Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to a severe decline in patient prognosis and survival. Recent advances in imaging and systemic treatments have increased the detection rates of brain metastases, yet clinical outcomes remain dismal due to the complexity of the metastatic tumor microenvironment (TME) and the lack of specific biomarkers for early detection and targeted therapy. The intricate interplay between NSCLC tumor cells and the surrounding TME in brain metastases is pivotal, influencing tumor progression, immune evasion, and response to therapy. This underscores the necessity for a deeper understanding of the molecular underpinnings of brain metastases, tumor microenvironment, and the identification of actionable biomarkers that can inform multimodal treatment approaches. The goal of this review is to synthesize current insights into the TME and elucidate molecular mechanisms in NSCLC brain metastases. Furthermore, we will explore the promising horizon of emerging biomarkers, both tissue- and liquid-based, that hold the potential to radically transform the treatment strategies and the enhancement of patient outcomes.

A systematic review of oncosurgical and quality of life outcomes following pelvic exenteration for locally advanced and recurrent rectal cancer.

INTRODUCTION: Pelvic exenteration (PE) is now the standard of care for locally advanced (LARC) and locally recurrent (LRRC) rectal cancer. Reports of the significant short-term morbidity and survival advantage conferred by R0 resection are well established. However, longer-term outcomes are rarely addressed. This systematic review focuses on long-term oncosurgical and quality of life (QoL) outcomes following PE for rectal cancer. METHODS: A systematic review of the PubMed®, Cochrane Library, MEDLINE® and Embase® databases was conducted, in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Studies were included if they reported long-term outcomes following PE for LARC or LRRC. Studies with fewer than 20 patients were excluded. FINDINGS: A total of 25 papers reported outcomes for 5,489 patients. Of these, 4,744 underwent PE for LARC (57.5%) or LRRC (42.5%). R0 resection rates ranged from 23.2% to 98.4% and from 14.9% to 77.8% respectively. The overall morbidity rates were 17.8-87.0%. The median survival ranged from 12.5 to 140.0 months. None of these studies reported functional outcomes and only four studies reported QoL outcomes. Numerous different metrics and timepoints were utilised, with QoL scores frequently returning to baseline by 12 months. CONCLUSIONS: This review demonstrates that PE is safe, with a good prospect of R0 resection and acceptable mortality rates in selected patients. Morbidity rates remain high, highlighting the importance of shared decision making with patients. Longer-term oncological outcomes as well as QoL and functional outcomes need to be addressed in future studies. Development of a core outcomes set would facilitate better reporting in this complex and challenging patient group.

What is the margin of error of surgeons and radiological imaging in diagnosing acute appendicitis?

Background: Acute appendicitis is the most common emergency requiring surgical intervention in general surgery. Negative appendectomy is defined as the removal of a pathologically normal appendix. Aim: In this study, we aimed to show our negative appendectomy rate. Materials and Methods: This study was carried out among 2990 patients who were operated on for appendicitis between 2015-2020 at the Health Sciences University, Istanbul Kanuni Sultan Suleyman Training, and Research Hospital. Accrual and historical records of the patients were analyzed using NCSS (Number Cruncher Statistical System) 2007 Statistical Software (Utah, USA) package program. The results were evaluated at the significance level of P < 0.05. Results: The mean age of all patients was 33. Of the patients, 1011 were women and 1979 were men. 27 of the women patients were pregnant. We requested a blood test (WBC count) and an abdominal ultrasound for all our patients who came with the complaint of abdominal pain in the right lower quadrant. Negative appendectomy was performed with ultrasonography in 622 patients with pathological diagnoses of lymphoid hyperplasia and fibrous obliteration (20.8%). We had abdominal computerized tomography (CT) for 285 patients and abdominal magnetic resonance imaging (MRI) for 16 of 27 pregnant women (59.25%) due to unclear clinical picture. Diagnostic laparoscopy was performed in 36 of the patients who underwent CT and 4 of the patients who underwent MRI since the diagnosis could not be made. We performed unnecessary appendectomy in 21.2% of the patients. Conclusion: With the increasing clinical follow-up experience of surgeons and developing technology in radiology, our aim is to minimize the negative appendectomy rate as much as possible.

Defining a role for systemic chemotherapy in local and advanced appendix adenocarcinoma.

BACKGROUND: Appendix adenocarcinomas (AAs) are rare tumours that often present late, with a propensity for peritoneal metastases (PMs). This study aimed to evaluate outcomes of AA patients undergoing cytoreductive surgery (CRS) with curative intent and determine the role of systemic chemotherapy. MATERIALS AND METHODS: Data were collected from a prospective database and classified according to World Health Organization (WHO) 2019 classification. Tumour clearance from CRS was described using a completeness of cytoreduction (CC) score ranging from 0 [no residual disease (RD)] to 3 (>2.5 cm RD). Patients with CC0-2 CRS received hyperthermic intraperitoneal chemotherapy (HIPEC). Systemic chemotherapy was categorised as 'prior' (>6 months before), 'neoadjuvant' (<6 months before), 'adjuvant' (<6 months after CC0-1 CRS) or 'palliative' (after CC2-3 CRS). Analyses used Kaplan-Meier and Cox regression methods. RESULTS: Between January 2005 and August 2021, 216 AA patients were identified for inclusion. Median age was 59 years (21-81 years). CRS/HIPEC was carried out in 182 (84%) patients, of whom 164/182 (76%) had mitomycin C HIPEC. CC0-1 was achieved in 172 (80%) patients. Systemic chemotherapy was given to 97 (45%) patients from the whole cohort and to 37/46 (80%) patients with positive nodes. Median overall survival (OS) was 122 months (95% confidence interval 61-182 months). After multivariate analysis, patients with acellular and lower-grade PM had similar OS to those with localised (M0) disease (P = 0.59 and P = 0.19). For patients with positive nodes, systemic chemotherapy was associated with reduced risk of death compared to no chemotherapy (P < 0.0019). CONCLUSION: This study identifies AA patients with positive lymph nodes derive the most benefit from systemic chemotherapy. We confirm the prognostic importance of stage and peritoneal grade, with excellent outcomes in patients with acellular mucin and lower-grade PM.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Long term oncologic outcomes from the international PSOGI registry.

The laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS + HIPEC) in highly selected patients was previously reported from the PSOGI registry with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to update this international PSOGI registry with a larger cohort of patients and a longer follow-up period. METHODS: An international registry was designed through a networking database (REDCAP®). All centers performing L-CRS + HIPEC were invited through PSOGI to submit data on their cases. Variables such as demographics, clinical outcomes, and survival were analyzed. RESULTS: A total of 315 L-CRS + HIPEC cases were provided by 14 worldwide centers. A total of 215 patients were included in the L-CRS + HIPEC group. The median peritoneal cancer index (PCI) was 3 (3-5). The median length of stay was 7 days (5-10) and the major morbidity (Clavien-Dindo ≥3) was 6.1% after 30 days. The 5-year disease-free survival (DFS) per tumor origin was: 94% for PMP-LG, 85% for PMP-HG, 100% for benign multicyst peritoneal mesothelioma (MPM), 37.4% for colonic origin, and 54%(at 3 years) for ovarian origin. The 5 years overall survival (OS) per tumor origin was: 100% for PMP-LG, PMP-HG and MPM; 61% for colonic origin, and 74% (at 3 years) for ovarian origin. In addition, a total of 85 patients were analyzed in the laparoscopic risk-reducing HIPEC (L-RR + HIPEC). The median length of stay was 5 days (4-6) and the major morbidity was 6% after 30 days. The 5-year DFS per tumor origin was: 96% for perforated low grade appendiceal mucinous neoplasm (LAMN II) and 68.1% for colon origin. The 5 years OS per tumor origin was: 98% for LAMN II and 83.5% for colonic origin. CONCLUSIONS: Minimally invasive CRS + HIPEC is a safe procedure for selected patients with peritoneal carcinomatosis in specialized centers. It improves perioperative results while providing satisfactory oncologic outcomes. L-RR + HIPEC represents a promising strategy that could be evaluated in patients with high risk of developing peritoneal carcinomatosis into prospective randomized trials.

Examining longitudinal markers of bladder cancer recurrence through a semiautonomous machine learning system for quantifying specimen atypia from urine cytology.

BACKGROUND: Urine cytology is generally considered the primary approach for screening for recurrence of bladder cancer. However, it is currently unclear how best to use cytological examinations for assessment and early detection of recurrence, beyond identifying a positive finding that requires more invasive methods to confirm recurrence and decide on therapeutic options. Because screening programs are frequent, and can be burdensome, finding quantitative means to reduce this burden for patients, cytopathologists, and urologists is an important endeavor and can improve both the efficiency and reliability of findings. Additionally, identifying ways to risk-stratify patients is crucial for improving quality of life while reducing the risk of future recurrence or progression of the cancer. METHODS: In this study, a computational machine learning tool, AutoParis-X, was leveraged to extract imaging features from urine cytology examinations longitudinally to study the predictive potential of urine cytology for assessing recurrence risk. This study examined how the significance of imaging predictors changes over time before and after surgery to determine which predictors and time periods are most relevant for assessing recurrence risk. RESULTS: Results indicate that imaging predictors extracted using AutoParis-X can predict recurrence as well or better than traditional cytological/histological assessments alone and that the predictiveness of these features is variable across time, with key differences in overall specimen atypia identified immediately before tumor recurrence. CONCLUSIONS: Further research will clarify how computational methods can be effectively used in high-volume screening programs to improve recurrence detection and complement traditional modes of assessment.

Open versus Closed technique for administration of heated intraperitoneal chemotherapy (HIPEC): Morbidity and Mortality outcomes from a high-volume centre.

BACKGROUND AND AIMS: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is an established treatment in selected patients with peritoneal metastases, delivered in the UK in specialist centres. HIPEC can be administered via the open coliseum technique as first described by Sugarbaker (O-HIPEC) or using a closed technique (C-HIPEC). Data comparing the safety and outcomes of these different approaches is limited. This study aims to compare morbidity and mortality rates of O-HIPEC and C-HIPEC following CRS for peritoneal metastases from colorectal cancer and appendiceal tumours. METHODS: Consecutive patients undergoing CRS with open (05/2019-04/2020) and closed (05/2020-04/2021) HIPEC were identified from a prospectively maintained database. Baseline data including primary pathology, HIPEC agent and major operative procedures were analysed using Chi-squared and Fishers exact tests to ensure comparability of groups. Primary outcomes were 30- and 60-day postoperative mortality and morbidity (Common Terminology Criteria for Adverse Events, CTCAE). Secondary outcomes were length of critical care and overall hospital stay. In addition, morbidity and mortality were compared between HIPEC agents (mitomycin and oxaliplatin/5-fluorouracil). RESULTS: 99 patients (39.3%) and 153 patients (60.7%) underwent O-HIPEC, C-HIPEC respectively. Groups were well matched for baseline demographics, pathology, and HIPEC agent. In the O-HIPEC and C-HIPEC groups respectively, the incidence of 60-day complications (CTCAE 1-4) was 40.4% vs 39.3% (chi squared 0.94) and severe complications (CTCAE 3-4) 14% vs 13% (Fisher's exact p = 1) There was no perioperative mortality but one death in each group within the follow up period. There was no difference in morbidity or mortality between those receiving mitomycin or oxaliplatin. CONCLUSION: Closed administration of HIPEC is safe with no difference in post-operative morbidity or mortality compared to open HIPEC administration. Differences in longer term oncological outcomes including overall survival and disease-free survival between open and closed HIPEC techniques are yet to be determined.

Ultrasound-guided day-case wide-bore percutaneous mucin aspiration in advanced pseudomyxoma peritonei.

AIM: To evaluate percutaneous ultrasound-guided day-case mucin aspiration in advanced pseudomyxoma peritonei (PMP) using a wide-bore drain with regards to its safety and efficacy. MATERIALS AND METHODS: All patients who underwent percutaneous mucin aspiration for PMP between 2019-2021 at a single national peritoneal tumour service were included in this study. Under local anaesthesia, a suction-enabled 28-32 F catheter was used for drainage following wire-guided track dilatation. The volume drained and difference in abdominal girth pre- and post-procedure were measured. Patients graded difficulty in breathing and abdominal discomfort pre- and post-procedure. Histology reports were reviewed. RESULTS: Sixteen patients received 56 percutaneous mucin aspirations between 2019-2021. The aetiology was a low-grade appendiceal mucinous neoplasm (LAMN) in 50% of patients. The mean amount of mucin drained was 7,320 ± 3,000ml (range 300-13,500 ml). The mean reduction in abdominal girth post-procedure was 12.2 ± 5 cm (range 0-27 cm). Only grade 1 complications were observed. CONCLUSION: Percutaneous ultrasound-guided day-case aspiration of mucin for advanced and recurrent PMP using a wide-bore drain is a safe and effective procedure. It may be used in the palliative setting or as a bridge to surgery in the very symptomatic patient or if there is a reversible contraindication to surgery.

The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: a consensus guideline.

This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.

Indications and outcomes for repeat cytoreductive surgery and heated intra-peritoneal chemotherapy in peritoneal surface malignancy.

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS: Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION: Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).

Long-term outcomes for patients with peritoneal acellular mucinosis secondary to low grade appendiceal mucinous neoplasms.

INTRODUCTION: Low grade appendiceal mucinous neoplasms (LAMN) are known to metastasise to the peritoneum resulting in pseudomyxoma peritonei (PMP). Literature suggests that the long-term outcome is dependent on the cellular grade of the peritoneal histology, less is known about the risk to patients with acellular mucinosis (AM) alone. This study aims to review long-term outcomes in patients with PMP treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC), whose peritoneal histology was AM secondary to LAMN. METHODS: Pathological and treatment outcomes were collected from a prospectively maintained database between 2005 and 2019. Data was collected on patients with LAMN and AM diagnosed following CRS/HIPEC. A single institution performed the surgery and pathology reporting, samples reported by three different pathologists. RESULTS: Of the 2079 patients with any appendiceal neoplasm referred between 2005 and 2019, 809 underwent CRS/HIPEC, 67 (8%) of those had PMP with purely AM secondary to a LAMN. In the AM group the median age was 59, 37 (55%) were female, follow up was for a median 39 (2-145) months. Inpatient mortality occurred in 1 patient (1.5%), disease specific mortality in 2 (3%), recurrence in 2 (3%) and disease progression in 1 (1.5%). CONCLUSION: This study has identified AM secondary to LAMN as a low risk group for recurrence following CRS/HIPEC compared with epithelial pathology. Given such a low rate of recurrence we would recommend low intensity surveillance post CRS/HIPEC. Agreed standardised pathological assessment is required to exclude cellular material in specimens and diagnose AM.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry.

INTRODUCTION: A laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS+HIPEC) in highly selected patients has been reported in small cohorts with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to analyse individual patient data from these international centres collected through the Peritoneal Surface Oncology Group International (PSOGI) L-CRS+HIPEC registry. METHODS: An international registry was designed through a networking database (REDCAP®). All centres performing L-CRS+HIPEC were invited through PSOGI to submit data on their cases. Patient's characteristics, postoperative outcomes and survival were analysed. RESULTS: Ten international centres contributed a total of 143 L-CRS+HIPEC patients during the study period. The most frequent indication was low grade pseudomyxoma peritonei in 79/143 (55%). Other indications were benign multicyst mesothelioma in 21/143(14%) and peritoneal metastasis from colon carcinoma in 18/143 (12,5%) and ovarian carcinoma in 13/143 (9%). The median PCI was 3 (2-5). The median length of stay was 6 (5-10) days, with 30-day major morbidity rate of 8.3% and 30-day mortality rate of 0.7%. At a median follow-up of 37 (16-64) months 126/143 patients (88.2%) were free of disease. CONCLUSIONS: Analysis of these data demonstrates that L-CRS+HIPEC is a safe and feasible procedure in highly selected patients with limited peritoneal disease when performed at experienced centres. While short to midterm outcomes are encouraging in patients with less invasive histology, longer follow up is required before recommending it for patients with more aggressive cancers with peritoneal dissemination.

Quality attributes of breads from high-quality cassava flour improved with wet gluten.

This study investigated the physical, chemical, and sensory attributes of breads produced from preheated high-quality cassava flour (PCF) and its composite with wheat flour (CWF). Wet gluten was added to the PCF and CWF for production of bread, while bread from wheat served as the control. Flour functionality was determined prior to bread production. The moisture contents of the flour samples were in the range of 12.80 to 14.21%, and PCF exhibited water absorption capacity (1.12 mL/g) comparable to that of wheat flour (WF) (1.10 mL/g). There were significant (P < 0.05) differences in color characteristics, except in L* values and breads produced from WF and CWF were similar in specific volume (3.85 to 4.21 mL/g) and firmness (2.04 to 2.64 N). Breads from WF and CWF exhibited similar crumb microstructure, though gas bubbles in the sample from PCF appeared less developed. Wheat bread had significantly (P < 0.05) higher calorie, crude protein and crude fat, but lower crude fiber, ash, and carbohydrate compared to other bread samples. Sensory evaluation showed that bread from PCF was not significantly different from 100% wheat bread in crust color, texture, and overall acceptability but was impaired in flavor. The study revealed the feasibility of bread baking from preheated cassava flour with added gluten extract. The bread produced had some quality attributes comparable to that of wheat bread. PRACTICAL APPLICATION: Bread from wheat-cassava composite flour with added gluten was similar to wheat bread in specific volume and firmness while sample from cassava flour with added gluten compared favorably well with wheat bread in crust color, texture, and overall acceptability. Findings from the study present wheat gluten extract as a viable component to be used in nonwheat flours for bread making. This could be a basis to further add value to the gluten churned out as a by-product in the wheat starch industry.

Biomarker concordance between primary colorectal cancer and its metastases.

BACKGROUND: The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) is well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review concordance between primary CRC and its metastatic sites. METHODS: A systematic review and meta-analysis of all published studies (1991-2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Studies without matched samples or using peripheral blood for biomarker analysis were excluded. FINDINGS: 61 studies including 3565 patient samples were included. Median biomarker concordance for KRAS (n = 50) was 93.7% [67-100], NRAS (n = 11) was 100% [90-100], BRAF (n = 22) was 99.4% [80-100], and PIK3CA (n = 17) was 93% [42-100]. Meta-analytic pooled discordance was 8% for KRAS (95% CI = 5-10%), 8% for BRAF (95% CI = 5-10%), 7% for PIK3CA (95% CI = 2-13%), and 28% overall (95% CI = 14-44%). The liver was the most commonly biopsied metastatic site (n = 2276), followed by lung (n = 438), lymph nodes (n = 1123), and peritoneum (n = 132). Median absolute concordance in multiple biomarkers was 81% (5-95%). INTERPRETATION: Metastatic CRC demonstrates high concordance across multiple biomarkers, suggesting that molecular testing of either the primary or liver and lung metastasis is adequate. More research on colorectal peritoneal metastases is required.

Physiological changes after colorectal surgery suggest that anastomotic leakage is an early event: a retrospective cohort study.

AIM: Anastomotic leakage (AL) is often identified 7-10 days after colorectal surgery. However, in retrospect, abnormalities may be evident much earlier. This study aims to identify the clinical time point when AL occurs. METHOD: This is a retrospective case-matched cohort comparison study, assessing patients undergoing left-sided colorectal resection between 2006 and 2015 at a specialist colorectal unit. Patients who developed AL (LEAK) were case-matched to two CONTROL patients by procedure, gender, laparoscopic modality and diverting stoma. Case note review allowed the collection of basic observation data and blood tests (leukocyte count, C-reactive protein, bilirubin, alanine transaminase, creatinine) up to postoperative day (POD) 4. The cohorts were compared, with the main outcome measure being changes in basic observation data. RESULTS: Of 554 patients, 49 developed AL. These were matched to 98 CONTROL patients. Notes were available for 105 patients (32 LEAK/73 CONTROL). Groups were similar in demographics, tumour or nodal status, preoperative radiotherapy, intra-operative air-leak integrity and drain usage. AL was detected clinically at a median of 7.5 days postoperatively. There was a significantly increased heart rate by the evening on POD 1 in LEAK patients (82.8 ± 14.2/min vs 75.1 ± 12.7/min, P = 0.0081) which persisted for the rest of the study. By POD 3, there was a significant increase in respiratory rate (18.0 ± 4.2/min vs 16.5 ± 1.3/min, P = 0.0069) and temperature (37.0 ± 0.4C vs 36.7 ± 0.3C, P = 0.0006) in LEAK patients. C-reactive protein was significantly higher in LEAK patients from POD 2 (165 ± 95 mg/l vs 121 ± 75 mg/l, P = 0.023). CONCLUSIONS: Physiological and biochemical changes associated with AL happen very early postoperatively, suggesting that AL may occur within 36 h after surgery, despite much later clinical detection.

Referral and treatment pathways for pseudomyxoma peritonei of appendiceal origin within a national treatment programme.

AIM: Pseudomyxoma peritonei (PMP) is a rare neoplasm of the appendix, which if untreated disseminates throughout the abdominal cavity and generates considerable morbidity. Since 2002 in the UK, patients with PMP have been managed via two nationally commissioned centres. We evaluated referrals and treatment pathways over time at the Manchester centre. METHOD: Data from all patients referred with suspected PMP were prospectively collected (2002-2015). Definitive treatment was cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy. Disease burden was quantified using the Peritoneal Cancer Index (PCI) (score 0-39) and complete cytoreduction (CC) defined by scores of 0/1. Novel treatment algorithms were developed for patients with low grade appendiceal mucinous neoplasm (LAMN) localized to the peri-appendiceal tissue. RESULTS: In all, 817 patients with confirmed PMP were referred increasing from 11 in 2002 to 103 in 2015. Disease burden was high with a mean PCI of 31 in the first quartile (Q1), levelling off to 15, 15, 17 thereafter (P = 0.002). The proportion of CC0/1 increased from 67% in Q1 to 77% Q2 and 74% Q3/4. Where complete cytoreduction was achieved, 5- and 10-year overall survival was 77% and 66%. The proportion of patients referred with localized LAMN increased over time reaching 25% each year since 2010 (Ptrend  < 0.0001). Two-thirds of localized LAMN now undergo laparoscopically assisted risk-reducing CRS. CONCLUSION: The establishment of a national treatment centre was associated with an initial presentation of patients with advanced disease. The programme has demonstrated a clear trend over time towards earlier referral and adoption of minimally invasive techniques for localized disease.

A perforation procedure for pulmonary atresia with intact ventricular septum : Egyptian experience and adaptations.

BACKGROUND: Pulmonary atresia with intact ventricular septum (PA-IVS) is an uncommon disorder with significant morphological heterogeneity. The use of percutaneous radiofrequency (RF)-assisted perforation of the atretic valve and subsequent balloon dilation provides a relatively easy but expensive procedure that is expected to establish ante-grade flow through the pulmonary valve in most patients. OBJECTIVES: The aim of the study was to attempt a cost reduction by using catheters and wires readily available in our catheter laboratory. METHODS: A total of 50 patients presenting with PA-IVS to Cairo University Children's Hospital (CUCH) were taken to the catheterization laboratory for radiofrequency perforation using the Baylis RFP-100 generator (Baylis Medical, Montréal, Canada) or the stiff end of a coronary wire. A hybrid approach was used in selected cases. RESULTS: The overall success rate for valve perforation was 92% (46 cases), 80% of which had successful primary perforation (40 cases). Success correlated with both tricuspid valve (TV) annulus and pulmonary valve (PV) annulus Z-scores, with P values of 0.2 and 0.5, respectively. CONCLUSION: The management of PA-IVS is complex. This is a disease that necessitates a dedicated team and working collaboration between the cardiologists and cardiac surgeons. Cost limitation is essential in developing countries and innovative ideas to reduce costs are essential, especially if comparable success can be expected.

Anastomotic leaks can be detected within 5 days following ileorectal anastomosis: a case-controlled study in patients with familial adenomatous polyposis.

AIM: To determine the earliest time point at which anastomotic leaks can be detected in patients undergoing total colectomy with primary ileorectal anastomosis for familial adenomatous polyposis. METHOD: This was a case-controlled study of 10 anastomotic leak patients vs 20 controls following laparoscopic total colectomy with ileorectal anastomosis for familial adenomatous polyposis (from 96 consecutive patients between 2006 and 2013). Panel time-series data regression was performed using a double subscript structure to include both variables. A generalized least squares multivariate approach was applied in a random effects setting to calculate correlations for observations, with anastomotic leak being the dependent variable. Univariate and multivariate regression calculations were then performed according to individual observations at each recorded time point. Time-series analysis was used to determine when a variable became significant in the leak group. RESULTS: Multivariate analysis identified a significant difference between leak and control groups in mean heart rate (P < 0.001), mean respiratory rate (P = 0.017) and mean urine output (P = 0.001). Time-point analysis showed that heart rate was significantly different between leak and control groups at postoperative day 4.25. Multivariate analysis identified a significant difference between groups in alanine transaminase (P = 0.006), bilirubin (P = 0.008), creatinine (P = 0.001), haemoglobin (P < 0.001) and urea (P = 0.007). There were no differences between groups with regard to markers of inflammation such as albumin, white blood cell count, neutrophil count and C-reactive protein. CONCLUSION: Anastomotic leaks can be detected early (within 4.5 days of surgery) through changes in physiological, blood test and observational parameters, providing an opportunity for early intervention in these patients to salvage the anastomosis.

Structural connectivity within neural ganglia: A default small-world network.

Diffusion tensor imaging (DTI) provides a unique contrast based on the restricted directionality of water movement in an anisotropic environment. As such, DTI-based tractography can be used to characterize and quantify the structural connectivity within neural tissue. Here, DTI-based connectivity within isolated abdominal ganglia of Aplysia californica (ABG) is analyzed using network theory. In addition to quantifying the regional physical proprieties of the fractional anisotropy and apparent diffusion coefficient, DTI tractography was used to probe inner-connections of local communities, yielding unweighted, undirected graphs that represent community structures. Local and global efficiency, characteristic path lengths and clustering analysis are performed on both experimental and simulated data. The relevant intensity by which these specific nodes communicate is probed through weighted clustering coefficient measurements. Both small-worldness and novel small-world metrics were used as tools to verify the small-world properties for the experimental results. The aim of this manuscript is to categorize the properties exhibited by structural networks in a model neural tissue to derive unique mean field information that quantitatively describe macroscopic connectivity. For ABG, findings demonstrate a default structural network with preferential specific small-world properties when compared to simulated lattice and random networks that are equivalent in order and degree.