Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC).

Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however, the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression remains poorly described. Patients and methods: Patients with EOC and sequential samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of stromal area with high sTILs defined as ≥50%; intra-epithelial TILs (ieTILs) scored semi-quantitatively (0-3) with high ieTILs ≥2. A smaller number were available for PD-L1 evaluation, cut-off for positivity was ≥5% staining. Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median 20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen following NACT (P = 0.0005); individually the impact of NACT varied with sTILs increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs were predictive of platinum-free interval (PFI), patients with PFI ≥6 months had significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P = 0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs, and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1-positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P = 0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell lines. On multivariate analysis, high sTILs both pre- and post-NACT were independent prognostic factors for progression-free survival (PFS) (HR 0.49, P = 0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD-L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase following NACT. Evaluation of immune parameters in the post-NACT tumour may help select patients for immunotherapy trials.

Fertility-sparing surgery in epithelial ovarian cancer: a systematic review of oncological issues.

Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer (EOC) has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely carried out for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless, the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with 'less favourable' prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed, but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathological analysis (or review) of the tumour by an expert pathologist.

[Sentinel lymph node biopsy in the management of early-stage ovarian cancer: A systematic review of the literature]. / Place du ganglion sentinelle dans la prise en charge du cancer de l'ovaire de stade précoce : revue de la littérature.

The initial management of early-stage ovarian cancer consists of staging surgery including pelvic and para-aortic lymphadenectomy. The use of the sentinel lymph node (SLN) procedure in this setting may decrease the morbidity associated with this surgery. The objective of this review was to evaluate the feasibility of the SLN procedure in ovarian cancer diagnosed at an early stage by comparing the different techniques used and their accuracy. A systematic literature search was performed on PubMed and ClinicalTrials.gov for articles in English or French about the SLN technique in ovarian cancer. Ten studies were included in the analysis, with a total of 179 patients. The main tracers used were Technetium-99m, indocyanine green, and patent blue, and the most common site of injection was the proper ovarian and unfundibulopelvic ligaments. The overall detection rate was 87.7%. Of the small number of cases of lymph node metastasis reported, the SLN procedure had a sensitivity of 90.9% and a negative predictive value of 98.8%. The sentinel node procedure appears to be feasible and safe and could be reliable in determining the lymph node status of patients with early-stage ovarian cancer.

Long-COVID Headache.

The so-called long COVID-19 is a set of symptoms that accompanies the patient even for months after discharge from the hospital. These symptoms include easy muscle fatigue, moderate breathlessness, persistent headache, the feeling of a foggy head, and the development of psychiatric disorders. In general, the quality of life of at least half of the patients who come out of the COVID-19 syndrome, both mild and severe, shows a markedly worsening despite having passed a difficult physical and psychological test. Among all the neurological disorders that can most frequently be found in the long COVID-19, it is important to consider the persistent headache symptomatology as a possible chronic sequela of the infection. Since there is not a definition in the International Headache Society classification of this type of headache, we must focus our attention on this long-COVID-19 headache especially because clinical studies are being planned to collect big data for the International Headache Society Classification Committee.

[Epithelial ovarian cancers and minimally invasive cytoreductive surgery after neoadjuvant chemotherapy: A systematic review]. / Cancers épithéliaux de l'ovaire et chirurgie de cytoréduction par voie mini-invasive après chimiothérapie néoadjuvante : revue systématique de la littérature.

INTRODUCTION: Advanced epithelial ovarian cancer (EOC) is associated with high mortality and often managed first with neoadjuvant chemotherapy (NACT) followed by debulking surgery. Laparoscopic surgery with or without robotic assistance (Minimally Invasive Surgery (MIS)) may represent a beneficial option for these patients. The objective of this literature review is to clarify the place of MIS in the management of advanced EOC for selected patients. METHOD: Pubmed, Cochrane and Clinicaltrials.gov online databases were used for this review, to select English or French published articles. RESULTS: We selected 11 original articles published between 2015 and 2020, 6 of which compared MIS and laparotomy. Among these 11 studies, 8 were retrospective cohorts, 2 were phase II trials, and one was a case-control study. In total, there were 3721 patients, of which 854 (23%) were treated with MIS. The robotic assistance was used with 224 patients (26%) of those MIS patients. Looking specifically at MIS patients, the laparoconversion rate was 9.5%, the rate of complete resection (CC-0) was 83.4%. Finally, the MIS complication rate was 1% intraoperatively and 12% postoperatively. The rate of complete resection, postoperative complication, as well as overall survival (OS) were comparable between patients treated with MIS or laparotomy. One study found an improved disease-free survival (DFS) in MIS versus laparotomy (18 months versus 12 months; P=0.027). CONCLUSION: MIS seems feasible, effective, and reliable in comparison to laparotomy for the completion of cytoreductive surgery after NACT without compromising oncological safety. Prospective randomized controlled trials are needed to confirm the role of MIS in advanced EOC.

COVID-19: is it just a lung disease? A case-based review.

Due to its extreme virulence, COVID-19 virus has rapidly spread, developing a severe pandemic. SARS-COV-2 mostly affected the respiratory tract, causing a severe acute lung failure. Although the infection of airways, COVID-19 can be associated with chronic and systemic damages still not so much known. The purpose of this research is to collect recent evidence in literature about systemic diseases caused by COVID-19. The format of the present article has features of a systematic case-based review (level of evidence), and it is structured as a case series report (patients of our COVID-19 Medicine Ward have been selected as cases). Data for this review have been selected systematically, taking evidence only from indexed journals and databases: PubMed, Scopus, MEDLINE, and Cochrane systems. Papers chosen included systematic reviews, case series, clinical cases, meta-analysis studies, and RCTs. We start collecting studies since 2003. The main keywords used were "COVID-19" "OR" "SARS" "OR" "SARS - COV 2" "AND" "systemic disease" / "nephropathy" / "cardiac pathology" / "central nervous system." Clinical cases belong to our COVID-19 Medicine Ward. One of the most severe COVID-19 clinical presentations includes cardiovascular problems, like myocarditis, pericarditis, and acute hearth failure. Cytokine release syndrome caused by COVID-19 develops severe acute kidney failure. It is still unknown the way coronavirus damages the liver, brain, and reproductive system. Considering the majority of the new studies about this pathology, it issues that COVID-19 is considered to be a multi-organ disease.

Gynaecologic cancer surgery and preservation of fertility.

For gynecological cancers, even at an early stage, the standard treatment is "radical excision" involving hysterectomy (radical or not) with bilateral salpingo-oophorectomy. But for young patients with early stage disease, many recent studies have focused on preservation of subsequent fertility by keeping at least one ovary and the uterus. The main objective of this fertility-sparing surgery is to preserve fertility, if this can be accomplished without increasing the oncological risks. Whether the initial site of the cancer is the cervix, uterine fundus or ovary, the oncologic validation of fertility-sparing treatment requires several evaluation criteria: a rigorous clinical, radiological and surgical staging to verify that the pathology is truly at an early initial stage; expert pathologic interpretation of biopsy specimens to validate the histological criteria of "good prognosis"; provision of complete and understandable patient education verifying the true objectives for this fertility-sparing treatment (whose intent is to retain a potential for subsequent fertility without guaranteeing it) and provision of an explanation of the oncological constraints and implications of fertility-sparing surgery in the event of a possible pregnancy. As always in oncology, this strategy demands teamwork requiring successive discussions with the patient and spouse and thorough discussion of the oncological safety of this fertility-sparing strategy in multidisciplinary consultation meetings before "giving a green light".

Brachytherapy as part of the conservative treatment for primary and recurrent vulvar carcinoma.

PURPOSE: There are only scarce data on the place of brachytherapy (BT) for treatment of vulvar carcinoma. Our institutional experience of interstitial BT for vulvar carcinoma patients is reported. METHODS AND MATERIALS: Clinical records of patients receiving low-dose-rate or pulsed-dose-rate BT as part of the primary treatment for primary/recurrent vulvar squamous cell carcinoma or as part of postoperative treatment between 2000 and 2015 were included. Patients, tumors, and treatment characteristics as well as clinical outcome were examined. RESULTS: A total of 26 patients treated with BT were identified. BT was delivered as part of primary intent treatment for locally advanced/recurrent cancer in 11 patients and as part of postoperative treatment in 15 patients. Median age at time of BT was 63 years (range, 41-88 years). Pulsed-dose-rate and low-dose-rate were used in 15 patients and 11 patients, respectively. BT was performed as a boost to the tumor bed following external beam radiotherapy (n = 13) or as the sole irradiation modality (n = 13). Total median dose at the level of primary tumor was 60 GyEQD2 (range, 55-60 GyEQD2). With mean followup of 41 months (range, 5 months-11.3 years), 11 patients experienced tumor relapse, and in two of them, site of relapse was only local. Three-year estimated disease-free survival and overall survival rates were 57% (95% confidence interval: 45-69%) and 81% (95% confidence interval: 72-90%), respectively. All toxicities were Grade 2 or less. CONCLUSIONS: Interstitial BT used as part of the primary or postoperative treatment of vulvar carcinoma is feasible with a satisfactory toxicity profile. Prognosis remains, however, dismal, with a high frequency of failures in patients with locally advanced tumors.

S.C.S. effectiveness in patients affected by peripheral chronic arterial disease: our 5 years experience.

Spinal cord stimulation (S.C.S.) showed a valid clinical effect in the treatment of chronic obliterative arteriopathy of the lower limbs at an advanced stage (III-IV stages) and of phantom limb pain syndrome (P.L.P.S.). Secretion patterns of various biochemical mediators were evaluated and mechanism, by which analgesic and vasodilatator actions occur, were thus accounted for. There is not agreement on this subject. We report our experience on 60 patients (age range 28-91), observed over the period 1987-92. Blood values of some chemical mediators (beta-endorphins, Kinins, Serotonin, PGE) were determined before and after stabilization of the S.C.S. implant (from 2 up to 6 months) and compared with the objective clinical and TCpO2 data. Statistical significance was checked of variations obtained (Student's "t" test). High significant increase of TCpO2, beta-endorphins, PGE, (p < 0.01) and the Kinins (p < 0.05) was found but there were no significant alteration of Serotonin. Results are explained and an S.C.S. effect at the spinal cord metamer level with a cortical integration (pointed out by the increase of the beta-endorphins) is suggested. Analgesic effectiveness and vasodilatator action of S.C.S. implant is stressed as long as it is carried out only when a correct indication is established in the absence of contraindications or important risk.

[Comparison of echo-Doppler and splenoportography in the hemodynamic evaluation of the portal system]. / Confronto tra eco-Doppler e splenoportografia nella valutazione emodinamica del circolo portale.

The Authors discuss the instrumental diagnosis of portal hypertension, comparing echo-Doppler and splenoportography by celiac artery catheterization, performed on 42 patients with cirrhosis. From the data obtained, there may be observed a clear correlation between angiographic and echographic criteria, correlated to the degree of illness. In particular echo-Doppler whether it possible, in a non-invasive way, to control the evolution of progressive haemodynamic resistance, and hepatic and splenic parenchyma, leaving to splenoportography the role to depict anatomic characteristics of portal circulation for a correct surgical program.

[The accuracy of FDG-PET/CT in early-stage cervical and vaginal cancers]. / Intérêt de la TEP-FDG dans les cancers du col de l'utérus et du vagin de stade précoce.

OBJECTIVE: [(18)F]fluoro-deoxy-glucose positron-emission tomography combined with integrated computed tomography (FDG-PET/CT) is commonly used for advanced stage cervical cancer but its efficiency is discussed in early stage. The aim of this study was to evaluate false negative rate of FDG-PET/CT in early-stage cervical and vaginal cancer. PATIENTS AND METHODS: Patients treated between 2005 and 2008 for stage IB1 cervical cancer and stage I vaginal cancer who underwent a FDG-PET/CT followed by a pelvic lymphadenectomy were studied. RESULTS: Eighteen patients were included with bilateral pelvic lymphadenectomy (16 cervical cancer, two vaginal cancer). The median age of patients was 41 years. Radical hysterectomy was performed for 16 patients, by a laparoscopic approach in 15 cases and by a laparotomic approach in one case. One patient had a simple hysterectomy and one had exclusive radiotherapy. No patient had pelvic or para-aortic fixation on FDG-PET/CT. Three patients have proven pelvic involvement and one had para-aortic metastases. The false-negative rate and negative predictive value of FDG-PET/CT were 17% and 83% respectively. DISCUSSION AND CONCLUSION: The accuracy of FDG-PET/CT imaging in predicting the pelvic nodal status is very low in patients with early-stage cervical and vaginal cancer and is not able to replace surgical exploration.

[Anastomosis between the left internal spermatic and splanchnic veins. Retrospective analysis of 305 patients]. / Anastomosi tra le vene spermatica interna sinistra e splancniche. Analisi retrospettiva su 305 pazienti.

PURPOSE: To investigate the presence and the rate of anastomoses between the internal spermatic vein (ISP) and visceral veins in patients with idiopathic varicocele. MATERIAL AND METHODS: We retrospectively reviewed the venographic findings of 305 patients (age range 14-40 years; mean age 28 years) with a US diagnosis of varicocele who were submitted to sclerotherapy from 1991 to 1997. All the venographic examinations had been carried out with selective injection of the ISP for complete mapping of gonadal vessels. RESULTS: The most frequent venographic patterns (type I) was identified in 139/305 patients (45.5%), type III was found in 86/305 (28.2%), type V in 37/305 (12.1%). Type IVb was found in 32 cases (10.4%) and type IVa in 9 (2.9%). Type II was seen in 2/305 patients only (0.6%). Single or double anastomoses between the ISP and portal or systemic veins were found in 34 patients (11.1%); a single or double communication with the left colic vein was observed in 24 cases (7.8%) and a communication with the paravertebral venous system in 10 patients (3.2%). Other anastomoses with the inferior mesenteric veins and splenic veins were seen in 7 and 4 patients (2.2% and 1.3%, respectively). DISCUSSION AND CONCLUSION: The presence of vascular variants and of communications of the ISP with the visceral veins needs accurate venographic studies preliminary to sclerotherapy and a skilled interventional radiologist in order to reduce the number of recurrences.

[Laser-assisted angioplasty in chronic obliterative arteriopathies of the lower limbs. The authors' personal experience]. / L'angioplastica laser-assistita nelle arteriopatie obliteranti croniche degli arti inferiori. Esperienza personale.

The laser represents one of the most interesting new methods of vascular surgery. As for laser-assisted angioplasty, the major clinical experience has come with Nd: Yag and Argon lasers. The authors comment on the 1989-1992 series of cases consisting of 51 arteries recanalized with a Nd:Yag laser--the patients were 42 men and 9 women, their mean age being 56.6 years. Four iliac obliterations, 36 femoropopliteal and 11 popliteotibial obliterations were treated surgically, according to the single anatomical radiologic circumstances. The immediate results showed 41 recanalizations (80.4%) 3 perforations (5.9%), 6 dissections (11.8%) and 2 distal emboli (3.9%). The long-term results, with a follow-up period ranging 6 months to 4 years (average: 1.8 years), were investigated with seriated c.w. Doppler, Doppler US and digital venous angiography and showed, in 34 examined patients, 22 patencies (64.7%), 8 stenoses > 50% (23.5%) and 3 occlusions (11.8%). These findings prove the value of laser-assisted--both percutaneous and surgical--angioplasty in the treatment of arterial occlusions both alone and combined with surgery. The results, whose positivity comes also from an eclectic interaction with surgery, and mostly from a systematic enhancement of the laser channel with balloon angioplasty, could be markedly improved upon by means of more selective and effective equipment.

[Server World-Wide Web on the Internet for the provision of clinical cases and digital radiologic images for training and continuing education in radiology]. / "Server World-Wide Web" su Internet per la distribuzione di casi clinici e immagini radiologiche digitali di supporto alla formazione e all'aggiornamento professionale nella radiologia.

The Internet, as a global computer network, provides opportunities to make available multimedia educational materials, such as teaching files and image databases, that can be accessed using "World-Wide Web" client browser to provide continuing medical education. Since August, 1995, at the Institute of Radiology-University of Palermo, we developed a World-Wide Web server on the Internet to provide a collection of interactive radiology educational resources such as teaching files and image database for continuing medical education in radiology. Our server is based on a UNIX workstation connected to the Internet via our campus Ethernet network and reachable at the uniform resource locator (URL) address: http:/(/)mbox.unipa.it/approximately radpa/ radpa.html. Digital CT and MR images for teaching files and image database are downloaded through an Ethernet local area network from a GE Advantage Windows workstation. US images will be acquired on-line through a video digitizing board. Radiographs will be digitized by means of a Charge Coupled Device (CCD) scanner. To set up teaching files, image database and all other documents, we use the standard "HyperText Markup Language" (HTML) to edit the documents, and the Graphics Interchange Format (GIF) or Joint Photographic Expert Group (JPEG) format to store the images. Nine teaching files are presently available on the server, together with 49 images in the database, a list of international radiological servers, a section devoted to the museum of radiology hosted by our Institute, the electronic version of the Journal Eido Electa. In the first 12 months of public access through the Internet, 12,280 users accessed the server worldwide: 45% of them to retrieve teaching files; 35% to retrieve images from the database; the remaining 20% to retrieve other documents. Placing teaching files and image database on a World-Wide Web server makes these cases more available to residents and radiologists to provide continuing medical education in radiology.