MRI classification of uterosacral ligament involvement in endometriosis: the Hôtel-Dieu classification.

OBJECTIVE: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep infiltrating endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis. METHODS: Twenty-two women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analysed retrospectively, blinded to histopathology, and a classification of the preoperative aspect of USLs linked to PPVs was designed. RESULTS: According to their aspects, 6 radiological types of USL were identified. The "L-category" corresponded to linear types with regular or irregular margins, including types 1, 2, 3A, and 3B. The "N-category" corresponded to haemorrhagic or nodular types, including types 4, 5A, 5B, and 6. For the L-category, PPVs ranged from 75% to 88%, depending on the USL radiological type. For the N-category, PPVs were 100% for each type. In women with endometriosis symptoms, MRI underestimated USL involvement, especially for type 1. Among the 6 uteri with lateral deviation, only one false-positive result concerning the stretched USL was induced. CONCLUSIONS: In women with endometriosis symptoms, our MRI classification identified 2 USL categories, corresponding to 2 kinds of PPV; in these symptomatic patients, a normal MRI does not rule out a DIE diagnosis. ADVANCES IN KNOWLEDGE: Our MRI classification of USL involvement in endometriosis may be used as a non-invasive staging of the disease, making it much clearer for clinicians and patients. Hence, we are able to propose a suitable diagnostic and therapeutic procedure for each radiological type.

Reasons why it is time to change imaging guidelines on endometriosis.

In light of the rising number of patients referred for magnetic resonance imaging (MRI) due to suspected endometriosis and the high expectations of these patients, there is a need for new imaging guidelines to optimally protocol and indicate MRI and transvaginal ultrasonography (TVUS) examinations. This is crucial for accurately addressing the inquiries of gynecologists, encompassing complete mapping and preoperative staging, and facilitating effective communication with patients. In this context, the development of a standardized lexicon, as well as dedicated imaging classifications, is recommended to aid in the comprehensive management of patients. CLINICAL RELEVANCE STATEMENT: The radiologist should use a standardized lexicon and provide a score along with details about the specific compartments affected by endometriosis disease. This helps in offering clearer guidance to the surgeon. KEY POINTS: • An optimal staging is based on the combination of clinical examination, transvaginal US, and MRI. • MRI is able to detect location that is hidden at the beginning of a laparoscopic surgery and thus the need for dedicated MR classifications to correctly stage the disease. • Deep pelvic endometriosis index (dPEI) classification is externally validated and highly correlated with operating time, hospital stay, and postoperative complications.

Metastatic Colorectal Cancer Treated with Combined Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Predictive Factors for Early Recurrence.

BACKGROUND: Selection of colorectal cancer patients with concomitant peritoneal (PM) and liver metastases (LM) for radical treatment with cytoreductive surgery (CRS), including liver resection and hyperthermic intraperitoneal chemotherapy (HIPEC), needs improvement. This retrospective, monocentric study was designed to evaluate the predictive factors for early recurrence, disease-free survival (DFS), and overall survival (OS) in such patients treated in a referral center. METHODS: Consecutive colorectal cancer patients with concomitant LM and PM treated with curative intent with perioperative systemic chemotherapy, simultaneous complete CRS, liver resection, and HIPEC in 2011-2022 were included. Clinical, radiological (before and after preoperative chemotherapy), surgical, and pathological data were investigated, along with long-term oncologic outcomes. A multivariate analysis was performed to identify predictive factors associated with early recurrence (diagnosed <6 months after surgery), DFS, and OS. RESULTS: Of more than 61 patients included, 31 (47.1%) had pT4 and 27 (40.9%) had pN2 primary tumors. Before preoperative chemotherapy, the median number of LM was 2 (1-4). The median surgical PCI (peritoneal carcinomatosis index) was 3 (5-8.5). The median DFS and OS were 8.15 (95% confidence interval [CI] 5.5-10.1) and 34.1 months (95% CI 28.1-53.5), respectively. In multivariate analysis, pT4 (odds ratio [OR] = 4.14 [1.2-16.78], p = 0.032]) and pN2 (OR = 3.7 [1.08-13.86], p = 0.042) status were independently associated with an early recurrence, whereas retroperitoneal lymph node metastasis (hazard ratio [HR] = 39 [8.67-175.44], p < 0.001) was independently associated with poor OS. CONCLUSIONS: In colorectal cancer patients with concomitant PM and LM, an advanced primary tumor (pT4 and/or pN2) was associated with a higher risk of early recurrence following a radical multimodal treatment, whereas RLN metastases was strongly detrimental for OS.

Endometriosis MR mimickers: T2-hypointense lesions.

Endometriosis is a common crippling disease in women of reproductive age. Magnetic resonance imaging (MRI) is considered the cornerstone radiological technique for both the diagnosis and management of endometriosis. While its sensitivity, especially in deep infiltrating endometriosis, is superior to that of ultrasonography, many sources of false-positive results exist, leading to a lack of specificity. Hypointense lesions or pseudo-lesions on T2-weighted images include anatomical variants, fibrous connective tissues, benign and malignant tumors, feces, surgical materials, and post treatment scars which may mimic deep pelvic infiltrating endometriosis. False positives can have a major impact on patient management, from diagnosis to medical or surgical treatment. This educational review aims to help the radiologist acknowledge MRI criteria, pitfalls, and the differential diagnosis of deep pelvic infiltrating endometriosis to reduce false-positive results. Critical relevance statement MRI in deep infiltrating endometriosis has a 23% false-positive rate, leading to misdiagnosis. T2-hypointense lesions primarily result from anatomical variations, fibrous connective tissue, benign and malignant tumors, feces, surgical material, and post-treatment scars. Key points • MRI in DIE has a 23% false-positive rate, leading to potential misdiagnosis.• Anatomical variations, fibrous connective tissues, neoplasms, and surgical alterations are the main sources of T2-hypointense mimickers.• Multisequence interpretation, morphologic assessment, and precise anatomic localization are crucial to prevent overdiagnosis.• Gadolinium injection is beneficial for assessing endometriosis differential diagnosis only in specific conditions.

Endometriosis MR mimickers: T1-hyperintense lesions.

Endometriosis is a chronic and disabling gynecological disease that affects women of reproductive age. Magnetic resonance imaging (MRI) is considered the cornerstone radiological technique for both the diagnosis and management of endometriosis. While MRI offers higher sensitivity compared to ultrasonography, it is prone to false-positive results, leading to decreased specificity. False-positive findings can arise from various T1-hyperintense conditions on fat-suppressed T1-weighted images, resembling endometriotic cystic lesions in different anatomical compartments. These conditions include hemorrhage, hyperproteic content, MRI artifacts, feces, or melanin. Such false positives can have significant implications for patient care, ranging from incorrect diagnoses to unnecessary medical or surgical interventions and subsequent follow-up. To address these challenges, this educational review aims to provide radiologists with comprehensive knowledge about MRI criteria, potential pitfalls, and differential diagnoses, ultimately reducing false-positive results related to T1-hyperintense abnormalities.Critical relevance statementMRI has a 10% false-positive rate, leading to misdiagnosis. T1-hyperintense lesions, observed in the three phenotypes of pelvic endometriosis, can also be seen in various other causes, mainly caused by hemorrhages, high protein concentrations, and artifacts.Key points• MRI in endometriosis has a 10% false-positive rate, leading to potential misdiagnosis.• Pelvic endometriosis lesions can exhibit T1-hyperintensity across their three phenotypes.• A definitive diagnosis of a T1-hyperintense endometriotic lesion is crucial for patient management.• Hemorrhages, high protein concentrations, lipids, and artifacts are the main sources of T1-hyperintense mimickers.

Morbidity, mortality, and prognostic factors in gestational trophoblastic neoplasia with liver metastasis.

BACKGROUND: Liver metastases of gestational trophoblastic neoplasia (GTN) are rare, but associated with poor prognosis. The additional concomitant presence of brain or intra-abdominal metastases, with liver metastases has been described as worsening factors, but the literature on this topic is reduced. OBJECTIVE: To estimate the overall mortality, specific hepatic morbidity, and mortality, and to identify prognostic factors for patients with GTN and liver metastases. METHOD: The medical records of 26 GTN patients with liver metastases registered in the French Center for Trophoblastic Diseases and treated between November 1999 and December 2019 were reviewed. Overall survival was described using Kaplan-Meier estimates. Prognostic factors were identified using univariate and multivariate Cox analyses. RESULTS: The 5-year overall survival rate was 60.7% for all patients with liver metastasis. The survival rate was higher in patients who achieved complete remission after first-line chemotherapy than in those who did not (100% vs 20%, p = 0.001). The only factor independently associated with prognosis was the presence of 6 or more liver metastases (5-year survival, 16.7% vs. 82.4% otherwise; HR =11.1, 95%CI, 2.3-53.1; p = 0.003). None of the five patients with a single liver metastasis died. CONCLUSION: GTN with liver metastasis is very rare (1.6%). The prognosis of patients seems to be improving. The results of this study are also reassuring for patients with complete remission after first-line combination chemotherapy, as well as for those with a single liver metastasis.

Primary Peritoneal Hepatoid Adenocarcinoma Patients Treated by Complete Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Hepatoid adenocarcinoma (HAC) is an extremely rare disease, which could develop from any thoraco-abdominal organ and which exhibits features mimicking hepatocellular carcinoma (HCC). Its diagnosis is thus highly challenging, so is the treatment of that disease. So far, 12 cases have been reported in the literature as issued from the peritoneum. These primary peritoneal HAC were associated with a dismal prognosis and heterogenous management. Two additional cases were described here, managed in a multidisciplinary way as rare peritoneal surface malignancies in an expert center, following the strategy based on a comprehensive tumor burden extension assessment and a radical approach combining iterative complete cytoreductive surgeries followed by hyperthermic intra-peritoneal chemotherapy (HIPEC) and limited systemic chemotherapy sequences. In particular, the choline PET-CT scan guided surgical exploration to reach a complete resection. The oncologic outcomes were promising with a first patient dying 111 months after the diagnosis and a second patient still alive at 43 months.

Multicenter External Validation of the Deep Pelvic Endometriosis Index Magnetic Resonance Imaging Score.

Importance: Preoperative mapping of deep pelvic endometriosis (DPE) is crucial as surgery can be complex and the quality of preoperative information is key. Objective: To evaluate the Deep Pelvic Endometriosis Index (dPEI) magnetic resonance imaging (MRI) score in a multicenter cohort. Design, Setting, and Participants: In this cohort study, the surgical databases of 7 French referral centers were retrospectively queried for women who underwent surgery and preoperative MRI for DPE between January 1, 2019, and December 31, 2020. Data were analyzed in October 2022. Intervention: Magnetic resonance imaging scans were reviewed using a dedicated lexicon and classified according to the dPEI score. Main outcomes and measures: Operating time, hospital stay, Clavien-Dindo-graded postoperative complications, and presence of de novo voiding dysfunction. Results: The final cohort consisted of 605 women (mean age, 33.3; 95% CI, 32.7-33.8 years). A mild dPEI score was reported in 61.2% (370) of the women, moderate in 25.8% (156), and severe in 13.1% (79). Central endometriosis was described in 93.2% (564) of the women and lateral endometriosis in 31.2% (189). Lateral endometriosis was more frequent in severe (98.7%) vs moderate (48.7%) disease and in moderate vs mild (6.7%) disease according to the dPEI (P < .001). Median operating time (211 minutes) and hospital stay (6 days) were longer in severe DPE than in moderate DPE (operating time, 150 minutes; hospital stay 4 days; P < .001), and in moderate than in mild DPE (operating time; 110 minutes; hospital stay, 3 days; P < .001). Patients with severe disease were 3.6 times more likely to experience severe complications than patients with mild or moderate disease (odds ratio [OR], 3.6; 95% CI, 1.4-8.9; P = .004). They were also more likely to experience postoperative voiding dysfunction (OR, 3.5; 95% CI, 1.6-7.6; P = .001). Interobserver agreement between senior and junior readers was good (κ = 0.76; 95% CI, 0.65-0.86). Conclusions and Relevance: The findings of this study suggest the ability of the dPEI to predict operating time, hospital stay, postoperative complications, and de novo postoperative voiding dysfunction in a multicenter cohort. The dPEI may help clinicians to better anticipate the extent of DPE and improve clinical management and patient counseling.

A PK-PD model linking biomarker dynamics to progression-free survival in patients treated with everolimus and sorafenib combination therapy, EVESOR phase I trial.

PURPOSE: The objective was to develop a pharmacokinetic-pharmacodynamic (PK-PD) model linking everolimus and sorafenib exposure with biomarker dynamics and progression-free survival (PFS) based on data from EVESOR trial in patients with solid tumors treated with everolimus and sorafenib combination therapy and to simulate alternative dosing schedules for sorafenib. PATIENTS AND METHODS: Everolimus (5-10 mg once daily, qd) and sorafenib (200-400 mg twice daily, bid) were administered according to four different dosing schedules in 43 solid tumor patients. Rich PK and PD sampling for serum angiogenesis biomarkers was performed. Baseline activation of RAS/RAF/ERK (MAPK) pathway was assessed by quantification of mRNA specific gene panel in tumor biopsies. The PK-PD modeling was performed using NONMEM® software. RESULTS: An indirect response PK-PD model linking sorafenib plasma exposure with soluble vascular endothelial growth factor receptor 2 (sVEGFR2) dynamics was developed. Progression-free survival (PFS) was described by a parametric time-to-event model. Higher decreases in sVEGFR2 at day 21 and higher baseline activation of MAPK pathway were associated with longer PFS (p = 0.002 and p = 0.007, respectively). The simulated schedule sorafenib 200 mg bid 5 days-on/2 days-off + continuous everolimus 5 mg qd was associated with median PFS of 4.3 months (95% CI 1.6-14.4), whereas the median PFS in the EVESOR trial was 3.6 months (95% CI 2.7-4.2, n = 43). CONCLUSION: Sorafenib 200 mg bid 5 days-on/2 days-off + everolimus 5 mg qd continuous was selected for an additional arm of EVESOR trial to evaluate whether this simulated schedule is associated with higher clinical benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932177.

Influence of Extraperitoneal Metastases on the Curative-Intent Management of Colorectal Peritoneal Metastases.

BACKGROUND: Selected patients with colorectal cancer peritoneal metastasis (CRPM) and extraperitoneal disease could be treated radically with a multimodal approach combining complete cytoreductive surgery, thermoablation, radiotherapy, and systemic and intraperitoneal chemotherapy. The impact of extraperitoneal metastatic sites (EPMS) in this setting remains unclear. PATIENTS AND METHODS: Patients with CRPM undergoing complete cytoreduction in 2005-2018 were grouped in: peritoneal disease only (PDO), one EPMS (1 + EPMS), two or more EPMS (2 + EPMS). A retrospective analysis compared overall survival (OS) and postoperative outcomes. RESULTS: Of 433 patients, 109 had 1 + EPMS and 31 had 2 + EPMS. Overall, 101 patients had liver metastasis, 19 lung metastasis, and 30 retroperitoneal lymph node (RLN) invasion. The median OS was 56.9 months. There was no significant OS difference between PDO and 1 + EPMS groups (64.6 and 57.9 months, respectively), whereas OS was lower in the 2 + EPMS group (29.4 months, p = 0.005). In multivariate analysis, 2 + EPMS [hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.33-6.12, p = 0.007], Sugarbaker's Peritoneal Carcinomatosis Index (PCI) > 15 (HR 3.86, 95% CI 2.04-7.32, p < 0.001), poorly differentiated tumors (HR 2.62, 95% CI 1.21-5.66, p = 0.015), and BRAF mutation (HR 2.10, 95% CI 1.11-3.99, p = 0.024) were independent poor prognostic factors, while adjuvant chemotherapy was beneficial (HR 0.33, 95% CI 0.20-0.56, p < 0.001). Patients with liver resection did not show higher severe complication rates. CONCLUSION: In patients with CRPM selected for a radical surgical approach, limited extraperitoneal disease involving one site, notably the liver, does not seem to significantly impair postoperative results. RLN invasion appeared as a poor prognostic factor in this population.

MRI restaging of rectal cancer: The RAC (Response-Anal canal-CRM) analysis joint consensus guidelines of the GRERCAR and GRECCAR groups.

PURPOSE: To develop guidelines by international experts to standardize data acquisition, image interpretation, and reporting in rectal cancer restaging with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Evidence-based data and experts' opinions were combined using the RAND-UCLA Appropriateness Method to attain consensus guidelines. Experts provided recommendations for reporting template and protocol for data acquisition were collected; responses were analysed and classified as "RECOMMENDED" versus "NOT RECOMMENDED" (if ≥ 80% consensus among experts) or uncertain (if < 80% consensus among experts). RESULTS: Consensus regarding patient preparation, MRI sequences, staging and reporting was attained using the RAND-UCLA Appropriateness Method. A consensus was reached for each reporting template item among the experts. Tailored MRI protocol and standardized report were proposed. CONCLUSION: These consensus recommendations should be used as a guide for rectal cancer restaging with MRI.

Comparison between CT-enterography and MR-enterography for the diagnosis of right-sided deep infiltrating endometriosis of the bowel.

OBJECTIVE: To compare computed tomography-enterography (CTE) and magnetic resonance-enterography (MRE) in the detection of right-sided bowel deep infiltrating endometriosis (DIE). MATERIALS AND METHODS: Fifty women with DIE who underwent preoperatively CTE and MRE were included. CTE and MRE were first analyzed separately by two independent readers who analyzed five bowel segments (cecum, appendix, ileocecal junction, distal ileum and proximal small bowel [i.e., proximal ileum and jejunum]) for the presence of DIE and then interpreted in consensus. CTE, MRE and CTE with MRE were compared in terms of sensitivity, specificity and accuracy. Interobserver agreement was assessed with kappa (κ) test. RESULTS: Using the reference standard 25 out 250 bowel segments were involved by DIE in 18 women and 225 were free of DIE. Sensitivity, specificity, and accuracy of CTE were 60% (95% confidence interval [CI]: 39-79), 93% (95% CI: 89-96) and 90% (95% CI: 85-93) for Reader 1, respectively, and 52% (95% CI: 31-72), 99% (95% CI: 97-100) and 94% (95% CI: 91-97) for Reader 2, with no differences in sensitivity (P = 0.564) and specificity (P = 0.181) between readers and fair interobserver agreement (κ = 0.37). For MRE these figures were 52% (95% CI: 31-72), 92% (95% CI: 88-95) and 88% (95% CI: 84-92) for Reader 1 and 60% (95% CI: 39-79), 99% (95% CI: 96-100) and 95% (95% CI: 91-97) for Reader 2, with no differences in sensitivity (P = 0.157) and specificity (P = 0.061) between readers and fair interobserver agreement (κ = 0.31). Significant differences in sensitivity (20%; 95% CI: 7-41) were found between CTE + MRE vs. CTE alone for Reader 1 and vs. MRE alone for Reader 2 (P = 0.041 for both) CONCLUSION: CTE and MRE have not different sensitivities and convey only fair interobserver agreement but are highly specific for the diagnosis of right-sided bowel DIE. CTE and MRE are complementary because they improve the detection of DIE implants when used in combination.

Comparison of Neoadjuvant Systemic Chemotherapy Protocols for the Curative-Intent Management of Peritoneal Metastases from Colorectal Cancer, Regarding Morphological Response, Pathological Response, and Long-Term Outcomes: A Retrospective Study.

BACKGROUND: Selected patients with colorectal cancer peritoneal metastases (CRPM) could be offered a curative-intent strategy based on complete cytoreductive surgery (CRS), potentially combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and perioperative systemic chemotherapy. The impact of different neoadjuvant systemic chemotherapy (NACT) regimens remains unclear due to a lack of comparative data. METHODS: Consecutive CRPM patients from a monocentric database who were treated with complete CRS after single-line NACT were included in this study. Chemotherapy regimens were tailored as a doublet drug (FOLFOX/FOLFIRI) with/without targeted therapy (anti-epidermal growth factor receptor/bevacizumab) and triplet-drug combination (FOLFIRINOX). Morphological response (MR) was assessed using the Response Evaluation Criteria in Solid Tumors criteria, and pathological response (PR) was assessed using the Peritoneal Regression Grading Score (PRGS). Long-term oncologic outcomes were compared. RESULTS: The cohort comprised 388 patients, including 127, 202, and 59 patients in the doublet, doublet + targeted, and triplet groups, respectively. MR rates were higher in the triplet (68.0%) and doublet + targeted groups (64.2%) when compared with the doublet group (42.4%, p = 0.003). Complete and major PRs were observed in 13.6% and 32.0% of patients, respectively. Higher MR rates were observed after doublet + targeted or triplet regimens, while no difference was observed for PR rates. In multivariate analysis, FOLFIRINOX was independently associated with better overall survival (hazard ratio 0.49, 95% confidence interval 0.25-0.96; p = 0.037). FOLFIRINOX also resulted in a higher rate of severe postoperative complications. CONCLUSIONS: In this retrospective study, a FOLFIRINOX regimen as NACT seemed to result in better long-term outcomes for CRPM patients after complete CRS/HIPEC, although with higher morbidity. Prospective studies are needed, including groups without NACT and those with FOLFIRINOX + bevacizumab.