Treatment Strategies and Prognosis of Patients With Synchronous or Metachronous Colorectal Peritoneal Metastases: A Population-Based Study.

BACKGROUND: This study aimed to compare treatment strategies and survival of patients with synchronous colorectal peritoneal metastases (CPM) and patients with metachronous CPM in a nationwide cohort. METHODS: All patients from the Netherlands Cancer Registry with synchronous or metachronous CPM whose primary colorectal cancer (CRC) was diagnosed between 1 January and 30 June 2015 were included in the study. Treatments were categorized as (A) cytoreductive surgery and hyperthermic intraperitoneal chemotherapy [CRS-HIPEC]; (B) palliative treatment; or (C) best supportive care. Overall survival (OS) for all the patients and disease-free survival (DFS) for those who underwent CRS-HIPEC were compared between the two groups. RESULTS: Of 7233 patients, 743 had a diagnosis of CPM, including 409 patients with synchronous CPM and 334 patients with metachronous CPM. The median OS was 8.1 months for the patients with synchronous CPM versus 12 months for the patients with metachronous CPM (p = 0.003). After multivariable correction, OS no longer differed between the patients with synchronous CPM and those with metachronous CPM (HR 1.03 [0.83-1.27]). The patients with metachronous CPM more often underwent CRS-HIPEC than the patients with synchronous CPM (16 % vs 8 %; p = 0.001). The two groups did not differ statistically in terms of DFS and OS (median DFS, 21.5 vs 14.1 months, respectively; p = 0.094; median OS, 37.8 vs. 35.8 months, respectively; p = 0.553). CONCLUSION: This population-based study showed that survival for the patients with synchronous CPM and patients with metachronous CPM did not significantly differ. This suggests that a similar prognosis may be expected for patients selected for treatment regardless of the onset of CPM.

Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial.

BACKGROUND: Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. METHODS: The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. CONCLUSION: This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. TRIAL REGISTRATION: Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Volume-outcome relationship of liver surgery: a nationwide analysis.

BACKGROUND: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. METHODS: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality. RESULTS: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. CONCLUSION: Hospital volume and postoperative outcomes were not associated.

ANTECEDENTES: La asociación entre el volumen hospitalario y los resultados de la cirugía hepática no está clara. Según la recomendación actual de las guías holandesas se requiere un volumen mínimo de 20 procedimientos anuales por centro. El objetivo de este estudio fue analizar la asociación entre el volumen hospitalario con los resultados postoperatorios en la auditoría hepatobiliar obligatoria holandesa a nivel nacional. MÉTODOS: Se realizó un estudio a nivel nacional en los Países Bajos. Se incluyeron todas las resecciones hepáticas registradas en la auditoría hepatobiliar holandesa entre 2014 y 2017. El volumen anual del centro se calculó y se clasificó en categorías de 20 procedimientos por año. Los objetivos principales fueron la morbilidad de mayor grado (Clavien-Dindo grado IIIA o superior) y la mortalidad hospitalaria o la mortalidad a los 30 días. RESULTADOS: Se realizaron un total de 5.590 resecciones en 34 centros con una mediana (rango intercuartílico) de volumen anual de 35 procedimientos (20-69). La tasa global de morbilidad mayor fue del 11% y la mortalidad del 2%. La mortalidad fue de 1,9% después de la resección por metástasis hepáticas colorrectales (colorectal liver metastases, CRLM), 1,2% para no CRLM, 0,4% para tumores benignos, 4,9% para carcinoma hepatocelular, y 10,3% para tumores biliares. Los centros de mayor volumen realizaron más resecciones hepáticas mayores y más resecciones por carcinoma hepatocelular y cáncer biliar. En el análisis multivariable después de ajustar por factores de riesgo conocidos de eventos adversos, no se observó ninguna asociación entre el volumen hospitalario y la morbilidad o mortalidad mayor. CONCLUSIÓN: No hubo asociación entre el volumen hospitalario y los resultados postoperatorios de la cirugía hepática en los Países Bajos.

Diagnostic performance of imaging for the detection of peritoneal metastases: a meta-analysis.

PURPOSE: Detection of peritoneal metastases (PM) is key in the staging and management of gastrointestinal and ovarian cancer patients. The purpose of this meta-analysis was to determine the diagnostic performance of CT, PET(CT), and (DW)MRI in detecting PM. METHODS: A literature search in Pubmed, Embase (Ovid), and Scopus was performed (January 1997-May 2018) to identify studies reporting on the accuracy of imaging PM in the diagnostic workup of gastrointestinal or ovarian cancers. Inclusion criteria were region-based or patient-based studies comprising > 15 patients, surgery/histology/radiological follow-up as a reference standard, and sufficient data to construct a 2 × 2 contingency table. Two observers performed data extraction. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model and hierarchical summary operating curves (HSROC) were generated. RESULTS: Of 3457 citations retrieved, twenty-four articles met all inclusion criteria. Thirty-seven datasets could be extracted for analysis including 20 for CT, 10 for PET(CT), and 7 for (DW)MRI. The pooled sensitivity, specificity, and DOR for the detection of PM for region-based studies for CT were 68% (CI, 46-84%), 88%(CI, 81-93%), and 15.9 (CI, 4.4-58.0) respectively; 80% (CI, 57-92%), 90% (CI, 80-96%), and 36.5 (CI, 6.7-199.5) for PET(CT), respectively; 92% (CI, 84-96%), 85% (CI, 78-91%), 63.3 (CI, 31.5-127.3) for (DW)MRI. In the patient-based group, not enough studies were included to make a pooled analysis for (DW)MRI and PET(CT). CONCLUSION: (DW)MRI and PET(CT) showed comparable diagnostic performance for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients. Since MRI is more widely available than PET(CT) in clinical practice, this potentially is the imaging method of choice in most centers in the future. KEY POINTS: • Detection of peritoneal metastases plays an important role in the accurate staging of cancer patients, however, there is no accepted reference standard for the imaging of peritoneal metastases • This meta-analysis shows that (DW)MRI provided the highest sensitivity for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients • Although (DW)MRI and PET(CT) show a comparable overall diagnostic performance, (DW)MRI seems to be the imaging method of choice since it is more available in daily practice than PET(CT).

Tissue diagnosis during colorectal cancer surgery using optical sensing: an in vivo study.

BACKGROUND: In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement. METHODS: DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue. RESULTS: Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement. CONCLUSION: This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175 .

Diffusion-weighted MRI assessment of the peritoneal cancer index before cytoreductive surgery.

BACKGROUND: Patients with limited peritoneal metastases from colorectal cancer may be candidates for an aggressive surgical approach including cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Selection is based on surgical inspection during laparoscopy or laparotomy. The aim of this study was to investigate whether diffusion-weighted MRI (DW-MRI) can be used to select patients for CRS-HIPEC. METHODS: This was a prospective study at a tertiary referral centre. Patients with confirmed or suspected colorectal peritoneal metastases scheduled for exploratory laparotomy or laparoscopy were eligible. Two radiologists assessed the peritoneal cancer index (PCI) on CT (CT-PCI) and DW-MRI (MRI-PCI). The reference standard was PCI at surgery. Radiologists were blinded to the surgical PCI and to each other's findings. The main outcome was the accuracy of DW-MRI in predicting whether patients had resectable disease (PCI less than 21) or not. RESULTS: Fifty-six patients were included in the study, of whom 49 could be evaluated. The mean(s.d.) PCI at surgery was 11·27(7·53). The mean MRI-PCI was 10·18(7·07) for reader 1 and 8·59(7·08) for reader 2. Readers 1 and 2 correctly staged 47 of 49 and 44 of 49 patients respectively (accuracy 96 and 90 per cent). Both readers detected all patients with resectable disease with a PCI below 21 at surgery (sensitivity 100 per cent). No patient was overstaged. The intraclass correlation (ICC) between readers was excellent (ICC 0·91, 95 per cent c.i. 0·77 to 0·96). MRI-PCI had a stronger correlation with surgical PCI (ICC 0·83-0·88) than did CT-PCI (ICC 0·39-0·44). CONCLUSION: DW-MRI is a promising non-invasive tool to guide treatment selection in patients with peritoneal metastases from colorectal cancer.

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial.

BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.

Chemotherapy intravenously in children with cancer at home, the nurse practitioner makes it possible!

BACKGROUND: Currently the entire treatment of a child with cancer is carried out in a specialized hospital. It would be ideal to conduct part of the treatment at home. This can only be done with adequately trained personnel. In the Netherlands, specialized pediatric oncology home care nurse practitioners have been trained to deliver this kind of care. Therefore, a pilot study was conducted to administer intravenous chemotherapy at home. PURPOSE: This study aimed to safely administer chemotherapy intravenously (iv) at home by specialized nurse practitioners and aimed to increase the quality of life (QOL) of the child and decrease the social burden in families with a child with acute lymphoblastic leukemia (ALL). METHOD: The pilot study was performed by well-trained home care nurse practitioners. Low-dose methotrexate iv and low-dose cytarabine iv were administered to 11 included children with ALL in their home environment. RESULTS: QOL increased whereas social burden decreased for patients and parents. Chemotherapy administration in the home environment was safe with the help of well-trained nurse practitioners. CONCLUSION: It is feasible to administer intravenous chemotherapy at home in a safe and efficient way. The role of the specialized pediatric oncology nurse practitioner is an essential one.

Histopathological and molecular classification of colorectal cancer and corresponding peritoneal metastases.

BACKGROUND: Patients with colorectal peritoneal carcinomatosis have a very poor prognosis. The recently developed consensus molecular subtype (CMS) classification of primary colorectal cancer categorizes tumours into four robust subtypes, which could guide subtype-targeted therapy. CMS4, also known as the mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4 status and histopathological features of colorectal peritoneal carcinomatosis were investigated in this study. METHODS: Fresh-frozen tissue samples from primary colorectal cancer and paired peritoneal metastases from patients who underwent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy were collected. Histopathological features were analysed, and a reverse transcriptase-quantitative PCR test was used to assess CMS4 status of all collected lesions. RESULTS: Colorectal peritoneal carcinomatosis was associated with adverse histopathological characteristics, including a high percentage of stroma in both primary tumours and metastases, and poor differentiation grade and high-grade tumour budding in primary tumours. Furthermore, CMS4 was significantly enriched in primary tumours with peritoneal metastases, compared with unselected stage I-IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15 of 16 patients with paired tumours had at least one CMS4-positive tumour location. CONCLUSION: Significant enrichment for CMS4 was observed in colorectal peritoneal carcinomatosis. Surgical relevance Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival of selected patients with colorectal peritoneal carcinomatosis, but recurrence is common. Histopathological and molecular analysis of colorectal peritoneal carcinomatosis could provide clues for development of novel therapies. In this study, colorectal peritoneal carcinomatosis was found to be enriched for tumours with high stromal content and CMS4-positive status. To further improve prognosis for patients with colorectal peritoneal carcinomatosis, therapies that target tumour-stroma interaction could be added to CRS-HIPEC.

Incidence of and risk indicators for vasa praevia: a systematic review.

BACKGROUND: Vasa praevia (VP) is a rare phenomenon that is assumed to increase the risk of severe complications, including fetal death. Critical data on its incidence are lacking, so there is no rational basis for prenatal screening. OBJECTIVES: To review the literature on the incidence and risk indicators for VP. SEARCH STRATEGY: We searched OVID MEDLINE, OVID EMBASE, the Cochrane Library and PubMed for case-control and cohort studies on incidence and risk indicators for VP. SELECTION CRITERIA: Two reviewers selected studies and scored their methodological quality. DATA COLLECTION AND ANALYSIS: We calculated the mean incidence of VP. We constructed 2 × 2 tables cross-classifying potential risk indicators against the incidence of VP to calculate common odds ratios and 95% confidence intervals, using the Mantel-Haenszel method. MAIN RESULTS: We included 13 studies (two prospective cohort studies, ten retrospective cohort studies and one case-control study) reporting on 569 410 patients with 325 cases of VP. Based on ten included cohort studies providing information on the incidence, the mean incidence of VP was 0.60 per 1000 pregnancies. We identified five different risk indicators and markers for VP: second-trimester placenta praevia, conception by assisted reproductive technologies, a bilobed or succenturiate placenta, umbilical cord insertion in the lower third part of the uterus at first-trimester ultrasound and velamentous cord insertion. Almost 83% of the cases of VP had one or more risk indicators. AUTHORS' CONCLUSIONS: In view of the low incidence, screening for VP in an unselected population is not advised. Targeted screening of women with one or more risk indicators as a part of routine mid-gestation scanning should be considered. TWEETABLE ABSTRACT: Vasa praevia is more common in placenta praevia, conception by ART, velamentous cord insertion and bilobed placenta.

Histological and Molecular Subclassification of Pancreatic and Nonpancreatic Periampullary Cancers: Implications for (Neo) Adjuvant Systemic Treatment.

The benefit of adjuvant chemotherapy for resected pancreatic ductal adenocarcinoma (PDAC) has been confirmed in randomized controlled trials. For nonpancreatic periampullary cancers (NPPC) originating from the distal bile duct, duodenum, ampulla, or papilla of Vater, the role of adjuvant therapy remains largely unclear. This review describes methods for distinguishing PDAC from NPPC by means of readily available and recently developed molecular diagnostic methods. The difficulties of reliably determining the exact origin of these cancers pathologically also is discussed. The review also considers the possibility of unintentional inclusion of NPPC in the most important adjuvant trials on PDAC and the subsequent implications for interpretation of the results. The authors conclude that correct determination of the origin of periampullary cancers is essential for clinical management and should therefore be systematically incorporated into clinical practice and future studies.

Systematic review of accuracy of ultrasound in the diagnosis of vasa previa.

OBJECTIVE: Vasa previa is an obstetric complication in which the fetal blood vessels lie outside the chorionic plate in close proximity to the internal cervical os. In women with vasa previa, the risk of rupture of these vessels is increased, thus potentially causing fetal death or serious morbidity. Our objective was to assess the accuracy of ultrasound in the prenatal diagnosis of vasa previa. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and PubMed for studies on vasa previa. Two reviewers independently selected studies on the accuracy of ultrasound in the diagnosis of vasa previa. The studies were scored on methodological quality using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Data on sensitivity and specificity were subsequently extracted. RESULTS: The literature search revealed 583 articles, of which two prospective and six retrospective cohort studies were eligible for inclusion in the qualitative analysis. All studies documented methods suitable for the prenatal diagnosis of vasa previa. Four out of the eight studies used transvaginal ultrasound (TVS) for primary evaluation, while the remaining four studies used transabdominal ultrasound and performed a subsequent TVS when vasa previa was suspected. The QUADAS-2 tool reflected poor methodology in six of the eight included studies, and prenatal detection rates varied from 53% (10/19) to 100% (total of 442,633 patients, including 138 cases of vasa previa). In the two prospective studies (n = 33,795, including 11 cases of vasa previa), transvaginal color Doppler performed during the second trimester detected all cases of vasa previa (sensitivity, 100%) with a specificity of 99.0-99.8%. CONCLUSION: The accuracy of ultrasound in the diagnosis of vasa previa is high when performed transvaginally in combination with color Doppler.

Risk of maternal and neonatal complications in subsequent pregnancy after planned caesarean section in a first birth, compared with emergency caesarean section: a nationwide comparative cohort study.

OBJECTIVE: To compare the difference in risks of neonatal and maternal complications, including uterine rupture, in a second birth following a planned caesarean section versus emergency caesarean section in the first birth. DESIGN: Prospective cohort study. SETTING: Population-based cohort in the Netherlands. POPULATION: Linked data set of outcomes for term caesarean section in a first birth followed by a consecutive delivery. METHODS: We conducted a prospective cohort analysis using data from the Dutch Perinatal Registry. We included primiparous women who gave birth to term singleton infants through planned or emergency caesarean from January 2000 through December 2007, and who had a second singleton delivery during the same period (n = 41,109). Odds ratios and adjusted odds ratios were calculated. MAIN OUTCOME MEASURES: Maternal and neonatal complications, specifically uterine rupture, in second births associated with planned and emergency caesareans in the first birth. RESULTS: Women with a history of a planned caesarean section in the first birth (n = 11,445) had a 0.24% risk for uterine rupture, compared with a 0.16% risk for women with a history of emergency caesarean section (n = 29,664; aOR 1.4, 95% CI 0.8-2.4). In multivariate logistic regression, women with planned caesareans in a first birth had a significantly increased risk of stillbirth (aOR 1.5, 95% CI 1.0-2.2) and postpartum haemorrhage (aOR 1.1, 95% CI 1.0-1.2) in second births, compared with women with emergency caesareans in the first birth. CONCLUSIONS: We found a moderately increased risk of postpartum haemorrhage and a small to moderately increased risk of uterine rupture and stillbirth as a long-term effect of prior planned caesarean delivery on second births.

'Going rural': driving change through a rural medical education innovation.

INTRODUCTION: Medical education across the globe is in a state of flux influenced by a number of drivers for change. In response, institutions are seeking to re-align their curricula to address the prevailing imperatives. Against this backdrop, the training of practitioners for practice in rural communities was identified as an educational priority, and led to the establishment of a rural clinical school (RCS) within a Faculty of Medicine and Health Sciences in South Africa in 2011. This article describes the students' experiences in the first year that this innovative educational model was implemented and explores the extent to which it influenced their thinking and practice. METHODS: A qualitative, formative evaluation study of the first year of implementation was undertaken. Data was generated from in-depth interviews. This article focuses on individual interviews conducted with the eight students at the RCS, which explored their experiences during a year-long clerkship. Transcripts of interviews were thematically analysed. RESULTS: Four themes emerged from the analysis: a learning experience that differed from what was experienced at the tertiary training hospital, an enabling clinical environment in the district and regional hospital, the positive role played by the specialists, and the influence of the community immersion. Underlying all of the responses was the building of relationships over time both with supervisors and with patients. Evident from the responses was that students' confidence in their clinical skills and decision-making abilities was heightened while their approaches to their own learning were enhanced. CONCLUSIONS: To respond to the call for educational reform and a heightened awareness of social realities, innovative approaches to the training of medical students, such as those adopted at the RCS, are indicated. It is argued that the learning facilitated by these rural medical education models has the potential to offer learning experiences that can lead to transformation through a change in practice and attitude among the students, and ultimately also enable curricular renewal at the institutional core.

Investigating locations of recurrences with MRI after CRS-HIPEC for colorectal peritoneal metastases.

PURPOSE: Patients with colorectal peritoneal metastases (PM) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are at high risk of recurrent disease. Understanding where and why recurrences occur is the first step in finding solutions to reduce recurrence rates. Although diffusion-weighted (DW) MRI is not routinely used in the follow-up of CRC patients, it has a clear advantage over CT in detecting the location and spread of (recurrent) PM. This study aimed to identify common locations of recurrence in CRC patients after CRS-HIPEC with MRI. METHOD: This was a single-centre retrospective study of patients with recurrent PM after CRS-HIPEC performed between January 2016 and August 2020. Patients were eligible for inclusion if they had both an MRI preoperatively (MRI1) and at the time of recurrent disease (MRI2). Two abdominal radiologists reviewed in consensus and categorized recurrences according to their location on MRI2 and in correlation with previous disease location on prior imaging (MRI1) and the surgical report of the CRS-HIPEC. RESULTS: Thirty patients were included, with a median surgical PCI of 7 (range 3-21) at the time of primary CRS-HIPEC. In total, 68 recurrent metastases were detected on MRI2, of which 14 were extra-peritoneal. Of the remaining 54 PM, 42 (78%) occurred where the peritoneum was damaged due to earlier resections or other surgical procedures (e.g. inserted surgical abdominal drains). Most recurrent metastases were found in the mesentery, lower abdomen/pelvis and abdominal wall (87%). CONCLUSIONS: Most recurrent PMs appeared in the mesentery, lower abdomen/pelvis and abdominal wall, especially where the peritoneum was previously damaged.

Sonographic measurement of lower uterine segment thickness to predict uterine rupture during a trial of labor in women with previous Cesarean section: a meta-analysis.

OBJECTIVE: To evaluate the accuracy of antenatal sonographic measurement of lower uterine segment (LUS) thickness in the prediction of risk of uterine rupture during a trial of labor (TOL) in women with a previous Cesarean section (CS). METHODS: PubMed and EMBASE were searched to identify articles published on the subject of sonographic LUS measurement and occurrence of a uterine defect after delivery. Four independent researchers performed identification of papers and data extraction. Selected studies were scored on methodological quality, and sensitivity and specificity of measurement of LUS thickness in the prediction of a uterine defect were calculated. We performed bivariate meta-analysis to estimate summary receiver-operating characteristics (sROC) curves. RESULTS: We included 21 studies with a total of 2776 analyzed patients. The quality of included studies was good, although comparison was difficult because of heterogeneity. The estimated sROC curves showed that measurement of LUS thickness seems promising in the prediction of occurrence of uterine defects (dehiscence and rupture) in the uterine wall. The pooled sensitivity and specificity of myometrial LUS thickness for cut-offs between 0.6 and 2.0 mm was 0.76 (95% CI, 0.60-0.87) and 0.92 (95% CI, 0.82-0.97); cut-offs between 2.1 and 4.0 mm reached a sensitivity and specificity of 0.94 (95% CI, 0.81-0.98) and 0.64 (95% CI, 0.26-0.90). The pooled sensitivity and specificity of full LUS thickness for cut-offs between 2.0 and 3.0 mm was 0.61 (95% CI, 0.42-0.77) and 0.91 (95% CI, 0.80-0.96); cut-offs between 3.1 and 5.1 mm reached a sensitivity and specificity of 0.96 (95% CI, 0.89-0.98) and 0.63 (95% CI, 0.30-0.87). CONCLUSIONS: This meta-analysis provides support for the use of antenatal LUS measurements in the prediction of a uterine defect during TOL. Clinical applicability should be assessed in prospective observational studies using a standardized method of measurement.

Disappearing colorectal liver metastases in the era of state-of-the-art triple-modality diagnostic imaging.

INTRODUCTION: Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS: This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS: Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION: Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.