesion. This allows a lasting biliary decompression with a good residual life.

[Urachal cyst. A case report and review of the literature]. / La cisti dell'uraco. Descrizione di un caso e revisione della letteratura.

The pathology of urachal disease is rarely seen. This article refers to a case of urachal cyst in a twenty-five-year-old male. In order to discuss the pathogenic, clinical and therapeutic aspects of this rare pathology, it is necessary to carry out a complete revision of the literature. Diagnosis is helped by ultrasound and CT scan of the lower abdomen, while fistulography is necessary when there is cutaneous drainage. The treatment consists of surgical approach which includes complete en-bloc excision of the cyst together with possible urachal residue. Such treatment is indispensable in order to avoid acute infection and/or malignant degeneration, frequent complications which are very serious.

[Small-cell carcinoma of the bladder: description of a case and review of the literature]. / Microcitoma della vescica: descrizione di un caso e revisione della letteratura.

Small-cell carcinoma (also known as oat-cell carcinoma) is a rare tumor that previously concerns the lung; small-cell carcinoma of the bladder is extremely rare (0.5% of all bladder malignancies). The Authors report here the case of a 78th years old man. Fourteen months before our observation he was submitted to a partial cystectomy for a small-cell carcinoma of the bladder cupola. There was no evidence of extra-vesical location at that moment and the patient was not submitted to any adjuvant therapy. At the moment of our observation the disease was very advanced and the patient died in a few time. The Authors discuss about the therapy of bladder small-cell carcinoma in the few cases described by the literature and about the survival of those patients. A radical surgical treatment in association with an adjuvant chemo- or radiotherapy appears as a better way to treat these patients. On account of this case the Authors agree with this choice and conclude that only a combined treatment can allow a better survival.

[Laparoscopic treatment of varicocele]. / Trattamento laparoscopico del varicocele.

Varicocele is frequently a contributing factor in male infertility. We performed laparoscopic treatment of varicocele in 6 patients. This procedure can be carried out through three ports and allows not only ligation and excision of the dilated testicular veins, but those veins branching through the back of the inguinal canal lower down. It is a quick operative procedure and we completed it within 30 minutes. All the patients have gone home on the 2 days and, to date, there have been no complications. During a follow-up period of 3-6 months it was possible to observe the disappearance of varicocele. It is possible to conclude that the laparoscopic procedure is simple and effective as more traditional methods.

[Surgery in aneurysms of the abdominal aorta in an outlying hospital]. / La chirurgia degli aneurismi dell'aorta addominale in un ospedale periferico.

Abdominal aortic aneurysms have become more frequently recognized due to an improved diagnostic approach and prolonged longevity. Therefore it can be argued that aneurysmal pathology must be entirely dealt with, including its surgical therapy, in outlying non-specialized hospitals. Elective surgical treatment of aortic aneurysms is mandatory in order to acquire the technique that will provide a satisfactory efficiency and reliability in the emergency treatment of ruptured aortic aneurysms. The basic supports of aortic aneurysm surgery in outlying hospitals are the availability of postoperative intensive therapy, a competent surgeon staff and an improved diagnostic approach in order to recognize those aneurysms which are operable by the staff and those requiring very complex reconstructive procedures such as thoraco-abdominal aortic aneurysms which must be transferred to highly specialized centres. An angiography service should be set up since it represents an important support for the operation of abdominal aneurysms; however in practice it proved to be non-essential in the present case. In contrast the intensive postoperative unit must be considered vital in view of the patient's risky conditions. The experience reported here is really positive as regards expanding aneurysms given elective surgery, in which cases there was no mortality either intra- or post-operatively. The follow-up varied from 3 to 7 years. Only one ruptured aneurysm was dealt with and the outcome was fatal owing to anuria caused by severe haemorrhagic shock. However, we cannot expect an acceptable efficiency level in emergency aneurysmectomy if the diagnostic and therapeutic approach does not guarantee full reliability in cases of elective aneurysmectomy.

Iatrogenic vascular injuries following lumbar disc surgery. Case report and review of the literature.

Iatrogenic vascular injuries are unusual complications of lumbar disc surgery. The incidence of such injuries is very low but probably underestimated because clinical manifestations may be extremely variable depending on the extension of trauma whether artery or vein are injured or both. Diagnosis is suspected when early signs of retroperitoneal hemorrhage appear, but may often be delayed for weeks or years because formation of a pseudoaneurysm or an arteriovenous fistula which may be of gradual onset and produce only a few symptoms at the onset. Prompt diagnosis and aggressive treatment can hope to improve current mortality of more than 50%. A case of venous and arterial injury is reported, successfully operated on with an original technique of ilio-caval patching to avoid caval ligation. A review of the literature shows the predisposing factors and complex anatomy of such injuries, the clinical picture and the management of the emergency.