The art of bowel surgery in gynecologic cancer.

The field of gynecologic oncology has witnessed a profound transformation in the practice of bowel resection over the years. This evolution, driven by innovative techniques and expanded surgical skills, has redefined the role of the surgeon. This review article delves into the historical journey of bowel surgery, its contemporary importance in cytoreductive procedures for gynecologic cancers, and the general principles of digestive surgery. From pioneering surgeons such as Lane, Broca, and Billroth to the introduction of mechanical staplers, this narrative unfolds the remarkable advances in the field. It highlights the critical need for meticulous training, anatomic mastery, aseptic measures, vascular support, tension-free anastomoses, and precise surgical techniques. These principles underpin the success of bowel resection and anastomosis in the complex landscape of gynecologic oncology.

SUCCOR morbidity: complications in minimally invasive versus open radical hysterectomy in early cervical cancer.

OBJECTIVE: The aim of this study was to compare the incidence of intra-operative and post-operative complications in open and minimally invasive radical hysterectomy for patients with early-stage cervical cancer. METHODS: Data were collected from the SUCCOR database of 1272 patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO), 2009) who underwent radical hysterectomy in Europe between January 2013 and December 2014. We reviewed the duration of the surgeries, estimated blood loss, length of hospital stay, intra-operative and post-operative complications. The inclusion criteria were age ≥18 years and histologic type (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Pelvic MRI confirming a tumor diameter ≤4 cm with no parametrial invasion and a pre-operative CT scan, MRI, or positron emission tomography CT demonstrating no extra-cervical metastatic disease were mandatory. Outcomes of interest were any grade >3 adverse events, intra-operative adverse events, post-operative adverse events, length of hospital stay, length of operation, and blood loss. RESULTS: The study included 1156 patients, 633 (54%) in the open surgery group and 523 (46%) in the minimally invasive surgery group. Median age was 46 years (range 18-82), median body mass index 25 kg/m2 (range 15-68), and 1022 (88.3%) patients were considered to have an optimal performance status (ECOG Performance Status 0). The most common histologic tumor type was squamous carcinoma (n=794, 68.7%) and the most frequent FIGO staging was IB1 (n=510, 44.1%). In the minimally invasive surgery group the median duration of surgery was longer (240 vs 187 min, p<0.01), median estimated blood loss was lower (100 vs 300 mL, p<0.01), and median length of hospital stay was shorter (4 vs 7 days, p<0.01) compared with the abdominal surgery group. There was no difference in the overall incidence of intra-operative and post-operative complications between the two groups. Regarding grade I complications, the incidence of vaginal bleeding (2.9% vs 0.6%, p<0.01) and vaginal cuff dehiscence was higher in the minimally invasive surgery group than in the open group (3.3% vs 0.5%, p<0.01). Regarding grade III post-operative complications, bladder dysfunction (1.3% vs 0.2%, p=0.046) and abdominal wall infection (1.1% vs 0%, p=0.018) were more common in the open surgery group than in the minimally invasive surgery group. Ureteral fistula was more frequent in the minimally invasive group than in the open surgery group (1.7% vs 0.5%, p=0.037). CONCLUSION: Our study showed that there was no significant difference in the overall incidence of intra-operative and post-operative complications between minimally invasive radical hysterectomy and the open approach.

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum (SUROVA trial).

BACKGROUND: Currently, a lively debate exists within the scientific community regarding the most suitable procedure for treating stages IIIB-IVB carcinoma of the ovary, fallopian tubes, and peritoneum. The options under most consideration are primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery. PRIMARY OBJECTIVE: To compare overall survival at 5 years in patients who underwent primary cytoreductive surgery versus neoadjuvant chemotherapy and interval cytoreductive surgery for stage IIIB-IVB ovarian cancer STUDY HYPOTHESIS: The treatment with primary cytoreductive surgery results in superior patient survival compared with neoadjuvant chemotherapy followed by interval cytoreductive surgery. TRIAL DESIGN: This is a multicenter, retrospective cohort observational study. Data will be collected from patients undergoing surgery in hospitals worldwide. Two arms will be compared: primary cytoreductive surgery and neoadjuvant chemotherapy followed by interval cytoreductive surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients must have suspected or histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages IIIB-IVB ovarian, peritoneal, or fallopian tube cancers. They must have undergone primary surgery or first course of neoadjuvant chemotherapy between January 1, 2018 and December 31, 2019. Based on all available information before the surgery (primary or interval), the patient must have been considered completely resectable. PRIMARY ENDPOINT: Overall survival at 5 years from the first treatment (chemotherapy in the case of neoadjuvant chemotherapy and cytoreduction in the case of primary cytoreductive surgery). SAMPLE SIZE: An estimated total of 5000 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: March 2025 TRIAL REGISTRATION: NCT06223763.

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer.

OBJECTIVE: The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. METHODS: A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. RESULTS: Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. CONCLUSION: Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.

SENECA study: staging endometrial cancer based on molecular classification.

OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). CONCLUSIONS: Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

Interfacial water on collagen nanoribbons by 3D AFM.

Collagen is the most abundant structural protein in mammals. Type I collagen in its fibril form has a characteristic pattern structure that alternates two regions called gap and overlap. The structure and properties of collagens are highly dependent on the water and mineral content of the environment. Here, we apply 3D AFM to characterize at angstrom-scale resolution the interfacial water structure of collagen nanoribbons. For a neutral tip, the interfacial water structure is characterized by the oscillation of the water particle density distribution with a value of 0.3 nm (hydration layers). The interfacial structure does not depend on the collagen region. For a negatively charged tip, the interfacial structure might depend on the collagen region. Hydration layers are observed in overlap regions, while in gap regions, the interfacial solvent structure is dominated by electrostatic interactions. These interactions generate interlayer distances of 0.2 nm.

Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.

Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-ß. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to in vivo anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the in vivo therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.