Cytosponge-TFF3 Testing can Detect Precancerous Mucosal Changes of the Stomach.

Gastric intestinal metaplasia (GIM) and gastric atrophy (GA) are associated with increased risk of gastric cancer and are indications for endoscopic surveillance when affecting the proximal stomach.1 Endoscopic screening is not cost-effective in areas with low-moderate incidence of gastric cancer2; noninvasive methods to detect GIM/GA are currently lacking.3.

T-cell receptor and chimeric antigen receptor in solid cancers: current landscape, preclinical data and insight into future developments.

PURPOSE OF REVIEW: The remarkable and durable clinical responses seen in certain solid tumours using checkpoint inhibitors and in haematological malignancies using chimeric antigen receptor (CAR) T therapy have led to great interest in the possibility of using engineered T-cell receptor (TCR) and CAR T therapies to treat solid tumours. RECENT FINDINGS: In this article, we focus on the published clinical data for engineered TCR and CAR T therapy in solid tumours and recent preclinical work to explore how these therapies may develop and improve. We discuss recent approaches in target selection, encouraging epitope spreading and replicative capacity, CAR activation, T-cell trafficking, survival in the immunosuppressive microenvironment, universal T-cell therapies, manufacturing processes and managing toxicity. SUMMARY: In haematological malignancies, CAR T treatments have shown remarkable clinical responses. Engineered TCR and CAR therapies demonstrate responses in numerous preclinical models of solid tumours and have shown objective clinical responses in select solid tumour types. It is anticipated that the integration of efficacious changes to the T-cell products from disparate preclinical experiments will increase the ability of T-cell therapies to overcome the challenges of treating solid tumours and note that healthcare facilities will need to adapt to deliver these treatments.

Chemotherapy for advanced gallbladder cancer (GBC): A systematic review and meta-analysis.

BACKGROUND: The benefit from chemotherapy, specifically for patients with gallbladder cancer (GBC), has been poorly explored since GBC is mostly studied jointly with other biliary tract cancers (BTC). METHODS: Eligible studies reporting outcome of palliative systemic chemotherapy for advanced GBC were identified through MEDLINE, cross-referencing and conferences (PROSPERO-CRD42019155745). Meta-analysis of proportions and calculation of pooled weighted means were performed. RESULTS: 58 eligible studies (n = 1,986 patients); cisplatin/gemcitabine (33 % of patients), gemcitabine/oxaliplatin (14 %) or gemcitabine monotherapy (9%). Estimated pooled overall radiological response rate(ORR), and pooled weighted mean progression-free (PFS) and overall survivals (OS) were 23.2 % (95 %-CI 20.0-26.5) (I2: 52.5 % (p < 0.001)), 4.8 months (95 %-CI 4.3-5.2) and 8.3 months (95 %CI 7.6-8.9), respectively. Patients with non-GBC BTCs achieved a lower ORR than GBC [odds ratio 0.65 (95 % CI, 0.50-0.84)]. CONCLUSIONS: GBC benefit from chemotherapy differs from other BTCs, with shorter PFS/OS despite higher ORR; new treatment options are urgently required for management of advanced GBC.

Does surgical procedure type impact postoperative pain and recovery in deep inferior epigastric artery perforator flap breast reconstruction?

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is the commonest flap used for breast reconstruction after mastectomy. It is performed as a unilateral (based on one [unipedicled] or two [bipedicled] vascular pedicles) or bilateral procedure following unilateral or bilateral mastectomies. No previous studies have comprehensively analyzed analgesia requirements and hospital stay of these three forms of surgical reconstruction. METHODS: A 7-year retrospective cohort study (2008-2015) of a single-surgeon's DIEP-patients was conducted. Patient-reported pain scores, patient-controlled morphine requirements and recovery times were compared using non-parametric statistics and multivariable regression. RESULTS: The study included 135 participants: unilateral unipedicled (n=84), unilateral bipedicled (n=24) and bilateral unipedicled (n=27). Univariate comparison of the three DIEP types showed a significant difference in 12-hour postoperative morphine requirements (P=0.020); bipedicled unilateral patients used significantly less morphine than unipedicled (unilateral) patients at 12 (P=0.005), 24 (P=0.020), and 48 (P=0.046) hours. Multivariable regression comparing these two groups revealed that both reconstruction type and smoking status were significant predictors for 12-hour postoperative morphine usage (P=0.038 and P=0.049, respectively), but only smoking, remained significant at 24 (P=0.010) and 48 (P=0.010) hours. Bilateral reconstruction patients' mean hospital stay was 2 days longer than either unilateral reconstruction (P<0.001). CONCLUSIONS: Although all three forms of DIEP flap breast reconstruction had similar postoperative pain measures, a novel finding of our study was that bipedicled DIEP flap harvest might be associated with lower early postoperative morphine requirements. Bilateral and bipedicled procedures in appropriate patients might therefore be undertaken without significantly increased pain/morbidity compared to unilateral unipedicled reconstructions.

Update on the Genetics of and Systemic Therapy Options for Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.

Systemic therapy of gallbladder cancer: review of first line, maintenance, neoadjuvant and second line therapy specific to gallbladder cancer.

Gallbladder cancer is the most common malignant cancer of the biliary tract and is distinct from other forms of biliary tract cancer in several of its risk factors and molecular aberrations. Locally advanced, unresectable and metastatic gallbladder cancer is associated with a poor prognosis and systemic chemotherapy is the main form of treatment available to these patients. This review is focused on the available evidence supporting the use of first-line chemotherapy specifically for gallbladder cancer. Numerous non-randomised studies have been published and certain forms of monotherapy and combination therapy can both lead to response rates (RRs) of approximately 40% and may prove to affect overall survival, most notably a recent phase II study of triplet therapy with gemcitabine, cisplatin and nab-paclitaxel. There are however relatively few randomised phases II and III studies on which to base recommendations, but they do demonstrate significant survival advantages of gemcitabine-containing combination therapies over best supportive care and chemotherapeutic monotherapy. The ABC-02 trial established the combination of gemcitabine and cisplatin as standard therapy in 2010, but more recent phase III studies reported as conference papers may support alternative, gemcitabine-containing doublet chemotherapy regimens such as gemcitabine in combination with oxaliplatin or S1. This manuscript also highlights the available data from studies examining maintenance chemotherapy, biomarkers, neoadjuvant therapy and second line studies in gallbladder cancer; unfortunately, there is insufficient evidence to make recommendations in these regards. The prognosis for unresectable and metastatic gallbladder cancer remains poor, and biomarkers for stratifying patients to particular first line therapies are not defined. This might be improved by gallbladder cancer specific analysis and reporting, and making histological primary specific data available publicly for further analysis.