Maternal and perinatal outcomes in nulliparous women with a booking body mass index exceeding 50 kg/m2.

BACKGROUND: Women with a body mass index (BMI) >35 kg/m2 carry an increased obstetric risk; however, the experience of the Class IV and above obese nulliparous women is less understood. AIMS: To describe maternal and perinatal outcomes in nulliparous women of booking BMI > 50 kg/m2. MATERIALS AND METHODS: A cohort study of 48 nulliparous women who delivered between 2015 and 2019 in a tertiary hospital and had a booking BMI > 50 kg/m2. Obstetric outcome data was collated via electronic and written patient records. The relationship between mode of delivery and BMI was assessed using direct logistic regression. Multiple pregnancies and severe congenital malformations (n = 3) were excluded. RESULTS: The mean booking BMI was 53.7 kg/m2 (SD 4.05) and mean maternal age was 30.4 years (SD = 5.7). Comorbidities included asthma (43%), essential hypertension (20%) and diabetes (61%). Antenatally, accuracy was compromised in 80% of morphology scans (n = 35). In the perinatal period, 33 women (68.8%) were induced compared to a spontaneous onset of labour in two (4.1%) women. There were nine elective caesarean sections (CS), five of which were for breech presentation. Of those who intended on vaginal delivery (n = 35), 51% (n = 18) had an emergency CS. In these women, the risk of CS increased by a factor of 1.36 for every one point increase in BMI > 50 kg/m2. The average gestational age was 37.5 weeks (SD 2.4) with 14% (n = 6) experiencing preterm deliveries. The incidence of babies born >90th percentile for gestational age was 15 (34%). CONCLUSION: Increased BMI impairs maternal and perinatal outcomes and significantly increases the risk of emergency CS. BMI > 50 kg/m2 is associated with higher-level interventions and obstetric complications.

Overcoming the Fibrotic Fortress in Pancreatic Ductal Adenocarcinoma: Challenges and Opportunities.

An overabundance of desmoplasia in the tumour microenvironment (TME) is one of the defining features that influences pancreatic ductal adenocarcinoma (PDAC) development, progression, metastasis, and treatment resistance. Desmoplasia is characterised by the recruitment and activation of fibroblasts, heightened extracellular matrix deposition (ECM) and reduced blood supply, as well as increased inflammation through an influx of inflammatory cells and cytokines, creating an intrinsically immunosuppressive TME with low immunogenic potential. Herein, we review the development of PDAC, the drivers that initiate and/or sustain the progression of the disease and the complex and interwoven nature of the cellular and acellular components that come together to make PDAC one of the most aggressive and difficult to treat cancers. We review the challenges in delivering drugs into the fortress of PDAC tumours in concentrations that are therapeutic due to the presence of a highly fibrotic and immunosuppressive TME. Taken together, we present further support for continued/renewed efforts focusing on aspects of the extremely dense and complex TME of PDAC to improve the efficacy of therapy for better patient outcomes.

Survival outcomes for patients with colorectal cancer with synchronous liver only metastasis.

BACKGROUND: Colorectal cancer with synchronous liver-only metastasis is managed with a multimodal approach, however, optimal sequencing of modalities remains unclear. METHODS: A retrospective review of all consecutive rectal or colon cancer cases with synchronous liver-only metastasis was conducted from the South Australian Colorectal Cancer Registry from 2006 to 2021. This study aimed to investigate how order and type of treatment modality affects overall survival. RESULTS: Data of over 5000 cases were analysed (n = 5244), 1420 cases had liver-only metastasis. There were a greater number of colon than rectal primaries (N = 1056 versus 364). Colonic resection was the preferred initial treatment for the colon cohort (60%). In the rectal cohort, 30% had upfront resection followed by 27% that had chemo-radiotherapy as 1st line therapy. For the colon cohort, there was an improved 5-year survival with surgical resection as initial treatment compared to chemotherapy (25% versus 9%, P < 0.001). In the rectal cohort, chemo-radiotherapy as the initial treatment was associated with an improved 5-year survival compared to surgery or chemotherapy (40% versus 26% versus 19%, P = 0.0015). Patients who were able to have liver resection had improved survival, with 50% surviving over 5 years compared to 12 months in the non-resected group (P < 0.001). Primary rectal KRAS wildtype patients who underwent liver resection and received Cetuximab had significantly worse outcomes compared to KRAS wildtype patients who did not (P = 0.0007). CONCLUSIONS: Where surgery is possible, resection of liver metastasis and primary tumour improved overall survival. Further research is required on the use of targeted treatments in patients undergoing liver resection.

Young-Onset Gastrointestinal Adenocarcinoma Incidence and Survival Trends in the Northern Territory, Australia, with Emphasis on Indigenous Peoples.

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990−2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18−50 years and >50 years. Results: A total of 1608 cases of GI adenocarcinoma were recorded during the time of the study. While the overall incidence in people 18−50 years remained unchanged over this time (p = 0.51), the rate in individuals aged >50 years decreased (IRR = 0.65 (95% CI 0.56−0.75; p < 0.0001)). Incidence rates were significantly less in females >50 years (IRR = 0.67 95% CI 0.59−0.75; p < 0.0001), and their survival was significantly better (HR = 0.84 (95%CI 0.72−0.98; p < 0.03)) compared to males. Overall survival across all GI subsites improved in both age cohorts, especially between 2010 and 2017 (HR = 0.45 (95%CI 0.29−0.72; p < 0.0007) and HR = 0.64 (95%CI 0.52−0.78; p < 0.0001), respectively) compared to 1990−1999, driven by an improvement in survival in colonic adenocarcinoma alone, as the survival remained unchanged in other GI subsites. The incidence was significantly lower in Indigenous patients compared to non-Indigenous patients, in both age cohorts (18−50 years IRR = 0.68 95% CI 0.51−0.91; p < 0.009 and >50 years IRR = 0.48 95% CI 0.40−0.57; p < 0.0001). However, Indigenous patients had worse survival rates (18−50 years HR = 2.06 95% CI 1.36−3.11; p < 0.0007 and >50 years HR = 1.66 95% CI 1.32−2.08; p < 0.0001). Conclusions: There is a trend towards an increased incidence of young-onset GI adenocarcinomas in the NT. Young Indigenous patients have lower incidence but worse survival across all GI subsites, highlighting significant health inequities in life expectancy. Targeted, culturally safe Indigenous community-focussed programs are needed for early detection and patient-centred management of GI adenocarcinomas.