Assessing the implications of sentinel lymph node removal in cervical cancer: an immunogenetic perspective - a SENTICOL ancillary study.

BACKGROUND: Cervical cancer's lymphatic spread primarily begins from the sentinel lymph nodes (SLNs), underlining their pivotal role in disease metastasis. However, these nodes' immune gene expression profiles and immunoregulation mechanisms have yet to be explored. METHODS: Our study aimed to elucidate the immune cell populations and their roles in the immune gene expression profile of negative SLNs compared with positive SLNs and non-SLNs using Nanostring RNA seq analysis. We performed a principal component analysis on the log2 normalized expression of 685 endogenous genes in the nCounter PanCancer Immune Profiling Panel, followed by an assessment of the differential expression of genes and immune cell type abundance. RESULTS: We found significant variations in gene expression among the groups, with negative SLNs displaying overexpression of genes related to tumor-infiltrating immune cells, specifically innate cell populations. They also demonstrated the upregulation of genes involved in antigen presentation and T-cell priming. In contrast, positive SLNs were enriched in regulatory networks, suggesting their potential role in immune evasion. A comparison of negative SLNs and non-SLNs revealed increased innate and adaptive immune cell types, underscoring the ongoing T cell response to tumor antigens. CONCLUSION: Our findings underscore a specific immunogenetic phenotype profile in negative SLNs, emphasizing their crucial role in the initial anticancer response, immunosurveillance, and the propagation of immune tolerance from the primary cervical tumor. These results highlight the potential of SLNs as a novel target for immunotherapy strategies and underscore the importance of new imaging methods for accurately identifying SLN status without removal. Future investigations are needed to understand further the immunological interplay within SLNs and their influence on cervical cancer progression.

Oncologic safety of autologous fat grafting in primary breast reconstruction after mastectomy for cancer.

INTRODUCTION: Autologous fat transfer (AFT) is widely used to improve results of breast reconstructive surgery, but its safety is controversial. Our objective was to evaluate the oncologic safety of AFT in a homogeneous population of patients who underwent a total mastectomy with immediate reconstruction for breast cancer. METHODS: We performed a retrospective cohort study by identifying all patients who underwent immediate breast reconstruction after mastectomy for breast cancer from 2007 to 2015 in our center. A patient group with AFT performed in the 24 months after mastectomy was compared to a control group. RESULTS: Five hundred fifty cases were included, of whom 136 (24.7%) underwent at least one fat graft transfer. Median age was 51 years. Reconstruction was performed in 465 (84.5%) with an implant reconstruction. The median time from mastectomy to AFT was 13.8 months. The median follow up was 55.2 months. A total of 53 events were observed, including 10 (7.4%) in the AFT group and 43 (10.4%) in the control group. There was no difference in 5-year recurrence-free survival (RFS) between the groups. In the subgroup analysis, only lymph node involvement in patients who underwent AFT in the first 24 months after oncologic surgery appeared as a risk factor of recurrence. Among the 104 patients with lymph node involvement, 5-year RFS was 69.2% in patients with lipofilling vs 92.5% in patients without it (p = 0 0.0351). CONCLUSION: Performing early lipofilling in primary breast reconstruction after mastectomy for cancer seems to be oncologically safe. Lymph node involvement increases the risk of recurrence in this population.

Open abdominal vacuum pack technique for the management of severe abdominal complications after cytoreductive surgery in ovarian cancer.

INTRODUCTION: The aim of this study was to evaluate the indications and management of grade III-IV postoperative complications in patients requiring vacuum-assisted open abdomen after debulking surgery for ovarian carcinomatosis. METHODS: Retrospective study of prospectively collected data from patients who underwent a cytoreductive surgery by laparotomy for an epithelial ovarian cancer that required postoperative management of an open abdomen. An abdominal vacuum-assisted wound closure (VAWC) was applied in cases of abdominal compartmental syndrome (ACS) or intra-abdominal hypertension, to prevent ACS. The fascia was closed with a suture or a biologic mesh. The primary aim was to achieve primary fascial closure. Secondary outcomes considered included complications of cytoreductive surgery (CRS) and open abdominal wounds (hernia, fistula). RESULTS: Two percent of patients who underwent CRS required VAWC during the study's patient inclusion period. VAWC indications included: (i) seven cases of gastro-intestinal perforation, (ii) three necrotic enterocolitis, (iii) two intestinal ischemia, (iv) three anastomotic leakages and (v) four intra-abdominal hemorrhages. VAWC was used to treat indications (i) to (iv) (which represented 73.7% of cases), to prevent compartmental syndrome. Primary fascia closure was achieved in 100% of cases, in four cases (21.0%) a biologic mesh was used. Median hospital stay was 65 days (range: 18-153). Four patients died during hospitalization, three of these within 30 days of VAWC completion. CONCLUSION: VAWC for managing open abdominal wounds is a reliable technique to treat surgical post-CRS complications in advanced ovarian cancer and reduces the early post-operative mortality in cases presenting with severe complications.

Impact of pattern of recurrence on post-relapse survival according to surgical timing in patients with advanced ovarian cancer.

OBJECTIVE: Our study aimed to evaluate the association between timing of cytoreductive surgery and pattern of presentation of the first recurrence in patients with advanced ovarian cancer. We also aimed to assess the impact of the pattern of recurrence on post-relapse overall survival according to surgical timing. METHODS: This retrospective multicenter study evaluated patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer. Patients had undergone either primary debulking surgery, early interval debulking surgery after 3-4 cycles of neoadjuvant chemotherapy, or delayed debulking surgery after 6 cycles, with minimal or no residual disease, between January 2008 and December 2015. Survival analyses were conducted using the Log-rank test and the Cox model. Cumulative incidences of the different patterns of recurrence were estimated using a competing risks methodology. RESULTS: A total of 549 patients were included: 175 (31.9%) patients had primary, 224 (40.8%) early interval, and 150 (27.3%) delayed debulking surgery. The cumulative incidence of peritoneal recurrences at 2 years was higher with increasing neoadjuvant cycles (24.4%, 30.9% and 39.2%; p=0.019). For pleural or pulmonary recurrences, it was higher after early interval surgery (9.9%, 13.0% and 4.1%; p=0.022). Median post-relapse overall survival was 33.5 months (95% confidence interval (CI) (24.3 to 44.2)), 26.8 months (95% CI (22.8 to 32.6)), and 24.5 months (95% CI (18.6 to 29.4)) for primary, early interval, and delayed debulking surgery groups, respectively (p=0.025). The pattern of recurrence in a lymph node (hazard ratio (HR) 0.42, 95% CI (0.27 to 0.64)), delayed surgery (HR 1.53, 95% CI (1.11 to 2.13)) and time to first recurrence (HR 0.95, 95% CI (0.93 to 0.96)) were associated with post-relapse overall survival. For primary and early interval surgery, lymph node recurrences were associated with significantly longer post-relapse overall survival. CONCLUSIONS: The pattern of first recurrence was associated with timing of surgery, with peritoneal recurrences being more frequent with the increasing number of cycles of neoadjuvant chemotherapy. Lymph node recurrences were associated with better prognosis, having higher post-relapse overall survival. This improved prognosis of lymphatic recurrences was not observed in patients who underwent delayed surgery.

Effect of medical treatments in disseminated peritoneal leiomyomatosis: a case report.

Disseminated peritoneal leiomyomatosis (DPL) is a rare gynecologic disease involving multifocal proliferation of myomas. The pathogenesis remains unclear. Although there is no standard treatment, medical therapies have attempted to suppress estrogen levels by using gonadotrophin-releasing hormone agonist and aromatase inhibitor (AI) therapy with differing degrees of success. Surgery is also an option in symptomatic patients, and in the event of partial or no response to medical treatments. We report a case of DPL in a young woman with a previous history of myomectomy. She was treated sequentially with ulipristal acetate and AI.

Delayed Hypersensitivity Reaction to Titanium-coated Polypropylene Mesh in Breast Reconstruction.

Breast implant reconstructions increasingly incorporate meshes like the synthetic nonresorbable titanium-coated polypropylene mesh commercialized as Tiloop (Pfm medical). We report the case of a 48-year-old woman, with a medical history of nickel allergy, who presented with an extensive erythematous eruption, a periprosthetic reaction, and an axillary node reaction, 18 months after a unilateral prophylactic mastectomy. We excluded infectious, sarcoidosis and carcinomatosis. The patient's medical history, the clinical evolution, and the particularly fast and complete healing after removal of the mesh were suggestive of an unusual allergic reaction to the titanium in the titanium-coated polypropylene mesh. Titanium allergies are very rare events, predominantly described in the dental and orthopedic fields. We also discussed the hypothesis of a tardive red breast syndrome related to a synthetic mesh, also mediated by immunological response as described recently in another case report.

Performance of Multiparametric Functional Imaging to Assess Peritoneal Tumor Burden in Ovarian Cancer.

PURPOSE: The aim of the study was to evaluate the clinical utility of pretreatment 18F-FDG PET/CT with quantitative evaluation of peritoneal metabolic cartography in relation to staging laparoscopy for ovarian carcinomatosis. PATIENTS AND METHODS: A retrospective review of prospectively collected data from 84 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IIIC to IV ovarian cancer was carried out. All patients had a double-blinded 18F-FDG PET/CT review. Discriminant capacity of metabolic parameters to identify peritoneal carcinomatosis in the 13 abdominal regions according to the peritoneal cancer index was estimated with area under the receiver operating characteristic curve (AUC). RESULTS: The metabolic parameter showing the best trade-off between sensitivity and specificity to predict peritoneal extension compared with peritoneal cancer index score was the metabolic tumor volume (MTV), with a Spearman ρ equal to 0.380 (P < 0.001). The AUC of MTV to diagnose peritoneal involvement in the upper abdomen (regions 1, 2, and 3) ranged from 0.740 to 0.765. MTV AUC values were lower in the small bowel regions (9-12), ranging from 0.591 to 0.681, and decreased to 0.487 in the pelvic region 6. 18F-FDG PET/CT also improved the detection of extra-abdominal disease, upstaging 35 patients (41.6%) from stage IIIC to IV compared with CT alone and leading to treatment modification in more than one third of patients. CONCLUSIONS: 18F-FDG PET/CT metrics are highly accurate to reflect peritoneal tumor burden, with variable diagnostic value depending on the anatomic region. MTV is the most representative metabolic parameter to assess peritoneal tumor extension.

[The child health nurse at the heart of complex care in neonatology]. / L'infirmière puéricultrice au cœur des soins complexes en néonatologie.

Child health nurses in neonatology provide complex, global and individualised care for newborns, in collaboration with other hospital professionals and working closely with the family. They also support parents and help them develop their skills. A central role for which the profession is now seeking to improve recognition.

Comparison of SPECT-CT with intraoperative mapping in cervical and uterine malignancies.

INTRODUCTION: The objective was to evaluate whether hybrid imaging combining single photon emission tomography with computed tomography (SPECT/CT) provides additional clinical value for dectection of sentinel lymph nodes (SLNs) compared with intraoperative combined mapping in uterine and cervical malignancies. METHODS: This was a retrospective study of prospectively collected data from patients with stages IA-IB2 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2018) or stage I endometrial cancer, who underwent preoperative SPECT/CT for SLN detection. All included patients had dual injection of technetium-99m (99mTc) with patent blue or indocyanine green. RESULTS: A total of 171 patients were included with 468 SLNs detected during surgery: 146/171 patients (85.4%) had both radiotracer and blue injection whereas 25/171 patients (14.6%) had radiotracer and indocyanine green injected. The overall detection rate was 95.3%. The detection rate of SLN mapping was 74.9% for SPECT/CT, 90.6% for 99mTc, 91.8% for blue dye, and 100% for indocyanine green. Bilateral drainage was found in 140 patients (81.9%), detected by 99mTc in 105 patients (61.4%), by blue in 99 patients (67.3%), by indocyanine green in 23 patients (92%), and by SPECT/CT in 62 patients (36.4%). Atypical SLN locations were identified by SPECT/CT in 64 patients (37.4%), by 99mTc in 28 patients (16.4%), by blue in 17 patients (9.9%), and by indocyanine green in 8 patients (4.7%). Sensitivity and negative predictive value of SLN biopsy to detect lymph node metastasis using dual injection of different intraoperative combined techniques were 88.9% and 97.5%, respectively. CONCLUSION: SPECT/CT enhanced topographic delineation of SLN and more accurately identified drainage to atypical locations. Fluorescent SLN mapping using indocyanine green offered the highest SLN detection rate. When indocyanine green was used, SPECT/CT did not increase SLN detection, and did not add further information to improve lymph node localization and removal.

Axillary node dissection in outpatient procedure, is it feasible and safe?

BACKGROUND: Outpatient procedure in cancer surgery is one of the tracks to guarantee the quality of care respecting the delay of support. The aim of this study was to assess the feasibility and safety of outpatients with axillary lymphadenectomy and the postoperative morbidity after outpatient's procedures compared to patients with classic hospitalization. METHODS: Patients who underwent axillary lymphadenectomy for breast cancer or melanoma were analyzed. We selected patients having axillary lymphadenectomy only or associated with another operative act compatible with outpatient's procedure (partial mastectomy, lumpectomy or skin excisions). RESULTS: Three hundred and forty-nine patients were included. Outpatient procedures were performed in 142 patients (40.7%) and inpatient procedures were performed in 207 patients (59.3%). All time complications combined, we found 148 patients with at least one complication: 77 patients (52.0%) and 71 patients (48.0%) in outpatient and inpatient group, respectively (p=0.0002). The main complication was seroma formation, it concerned 104 patients Among them, Seroma formation was more frequent in ambulatory group, 60 patients (57.7%) and 44 patients (42.3%) in traditional hospitalization (p<0.0001) but 58.7% (61/104) needed only one aspiration and all complications were managed in outpatient. CONCLUSION: Complications (mostly seroma) appeared usually after hospitalization discharge and they were known and simple to take in charge. A precise preoperative information concerning post-operative morbidity, specially seroma allows a better comprehension and acceptation of this side effect. We believe that this surgery is feasible and safe in outpatient procedure.

TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model.

Following the successful synthesis of a C-functionalized version of the TE1PA ligand, a monopicolinate cyclam, we looked to demonstrate its in vivo properties versus DOTA and NOTA, after conjugation on the 9E7.4 rat antibody, an IgG2a against CD138 murine, which has relevant properties for multiple myeloma targeting. For each ligand, different conjugation approaches had been considered to select the most appropriate for the comparative study. The p-SCN-Bn-TE1PA, NHS-DOTA, and p-SCN-Bn-NOTA were finally chosen for conjugation and radiolabeling tests. For in vivo comparison, we used a model of subcutaneous grafted mice with 5T33 tumor cells. In vitro tests and immuno-PET study highlighted 64Cu-9E7.4-p-SCN-Bn-NOTA as the least attractive. Further competitive biodistribution and hepatic metabolic studies at 2, 24, and 48 h post-injection (100 µg radiolabeled with 10 MBq of 64Cu) were then performed with the 64Cu-9E7.4-p-SCN-Bn-TE1PA and 64Cu-9E7.4-NHS-DOTA. Results show a better in vivo resistance of 64Cu-9E7.4-p-SCN-Bn-TE1PA to transchelation compared to 64Cu-9E7.4-NHS-DOTA, especially at later times. This was confirmed with 64Cu-9E7.4-p-SCN-Bn-NOTA at 48 h PI. 64Cu-9E7.4-p-SCN-Bn-TE1PA also demonstrated an excellent hepatic clearance. 64Cu-9E7.4-p-SCN-Bn-TE1PA displayed an overall superiority compared to 64Cu-9E7.4-NHS-DOTA and 64Cu-9E7.4-p-SCN-Bn-NOTA in terms of in vivo stability, reinforcing the usefulness of the p-SCN-Bn-TE1PA ligand for 64Cu immuno-PET imaging.

Synthesis of C-functionalized TE1PA and comparison with its analogues. An example of bioconjugation on 9E7.4 mAb for multiple myeloma 64Cu-PET imaging.

In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized. This led to an architecture that is comparable to that of other commercially available bifunctional copper(ii) chelators such as p-SCN-Bn-DOTA already used in clinical trials for 64Cu-immuno-PET imaging. The C-functionalization of TE1PA on one carbon atom in the ß-N position of the cyclam backbone was successfully achieved by adapting our patented methodology to the huge challenge, allowing the regiospecific mono-N-functionalization of the unsymmetrical ligand. The obtained ligand p-SCN-Bn-TE1PA was coupled to a 9E7.4 murine antibody (mAb), an IgG2a anti CD-138 for multiple myeloma (MM) targeting. The conjugation efficiency was assessed by looking at the 64Cu radiolabeling and the radiopharmaceutical 64Cu-9E7.4-p-SCN-Bn-TE1PA immunoreactivity, and in particular by comparing with 9E7.4-p-SCN-Bn-NOTA and 9E7.4-p-SCN-Bn-DOTA obtained from commercial and presumably highly efficient chelators NOTA and DOTA, respectively. The results are quite clear, showing that p-SCN-Bn-TE1PA has a coupling rate 5 times higher and an immunoreactivity 1.5 to 2 times greater than those of its two competitors. p-SCN-Bn-TE1PA also outperforms TE1PA conjugated via its carboxylic function on the same antibody. The first 64Cu-immuno-PET preclinical study in a syngeneic model of MM was performed, confirming the good in vivo properties of 64Cu-9E7.4-p-SCN-Bn-TE1PA for PET imaging, considering the high clearance even after 24 h and the particularly important tumor-to-liver ratio that was increasing at 48 h.