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The rapidly increasing volumes of data and the need for big data analytics have emphasized the need for algorithms that can accommodate incomplete or noisy data. The concept of recurrency is an important aspect of signal processing, providing greater robustness and accuracy in many situations, such as biological signal processing. Probabilistic fuzzy neural networks (PFNN) have shown potential in dealing with uncertainties associated with both stochastic and nonstochastic noise simultaneously. Previous research work on this topic has addressed either the fuzzy-neural aspects or alternatively the probabilistic aspects, but currently a probabilistic fuzzy neural algorithm with recurrent feedback does not exist. In this article, a PFNN with a recurrent probabilistic generation module (designated PFNN-R) is proposed to enhance and extend the ability of the PFNN to accommodate noisy data. A back-propagation-based mechanism, which is used to shape the distribution of the probabilistic density function of the fuzzy membership, is also developed. The objective of the work was to develop an approach that provides an enhanced capability to accommodate various types of noisy data. We apply the algorithm to a number of benchmark problems and demonstrate through simulation results that the proposed technique incorporating recurrency advances the ability of PFNNs to model time-series data with high intensity, random noise.

Background: Recurrent pulmonary tuberculosis (RPTB) is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. Methods: Between September 1st 2019 and January 31st 2020, we performed a prospective case controlled study of clinical and imaging features of patients with recurrent pulmonary tuberculosis and compared them with those of newly diagnosed PTB cases. Recurrent PTB was defined as a patient with bacteriologically confirmed active PTB who was previously successfully treated for PTB and was cured. A control was defined as a patient who presents for the first time with bacteriologically confirmed PTB. Clinical and radiological features were assessed and documented. Chi-square and t-test were used to test the difference between proportion and continuous data, respectively. Logistic regression analysis was done to determine factors associated with RPTB using SPSS version 23 software. Results: A total of 312 patients with PTB were enrolled (104 RPTB cases and 208 newly diagnosed controls). Clinically hemoptysis was more common in RPTB compared to controls 28/104 (26.9%) vs 35/208 (16.8%), P = 0.036. Chest pain was significantly less common among patients with RPTB compared to controls 33 (31.7%) vs 92 (44.2%), P = 0.034. A higher proportion of RPTB presented with cavitation 34/104 (32.7%) compared to control 44/208 (21.2%) P = 0.027. The median score for lung pathology was higher among patients with RPTB (50) compared to controls (30); P = 0.001. Lung function of patients with RPTB at diagnosis of index TB were more likely to show mixed restrictive and obstructive pattern 36/104 (34.6%) compared to controls 31/208 (14.9%). p

Introduction To investigate the efficacy and safety of proton-beam irradiation (PBI) combined with intravitreal conbercept (IVC) injection for refractory or recurrent polypoidal choroidal vasculopathy (PCV). Methods A prospective interventional clinical trial included 12 patients with refractory PCV (defined as persistent exudation or fluid after six consecutive injections at monthly intervals and/or photodynamic therapy) or recurrent PCV (defined as new exudative signs after six monthly injections and/or photodynamic therapy) treated between January 2019 and September 2020. Every patient underwent single PBI (14 GyE) with concomitant IVC (0.5 mg) within 1 week and further doses of IVC were administered pro re nata. Results By the 12-month follow-up, the subretinal fluid was completely absorbed in 9 eyes (81.8%). The angiographic regression and closure rates of the polyps were 60% (12/20) and 90% (18/20), respectively. The mean number of IVC injections was 3.1 ± 1.37. The mean BCVA improved by 20 letters (P = 0.006). The mean central macular thickness (CMT) decreased from 476.50 ± 123.63 μm to 317.70 ± 89.34 μm (P = 0.004). The areas of branching vascular networks and polyps decreased by 37.2% and 72.3%, respectively. Radiation retinopathy was observed in five eyes, but no systemic adverse events were observed. Conclusion PBI combined with IVC appears to promote polyp regression and closure, reduce CMT, and improve BCVA, with a favorable safety profile, after 12 months. Therefore, PBI may be a useful adjuvant therapy for patients with refractory or recurrent PCV. Trial registration Proton-Beam Irradiation Combined with Intravitreal Conbercept for Refractory or Recurrent Polypoidal Choroidal Vasculopathy: Prospective Phase II Clinical Study (ChiCTR2000038987).

Introduction. Currently, despite the use of modern and high-tech methods of surgical treatment of patients with varicose veins and hernias of the anterior abdominal wall in the long-term period, relapses of the disease occur in 1.7-14% of cases. The combination of postoperative recurrence of inguinal hernia and varicosis is an infrequent type of multiple surgical pathology.Case report. The article presents a clinical observation of a patient with a relapse of varicosis and an inguinal hernia, who underwent a total of three surgical interventions before admission to the clinic. Detailed ultrasound diagnostics made it possible to establish the cause of the relapse and develop optimal surgical tactics, taking into account the individual characteristics of the disease and the nature of previous operations. Taking into account the anatomical proximity and one-sided localization of pathological processes, the patient underwent a simultaneous operation from one access. A day later, the postoperative pain intensity was rated with a visual analogue scale at 4.2 scores, a patient administered analgesics to relieve pain within two postoperative days. Class 2 compression stockings were used for the compression therapy. The patient was discharged from the clinic in satisfactory condition the following day after the intervention, complaining of minor pain in the surgical wound area. The postoperative period was uneventful, without complications. Pain, restriction of movement were observed within 4 days after surgery. The sutures were removed after 7 days, the wound healed by primary intention healing.Conclusions. The use of a simultaneous operation allows a radical correction of both diseases, to reduce the psychological burden on the patient, to improve the aesthetic result of the intervention, to avoid thrombotic complications and hernia infringement in the postoperative period.

Background Recurrent primary pyogenic ventriculitis has not been reported previously. We present a unique case of recurrent primary pyogenic ventriculitis in an adult. And we believe that our study makes a significant contribution to the literature. Case presentation An adult woman with uncontrolled diabetes experienced two episodes of pyogenic ventriculitis caused by Escherichia coli over 4 years. She had typical imaging features, and the source of infection was undetermined. After antibiotic treatment, she recovered fully. Conclusions Early recognition and therapy will improve patient prognosis.

Objective: We conducted this study to determine the associations of possible risk factors and prevalence of recurrent otitis media with effusion (OME) in a cohort of children in Upper Egypt. Methods: This was a cross-sectional study undertaken in two tertiary referral centers in Upper Egypt. Associations of possible risk factors with prevalence of recurrent OME were studied. Multi-factor logistic regression analysis was done to recognize the statistically significant risk factors associated with recurrent OME. Results: We collected the data of 2003 pediatric patients, of which 1016 were males (50.7%). A total number of 310 children have OME, including 159 males (51.3%). The prevalence rate of OME in our cohort was 15.5%. Multi-factor logistic regression analysis of the risk factors related to recurrent OME showed it was strongly associated with adenoid hypertrophy (P

BACKGROUND With rapid and extensive administration of inactivated coronavirus disease 2019 (COVID-19) vaccine to the general population in China, it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination. CASE SUMMARY Here we report the first case of Bell’s palsy after the first dose of inactivated COVID-19 vaccine in China. The patient was a 36-year-old woman with a past history of Bell’s palsy. Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine, the patient developed right-side Bell’s palsy and binoculus keratoconjunctivitis. Prednisone, artificial tears and fluorometholone eye drops were applied. The patient’s symptoms began to improve by day 7 and resolved by day 54. CONCLUSION As mRNA COVID-19 vaccine trials reported cases of Bell’s palsy as adverse events, we should pay attention to the occurrence of Bell’s palsy after inactivated COVID-19 vaccination. A history of Bell’s palsy, rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell‘s palsy after COVID-19 vaccination.

Auricular pseudocysts (APs) are benign intercartilaginous cysts at the auricle. Various therapeutic options have been used to treat APs, but they frequently recur in usual clinical practice. Here, we report a case of AP successfully treated using a silicon cast. A 65-year-old male presented with a cyst on his right auricle. Although a local injection of steroid was administered, the cyst had recurred. A dental silicon cast was applied after removal of the contents of the cyst by suction. There was no recurrence of the cyst 6 years after that treatment. Dental silicon casts are a novel technique for an appropriate fixation over auricles in the treatment of APs and had an effective therapeutic result in our case.

Background Recurrent coronavirus disease 2019 (COVID-19) infection is an emerging problem and may prove to be one of the greatest problems in controlling the pandemic in the future. Recurrent infections can be due to reactivation of dormant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or reinfection with similar or different strains of SARS-CoV-2. Case presentation Here we present an interesting case of a health care worker working as a laboratory assistant at a COVID-19 laboratory who developed recurrent COVID-19 infection. He did not develop an immune response after the first episode of COVID-19; however, immunoglobulin G (IgG) antibodies were detected after the second episode. Conclusions Through this case, we discuss the concept of reactivation and reinfection in the post-COVID period. We suggest that standard guidelines should be established to check for viral shedding and immune response among cured cases of COVID-19 after discharge via serial real-time polymerase chain reaction (RT-PCR) testing and IgG antibody detection. Further, strict hygiene practices should be stressed to these patients with possibility of COVID-19 recurrence.

We report a case of an epiretinal membrane (ERM) in a 3-year-old girl, which was accidently discovered after a strabismus surgery. The ERM occurred twice in 2 years and spontaneously released within 3 months, which has not been previously reported.

Cervical spontaneous spinal epidural hematoma (CSSEH) is a rare condition that can be potentially fatal if not properly diagnosed and managed. While prompt surgical decompression and evacuation of the hematoma are generally considered as the first line of treatment, mild cases that were managed through observation and conservative treatment have been reported. Our patient was a 24-year-old man who experienced two CSSEH events 8 months apart, both of which were managed conservatively. This was a rare case of recurrent CSSEH in which recovery was achieved without surgical intervention. We believe conservative treatment with close observation may be effective in CSSEH patients presenting with mild neurologic symptoms who have a tendency towards spontaneous neurologic improvement.

Metastatic adamantinoma involving the spine is an extremely rare occurrence. In this case report, we present a patient with recurrent adamantinoma of the tibia which was found to have metastasized to the spine. The metastatic involvement was diagnosed pathologically, status post CT guided percutaneous core needle biopsy, performed after the patient returned with concerning symptoms and imaging findings suggestive of metastasis. The patient was ultimately treated surgically with vertebrectomy and reconstruction. A thoughtful review of this disease process is explored, emphasizing the pathology, imaging characteristics, and pertinent differential diagnostic considerations. While uncommon, knowledge of this rare disease process and its presentation can improve future patient diagnosis and outcomes.

Background The anatomical variation of the frontal sinus and its intimate relation to the skull base and orbit makes its surgery demanding. The extended endoscopic frontal sinus surgery allows wide better drainage and preventing the recurrence of the disease. Fourteen patients underwent EEFSS from May 2017 to May 2019. These patients are nine patients presented by chronic recurrent frontal sinusitis, three patients presented by chronic recurrent fronto ethmoidal mucocele and two patients with chronic recurrent external frontal fistula. Draff III done for ten patients of them and Draff IIB done for four patients of them. This study is designed for evaluating the efficacy of the extended endoscopic frontal sinus surgery (E E F S S) in management of chronic and recurrent frontal sinus diseases. Results The neo opening of the restored frontal sinus was remained opened with Draff III with high success rate; two patients from four patients with Draff IIb were with closed nasofrontal duct. The main follow-up was 12 months; the patients were followed up post-operatively for many office visits without any other manifestations. Conclusion The chronic recurrent frontal sinus diseases can be treated successfully with extended endoscopic frontal sinus surgery (E E F S S). The extended endoscopic frontal sinus surgery (Draff III) provides good results with low morbidity and less post-operative care.

Incidence of reported cases of genital herpes in different countries has increased dramatically during the last years, which is essentially caused by spread of asymptomatic or atypical types of herpes. Frequent relapses of herpes infection are characterized by changes in the immunological status. The authors of presented article analysed the findings of foreign and domestic studies on the treatment of the disease, systematized information about the features of antiviral chemotherapy drugs used in the treat-ment of genital herpes, identified criteria for the efficacy and duration of suppressive therapy, and the feasibility of its combination with courses of immunomodulatory drugs. The article summarizes the authors’ own experience in the treatment of genital herpes in 50 patients, who were randomly divided into 2 groups: (active treatment) group 1 consisted of 25 women who received antiviral (acyclovir and its analogues) and immunomodulatory therapy (aminodihydrophthalasindione sodium, suppositories), (comparison) group 2 consisted of 25 patients who received antiviral therapy only. The following were criteria for the inclusion of patients: genital herpes history, clinical presentation of genital herpes during the prodromal period or exacerbation, and no more than 48 hours after the rash occurred.The results of evaluation of the treatment effectiveness showed that the vesicles disappeared and the crusts formed during aminodihydrophthalasindione sodium therapy in the active treatment group of patients as early as Day 2-5 after starting treatment, while the acute phase of local inflammation in the comparison group was reversed only by Day 4-5. Complete reepitheli-alization occurred in the active treatment and comparison groups by Day 6-7 of the treatment. At the same time, the PCR test did not detect HSV-2 in smears in 24 (96.0%) women in the active treatment group and in 25 (88.0%) women in the comparison group. No one had any fresh rashes in the course of treatment with the drug. In addition, the authors reported prolongation of clinical remission in the active treatment group up to 5 months (up to 55 days on average).As can be seen from the above, the inclusion of immunomodulatory drugs in the combination specific antiviral therapy leads to faster achievement of the clinical effect, allows to reduce frequency of relapses and improves the patients’ quality of life.

Purpose Use of stereotactic ablative radiotherapy (SABR) in the treatment of recurrent or metastatic lesions from a primary gynecologic cancer is a relatively new concept. The present study aims to assess the safety, efficacy, and possible toxicity profile of CyberKnife SABR, recurrent or metastatic disease. Materials/Methods CyberKnife VSI-based SABR was offered to 20 oligometastatic/recurrent gynecological cancer patients between 2013 and 2019. Patient, tumor, and treatment characteristics including radiotherapy details, clinical outcome in terms of local control rates, and toxicities are reported in this study. Results Twenty-five recurrent or oligometastatic lesions for 20 primary gynecologic cancer patients including cervical (n = 8), ovarian (n = 6), endometrial (n = 5), and vulvar (n = 1) cancers were analyzed. Of these, 4 (16%) were intracranial lesions and remaining 21 (84%) were extracranial, consisting of 14 (67%) extrapelvic and 7 (33%) pelvic lesions. The median SABR dose delivered was 60 Gy biologically effective dose (range 42–133 Gy) in an average of four fractions (range 1–6). The mean follow-up was 18 (range 2–70) months. Local tumor control was achieved in 82% of patients. There was no grade ≥ 3 toxicity recorded. Conclusion Our study results suggest that CyberKnife SABR is an effective treatment modality with no major morbidity in patients with recurrent or oligometastatic gynecological cancers.

I present a case of an adenocarcinoma in a retrorectal cyst in a 63-year-old female with a prior history of a congenital cyst excised as a newborn. The patient had a resection with positive margins, followed by chemotherapy and radiotherapy at progression. Her disease did not respond to chemotherapy or radiotherapy and she died with systemic manifestations related to her disease 28 months after diagnosis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is an autoimmune synaptic encephalitis likely mediated by neuronal surface antibody. Clinically, it is characterized by a variety of neurological and psychiatric symptoms, predominantly affecting young women. Recurrent anti-NMDAR cases combined with double-antibody positive during pregnancy have not been reported. We report a 19-year-old pregnant woman with recurrent anti-NMDAR encephalitis and double-antibody positive. Through our case report and a review of the literature, we hope to heighten an awareness of anti-NMDAR encephalitis, particularly in a pregnant setting.

Although the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR) is low in the diagnosis of coronavirus disease 2019 (COVID-19), it is the gold standard. Clinical improvement is prioritized in the follow-up of patients with COVID-19 who are followed as possible or definitive cases. Although the priority in the discharge decision is the resolution of complaints, it is also important to see radiological improvement and RT-PCR negativity. A total of 2 of our patients who were hospitalized and treated in our clinic with a diagnosis of COVID-19 were discharged after their complaints were resolved and their treatment was completed. The patients had 2 negative RT-PCR results at discharge. Both of them presented to the hospital with symptoms such as fever, cough, and shortness of breath after the discharge, and both showed positive RT-PCR results. Considering recurrent COVID-19 infection, we aimed to present treatment and the 2 cases we followed.

Highlights • A patient underwent open surgical debridement for Type I Morel-Lavallée lesion. • He further developed two recurrences despite percutaneous aspiration. • Sclerotherapy was considered, but established sclerosants were unavailable. • Povidone iodine was used as a sclerosant successfully. • Povidone iodine is an alternative sclerosant for recurrent Morel-Lavallée lesion., Introduction and importance A Morel-Lavallee lesion is a closed degloving injury due to traumatic separation of the hypodermis from underlying fascia. Accumulation of hemolymphatic fluid that occurs is a potential habitat for bacteria. Management options include percutaneous aspiration, open debridement, or a non-surgical approach, each with recurrence risk. In the event of recurrence, sclerotherapy is used. In this case report, after reviewing povidone iodine's efficacy in treating seromas, we used it as a sclerosant for recurrent Morel-Lavallee lesion as the more established options were unavailable in our setting. Case presentation A 49-year-old with no known comorbid presented following a motor traffic accident, with left lateral thigh swelling. He was stable systematically, with a tense, tender left lateral thigh swelling and intact neurovascular assessment distally. X-ray and computed tomography ruled out skeletal and vascular injuries. Magnetic resonance imaging revealed a 580 ml type 1 Morell-Lavallee lesion. Open surgical debridement was done to drain and debride the lesion. He developed two recurrences that necessitated percutaneous aspiration. Doxycycline and talc sclerosants were considered; however, due to their unavailability, povidone iodine was used. It is now five months post-intervention without increased pain, recurrence, or wound complications. Clinical discussion Recurrence is hypothesized to be due to the persistence of fluid loculations, unobliterated dead space, and pseudocyst formation. Sclerotherapy stimulates inflammation that results in fibrosis of the cavity walls causing its obliteration. Doxycycline, the most studied sclerosant in Morel-Lavallée lesion has an efficacy of 95.7%. Conclusion The current report is the first successful use of povidone iodine for sclerotherapy of recurring Morel-Lavallée lesions. Based on povidone iodine experiences as a sclerosant, it is associated with increased analgesic requirements. We cautiously propose its use as an alternative in settings where talc powder and doxycycline powder are unavailable.

Purpose: To characterize the sequelae of microsporidia keratoconjunctivitis (MKC) and outline its management. Methods: Retrospective analysis of microbiologically proven MKC returned with persistent disease between January 2015 and December 2019 was done. Demographics, clinical features, management, and outcome were analyzed. Results: Sixteen patients (21 eyes) of 332 treated for MKC returned with the persisting disease. The mean age of 11 males (68.7%), and 5 females was 35.1 ± 12.2 years. Three-quarter of them did not have a known predisposing risk factor and one-quarter of them were referred for chronic conjunctivitis. Past medications included topical antivirals (n = 8) and topical corticosteroid (n = 6). Three predominant presentations were persistent (>3 weeks) superficial punctate keratitis (SPKs, n = 7), sub-epithelial infiltrates (SEIs, n = 13), and uveitis (n = 2). The lesions recurred in eight eyes (SPK and SEI 4 each) after a disease-free interval of 60.4 ± 40.6 days; there were 13 episodes of recurrence. Topical low potent corticosteroids (loteprednol/fluorometholone), and tacrolimus ointment 0.03% were used in 17 (80.9%) and 8 (38%) eyes, respectively, for a mean duration of 44.8 ± 31.6 and 226.8 ± 180.5 days, respectively. At follow-up, 172.3 ± 183.6 days, visual recovery was statistically significant in persistent eyes (BCVA 0.07 ± 0.07 logMAR; P < 0.00001) but, not in recurrent eyes (BCVA 0.16 ± 0.08 logMAR; P = 0.07). Five of 21 eyes were left with residual significant scar. Conclusion: The sequelae of microsporidial keratoconjunctivitis are not uncommon. Topical 0.03% tacrolimus ointment appeared to be an effective corticosteroid-sparing agent for the treatment of SEIs and prevention of recurrence.

Depending on the developing laparoscopic technique and experience, the treatment of cesarean scar choriocarcinoma can be safely performed laparoscopically by experts.

Introduction Growing interest has focused on the relation between chronic endometritis (CE) or asymptomatic inflammation of the endometrium and recurrent miscarriage (RM).The aim of the study was to assess the relation between CE and RM and the accuracy of hysteroscopy in diagnosing CE. Material and methods One hundred and ten (110) women with unexplained RM were included in this study. Participants were subjected to diagnostic hysteroscopy for uterine cavity, and endometrium evaluation. The diagnosis of CE during hysteroscopic examination was based on CE-related hysteroscopic signs (micro-polyps, stromal edema, and/or hyperemia). At the end of hysteroscopy, an endometrial biopsy was taken from participants for culture, and immunohistochemical (IHC) staining. Collected data were analyzed to assess the relation between CE and RM and the accuracy of hysteroscopy in diagnosing CE. Results The prevalence of CE in women with RM was 31.8% using CE-related hysteroscopic signs, while it was 38.2% using IHC staining and endometrial cultures (p = 0.4). CE-related hysteroscopic signs had 64.1% sensitivity, 85.9% specificity, 71.4% positive predictive value (PPV), 81.3% negative predictive value (NPV), and 78.2% overall accuracy in diagnosing CE. Most cases of CE (> 81%) were caused by Mycoplasma and common pathogens. Conclusions The prevalence of CE in women with RM was 31.8% using CE-related hysteroscopic signs, while it was 38.2% using IHC staining and endometrial cultures. CE-related hysteroscopic signs had 64.1% sensitivity, 85.9% specificity, 71.4% PPV, 81.3% NPV, and 78.2% overall accuracy in diagnosing CE. Most cases of CE (> 81%) were caused by Mycoplasma and common pathogens.

Introduction. Depression in patients with advanced breast cancer is a serious comorbidity that affects the quality of life of these patients, and their survival rates. Objective. This study aims at systematically reviewing the current literature with data on the prevalence of depression symptoms in metastatic and recurrent breast cancer patients, examining the pooled mean prevalence of depression symptoms and potential sources of heterogeneity. Methods. An extensive systematic review of PubMed, Web of Science, Scopus, ScienceDirect, Google Scholar, American Doctoral Dissertations and Open Grey databases, and the following reference list hand-search was performed to retrieve studies from January 2005. Results. We identified 11 eligible studies that assessed 1223 patients on the presence of depression symptoms, and 465 patients met the criteria. According to the random-effects model, the pooled mean prevalence of depression was 38.23% (95% CI [30.92; 45.83]; I2= 87%; Q (df =10)=77.89, p-value < 0.01). Patients with metastatic stage had a slightly higher prevalence of depression symptoms compared to recurrent breast cancer patients. Conclusion. Prevalence of depression symptoms among advanced breast cancer patients is high. It is important to improve psychological prevention methods to decrease the occurrence of depression, as breast cancer patients start receiving care from primary diagnosis and offer continuous support and treatment to meet their psychological needs.

Branch retinal artery occlusion (BRAO) accounts for approximately 40% of retinal artery obstructive disease. The visual prognosis is relatively good, with the exception of recurrent BRAO. Recurrent BRAO may be idiopathic or associated with conditions such as systemic vasculitides, blood dyscrasias, floppy mitral valve syndrome, or Susac syndrome. This report describes a patient who presented with an inferior BRAO without any indication of systemic disease. There was a history of a superior BRAO in the same eye. Patients with a BRAO are at significant risk for future cardiovascular and cerebrovascular events and these patients should be referred to a neurologist and a cardiologist immediately after diagnosis.

Anal squamous cell carcinoma (SCC) is a relatively rare cancer comprising less than 2.5% of all gastrointestinal malignancies. The standard treatment for anal SCC is primary chemoradiation therapy which can result in complete regression. After successful treatment, the 5-year survival is approximately 80%. However, up to 30% of patients experience recurrent persistent or recurrent disease. The role of surgery in the treatment of anal cancer, therefore, is limited to the management of recurrent or persistent disease with abdominoperineal resection and/or en bloc adjacent organ excision. Salvage surgery after irradiated anal cancer can be technically demanding in terms of acquisition of oncologically safe surgical margins and minimization of postoperative morbidity. In addition, 5-year survival outcomes after salvage resection have been reported to vary from 23% to 69%. Positive resection margins are generally regarded as the important risk factor associated with poor survival outcome. Perineal wound complications are the most common major postoperative morbidity. Because of the challenges of primary wound closure after salvage abdominoperineal resection, myocutaneous flap reconstruction has been performed to reduce the severity of perianal would complications. We, therefore, descriptively reviewed contemporary published evidence describing the treatment and outcomes after salvage surgery for persistent or recurrent anal SCC.

Introduction: Pembrolizumab is an immune checkpoint inhibitor with high specificity for binding to the programmed cell death 1 (PD-1) receptor. It has been approved by the FDA in patients with recu...

Persistent human papillomavirus (HPV) infection is associated with the development of oropharyngeal squamous cell carcinoma (OPSCC), and increasing incidences of OPSCC are reported. The generally favorable treatment outcome in patients with HPV-driven OPSCC has brought de-escalation of treatment into discussion. Nevertheless, 13% to 25% develop a relapse within two years after current standard treatment. New biomarkers are urgently required to monitor therapy response, tumor burden, and minimal residual disease during follow-up. This observational study examined 50 patients with OPSCC to investigate plasma cell-free (cf) HPV-DNA derived from tumor cells before therapy and during follow-up. Real-time quantitative PCR was applied to quantify the DNA concentration of HPV oncogenes E6 and E7. A total of 85.7% of pretreatment samples from patients with HPV-driven OPSCC (n = 28) were positive for at least one marker, and cfHPV-DNA concentration increased with tumor size. Virtually no signals were detected in HPV-negative OPSCC patients (n = 20; P ≤ 0.001). Patients without clinical evidence of recurrence had significantly reduced cfHPV-DNA concentrations after therapy (P ≤ 0.001). Conversely, cfHPV-DNA levels increased or remained above threshold in five patients who had residual disease or developed recurrence. In conclusion, plasma cfHPV-DNA detection correlates with the clinical course of disease in patients with HPV-driven OPSCC. Consequently, extensive clinical investigation should be considered if cfHPV-DNA is detected during follow-up of patients with HPV-driven OPSCC.

Background Vulvoperineal defects resulting from surgical treatment of (pre)malignancies may result in reconstructive challenges. The vertical rectus abdominis muscle flap and, more recently, the fasciocutaneous lotus petal flap are often used for reconstruction in this area. The goal of this review is to compare the postoperative complications of application of these flaps.Methods:A comprehensive literature search of the PubMed, MEDLINE and Cochrane Library databases was performed until 6 June 2020. Search terms included the lotus petal flap, vertical rectus abdominis muscle flap and the vulvoperineal area. Articles were independently screened by two researchers according to the PRISMA-guidelines.Results:A total of 1074 citations were retrieved and reviewed, of which 55 were included for full text analysis. Following lotus petal flap reconstructions, the complication rate varied from 0.0% to 69.9%, with more complications concerning the recipient site compared with the donor site complications (26.0% versus 4.5%). Following vertical rectus abdominis muscle flap reconstructions the complication rate varied between 0.0% and 85.7% with almost twice the number of recipient site complications compared to donor site complications (37.1% versus 17.8%).Conclusions:Overall, the lotus petal flap has lower complication rates at both the donor and the recipient site compared with the vertical rectus abdominis muscle flap. When both options seem viable, the lotus petal flap procedure may be preferred on the basis of the reported lower complication rates.

Highlights • Liposarcomas are a malignant transformation of fat tissue, found in two major subtypes according to their differentiation. • Enhanced CT is essential for diagnosis and confirmed by percutaneous large core needle guided biopsies. • Surgery remains the standard practice in treating non-metastatic liposarcomas. • No clear definition for giant liposarcoma, Only 52 cases reported between 1998 and July 2020. • Our patient has the longest reported follow up in the literature of 10 years, with 3 operations and 3 recurrences., Introduction This case is of a patient with a recurrent giant retroperitoneal liposarcoma, followed-up and operated multiple times over 10 years. We report this case because of its rarity and review all previous articles reporting “Giant Retroperitoneal Liposarcoma” in the English literature. Case description A 70 years old man presented to our clinic for dizziness and fatigue. He was incidentally found to have a large retroperitoneal mass filling all the length of the abdominal cavity and shifting all intraabdominal viscera and kidney to the left side. En bloc excision of a 50 × 30 × 18 cm, 9 kg tumor was performed. Final pathology revealed a well-differentiated liposarcoma. Five years later, the patient was reoperated for recurrence and a well-differentiated liposarcoma was excised in 2 pieces (the biggest measuring 14 × 11 × 7 cm) along with the appendix. Four years later the patient was operated on again for a second recurrence, and again a well-differentiated liposarcoma (16 × 10 × 7 cm) extending into the right inguinal canal was excised. One year thereafter, the patient was diagnosed with a third recurrence (22 × 12 cm). Discussion Retroperitoneal Liposarcomas are rare tumors, presenting with different histological differentiation. They are diagnosed using multiple imaging modality, mainly CT scan, and it is confirmed by percutaneous large core needle biopsy. R0 Surgical excision remains the proper treatment for non-metastatic tumors, which may necessicate multiorgan resection. They rarely grow to reach a large size and be labled as “Giant Retroperitoneal Liposarcoma”.

Background Neurofibroma can be a clinical manifestation of neurofibromatosis, which is a benign neurogenic tumor that occurs sporadically. Neurofibromas in the abdomen usually appear in the retroperitoneal space. Reports on neurofibromas in the abdominal wall are rare, and multiple recurrent neurofibromas in this area have not yet been reported. Case summary This is a case of a 73-year-old man who suffered from multiple recurrent neurofibromas in the abdominal wall for 16 years and received 13 surgical treatments. Conclusion We need to pay due attention to its treatment, and primary surgery should be designed thoroughly.

BACKGROUND Drug-eluting beads transarterial chemoem-bolization (DEB-TACE) has the advantages of slow and steady release, high local concentration, and low incidence of adverse drug reactions compared to the traditional TACE. DEB-TACE combined with sequentially ultrasound-guided radiofrequency ablation (RFA) therapy has strong anti-cancer effects and little side effects, but there are fewer related long-term studies until now. AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma (HCC). METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited. Forty patients with untreated HCC were included in Group A, and 36 patients with recurrent HCC were included in Group B. In addition, 40 patients with untreated HCC who were treated with hepatectomy were included in Group C. The serological examination, preoperative magnetic resonance imaging examination, and post-treatment computed tomography enhanced examination were performed for all patients. The efficacy was graded as complete remission (CR), partial remission (PR), stable disease and progressive disease at the 3rd, 6th, and 9th. All patients were followed up for 3 years and their overall survival (OS), disease-free survival (DFS) were assessed. RESULTS The efficacy of Group A and Group C was similar (P > 0.05), but the alanine aminotransferase, aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C (all P < 0.05). The proportions of CR (32.5%), PR (37.5%) were slightly higher than Group A (CR: 27.5%, PR: 35%), but the difference was not statistically significant (χ2 = 0.701, P = 0.873). No operational-related deaths occurred in Group A and Group C. The OS (97.5%, 84.7%, and 66.1%) and the DFS (75.0%, 51.7%, and 35.4%) of Group A at the 1st, 2nd, and 3rd year after treatment were similar with those of Group C (OS: 90.0%, 79.7%, and 63.8%; DFS: 80.0%, 59.7%, and 48.6%; P > 0.05). The OS rates in Group A and Group B (90%, 82.3%, and 66.4%) were similar (P > 0.05). The DFS rates in Group B (50%, 31.6%, and 17.2%) were lower than that of Group A (P = 0.013). CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy. Patients with recurrent HCC could get a longer survival time through the combined treatment.

Background Acute small bowel obstruction is a common surgical emergency usually caused by abdominal adhesions, followed by intraluminal tumors from metastatic disease. Although lymphomas have been known to cause bowel obstruction, Burkitt lymphoma is seldom reported to induce an obstruction in the adult population. Case presentation A 78-year-old Hispanic man with a history of abdominal interventions presented to our hospital with abdominal pain. Computed tomography revealed a partial small bowel obstruction attributed to local inflammation or adhesions. Medical management with bowel rest and nasogastric decompression resulted in resolution of symptoms and quick discharge. He returned 2 days later with worsening abdominal pain. Repeat imaging showed progression of the partial small bowel obstruction, but with an additional 1.6-cm nodular density abutting the anterior aspect of the gastric antrum and lobulated anterior gastric antral wall thickening. He was taken to the operating room, where several masses were found. Intraoperative frozen sections were consistent with lymphoma, and pathology later revealed Burkitt lymphoma. Disease was found on both sides of the diaphragm by positron emission tomography. After the initial resection and adjuvant chemotherapy, the patient is alive and well about 14 months after resection. Conclusions Small bowel obstruction is uncommonly due to Burkitt lymphoma in the geriatric population and is more frequently seen in the pediatric and young adult populations. Burkitt lymphoma is very aggressive with rapid cell turnover leading to significant morbidity. The rapid recurrence of an acute abdominal process should prompt an investigation for a more sinister cause such as malignancy.

Graphical abstract, Highlights • TCM is an increasingly recognized clinical entity. • Variants include apical, midventricular, basal, and focal. • The authors present a unique case in which one patient developed three variants.

Thrombophilia is caused by several genetic and acquired factors. Existence of more than one genetic factor may increase the risk of developing recurrent thrombotic events. Here, we present a case of a 48-year-old male with a known history of deep venous thrombosis and a known mutation in factor V Leiden combined with mild protein S deficiency, who presented with a painful swelling in the left leg. Moreover, the patient had a history of diabetes, dyslipidemia and obesity. Prothrombin time and platelet count were within the normal range. The international normalized ratio and activated partial thromboplastin time were 3.21 and 36.7 s, respectively. The Doppler study showed a thrombus in the saphenous vein, and complementary genetic screening investigations revealed heterozygous mutation for prothrombin (G20210A). A diagnosis of multifactorial genetic thrombophilia was established. The patient was treated with warfarin, which resulted in significant improvement in the follow-ups, and at the time of reporting this case, there were no clinical or biological signs of thrombosis. The presence of multiple hereditary and acquired thrombophilic factors is a rare clinical presentation that requires close monitoring, for which a lifelong anticoagulation therapy should be discussed based on the clinical response of the patient.

There are few treatment guidelines for locally recurrent esophageal cancer after trimodality treatment (pre-operative chemoradiation followed by surgery) in patients with a poor performance status. The purpose of this single institutional, retrospective study was to evaluate the clinical outcomes and toxicities of definitive-intent re-irradiation for patients with recurrent esophageal cancer with a poor performance status [ECOG (Eastern Cooperative Oncology Group) ≥2]. Seven patients were identified with a median age of 74 years (range, 61-81 years). Four patients were ECOG 2 and three patients were ECOG 3. The median follow-up time after re-irradiation was 49 months. The median interval between initial radiotherapy and re-treatment was 32 months. Six patients received concurrent chemotherapy [carboplatin + paclitaxel in three patients; folinic acid, fluorouracil, oxaliplatin (FOLFOX) + 5-fluorouracil in one patient; FOLFOX in one patient, and capecitabine in one patient]. At the last follow-up, the six patients who underwent concurrent chemotherapy had stable disease (86%), while the one who did not receive chemotherapy progressed (14%). Two patients developed metastases. Three patients developed acute (6 months) were limited to grades 1 and 2 dysphagia and pneumonitis in four patients. In conclusion, definitive re-irradiation of recurrent esophageal cancer in patients with a poor performance status appears to be safe with acceptable acute toxicity and late complications. It also appears to result in durable local control when combined with chemotherapy, albeit with a small number of patients and limited follow-up.

Urinary tract infection (UTI) is a common condition in women. There is an increased concern on reduction of bacterial susceptibility resulting from wrongly prescribing antimicrobials. This paper summarizes the recommendations of four Brazilian medical societies (SBI - Brazilian Society of Infectious Diseases, FEBRASGO - Brazilian Federation of Gynecology and Obstetrics Associations, SBU - Brazilian Society of Urology, and SBPC/ML - Brazilian Society of Clinical Pathology/Laboratory Medicine) on the management of urinary tract infection in women.Asymptomatic bacteriuria should be screened at least twice during pregnancy (early and in the 3rd trimester). All cases of significant bacteriuria (≥105 CFU/mL in middle stream sample) should be treated with antimicrobials considering safety and susceptibility profile. In women with typical symptoms of cystitis, dipsticks are not necessary for diagnosis. Urine cultures should be collected in pregnant women, recurrent UTI, atypical cases, and if there is suspicion of pyelonephritis. First line antimicrobials for cystitis are fosfomycin trometamol in a single dose and nitrofurantoin, 100 mg every 6 hours for five days. Second line drugs are cefuroxime or amoxicillin-clavulanate for seven days. During pregnancy, amoxicillin and other cephalosporins may be used, but with a higher chance of therapeutic failure.In recurrent UTI, all episodes should be confirmed by urine culture. Treatment should be initiated only after urine sampling and with the same regimens indicated for isolated episodes. Prophylaxis options of recurrent UTI are behavioral measures, non-antimicrobial and antimicrobial prophylaxis. Vaginal estrogens may be recommended for postmenopausal women. Other non-antimicrobial prophylaxis, including cranberry and immunoprophylaxis, have weak evidence supporting their use. Antimicrobial prophylaxis may be offered as a continuous or postcoital scheme. In pregnant women, options are cephalexin, 250-500 mg and nitrofurantoin, 100 mg (contraindicated after 37 weeks of pregnancy). Nonpregnant women may use fosfomycin trometamol, 3 g every 10 days, or nitrofurantoin, 100 mg (continuous or postcoital).

Objective Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China; furthermore, >80% of cases worldwide occur in South China. This study analyzed the use of peripheral blood inflammatory markers as prognostic factors in patients with local recurrence and distant metastasis after radiochemotherapy for NPC. Methods A retrospective analysis was carried out on the prognosis of 99 NPC patients with pathological and imaging diagnosis after radiochemotherapy at The First Affiliated Hospital of Nanchang University between 2010 and 2018．The Kaplan–Meier method was used to calculate survival rates, log–rank tests were used for univariate prognostic analysis, and a Cox regression model was used for multivariate prognostic analysis. Results Univariate analysis showed that treatment plan (χ2 = 8.895, P = 0.003), primary platelet count (χ2 = 3.92, P = 0.048), and primary lactate dehydrogenase level (LDH; χ2 = 22.138, P

Background: Prognosis of oral squamous cell carcinoma (OSCC) can be predicted by evaluating both clinicopathological parameters and molecular markers. Understanding the reasons of recurrence is important to increase the morbidity and mortality of the patient. Objectives: The objectives are to study the immunoexpression of p53 and Ki-67 in recurrent and non recurrent OSCC. And correlate the clinicopathological parameters among non-recurrent and recurrent OSCC to predict the prognosis of OSCC. Methods: Clinicopathological and immunoexpression of p53 and Ki-67 at the histologically negative margin (HNM) and invasive tumor front (ITF) were assessed in 50 cases of non-recurrent and recurrent OSCC. Overall survival and disease free survival was estimated. Statistical tests like Mann Whitney U test, t Test, Pearson correlation coefficient, Kaplan Meier curve and Log Rank test were used. Results: The Labelling Index (LI) of p53 and Ki-67 was marginally higher in recurrent than in non-recurrent OSCC cases. When compared with clinicopathologic parameters, non-recurrent OSCC cases showed no significance with p53 LI in margin and ITF except for site, muscle invasion, pattern of invasion (POI) and muscle invasion, whereas in recurrent OSCC cases p53 LI in HNM and ITF did not show any statistical significance except for duration. In both groups, OS and DFS was higher in patients with lesser LI while higher in the greater LI but more number of deaths occurred in this category respectively. Conclusion: To conclude p53 and Ki-67 positivity in the HNM and ITF of non-recurrent and recurrent OSCC was seen and thus can be an important marker for identification of high and low risk individuals.

Objective: To assess the clinical efficacy and safety of transarterial embolization (TAE) in simultaneous combination with computed tomography (CT)-guided radiofrequency ablation (RFA) for recurrent or residual hepatocellular carcinoma (HCC), and to determine the risk factors influencing local tumor progression following this procedure. Methods: One hundred eighteen patients with recurrent or residual HCC (tumor size, 10–30 ​mm) underwent RFA. During the 19-month follow-up, 59 patients received RFA only (RFA group), and the remaining 59 received RFA immediately after TAE (TAE ​+ ​RFA group). All patients were followed up to observe the short-term therapeutic effects and complications. The cumulative local tumor progression rates in both groups were calculated using unpaired Student’s t tests and the Kaplan-Meier method. Results: The rate of major complications was 5.08% in the TAE ​+ ​RFA group and 3.39% in the RFA group. The overall response rate was 96.61% in the TAE ​+ ​RFA group and 79.66% in the RFA group (P ​= ​0.008). The disease control rate was significantly higher in the TAE ​+ ​RFA group than in the RFA group (94.92% vs. 79.66%, P ​= ​0.024). The median time to local tumor progression was 4.8 months in the RFA group and 9.6 months in the TAE ​+ ​RFA group. The cumulative local tumor progression rate at 1 year was 10.60% in the RFA group and 23.60% in the TAE ​+ ​RFA group (P ​= ​0.016). Conclusion: TAE in simultaneous combination with CT-guided RFA was effective and safe against recurrent or residual HCC. Local tumor progression can be minimized by the complete ablation of targeted iodized oil deposits after simultaneous TAE. Keywords: Transarterial embolization, Computed tomography-guided, Recurrent, Residual, Hepatocellular carcinoma

Glioblastoma is the most frequent and aggressive primary brain tumor, characterized by extensive brain invasion and rarely, systemic metastases. The pathogenesis of metastatic glioblastoma is largely unknown. We present the first integrated clinical/histologic/genetic analysis of 5 distinct brain and lung foci from a unique case of recurrent, multifocal, multicentric and metastatic glioblastoma. The initial right frontotemporal gliosarcoma received standard surgical/chemoradiation therapy and recurred 1.5 years later, co-occurring with three additional masses localized to the ipsilateral temporal lobe, cerebellum and lung. Synchronous metastatic lung carcinoma was suspected in this long-term smoker patient with family history of cancer. However, glioblastoma was confirmed in all tumors, although with different morphologic patterns, including ependymomatous and epithelioid. Genomic profiling revealed a germline FANCD2 variant of unknown significance, and a 4-gene somatic mutation signature shared by all tumors, consisting of TERT promoter and PTEN, RB1 and TP53 tumor suppressor mutations. Additional GRIN2A and ATM heterozygous mutations were selected in the cerebellar and lung foci, but were variably present in the supratentorial foci, indicating reduced post-therapeutic genetic evolution in brain foci despite morphologic variability. Significant genetic drift characterized the lung metastasis, likely explaining the known resistance of circulating glioblastoma cells to systemic seeding. MET overexpression was detected in the initial gliosarcoma and lung metastasis, possibly contributing to invasiveness. This comprehensive analysis sheds light on the temporospatial evolution of glioblastoma and underscores the importance of genetic testing for diagnosis and personalized therapy.

Highlights • Intestinal malrotation and midgut volvulus in adulthood are rare events. • Reports of recurrence among adults are very scarce. The rate of recurrence and optimal surgical management are yet to be determined. • Bowel fixation procedures may be considered in Ladd procedures for adult midgut volvulus in order to reduce recurrence., Introduction Intestinal malrotation is a rare condition, with an incidence estimated between 0,2 to 1%. Most cases are diagnosed and treated during childhood. Adult presentations are rare and most adults present with chronic nonspecific complaints. Midgut volvulus is the most feared complication of intestinal malrotation, far more common among the pediatric than the adult population. Presentation in adulthood with a midgut volvulus accounts for a minority of these patients (15%). The Ladd procedure is the standard surgical management of midgut volvulus and intestinal malrotation. Most evidence on the outcomes of the Ladd procedure originates from studies on pediatric population and the recurrence among children who have had a Ladd procedure is low (2–7%). Presentation of case We report an exceedingly rare case of a patient who presented in adulthood with a midgut volvulus and less than two years after undergoing Ladd procedure presented with a recurrence of the midgut volvulus. The recurrent midgut volvulus was successfully treated by a fixation procedure (cecopexy and duodenopexy). Conclusion Reports of midgut volvulus in adult patients are scarce and reports of recurrence even scarcer hence the rate of recurrence among adult patients has yet to be determined. The recurrence rate in some of the available adult series is much higher than the rate reported among children. Should the rate of recurrence among adult patients prove higher, it poses the question of whether the Ladd procedure should be modified to include bowel fixation when performed in adults.

Giant cell tumour of bone (GCTB) is a locally aggressive benign bone tumour. Though surgery is the mainstay of treatment, recurrence rate is 8% even after extended curettage. Recurettage does not guarantee no recurrence of the tumour. The RANKL-RANK interaction, which leads to the differentiation and functioning of the osteoclast like giant cells are responsible for the osteolytic activity of tumour. Denosumab a RANK ligand inhibitor can be used in recurrent GCTB. We report two cases, where denosumab was used in recurrent GCTB with encouraging results.

Pyogenic granuloma (PG) is a benign lesion, with a female predilection, commonly associated with local irritation or trauma. We report an unusual, destructive case of PG, displaying excessive loss of blood and destruction of alveolar bone leading to the loss of maxillary anterior teeth in an 18-year-old female, compromising function and esthetics. The incisional and excisional biopsy specimen of this recurrent lesion obtained during a 5-year span was studied, which revealed an increase in vascularity and extensive proliferation of endothelial cells admixed with varying degree of inflammatory cell infiltrate. The clinical, radiographic, and histopathological diagnostic tools enabled to precisely diagnose the lesion as an aggressive variant of PG, distinguishing it from other vascular neoplasms. No recurrence has been noted during a 5-year follow-up. The clinicians should be aware of the aggressive and destructive clinical behavior of PG to avoid the inadvertent treatment of this reactive lesion.

Highlights • High-grade endometrial stromal sarcoma (HG-ESS) behaves in a more aggressive manner with a poorer overall prognosis than low-grade ESS. • Recurrence develops in one-half to two-third of patients with High-grade endometrial stromal sarcoma. • The major therapeutic procedure of patients with single site recurrent HG-ESS is primarily surgical resection. • Interdisciplinary and interprofessional teamwork are important in management of recurrent HG-ESS., Introduction High-grade endometrial stromal sarcoma (HG-ESS) is a rare pathological type of uterine sarcoma. Over 80 % of affected patients would experience recurrences within a few years of initial presentation. Such case is rare and therefore, we need to report the case including the management. Information on performing good surgical techniques is important. Case presentation A 55-year-old female patient was referred after having a total hysterectomy and bilateral salphingoophorectomy at a private hospital. Results of pathologic examination showed that the patient had HG-ESS. The patient subsequently received adjuvant chemotherapy. The regimens used were Carboplatin (AUC-6) and Paclitaxel (175 mg/m2). Within five months following the chemotherapy, she complained rapid abdominal enlargement, which was a clinically mobile palpable solid mass at the level of the navel. Imaging findings suggested recurrent endometrial stromal sarcoma in the abdominal wall. Wide excision and frozen section, which were continued with mesh insertion and abdominal wall reconstruction, were then performed. Discussion Recurrence develops in one-half to two-third of patients with HG-ESS. It has been reported that the sites of recurrence usually include multiple lung metastases, peritoneal metastases, and/or local recurrences. There is currently no standard therapy for patients with recurrence of the disease as HG-ESS is a rare clinical entity. Treatment has been defined based on experiences gained from retrospective case reports. Conclusion Successful management of patients with recurrent abdominal wall HG-ESS requires interdisciplinary and interprofessional teamwork. Multi-centre prospective trials are required to develop a guideline of optimal treatment for the disease entity, particularly the recurrence.

Reconstruction method choice in recurrent head and neck cancer depends on surgical history, radiation therapy dosage, conditions of recipient vessels, and general patient condition. Furthermore, when defects are multiple or three dimensional in nature, reconstruction and flap choice aimed at rebuilding the functional structure of the head and neck are difficult. We experienced successful reconstruction of recurrent laryngeal cancer requiring reconstruction of esophageal and tracheostomy stroma defects using a chimeric two-skin anterolateral thigh flap with a single pedicle.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR)= 1.02 (0.66-1.58), two-sided P= 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR= 0.95 (0.59-1.52), P= 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade =3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).