Evaluation of the Outcome of Local Surgery for Stomal Prolapse

We reviewed the results of local surgical treatment of stoma prolapse, a long-term complication of stoma construction. Fifteen patients treated for stomal prolapse between 2009 and 2020 at the authors’ and affiliated hospitals were included in this study. The treatment comprised local laparotomic stomal reconstruction (LLSR) in nine patients and stapling repair (SR) in six. We compared and evaluated the clinical and surgical information and postoperative complications. Operation time was significantly shorter in the SR group than in the LLSR group: 20 and 53 min, respectively (p = 0.036). The duration of postoperative hospitalization was shorter in the SR group than in the LLSR group: 5.5 and 8 days, respectively; the difference was not significant (p = 0.088). No short-term complications were found in either group. Regarding long-term, postoperative complications, parastomal hernias developed after 2.5 years in one patient in the LLSR group and after 6 months in one patient in the SR group; both patients had histories of parastomal hernia surgery and had relatively high body mass indices. Local surgery for stomal prolapse was minimally invasive and performed safely. In patients with a history of surgery for parastomal hernia, attention must be paid to the potential of parastomal hernia developing as a postoperative complication.

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial

BackgroundToripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1. We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC).MethodsWe conducted a single-arm, phase II trial with patients with rNPC who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate at 3 months post radiotherapy. The secondary endpoints included safety profiles, progression-free survival (PFS).ResultsBetween May 2019 and January 2020, a total of 25 patients with rNPC were enrolled (18 men (72.0%) and 7 women (28.0%); median (IQR) age, 49.0 (43.5–52.5) years). With a median (IQR) follow-up duration of 14.6 months (13.1–16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month PFS was 91.8% (95% CI 91.7% to 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine kinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively.ConclusionsToripalimab combined with IMRT was tolerable and showed promising antitumor activity in patients with rNPC.Trial registration numberNCT03854838.

Role of locoregional surgery in treating FIGO 2009 stage IVB cervical cancer patients: a population-based study

ObjectiveWe aimed to analyse the clinical value of primary site surgery in improving the cancer-specific survival (CSS) and overall survival (OS) of initial metastatic cervical cancer patients.DesignA population-based retrospective study.SettingNational Cancer Institute’s Surveillance, Epidemiology and End Results database.ParticipantsWe analysed 1390 patients with the International Federation of Gynecology and Obstetrics 2009 stage IVB cervical cancer with complete clinical data treated between 2010 and 2016.InterventionsPrimary site surgery.MeasuresPropensity score matching (PSM) with a ratio of 1:2 was used to balance measure covariates of comparison groups. Survival time was calculated using Kaplan-Meier methods and compared by the log-rank test. To eliminate the bias of site-specific metastasis, clinicopathological factors and subsequent therapy on survival analysis, subgroup analyses stratified by metastasis type, clinicopathological factors and subsequent therapy were employed to evaluate the effect of cervical surgery on survival. Combination of directed acyclic graph and change-in-estimate procedures was performed to indentified confounders, and Cox regression was used to assess the survival benefit of cervical surgery for primary metastatic cervical cancer patients. The consistency of our findings was evaluated through sensitivity analysis.ResultsMatching resulted in two comparison groups with minor differences in most variables. Pre-and-post-PSM, the median CSS and OS in the surgery group were 1.3 and 1.5, 1.1 and 1.2 times of those in the non-surgery group, respectively. Primary site surgery conferred prognosis superiority for patients with metastases to distant lymph node and other sites rather than organ metastases. After PSM and adjusting confounders, local surgery reduced the cancer related and overall mortality rates by 31% and 30%, respectively.ConclusionsSurgical procedures could promote survival in patients with primary metastatic cervical cancer and should be considered a therapeutic option for carefully chosen patients.

A Nomogram-Based Risk Classification System Predicting the Overall Survival of Patients With Newly Diagnosed Stage IVB Cervix Uteri Carcinoma

Background: This study constructed and demonstrated a model to predict the overall survival (OS) of newly diagnosed distant metastatic cervical cancer (mCC) patients.Methods: The SEER (Surveillance, Epidemiology, and End Results) database was used to collect the eligible data, which from 2010 to 2016. Then these data were separated into training and validation cohorts (7:3) randomly. Cox regression analyses was used to identify parameters significantly correlated with OS. Harrell's Concordance index (C-index), calibration curves, and decision curve analysis (DCA) were further applied to verify the performance of this model.Results: A total of 2,091 eligible patients were enrolled and randomly split into training (n = 1,467) and validation (n = 624) cohorts. Multivariate analyses revealed that age, histology, T stage, tumor size, metastatic sites, local surgery, chemotherapy, and radiotherapy were independent prognostic parameters and were then used to build a nomogram for predicting 1 and 2-year OS. The C-index of training group and validation group was 0.714 and 0.707, respectively. The calibration curve demonstrated that the actual observation was in good agreement with the predicted results concluded by the nomogram model. Its clinical usefulness was further revealed by the DCAs. Based on the scores from the nomogram, a corresponding risk classification system was constructed. In the overall population, the median OS time was 23.0 months (95% confidence interval [CI], 20.5–25.5), 12.0 months (95% CI, 11.1–12.9), and 5.0 months (95% CI, 4.4–5.6), in the low-risk group, intermediate-risk group, and high-risk group, respectively.Conclusion: A novel nomogram and a risk classification system were established in this study, which purposed to predict the OS time with mCC patients. These tools could be applied to prognostic analysis and should be validated in future studies.

Clinicopathological Characteristics and Prognosis in Endometrial Cancer With Bone Metastasis: A SEER-Based Study of 584 Women

PurposeBone metastasis from endometrial cancer (EC) is rare and poorly described. The purpose of the present study was to investigate the correlation between the clinically accessible factors and survival time among EC patients with bone metastasis.Patients and MethodsWe retrospectively identified and reviewed EC patients with bone metastasis from 2010 to 2016, based on the Surveillance, Epidemiology and End Results (SEER) database. Univariable and multivariable Cox regressions were applied to evaluate the effects of clinical variables on survival. Kaplan–Meier plots were used to visually demonstrate the correlation between independent risk factors and survival.ResultsClinical data of 584 EC patients with bone metastasis from the SEER database were analyzed. EC patients with bone metastasis experienced extremely poor survival, with 1-year overall survival (OS) and cancer-specific survival (CSS) rates 33.8 and 35.8%, respectively. Variables associated with OS and CSS in the univariable analysis included race, tumor grade, tumor subtype, tumor size, lung, liver and brain metastases, surgery, radiotherapy, and chemotherapy. In the multivariable analysis, tumor grade, tumor subtype, liver and brain metastases, local surgery, and systemic chemotherapy remained independent risk factors for OS and CSS. However, local radiotherapy was an independent predictor of OS, not CSS.ConclusionsWe identified several factors affect the survival of EC patients with bone metastasis, which is useful for clinicians to assess patients’ outcomes. Our study supports surgery and radiotherapy of primary EC, and systemic chemotherapy for prolonging survival among EC patients with bone metastasis, which lays a solid foundation for defining optimal treatment strategy in this specific cohort.

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: An open-label single-arm, phase II trial.

6023 Background: Toripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 (PD-1). We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC). Methods: We conducted a single-arm, phase II trial with rNPC patients who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate (ORR). The secondary endpoints included safety profiles, progression-free survival (PFS). Results: Between May 2019 and January 2020, a total of 25 rNPC patients were enrolled (18 men [72.0%] and 7 women [28.0%]; median [IQR] age, 49.0 [43.5-52.5] years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month progression-free survival was 91.8% (95% CI 91.7% - 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine phosphokinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively. Conclusions: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in rNPC patients. Clinical trial information: NCT03854838.

First-in-human administration of CEB-01, a novel drug delivery implant matrix, in patients with recurrent or locally advanced retroperitoneal soft tissue sarcoma (RPS) after surgery: Preliminary safety and pharmacokinetics report.

11554 Background: RPS local recurrence after radical surgery (SX) is frequent and a major cause of death. Locally delivered CHT by a biocompatible and biodegradable implant matrix (CEB-01) loaded with SN-38 and placed in the surgical bed during SX may increase local control and survival in RPS patients with reduced systemic toxicity. Methods: This is a multicentre, open label, first-in-human phase 1 trial comprising a dose-escalation phase (3 cohorts with total SN-38 doses of 9, 18 and 36 mg respectively), followed by an expansion cohort at the recommended phase 2 dose (RP2D). Recurrent or locally advanced RPS patients candidates for local surgery, with no option of systemic treatment, ECOG < 2, life expectancy > 6 months, and normal organ function are eligible. Primary objective is to determine RP2D, defined as the dose level at which less than 33% of patients present dose limiting toxicity (DLT) in a minimum of 6 at-risk patients during the first two weeks after SX. DLT is defined as any Grade ≥3 toxicity. Secondary objectives include safety, time to recurrence, biomarkers, pharmacokinetics (PK) and quality of life (QoL). Here we report preliminary safety, efficacy, and PK data for the initial patients enrolled. Results: First cohort of 9 mg SN-38 was completed in february 2021, with the inclusion of three patients with dedifferentiated liposarcoma, (grade 2-3) Patients were male, age 65 to 74, with ECOG of 0-1. Optimal SX were performed for recurrent/metastatic disease (2 patients) or locally advanced disease (1 patient) with complete (R0) and optimal (R1) outcomes. There were no surgical complications attributed to the SN-38 treatment. One patient suffered from grade 2 (Dindo Clavien classification) intestinal subocclusion due to SX complication resolved with medical treatment at day 5. Frequency and severity of adverse events (AE) was low. All the patients presented transitory abdominal discomfort and seroma. AEs consisted of one catheter infection and one hypomagnesemia, both grade 3. Only one treatment related AE (TRAE) consisting of alopecia grade 1 was reported. There were no DLTs observed during the first administrations of CEB-01 (9 mg SN38). SN38 and its glucuronidated SN-38 systemic levels were low, reaching a peak (Cmax) of 0.60 and 3.3 ng/mL at 2 and 6 hours respectively, and were detectable 27 days after CEB-01 implantation in the surgical bed, at 0.1 and 0.6 ng/mL respectively. Conclusions: CEB-01 biocompatible and resorbable implant matrix loaded with SN38 has proven to be safe upon first human administrations in RPS patients, with scarce low grade AEs and TRAE. Preliminary PK indicates low, prolonged, systemic SN-38 exposure as expected. Currently the second cohort of this trial is open for recruitment. Clinical trial information: NCT04619056.

SARS-CoV-2 Antibody Screening in Healthcare Workers in Non-Infectious Hospitals in Two Different Regions of Southern Poland (Upper Silesia and Opole Voivodeships): A Prospective Cohort Study

(1) Background: Detection of asymptomatic or subclinical human coronavirus SARS-CoV-2 infection in healthcare workers (HCWs) is crucial for understanding the overall prevalence of the new coronavirus and its infection potential in public (non-infectious) healthcare units with emergency wards. (2) Methods: We evaluated the host serologic responses, measured with semi-quantitative ELISA tests (IgA, IgG, IgM abs) in sera of 90 individuals in Hospital no. 4 in Bytom, 84 HCWs in the University Hospital in Opole and 25 in a Miasteczko Śląskie local surgery. All volunteers had negative RT-PCR test results or had not had the RT-PCR test performed within 30 days before sampling. The ELISA test was made at two different time points (July/August 2020) with a 2-weeks gap between blood collections to avoid the “serological window” period. (3) Results: The IgG seropositivity of asymptomatic HCWs varied between 1.2% to 10% (Opole vs. Bytom, p < 0.05; all without any symptoms). IgA seropositivity in HCWs was 8.8% in Opole and 7.14% in Bytom. IgM positive levels in HCWs in Opole and Bytom was 1.11% vs. 2.38%, respectively. Individuals with IgA and IgM seropositivity results were observed only in Opole (1.19%). More studies are needed to determine whether these results are generalizable to other populations and geographic as well as socio-demographic locations. (4) Conclusions: 100% of IgG(+) volunteers were free from any symptoms of infection in the 30 days before first or second blood collection and they had no awareness of SARS-CoV-2 infection. Asymptomatic HCWs could spread SARS-CoV-2 infection to other employees and patients. Only regular HCWs RT-PCR testing can reduce the risk of SARS-CoV-2 spreading in a hospital environment. The benefit of combining the detection of specific IgA with that of combined specific IgM/IgG is still uncertain.

Flaps in adult urethrocutaneous fistula repair: a report of two cases with the review of literature

Urethrocutaneous fistula (UCF) poses a challenge to the reconstructive urologist in terms of its location, patient’s expectations, availability of tissues for interposition, wound infection and chances of recurrence. Also, patient-related factors, such as uncontrolled diabetes, local surgery with extensive tissue loss, prior history of radiation, poor nutritional status and presence of any distal obstruction in the urethra severely affect the outcomes of a good repair with vascularised flap. We report two cases of UCF repair in adults using scrotal and gracilis muscle flaps (GMFs), their anatomic basis, technicality and advantages. The scrotal flap was used in the first case where it was freely available and GMF in second case where the patient had already undergone extensive local tissue debridement for Fournier’s gangrene and hence, we had to look for a distant flap for protection of the UCF repair. Both patients had an uneventful recovery, there were no early or late treatment-related complications and follow-up after the third and sixth month of surgery revealed no recurrence and the patients are voiding well.