Peri-operative thrombophilia in patients undergoing liver resection for colorectal metastases.

BACKGROUND: Routine chemical venous thromboembolism (VTE) prophylaxis for liver surgery remains controversial, and often delayed post-operatively due to perceived bleeding risk. This study asked whether patients undergoing hepatectomy for colorectal metastases (CRM) were at risk from VTE pre-operatively, and the impact of hepatectomy on that risk. METHODS: Single-centre prospective observational cohort study of patients undergoing open hepatectomy for CRM, comparing pre-, peri- and post-operative haemostatic variables. RESULTS: Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. There were 28 (46.7%) major resections, with median (interquartile range [IQR]) blood loss 150.0 (76.3-263.7) mls, no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high median factor VIIIC and increased thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater median drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001, 0.005, 0.001 respectively). Patients with parenchymal transection times greater than median (40 min), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65(0.93-2.70)2ddCt], versus quicker transections [0.99(0.69-1.28)2ddCt, p = 0.020]. CONCLUSIONS: Patients with CRM are prothrombotic pre-operatively, an effect exacerbated by hepatectomy, particularly longer, complex resections, suggesting chemical thromboprophylaxis be considered early in the patient pathway.

The effect of modified Pilates-based positions on pelvic floor electromyographic (EMG) activity; a pilot study.

INTRODUCTION: The evidence regarding the effect of exercise, specifically Modified Pilates (MP), on pelvic floor muscles (PFMs) is limited. We report our pilot study using the MAPLe® device to assess the effect of MP type exercises on PFM electomyographic (EMG) activity and whether PFM contraction could be performed during specific MP exercises. METHODS: The MAPLe® device was used to measure EMG activity of PFMs in healthy volunteers in different MP positions. Positions were divided into 'neutral', 'core' and 'plank' and EMG readings were taken at rest, during Valsalva and during active contraction. RESULTS: Twenty volunteers were recruited. The median age was 35 (IQR 27-39.5) years. Higher EMG readings were seen in 'core' and 'plank' positions at rest. No position inhibited a conscious contraction and positions which engaged core muscles provoked an augmented contraction. CONCLUSION: This is the first study to show that when MP positions are held for short periods of time, in asymptomatic women, the changes in PFM EMG are higher. This suggests that a stronger muscle contraction can be achieved when the core is co-contracted. Higher EMG readings were seen during 'core' and 'plank' positions; despite this, further activation with a conscious PFM contraction was still achievable.

Mode of Presentation in 1070 Patients With Perforated Epithelial Appendiceal Tumors, Predominantly with Pseudomyxoma Peritonei.

BACKGROUND: Perforated epithelial appendiceal tumors are uncommon and can give rise to pseudomyxoma peritonei. Pseudomyxoma peritonei is rare, almost always of appendiceal origin, and presents in various ways relevant to abdominal surgeons. OBJECTIVE: The aim of this study was to report the mode of presentation of pseudomyxoma peritonei of appendiceal origin in patients treated in a high-volume UK peritoneal malignancy center. DESIGN: A retrospective observational study was conducted. SETTINGS: This was a single-center study. PATIENTS: Retrospective analysis of a prospective database of consecutive patients undergoing surgery between March 1994 and December 2016 was performed. MAIN OUTCOME MEASURES: Mode of presentation was classified into 7 categories: "histological diagnosis at abdominal surgery for presumed appendicitis," "probable pseudomyxoma peritonei" based on abnormality on cross-sectional imaging (± image-guided biopsy)," "abnormal imaging (other cause suspected) and operative finding of pseudomyxoma peritonei," "diagnostic laparoscopy," "ovarian mass," "new-onset hernia," and "miscellaneous." RESULTS: Overall, 1070 patients underwent surgery (female 61%, male 39%); median age was 57. The mode of presentation was abnormality on cross-sectional imaging in 324 of 1070 patients (30.3%), histological diagnosis at emergency surgery for presumed appendicitis in 203 of 1070 patients (19%), and abnormal imaging with eventual pseudomyxoma peritonei diagnosis in 180 of 1070 patients (16.8%); 124 of 651 women (19.2%) presented with an ovarian mass. New-onset hernia was the presenting feature in 9.9%; 83 of 1070 patients (7.7%) were diagnosed at diagnostic laparoscopy, and 32 of 1070 patients (3%) were described as "miscellaneous." Overall, 775 of 1070 patients (72.4%) had complete cytoreductive surgery with 10-year survival of 63.5%. LIMITATIONS: Results are limited by the retrospective nature of the study, radiological improvements over the study period, and the number of patients who had overlapping features at presentation. CONCLUSION: Perforated appendiceal tumors present in various ways but predominantly at cross-sectional imaging or coincidentally at laparoscopy or laparotomy. All abdominal surgeons will occasionally encounter cases, often unexpectedly, and recognition and referral to a specialized unit results in excellent outcomes in most cases. See Video Abstract at http://links.lww.com/DCR/B256. MODO DE PRESENTACIÓN EN 1070 PACIENTES CON TUMORES EPITELIALES APENDICULARES PERFORADOS, PREDOMINANTEMENTE CON PSEUDOMIXOMA PERITONEAL: Los tumores epiteliales apendiculares perforados son poco frecuentes y pueden dar lugar a Pseudomyxoma peritonei. El pseudomixoma peritoneal es raro, casi siempre de origen apendicular, y se presenta de diversas formas relevantes para los cirujanos abdominales.El objetivo fue informar el modo de presentación del Pseudomixoma peritoneal de origen apendicular en pacientes tratados en un centro de malignidad peritoneal de alto volumen en el Reino Unido.Se realizó un estudio observacional retrospectivo.Este fue un estudio de centro único.Análisis retrospectivo de una base de datos prospectiva de pacientes consecutivos sometidos a cirugía entre marzo de 1994 y diciembre de 2016.El modo de presentación se clasificó en 7 categorías: "diagnóstico histológico en la cirugía abdominal por presunta apendicitis", "probable Pseudomixoma peritoneal" basado en la anormalidad en la imagen de corte transversal (biopsia guiada por imagen +/-), "imagen anormal (se sospecha otra causa) y hallazgo quirúrgico de Pseudomixoma peritoneal", "laparoscopia diagnostica", "masa ovarica", "hernia de reciente aparicion" y "varios".En total, 1070 pacientes fueron operados (mujeres 61%, hombres 39%); edad media 57. El modo de presentación fue anormalidad en la imágen transversal en 324/1070 (30.3%), el diagnóstico histológico en cirugía de emergencia por presunta apendicitis en 203/1070 (19%), la imágen anormal con eventual diagnóstico de Pseudomixoma peritoneal en 180 / 1070 (16.8%), 124/651 (19.2%) las mujeres presentaron una masa ovárica. La hernia de reciente aparición fue la característica de presentación en 9.9%, 83/1070 (7.7%) fueron diagnosticados por laparoscopia diagnóstica y 32/1070 (3%) "misceláneos". En general, 775/1070 (72,4%) se sometió a cirugía citorreductora completa con una supervivencia a 10 años del 63,5%.Una deficiencia es que los resultados están limitados por la naturaleza retrospectiva del estudio, las mejoras radiológicas a lo largo del período de estudio, y varios pacientes tenían características superpuestas en la presentación.Los tumores apendiculares perforados se presentan de varias maneras, pero predominantemente en imágenes transversales o casualmente en laparoscopia o laparotomía. Todos los cirujanos abdominales encontrarán ocasionalmente con casos, a menudo inesperados, y el reconocimiento y la derivación a una unidad especializada da lugar a excelentes resultados en la mayoría de los casos. Consulte Video Resumen en http://links.lww.com/DCR/B256.).

The pre-operative neutrophil-lymphocyte ratio predicts overall and disease-free survival following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with pseudomxyoma peritonei of appendiceal origin.

AIM: The neutrophil-lymphocyte ratio (NLR) and other inflammation-based scores have been used as a prognostic tool to predict survival in solid tumours including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic value of this marker and risk stratify PMP patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Retrospective analysis was conducted of a prospectively collected database of patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was calculated by dividing the pre-operative neutrophil count by lymphocyte count. Predicted overall survival (OS) and disease-free interval (DFI) were calculated using a Kaplan-Meier survival model. RESULTS: The study included 699 patients, stratified into four groups as defined by their NLR. Group A: 200 (28.6%) patients (NLR = 0.10-2.00), Group B: 160 (22.8%) patients (NLR = 2.10-2.78), Group C: 184 (26.3%) patients (NLR = 2.79-4.31) and Group D: 155 (22.2%) patients (NLR ≥ 4.32). The median follow-up for this cohort was 36 months. The predicted DFI was 132.2, 113.1, 84.4 and 47.9 months and the OS was 141.1, 117.6, 88.7 and 51.2 months for Groups A, B, C and D, respectively. As the NLR increases, there is a reduction in long-term survival. CONCLUSION: The pre-operative NLR is cost effective and has equivalent prognostic value to pre-operative tumour markers for patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may have a role in predicting outcomes following CRS and HIPEC for patients with PMP of appendiceal origin.

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre. METHODS: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016. RESULTS: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49 years (range 21-73 years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2-115.4) and 58.8 (47.4-70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival. CONCLUSION: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

Diagnostic and therapeutic laparoscopy in assessment and management of patients with appendiceal neoplasms.

INTRODUCTION: Radiological imaging often underestimates the extent of low volume peritoneal disease. The benefit of laparoscopy in assessing peritoneal metastases from colorectal and gastric cancer is accepted, but is inconclusive for appendiceal malignancy. We report our experience of diagnostic (DL) and therapeutic laparoscopy (TL) in patients with appendiceal tumours to determine indications and role in assessment and management. METHODS: A retrospective review of a National Peritoneal Malignancy Centre's prospectively maintained database was performed. All patients with appendiceal neoplasms who underwent DL or TL between September 2011 and January 2016 were included. The indications and outcomes of the laparoscopy, complications and interval to laparotomy were evaluated. RESULTS: Six hundred and eighty-five patients underwent surgery for appendiceal neoplasms during the study period, of which 73 (10.6%) underwent laparoscopy (50 DL, 23 TL). The main indications for DL were to clarify imaging and stage patients with high-risk histology. Indications for TL were an abnormal appendix without gross pseudomyxoma peritonei (PMP) or with low volume PMP, and concerns for fertility in the presence of PMP. DL resulted in 16 patients (32%) avoiding laparotomy because of extensive disease or no tumour found. Overall, 28 patients were assessed to have resectable disease and at laparotomy, 25/28 had complete cytoreduction with three patients unresectable. In the TL group, appendicectomy and peritoneal lavage was achieved in all four women with fertility concerns, allowing them to conceive thereafter. There were no complications. CONCLUSIONS: Patients with high-risk appendiceal neoplasm may benefit from DL, and potentially avoid unnecessary laparotomy. TL is useful in patients with low volume PMP and may aid fertility in selected patients.

Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. OBJECTIVE: The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. DESIGN: Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. SETTINGS: The study was conducted at a high-volume tertiary referral center for peritoneal malignancy. PATIENTS: Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. RESULTS: Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8-127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. LIMITATIONS: The retrospective nature limits the interpretation of these results. CONCLUSIONS: Complete cytoreduction was achieved in all of the patients, with excellent long-term survival. The incidence of peritoneal spread (57%) compared with nodal involvement (15%) supports cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as definitive treatment rather than prophylaxis in patients with high-grade appendix tumors, even without radiologically detectable disease. High-grade appendix tumors benefit from early aggressive operative management to deal with potential peritoneal and nodal spread and should be considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. See Video Abstract at http://links.lww.com/DCR/A360.

Advanced Pseudomyxoma Peritonei Requiring Gastrectomy to Achieve Complete Cytoreduction Results in Good Long-Term Oncologic Outcomes.

BACKGROUND: Optimal outcomes in pseudomyxoma peritonei (PMP) require complete macroscopic tumor removal by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Partial or complete gastrectomy may be required with ongoing debate as to the risks and benefits of gastrectomy in what is often a low-grade malignancy. METHODS: Retrospective single-center analysis of 1014 patients undergoing CRS and HIPEC for PMP of appendiceal origin. Complications and survival were compared in patients who had gastrectomy versus the nongastrectomy cohort. RESULTS: Of 1014 patients, 747 (74 %) had CRS and HIPEC with complete cytoreduction. Overall, 86 (12 %) of 747 had partial (n = 80) or total (n = 6) gastrectomy. Median age was 55 years for gastrectomy patients and 56 for nongastrectomy patients (p = 0.591). Preoperative tumor markers [carcinoembryonic antigen, carbohydrate antigen (CA) 125 and CA19-9] were elevated more frequently in the gastrectomy group compared to the nongastrectomy group [81, 61 and 81 % compared to 41 % (p = 0.001), 20 % (p = 0.001) and 39 % (p = 0.001), respectively]. The proportion of high-grade histology was similar in the two groups (gastrectomy 19 % vs. nongastrectomy 18 %, p = 0.882). Postoperative complications (Clavien-Dindo III-IV) were 31 % for the gastrectomy group and 13 % for the nongastrectomy group (p = 0.001). The 30-day postoperative mortality was 3 (0.5 %) of 661 for the nongastrectomy group and 1 (1.2 %) of 86 for the gastrectomy group (p = 0.387). Three- and 5-year overall survival were 96 and 88 % in the nongastrectomy group and 87 and 77 % in the gastrectomy group (p = 0.018). Three- and 5-year disease-free survival were 89 and 77 % in the nongastrectomy group versus 66 and 48 % in the gastrectomy group (p = 0.001). CONCLUSIONS: Gastrectomy is an essential component of complete cytoreduction in advanced PMP and was required in 12 % of patients with good long-term survival.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: an emerging treatment option for advanced goblet cell tumors of the appendix.

BACKGROUND: The debate remains whether appendiceal goblet cell cancers behave as classical carcinoid or adenocarcinoma. Treatment options are unclear and reports of outcomes are scarce. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is considered optimal treatment for peritoneal involvement of other epithelial appendiceal tumors. METHODS: Prospective cohorts of patients treated for advanced appendiceal tumors from three peritoneal malignancy centres were collected (1994-2011). All patients underwent complete CRS+HIPEC, when possible, or tumor debulking. Demographic and outcome data for patients with goblet cell cancers were compared to patients with low- or high-grade epithelial appendiceal tumors treated during the same time period. RESULTS: Details on 45 goblet cell cancer patients were compared to 708 patients with epithelial appendix lesions. In the goblet cell group, 57.8 % were female, median age was 53 years, median peritoneal cancer index (PCI) was 24, and CRS+HIPEC was achieved in 71.1 %. These details were similar in patients with low- or high-grade epithelial tumors. Lymph nodes were involved in 52 % of goblet cell patients, similar to rates in high-grade cancers, but significantly higher than in low-grade lesions (6.4 %; p < 0.001). At 3 years, overall survival (OS) was 63.4 % for goblet cell patients, intermediate between that for high-grade (40.4-52.2 %) and low-grade (80.6 %) tumors. On multivariate analysis, tumor histology, PCI, and achievement of CRS+HIPEC were independently associated with OS. CONCLUSIONS: This data supports the concept that appendiceal goblet cell cancers behave more as high-grade adenocarcinomas than as low-grade lesions. These patients have reasonable long-term survival when treated using CRS+HIPEC, and this strategy should be considered.

Right Hemicolectomy and Appendicectomy as Treatments for Goblet Cell Adenocarcinoma: A Comparative Analysis of Two Large National Databases.

INTRODUCTION: Right hemicolectomy (RHC) remains the treatment standard for goblet cell adenocarcinoma (GCA), despite limited evidence supporting survival benefit. This study aims to explore factors influencing surgical management and survival outcomes among patients treated with RHC or appendicectomy using NCRAS (UK) and SEER (USA) data. METHODS: A retrospective analysis was conducted using 998 (NCRAS) and 1703 (SEER) cases. Factors influencing procedure type were explored using logistic regression analyses. Overall survival (OS) probabilities and Kaplan-Meier (KM) plots were generated using KM analysis and the log-rank test compared survival between groups. Cox regression analyses were performed to assess hazard ratios. RESULTS: The NCRAS analysis revealed that age and regional stage disease were determinants of undergoing RHC, with all age groups showing similar odds of receiving RHC, excluding the 75+ age group. The SEER analysis revealed tumour size > 2 cm, and receipt of chemotherapy were determinants of undergoing RHC, unlike the distant stage, which was associated with appendicectomy. Surgery type was not a significant predictor of OS in both analyses. In NCRAS, age and stage were significant predictors of OS. In SEER, age, stage, and Black race were significant predictors of worse OS. CONCLUSIONS: The study shows variations in the surgical management of GCA, with limited evidence to support a widespread recommendation for RHC.

Sex Differences in the Survival of Patients with Neuroendocrine Neoplasms: A Comparative Study of Two National Databases.

BACKGROUND: Neuroendocrine neoplasms (NENs) are increasing in incidence globally. Previous analysis of the UK cancer database (National Cancer Registration and Analysis Service (NCRAS)) showed a notable female survival advantage in most tumour sites. This study aims to compare NCRAS to the Surveillance, Epidemiology, and End Results Program (SEER) to validate these results using the same statistical methods. METHODS: A total of 14,834 and 108,399 patients with NENs were extracted from NCRAS and SEER, respectively. Sixty-months survival for both males and females for each anatomical site of NENs were calculated using restricted mean survival time (RMST) and Kaplan-Meier Survival estimates. The sixty-month RMST female survival advantage (FSA) was calculated. RESULTS: FSA was similar in NCRAS and SEER. The highest FSA occurred in lung and stomach NENs. CONCLUSIONS: The data from SEER confirm the findings published by NCRAS. Female survival advantage remains unexplained.

Complete cytoreduction for pseudomyxoma peritonei is optimal but maximal tumor debulking may be beneficial in patients in whom complete tumor removal cannot be achieved.

BACKGROUND: Pseudomyxoma peritonei is a diffuse peritoneal malignancy that generally originates form a perforated appendiceal tumor. Optimal treatment requires extensive surgical resection to achieve complete cytoreduction combined with hyperthermic intraperitoneal chemotherapy. In a proportion of patients this is impossible, in particular, owing to extensive irresectable small-bowel involvement. There is ongoing debate as to the role of maximal tumor debulking in such cases. OBJECTIVE: : The aim of this study was to assess the outcomes of patients who underwent major tumor debulking for pseudomyxoma peritonei of appendiceal origin and to compare outcomes with patients who had complete cytoreduction during the same period. DESIGN: This is a retrospective study. SETTINGS: This investigation was conducted at a tertiary referral center for peritoneal surface malignancy. PATIENTS: A prospective database of 953 consecutive patients with peritoneal malignancy undergoing surgery at a UK national referral center between 1994 and 2012 was analyzed. Of these patients, 748 (78%) had surgery for pseudomyxoma peritonei of appendiceal origin. MAIN OUTCOME MEASURES: Survival, morbidity, and mortality in both groups were compared. Univariate and multivariate analyses were performed to identify negative prognostic factors in the group that underwent major tumor debulking. RESULTS: Complete cytoreductive surgery was achieved in 543/748 (73%) patients, and 205 (27%) had maximal tumor debulking. Median age was 56 years (172 (31.7%) men) in the complete cytoreductive surgery group and 59 years (108 (52.7%) men) in the maximal tumor debulking group. Overall survival at 3, 5, and 10 years was 90%, 82%, and 64% in the complete cytoreductive group and 47%, 30%, and 22% in the maximal tumor debulking group. The median survival in the maximal tumor debulking group was 32.8 months (95% CI, 24.1-41.5). LIMITATIONS: The retrospective analysis of prospective data was a limitation of this study. CONCLUSIONS: Maximal tumor debulking may help patients with pseudomyxoma peritonei in whom complete cytoreduction cannot be achieved with almost half alive at 3 years with long-term survival in some.

Operability and early outcome in 48 Irish patients with peritoneal malignancy treated by surgery and intraperitoneal chemotherapy in a specialized centre.

BACKGROUND: In selected cases of peritoneal malignancy a novel approach of complete macroscopic tumour removal by extensive surgical cytoreduction, combined with intraperitoneal chemotherapy, provides a possibility of cure. The experience with 48 consecutive Irish cases undergoing laparotomy in a specialized centre is reported. PATIENTS AND METHODS: A subset of 48 Irish patients out of a total of 120 cases with peritoneal malignancy underwent surgery between September 1999 and March 2011 in an English National referral centre. Overall 37/48 (77%) had appendiceal mucinous tumours with pseudomyxoma peritonei type syndrome. The treatment strategy involved macroscopic complete tumour removal (complete cytoreduction) combined with intra-operative, intraperitoneal chemotherapy. RESULTS: Overall 30/48 (62.5%) had complete cytoreduction, 15/48 (31.3%) had major debulking and 3 (4.2%) had laparotomy and biopsy only. The median (range) operating time in hours was 9.8 (4.8-16) in the 30 who had complete cytoreduction compared with 6.3 (4.5-11) in the 15 who had debulking (p = 0.019). There was no post-operative mortality. Overall five year survival for the complete tumour removal group was 66% compared with 12% for those only amenable to major debulking. CONCLUSION: This novel strategy of cytoreduction combined with intraperitoneal chemotherapy is effective in selected patients with peritoneal malignancy. The complex surgery is particularly effective for appendiceal tumours and provides the only possibility of cure in this challenging disease.

Development and Validation of Nomograms to Predict Survival in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin.

Importance: Pseudomyxoma peritoni, a rare condition characterized by mucinous ascites and peritoneal deposits, mainly originates from a ruptured mucinous appendix tumor and is considered an indolent disease but can progress and become fatal. Optimal treatment to improve cure and survival rates involves complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Accurate predictive models are useful in supporting and informing treatment strategies and stratifying patient follow-up. Objective: To evaluate the prognostic significance of clinically important variables and generate validated nomograms to predict overall (OS) and disease-free survival (DFS) following CCRS and hyperthermic intraperitoneal HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin. Design, Setting, and Participants: This retrospective study used prospectively collected data on patients who had cytoreductive surgery (CRS) and HIPEC in a single institution between 1994 and 2018. The cohort was randomly allocated into development (70%) and validation (30%) sets. Univariate and multivariate analyses were performed with Cox proportional hazards regression. Main Outcomes and Measures: A prediction model was developed with significant prognostic factors identified by multivariate analysis. The model's prognostic performance was evaluated with the concordance index (C index). The nomogram was calibrated by comparing the predicted and observed probabilities. Results: Of 2637 CRS and HIPEC operations, 1102 patients (female, 64.4%; median age [IQR], 57.0 [48.0-66.0] years) (41.8%) had CCRS for PMP of appendiceal origin. Elevated tumor markers, peritoneal carcinomatosis index, gastrectomy, and tumor grade were independent predictive factors for DFS. Gender, age, elevated tumor makers, peritoneal carcinomatosis index, and tumor grade influenced OS. The nomograms were generated with respective prognostic factors. The nomograms showed good performance in predicting survival. Median OS of the cohort was 16.5 years (95% CI, 13.7-19.2) with a 5-year probability of survival of 80.2%. The median DFS was 10.3 years (95% CI, 7.2- 13.3) and the 5-year probability of recurrence-free survival was 60.5%. Conclusions and Relevance: Clinically important independent predictors for survival and recurrence were selected to develop the nomograms for OS and DFS. These 2 nomograms are user friendly and useful tools for patient management with clinical trial design applications.

Sex Differences in Survival from Neuroendocrine Neoplasia in England 2012-2018: A Retrospective, Population-Based Study.

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England's National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73-5.90) to 10.26 (6.6-14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

Dukes C colorectal cancer: is the metastatic lymph node ratio important?

PURPOSE: Although the regional lymph node status is essential for staging of colorectal cancer, the importance of the total number of collected nodes remains controversial. Our aim was to examine the impact of the metastatic lymph node ratio (LNR) on the survival of patients with Dukes C colorectal cancer. METHODS: All patients with Dukes C histology were selected from a prospectively collected database of all colorectal cancers resected between 1997 and 2007 at our institution. Demographic, histopathological and adjuvant treatment data were collected. The total number of positive lymph nodes was divided by the total number of lymph nodes examined to calculate the LNR. Patients were categorised into LNR groups 1 to 5 according to cut-off points: ≤0.1, 0.21, 0.36, 0.6 and ≥0.61. Survival from the date of operation was calculated using Kaplan-Meier estimates. Multivariate analysis was performed to identify those factors influencing survival. RESULTS: Of 1,098 patients who underwent colorectal cancer resections, 41% were staged as Dukes C. Sixty-four percent of patients received chemotherapy. The median number of lymph nodes harvested and positive for tumour were 11 (range 1-52) and 4 (range 1-28), respectively. In patients who received chemotherapy, 5-year survival was 69.3% for LNR 1 and 23.6% for LNR 5. When no chemotherapy was given, the 5-year survival was 43.1% for LNR 1 and 8.7% for LNR 5. CONCLUSIONS: Current evaluation of positive lymph nodes may not accurately stage Dukes C colorectal cancer. The assessment of the LNR is a useful prognostic method in this heterogenous group of patients.

Extrahepatic versus intrahepatic hilar control for right hepatectomy: an updated experience.

BACKGROUND: Inflow control prior to transection for right hepatectomy may be achieved either by dissection and ligation of the individual hilar structures outside of the liver (EHD) or by mass stapling of the inflow structures within the hepatic parenchyma. Our preference is for the anterior intrahepatic approach (AIA) with mass stapling, in order to minimise the risk of inadvertent injury of the left-sided inflow and to preserve as much parenchyma as possible. In this paper, we present our experience over the last 10 years and compare it with results from the EHD technique. METHODS: Data for a 10-year period from 2000 to 2010 were extracted retrospectively from a prospectively collected database. Results in each group were measured by a combination of technical and oncological outcomes. Groups were compared by way of descriptive statistics and differences tested for significance by appropriate statistical means. RESULTS: 411 right hepatectomies were performed for colorectal metastases. Of these, 242 were by AIA and 169 by EHD. Both groups were well matched in demographic terms and according to disease burden, although more extended resections were performed in the EHD group. Operative duration (433 vs. 350 min), blood loss (420 vs. 348 ml) and incidence of bile leaks (4 vs. 2) were all lower in the AIA group. All other technical and oncological outcomes were equivalent. CONCLUSION: The AIA approach provides equivalent morbidity, mortality and oncological outcome to the EHD dissection technique and may confer the benefits of being safer and providing greater scope to preserve hepatic parenchyma.

Detailed liver-specific imaging prior to pre-operative chemotherapy for colorectal liver metastases reduces intra-hepatic recurrence and the need for a repeat hepatectomy.

BACKGROUND: Neoadjuvant chemotherapy for colorectal liver metastases (CRLM) reduces the accuracy of liver imaging which may understage patients pre-operatively. Retrospective review of a prospective database to determine whether liver-specific magnetic resonance imaging (MRI) prior to pre-operative chemotherapy affects intra-hepatic recurrence and long-term outcome after hepatectomy. PATIENTS AND METHODS: Between 2003 and 2009, 242 patients with CRLM underwent a hepatectomy after ≥3 cycles of oxaliplatin or irinotecan-based chemotherapy. All had a liver-specific MRI immediately pre-operatively. The outcome of patients who had a liver-specific MRI prior to chemotherapy (PCI group, n= 92) was compared with those who did not (non-PCI group, n= 150). RESULTS: A liver-specific MRI pre-chemotherapy changed the staging in 56% of patients. At a median (range) follow-up of 55 (6-94) months, there was a higher incidence of intra-hepatic recurrence at a new site in the non-PCI group (65% vs. 48% in the PCI group, P= 0.041) and an increased rate of recurrence in patients with the same number of lesions pre- and post-chemotherapy [hazard ratio (HR) 2.02, 1:10-3.37, P= 0.024]. The non-PCI group underwent more repeat hepatectomies than the PCI group (24.7% vs. 13%, P= 0.034), achieving similar long-term survival. CONCLUSIONS: A liver-specific MRI prior to chemotherapy reduces intra-hepatic recurrence and avoids a repeat hepatectomy.

Fear of cancer recurrence in peritoneal malignancy patients following complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): an observational study protocol.

INTRODUCTION: Fear of cancer recurrence (FCR) is correlated with higher depression levels, worse quality of life and increased utilisation of healthcare services. There is no research on FCR in peritoneal malignancy (PM) patients-a rare type of abdominal cancer. This study aims to explore the prevalence, trajectory, demographic and clinical characteristics that are associated with FCR and its relationship with quality of life in PM patients. METHODS AND ANALYSIS: This is a cross-sectional study. Validated measures will be used to collect data on the levels of FCR (Fear of Cancer Recurrence Inventory-Short Form) and quality of life (36-Item Short-Form Health Survey) of PM patients who have had surgery in the last 5 years at the Peritoneal Malignancy Institute in Basingstoke Hospital (minimum N=260). Descriptive statistics, Pearson χ2 tests and correlational tests will be used to analyse the data. ETHICS AND DISSEMINATION: Ethical approval was obtained from the HRA and Health and Care Research Wales (HCRW). The results of this study will be shared with the participants of this study, presented at conferences and PM patients' days in the form of presentations or posters, and published in a scientific journal. DISCUSSION: The results of this exploratory study will be used to inform a multicentre observational study to explore the effect of FCR on PM patients' mental health (depression and anxiety), quality of life and healthcare utilisation which will inform a multicentre randomised controlled trial to assess the effectiveness of using evidenced-based interventions to lower FCR in PM patients.

Seroprevalence to adeno-associated virus type 6 in people with hemophilia B from a UK adult cohort.

Background: Gene therapy shows promise as a potential "cure" for hemophilia A and B. Adeno-associated virus (AAV) vectors are the leading platform to deliver modified genetic code of factor VIII or IX to the liver effecting endogenous production. Patient exposure to wild-type AAV leads to the formation of neutralizing factors, which can prevent successful transduction. It is thus important to establish the seroprevalence of the AAV serotypes in people with hemophilia to aid prediction of successful gene transfer. The seroprevalence of AAV6 in UK people with hemophilia B is not yet reported. Objectives: We studied the prevalence of anti-AAV6 neutralizing factors in UK people with hemophilia B (n = 49). We collected data on people's hepatitis C exposure and treatment with plasma-derived factor IX (FIX) to identify if there was correlation with AAV6 exposure. Methods: Serum samples and patient data were collected from 49 people with hemophilia B registered at UK hemophilia comprehensive care centers. The samples were tested for neutralizing factors to AAV6 using a cell-based transduction inhibition assay. Results: Thirty-one percent of patients had serum neutralization against AAV6. There was no correlation between AAV6 seropositivity and previous treatment with plasma-derived FIX products or hepatitis C exposure. Conclusion: Based on limited data, there is no evidence of association between the presence of AAV6 neutralizing factors in people with hemophilia B and exposure to contaminated plasma derivatives. The frequency of AAV6 neutralizing factors in our hemophilia B cohort is similar to UK people with hemophilia A and non-hemophilia populations.