What is the optimum post treatment surveillance imaging protocol for low grade appendiceal mucinous neoplasms and pseudomyxoma peritoneii?

Appendiceal mucinous neoplasms are rare and can be associated with the development of disseminated peritoneal disease known as pseudomyxoma peritonei (PMP). Mucinous tumours identified on appendicectomy are therefore followed up to assess for recurrence and the development of PMP. In additional, individuals who initially present with PMP who are treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are followed up to assess for recurrence. However, despite the concerted efforts of multiple expert groups, the optimal imaging follow-up protocol is yet to be established. The purpose of this paper is to review the available evidence for imaging surveillance in these populations to identify the optimum post-resection imaging follow-up protocol.

Geotemporal Fluorophore Biodistribution Mapping of Colorectal Cancer: Micro and Macroscopic Insights.

Fluorescence-guided oncology promises to improve both the detection and treatment of malignancy. We sought to investigate the temporal distribution of indocyanine green (ICG), an exogenous fluorophore in human colorectal cancer. This analysis aims to enhance our understanding of ICG's effectiveness in current tumour detection and inform potential future diagnostic and therapeutic enhancements. METHODS: Fifty consenting patients undergoing treatment for suspected/confirmed colorectal neoplasia provided near infrared (NIR) video and imagery of transanally recorded and ex vivo resected rectal lesions following intravenous ICG administration (0.25 mg/kg), with a subgroup providing tissue samples for microscopic (including near infrared) analysis. Computer vision techniques detailed macroscopic 'early' (<15 min post ICG administration) and 'late' (>2 h) tissue fluorescence appearances from surgical imagery with digital NIR scanning (Licor, Lincoln, NE, USA) and from microscopic analysis (Nikon, Tokyo, Japan) undertaken by a consultant pathologist detailing tissue-level fluorescence distribution over the same time. RESULTS: Significant intra-tumoural fluorescence heterogeneity was seen 'early' in malignant versus benign lesions. In all 'early' samples, fluorescence was predominantly within the tissue stroma, with uptake within plasma cells, blood vessels and lymphatics, but not within malignant or healthy glands. At 'late' stage observation, fluorescence was visualised non-uniformly within the intracellular cytoplasm of malignant tissue but not retained in benign glands. Fluorescence also accumulated within any present peritumoural inflammatory tissue. CONCLUSION: This study demonstrates the time course diffusion patterns of ICG through both benign and malignant tumours in vivo in human patients at both macroscopic and microscopic levels, demonstrating important cellular drivers and features of geolocalisation and how they differ longitudinally after exposure to ICG.

Acute colonic pseudo-obstruction post-cesarean section is not a benign entity: A case series and review of the literature.

Acute colonic pseudo-obstruction (ACPO) is an infrequent occurrence after cesarean section. Anecdotal evidence suggests that the clinical course of ACPO in the obstetric setting is different to that seen in non-pregnant adult patients with ACPO secondary to alternative causes, such as systemic illnesses, the use of certain medications, and after non-abdominal surgery. The risk of progression to ischemia and perforation, as well as the need for emergency surgery, appears to be higher after cesarean section. Here we describe the clinical course of ACPO in four patients after cesarean section from our institution, followed by a review of the literature and a discussion of the important issues surrounding this condition in the postpartum time period. The findings from our cohort of patients and the reports from the medical literature support a hands-on combined approach from a group of specialists including obstetricians, surgeons, radiologists, and enterostomal therapists. Immediate imaging followed by regular observation is mandatory for any patient being managed conservatively. Early use of endoscopic decompression should be considered for patients who are not resolving with a conservative approach. Clinical signs of peritonism or radiological signs of ischemia or perforation in patients with ACPO mandate immediate surgical intervention. Appropriate postoperative care is necessary to deal with the complex physiological and psychological consequences of emergency surgery and potential stoma formation so soon after cesarean section.

Real-time administration of indocyanine green in combination with computer vision and artificial intelligence for the identification and delineation of colorectal liver metastases.

Introduction: Fluorescence guided surgery for the identification of colorectal liver metastases (CRLM) can be better with low specificity and antecedent dosing impracticalities limiting indocyanine green (ICG) usefulness currently. We investigated the application of artificial intelligence methods (AIM) to demonstrate and characterise CLRMs based on dynamic signalling immediately following intraoperative ICG administration. Methods: Twenty-five patients with liver surface lesions (24 CRLM and 1 benign cyst) undergoing open/laparoscopic/robotic procedures were studied. ICG (0.05 mg/kg) was administered with near-infrared recording of fluorescence perfusion. User-selected region-of-interest (ROI) perfusion profiles were generated, milestones relating to ICG inflow/outflow extracted and used to train a machine learning (ML) classifier. 2D heatmaps were constructed in a subset using AIM to depict whole screen imaging based on dynamic tissue-ICG interaction. Fluorescence appearances were also assessed microscopically (using H&E and fresh-frozen preparations) to provide tissue-level explainability of such methods. Results: The ML algorithm correctly classified 97.2 % of CRLM ROIs (n = 132) and all benign lesion ROIs (n = 6) within 90-s of ICG administration following initial mathematical curve analysis identifying ICG inflow/outflow differentials between healthy liver and CRLMs. Time-fluorescence plots extracted for each pixel in 10 lesions enabled creation of 2D characterising heatmaps using flow parameters and through unsupervised ML. Microscopy confirmed statistically less CLRM fluorescence vs adjacent liver (mean ± std deviation signal/area 2.46 ± 9.56 vs 507.43 ± 160.82 respectively p < 0.001) with H&E diminishing ICG signal (n = 4). Conclusion: ML accurately identifies CRLMs from surrounding liver tissue enabling representative 2D mapping of such lesions from their fluorescence perfusion patterns using AIM. This may assist in reducing positive margin rates at metastatectomy and in identifying unexpected/occult malignancies.

Proteotranscriptomic classification and characterization of pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous. Here, we use a multi-omics approach to uncover the molecular factors underlying this heterogeneity. Transcriptomic analysis of 84 PNEN specimens, drawn from two cohorts, is substantiated with proteomic profiling and identifies four subgroups: Proliferative, PDX1-high, Alpha cell-like and Stromal/Mesenchymal. The Proliferative subgroup, consisting of both well- and poorly differentiated specimens, is associated with inferior overall survival probability. The PDX1-high and Alpha cell-like subgroups partially resemble previously described subtypes, and we further uncover distinctive metabolism-related features in the Alpha cell-like subgroup. The Stromal/Mesenchymal subgroup exhibits molecular characteristics of YAP1/WWTR1(TAZ) activation suggestive of Hippo signaling pathway involvement in PNENs. Whole-exome sequencing reveals subgroup-enriched mutational differences, supported by activity inference analysis, and identifies hypermorphic proto-oncogene variants in 14.3% of sequenced PNENs. Our study reveals differences in cellular signaling axes that provide potential directions for PNEN patient stratification and treatment strategies.

Should you repeat mismatch repair testing in cases of tumour recurrence? An evaluation of repeat mismatch repair testing by the use of immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts.

AIMS: The role of mismatch repair (MMR) testing has evolved from identifying Lynch syndrome patients to predicting response to immune checkpoint inhibitors. This has led to requests from clinicians to retest recurrences of MMR-proficient primary tumours in the hope that the recurrence may show a different MMR status and qualify the patient for treatment. We aimed to determine whether repeat testing is warranted. METHODS AND RESULTS: We evaluated recurrent tumours (local recurrences or metastases) from 137 patients with MMR-proficient primary tumours of the gastrointestinal and gynaecological tracts. The local recurrences and metastases all occurred at least 30 days after resection of the primary tumour. We used a combination of a tissue microarray and whole slide staining to perform immunohistochemistry (IHC) for PMS2, MLH1, MSH2, and MSH6, and compared the results with the MMR status of the primary tumour. Three of 137 (2%) initially showed a discordant staining pattern. However, further investigation showed that these discordances were attributable to some of the known pitfalls associated with MMR IHC interpretation - post-radiotherapy loss of MSH6 expression and subclonal loss of MLH1 staining. We did not identify any cases with a genuine discordance in MMR status. CONCLUSION: We conclude that repeat MMR IHC testing of recurrences is not warranted, as MMR status does not change relative to that of the primary tumour.

Leukaemia inhibitory factor is associated with treatment resistance in oesophageal adenocarcinoma.

Oesophageal cancer is an aggressive disease with a poor 5 year survival rate of <20% of diagnosed patients. Unfortunately, only 20-30% Oesophageal Adenocarinoma (OAC) patients show a beneficial response to neoadjuvant therapy (neoCT). Inflammation influences OAC given the increased risk of cancer development and poor outcome for obese patients where altered secretion of adipokines and cytokines from adipose tissue contributes a pro-tumourigenic environment. We carried out a large proteomics screen of 184 proteins to compare the inflammatory and oncogenic profiles of an isogenic radioresistant in-vitro model of OAC. We found that leukaemia inhibitory factor (LIF), an IL-6 type cytokine, was significantly elevated in radioresistant OAC cells (p=0.007). Furthermore, significantly higher circulating levels of LIF were present in the serum from treatment-naive OAC patients who had a subsequent poor pathological response to neo-adjuvant therapy, (p=0.037). Quantitative PCR analysis revealed expression of LIF receptor (LIFR) may function as a predictive indicator of response to neo-adjuvant chemoradiation therapy in OAC. LIF was demonstrated to be actively secreted from human OAC treatment-naïve biopsies and significantly correlated with the secretion of bFGF, VEGF-A and IL-8 (p<0.05, R=1), (p<0.05, R=0.9429), and (p<0.05, R=1) respectively. Importantly, LIF secretion negatively correlated with tumour infiltrating lymphocytes in pre-treatment OAC patient biopsies, (r=-0.8783, p=0.033). Elevated circulating LIF is a marker of poor response to neo-adjuvant treatment in OAC and secretion of this chemokine from the tumour is tightly linked with pro-tumourigenic mediators including bFGF, VEGF-A and IL-8. Targeting this pathway may be a novel mechanism enhance neoadjuvant treatment responses in OAC.