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There is ongoing controversy concerning the indications and benefits of early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with pseudomyxoma peritonei. The main contra-indications preventing wide-spread use of EPIC are reports of an increased postoperative morbidity with no clear evidence of oncological benefit. This paper reports a single high volume institution experience with EPIC over a 25-year period.This is a retrospective analysis of a single institution prospective database of patients undergoing CRS and HIPEC for appendiceal neoplasms from March 1994 to December 2019. Sub group analysis of patients who received EPIC with 5FU 15mg/m2 is reported and compared with patients who did not receive EPIC.Overall, 632/1564 (40%) received EPIC. Patients who received EPIC were younger (median age 55 (IQR 45-63) vs 59 (IQR 50-68)) with similar extent of disease to those who did not have EPIC. EPIC was more likely to be given after complete cytoreduction. The use of EPIC has reduced over the last 25 years from 78% of patients initially to 16% most recently. Length of stay in critical care and total hospital stay were longer in patients who received EPIC but surprisingly major morbidity (Clavien Dindo Grade3) was lower (p = 0.001).EPIC can be administered safely following CRS and HIPEC for PMP of appendix origin when used in carefully selected patients in a high-volume centre. Randomised trials are needed to establish impact on disease free and overall survival to optimize selection criteria.

Objectives The Peritoneal Surface Oncology Group International (PSOGI) consensus subdivided pseudomyxoma peritonei (PMP) into four groups according to histopathological features. The aim of this paper is to report survival outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from a national referral centre and to correlate the PSOGI classification with survival. Methods A retrospective study of a prospectively maintained database was performed. Consecutive patients treated with CRS + HIPEC for PMP of appendiceal origin were included (September-2013 to December-2021). Pathological features of the peritoneal disease were used to classify patients into the four groups proposed by PSOGI. Survival analysis was performed to evaluate the correlation of pathology on overall survival (OS) and disease-free survival (DFS). Results Overall, 104 patients were identified; 29.6 % were reclassified as acellular mucin (AM), 43.9 % as low-grade mucinous carcinoma peritonei (LGMCP), 22.4 % as high-grade MCP (HGMCP) and 4.1 % as HGMCP with signet ring cells (HGMCP-SRC). Median PCI and rate of optimal cytoreduction were 19 and 82.7 %, respectively. Median OS and DFS were not reached, 5-year OS and DFS were 88.6(SD 0.04) % and 61.6(SD 0.06) %, respectively. Log-Rank test revealed significant differences in terms of OS and DFS across the different histological subgroups (p Conclusions Survival outcomes after CRS + HIPEC for PMP are excellent. The PSOGI pathological classification correlates with OS and DFS, but differences were not significant at multivariate analysis when adjusted for other prognostic factors.

Deciphering the dominant controls on groundwater-surface water-climate connections is critical to understanding water cycles in arid environments, yet persistent uncertainties remain. The growing demand for critical minerals such as lithium and associated water demands has amplified the urgency to address these unknowns. We present an integrated hydrological analysis of the Dry Andes utilizing a uniquely large and comprehensive set of tracer data (3H, 18O/2H) and physical observations. We find two strongly decoupled hydrological systems which interact only under specific hydrogeological conditions where preferential conduits have developed. These conduits which efficiently transport contemporary water (wks to yrs old) in the system control the interplay between modern hydroclimate variations and groundwater aquifers. Contemporary waters account for a small portion of basin budgets but are critical to sustaining surface waters, as a result, these systems are sensitive to short-term climate and anthropogenic perturbations. This framework describes a new understanding of dominant controls on natural water cycles intrinsic to these arid mountain systems.

BACKGROUND: Selection of patients for preoperative treatment in rectal cancer is controversial. The new 2020 National Institute for Health and Care Excellence (NICE) guidelines, consistent with the National Comprehensive Cancer Network guidelines, recommend preoperative radiotherapy for all patients except for those with radiologically staged T1-T2, N0 tumours. We aimed to assess outcomes in non-irradiated patients with rectal cancer and to stratify results on the basis of NICE criteria, compared with known MRI prognostic factors now omitted by NICE. METHODS: For this retrospective cohort study, we identified patients undergoing primary resectional surgery for rectal cancer, without preoperative radiotherapy, at Basingstoke Hospital (Basingstoke, UK) between Jan 1, 2011, and Dec 31, 2016, and at St Marks Hospital (London, UK) between Jan 1, 2007, and Dec 31, 2017. Patients with MRI-detected extramural venous invasion, MRI-detected tumour deposits, and MRI-detected circumferential resection margin involvement were categorised as MRI high-risk for recurrence (local or distant), and their outcomes (disease-free survival, overall survival, and recurrence) were compared with patients defined as high-risk according to NICE criteria (MRI-detected T3+ or MRI-detected N+ status). Kaplan-Meier and Cox proportional hazards analyses were used to compare the groups. FINDINGS: 378 patients were evaluated, with a median of 66 months (IQR 44-95) of follow up. 22 (6%) of 378 patients had local recurrence and 68 (18%) of 378 patients had distant recurrence. 248 (66%) of 378 were classified as high-risk according to NICE criteria, compared with 121 (32%) of 378 according to MRI criteria. On Kaplan-Meier analysis, NICE high-risk patients had poorer 5-year disease-free survival compared with NICE low-risk patients (76% [95% CI 70-81] vs 87% [80-92]; hazard ratio [HR] 1·91 [95% CI 1·20-3·03]; p=0·0051) but not 5-year overall survival (80% [74-84] vs 88% [81-92]; 1·55 [0·94-2·53]; p=0·077). MRI criteria separated patients into high-risk versus low-risk groups that predicted 5-year disease-free survival (66% [95% CI 57-74] vs 88% [83-91]; HR 3·01 [95% CI 2·02-4·47]; p

The concept of significant polyps and early colorectal cancer encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. The assessment and management of these lesions is contentious and increasingly important due to the significant risk of over- or undertreatment.Following the recommendations of the Significant Polyps and Early Colorectal Cancer National Program, we implemented a dedicated multidisciplinary team meeting and analyzed the influence on patient outcomes.This was a retrospective study using a prospectively collected database of patients discussed at the dedicated multidisciplinary team meeting.This study was conducted in a single tertiary-care center.Consecutive patients with significant polyps and early colorectal cancer were identified either through the Bowel Cancer Screening Program or colonoscopy for symptomatic patients.Proportions of patients who had organ preservation, and secondary treatment and recurrence rate served as outcome measures.Overall, 135 patients discussed at the dedicated multidisciplinary team meeting were included, with a median age of 71 years. Median size of the lesions was 25 mm, and 39% were in the rectum. Patients were discussed either after the lesion was removed during the initial colonoscopy (n = 38), of whom 16 (42%) had unexpected cancer, or had no initial treatment with subsequent case review (n = 97). Of these 97 patients, 46 underwent endoscopic excision (26% cancer), 20 trans-anal excision (10% cancer), 23 primary surgical resection (35% cancer), and 8 had no treatment. In 104 (82%) patients, organ preservation was achieved. Secondary surgery was required in 7 of 104 (6.7%) patients after local excision due to radical treatment of high-risk T1 lesions, local recurrence, or patients' decisions. The cumulative hazard estimates for recurrence after a median follow-up of 18.5 months was less than 10% for both benign and malignant lesions.This study was limited by its relatively small sample size and single-center setting.A dedicated multidisciplinary team meeting improved the management of significant polyps and early colorectal cancer, safely refining organ preservation for patients, with low recurrence rates. See Video Abstract at http://links.lww.com/DCR/B826.ANTECEDENTES:El concepto de pólipos complejos y cáncer colorrectal temprano abarca engloba pólipos avanzados que no es posible la reseccion endoscopica rutinaria, o aquellos en los que no se puede excluir malignidad. La evaluación y el manejo de estas lesiones es controversial y cada vez más importante debido al riesgo significativo de ser tratadas o no.OBJETIVO:Siguiendo las recomendaciones del Programa Nacional de Pólipos Complejos y Cáncer Colorrectal Temprano, implementamos reuniónes del equipo multidisciplinario especializado y analizamos el impacto en los resultados de los pacientes.DISEÑO:Estudio retrospectivo sobre una base de datos recopilada prospectivamente de los pacientes discutidos en la reunión del equipo multidisciplinario especializado.AJUSTE:Este estudio se realizó en un centro de atención terciaria.PACIENTES:Pacientes consecutivos con pólipos complejos y cáncer colorrectal temprano identificado a través del Programa de detección de cáncer intestinal o colonoscopia para pacientes sintomáticos.PRINCIPALES MEDIDAS DE RESULTADO:Proporción de pacientes que tuvieron preservación de órganos, tratamiento secundario y tasa de recurrencia.RESULTADOS:En total, se incluyeron 135 pacientes discutidos en la reunión del equipo multidisciplinario especializado dedicada, con una media de edad de 71 años. El tamaño medio de las lesiones fue de 25 mm y el 39% estaban en el recto. Se discutio de los pacientes después de que se resecara la lesión durante la colonoscopia inicial [n = 38, de los cuales 16 (42%) tenían un cáncer imprevisto] o no recibieron tratamiento de inicio, con revisión posterior del caso (n = 97). De estos, 46/97 fueron sometidos a resección endoscópica (26% cáncer), 20/97 resección transanal (10% cáncer), 23/97 resección quirúrgica primaria (35% cáncer) y 8/97 no recibieron tratamiento. En 104 (82%) pacientes, se logró la preservación de órgano. Cirugía secundaria fue requeria en 7/104 (6,7%) pacientes después de la resección local debido a tratamiento radical de lesiones T1 de alto riesgo, recidiva local o decisión del paciente. Las estimaciones de riesgo acumulativo de recurrencia después de una media de seguimiento de 18,5 meses fue inferior al 10% tanto para las lesiones benignas como para las malignas.LIMITACIONES:Tamaño de muestra relativamente pequeño y entorno de un solo centro.CONCLUSIONES:La Reunion del equipo multidisciplinario especializado mejoró el manejo de los pólipos complejos y cáncer colorrectal temprano, refinando de manera segura la preservación de órganos para los pacientes, con bajas tasas de recurrencia. Consulte Video Resumen en http://links.lww.com/DCR/B826. (Traducción- Dr. Francisco M. Abarca-Rendon).

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. Materials and methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated. (c) 2021 Published by Elsevier Ltd.

To report our experience with the combination of radical surgical excision and intestinal transplantation in patients with recurrent Pseudomyxoma Peritonei (PMP) not amenable to further Cytoreductive surgery (CRS).CRS and heated intra-operative peritoneal chemotherapy is an effective treatment for many patients with PMP. In patients with extensive small bowel involvement, or non-resectable recurrence, disease progression results in small bowel obstruction, nutritional failure, fistulation, with resulting abdominal wall failure.Between 2013-2022, patients with PMP who had nutritional failure and were not suitable for further CRS underwent radical debulking and intestinal transplantation at our centre.15 patients underwent radical exenteration of affected intra-abdominal organs, and transplantation adapted according to the individual case. Eight patients had isolated small bowel transplantation and seven patients underwent modified multi-visceral transplantation. Additionally, in seven patients with significant abdominal wall tumour involvement, a full thickness vascularized abdominal wall transplant was performed. Two of the 15 patients died within 90 days due to surgically related complications. Actuarial 1-year and 5-year patient survivals were 79% and 55% respectively. The majority of the patients had significant improvement in quality of life after transplantation. Progression/recurrence of disease was detected in 91% of patients followed up for more than six months.Intestinal/multi-visceral transplantation enables a more radical approach to the management of PMP than can be achieved with conventional surgical methods and is suitable for patients for whom there is no conventional surgical option. This complex surgical intervention requires combined skills of both peritoneal malignancy and transplant teams.

Introduction The incidence and patterns of local recurrence of colon cancer are not well reported. The aim of this study was to investigate the contemporary rates and patterns of local recurrence after sigmoid cancer resection, comparing pre and post-operative biomarkers in predicting local disease recurrence. Materials and methods A multi-centre, retrospective analysis of 414 patients undergoing resectional surgery for sigmoid colon cancer was conducted. Multivariable Cox Proportional Hazard models were created to identify variables associated with local disease recurrence. Patterns of recurrence and prognostic significance of pre and post-operative variables were identified. Results In 414 patients, the local recurrence rate was 12.6%. The R1/R2 rate was 2.4%. Local recurrence occurred most commonly within the peri-anastomotic region (50%), followed by the peritoneum (33%). On multivariate analysis, local recurrence was predicted by pathological T stage (HR 1.15) and R1 resection (HR 2.95), but also computerised tomography (CT) identified tumour deposits (HR 2.40) and local peritoneal infiltration (2.70). Conclusions Contemporary local recurrence rates for sigmoid cancer are high at 12.6%. Outcomes may be improved if local recurrence is reduced at the most common sites such as the peri-anastomotic area or peritoneum. Extra-nodal CT-imaging biomarkers of local peritoneal infiltration and tumour deposits were prognostically significant on multivariate analysis in addition to pathology staging variables.

Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non-alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied.A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub-study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non-alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri-operatively, with an ALT 5 defined as acute liver injury (ALI). Mann-Whitney U test or Fisher's exact test was utilized and the Kaplan-Meier method for survival.42% (n = 234/559) of patients had CT-defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non-HS patients (p 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non-HS cohorts (11%). Operative complication severity was similar in both cohorts. 5-yr survival was 53% (HS) vs 50% (p = 0.890).This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.

The management of colorectal peritoneal metastases continues to be a challenge but recent evidence suggests cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival. Uncertainty about the relationship between age and tumour biology makes patient selection challenging particularly when reported procedure related morbidity is high and impact on survival outcomes unknown. The UK and Ireland Colorectal Peritoneal Metastases Registry was reviewed to assess the influence of age on efficacy of CRS and HIPEC.A review of outcomes from the UK and Ireland Colorectal Peritoneal Metastases Registry was performed. Data from 2000 to 2021 were included from five centres in the UK and Ireland, and the cohort were sub-divided into three age groups;45 years, 45-65 years and65 years old. Primarily, we examined post-operative morbidity and survival outcomes across the three age groups. In addition, we examined the impact that the completeness of cytoreduction, nodal status, or adverse pathological features had on long-term survival.During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were45 years, 549 patients(48.2%) aged 45-65 years and 387 patients(34%)65 years. Overall, median length of surgery (CRS and HIPEC), median PCI score and rate of HIPEC administration was similar in all three groups, as was overall rates of major morbidity and/or mortality. Complete cytoreduction rates (CC0) were similar across the three cohorts; 77%, 80.6% and 81%, respectively. Median overall survival for all patients was 38 months following complete cytoreduction.Age did not appear to influence morbidity or long-term survival following CRS and HIPEC. When complete cytoreduction is achieved survival outcomes are good. The addition of HIPEC can be performed safely and may reduce local recurrence within the peritoneum.

Aims There is epidemiological evidence suggesting that the incidence of appendicular neoplasms is increasing. The purpose of this study is to assess the incidence of appendix neoplasms in patients undergoing colorectal cancer resection in a unit where standard of care is appendectomy, with consent, when left colon or rectal cancer resection is performed. Methods This is a retrospective single-centre study on a prospectively collected data base of 718 consecutive patients undergoing colorectal cancer resection between January 2015 and June 2021. The primary outcome was the proportion of histologically abnormal appendix specimens at incidental appendectomy. Secondary outcome was complications from incidental appendectomy. Results Overall, 222/718(31%) patients had previous appendectomy. The remaining 496 comprised 169/496 (34%) who had a right-/extended-right hemicolectomy or sub-total colectomy which incorporates appendectomy, and 327/496(66%) who had left-sided resection (left-hemicolectomy, anterior resection or abdomino-perineal excision) with incidental appendectomy. At definitive histology, 454(92%) had a normal appendix, 13(2.6%) had inflammatory appendix pathology, 17(3.4%) had a hyperplastic/serrated polyp and 12(2.4%) had an appendix neoplasm, which included 5 carcinoids and 7 low-grade appendiceal mucinous neoplasms (LAMN). In the 327 patients who had incidental appendectomy, 7(2.1%) had a neoplasm (4 carcinoid and 3 LAMN). There were no complications attributable to appendectomy. Conclusion Patients undergoing left sided colorectal cancer surgery with an appendix in situ should be counselled on the benefits of co-incidental appendectomy to treat the small proportion with synchronous neoplasms and inflammation and eradicate the risk of metachronous appendicitis or a subsequent appendix tumour.

The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics.Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier.A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS ( P0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS ( P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively ( P =0.03). In-hospital mortality, respectively, was 1% versus 2% ( P =0.9), and Clavien DindoIII 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42).Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.

The European and American colonoscopy guidelines recommend mandatory photodocumentation of caecal intubation to allow retrospective analysis and improve outcomes. We aim to demonstrate whether photodocumentation of caecal intubation improves colonoscopy outcomes. We extracted images and procedural data from 317 consecutive colonoscopies. Images were anonymised and reviewed by four expert reviewers who scored their certainty that caecal intubation was achieved. Statistical analysis correlated adequately and inadequately photodocumented cases with polyp detection rate (PDR) and adenoma detection rate (ADR). The patients’ mean age was 59.4 years and 52% were male. Eighty-one percent were performed by consultant endoscopists and 19% by specialist registrar. Sixty-five percent of these procedures were performed by gastroenterologists and 35% by surgical endoscopists. Fifty-three percent were deemed to have adequately demonstrated photographic evidence of caecal intubation. Statistical analysis comparing adequately and inadequately photodocumented cases: the PDR of procedures with confirmed caecal intubation was greater than procedures without photographic evidence (40% vs 34%). Similarly, the ADR of photographically confirmed cases was greater than that of inadequately photodocumented cases (25% vs 18%). The number of images taken per procedure positively correlated with photographic documentation of caecal intubation. While failing to reach statistical significance, there was a nominal difference in ADR and PDR demonstrated between the two groups, and with predominantly positive confidence intervals, this might suggest that a larger sample size could result in significance in favour of photodocumentation of caecal intubation. Future studies would be warranted. However, endoscopists that take more images were more likely to have proven caecal intubation.

Background Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

OBJECTIVE The aim of this study was to propose and test a novel adverse pathology classification in AEG. BACKGROUND Recent scientific advances show genomic and molecular concordance across all AEG types, suggesting a rationale for a biologic classification. We tested a 3-dimension adverse pathology classification across the entire junction and per Siewert anatomic subtype. METHODS Of 1625 patients with AEG, 650 underwent radical surgery, 55% post-neoadjuvant therapy (NeoT). Adverse features defined a priori were poor differentiation (PD), lymphatic invasion (LI), vascular invasion (VI), and perineural invasion (PN), with 3 groupings: 0 (no adverse feature), 1 to 2, and 3 to 4. Multivariable logistic and Cox proportional hazards regression were applied. RESULTS For adverse pathology, 31%, 46%, and 23% had 0, 1 to 2, and 3 to 4, respectively. Fifty percent of cases were AEG I, 25% AEG II, and 25% AEG III. Median survival was not reached, 49 and 17 months for 0, 1 to 2, and 3 to 4 adverse pathology, respectively (P < 0.001), and 76, 51, and 34 months for AEG I, II, and III, respectively (P < 0.001); AEG I was significantly (P< 0.001) associated with lower c (y)pT and c (y)pN stages, and LI, VI, PN, and PD (poor vs other). The pathology model was significant for survival along with (y)pT and (y)pN, and predicted response to chemotherapy and chemoradiation irrespective of anatomic subtype (P < 0.001). CONCLUSION A novel classification using standard pathology as proxy for poor biology is associated with survival and response to therapy. This effect is observed across the entire AEG spectrum, highlighting how biology should be aligned with anatomy in the modern paradigm of AEG management and design of clinical trials.

This study aimed to describe short- and medium-term longitudinal quality-of-life (QoL) outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Consecutive patients undergoing CRS and HIPEC were recruited. The primary outcome was QoL, measured using the short-form 36 questionnaire and expressed as a physical component score (PCS) and a mental component score (MCS), with higher scores representing better QoL. Data were collected prospectively at baseline and before discharge, then 3, 6, and 12 months postoperatively. Trajectories of the PCS and MCS were described for the study period and grouped according to a peritoneal carcinomatosis index (PCI) (≤ 12 vs. ≥ 13) and a completeness of cytoreduction (CC) score (CC0 vs. CC1–CC3). Overall, 117 patients underwent CRS and HIPEC and 115 (98.3%) of the 117 patients participated in the study. The main primary pathology was colorectal in 52 (45%) of the 115 patients and appendiceal in 27 (23.5%) of the 115 patients. The median baseline PCS [48.16; interquartile range (IQR), 38.6–54.9] had decreased at pre-discharge (35.34; IQR, 28.7–41.8), then increased slightly at 3 months (42.54; IQR, 37.6–51.6), before returning to baseline within 6 months (48.35; IQR, 39.1–52.5) and remaining unchanged 12 months after surgery (48.55; IQR, 40.8–55.5). The MCS remained unchanged during the study period. The patients with a PCI of 13 or higher had worse PCS and MCS during the postoperative period than the patients with a PCI of 12 or lower. The CRS and HIPEC procedures impaired PCS, with scores returning to baseline within 6 months after surgery, whereas MCS remained unchanged. The patients with a lower PCI had better postoperative QoL outcomes. For patients with peritoneal malignancy, CRS and HIPEC can be performed with acceptable short- to medium-term QoL outcomes.

Visceral obesity, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) represent risk factors for esophageal adenocarcinoma (EAC). The prevalence of NAFLD, and its impact on the hepatic response to esophageal cancer surgery, has never been systematically evaluated, and was the focus of this study. Methods Consecutive patients (n = 547) treated with curative intent for esophageal cancer from 2007–2017 were studied. In an unselected subgroup (n = 138), liver biopsies were collected intraoperatively and assessed for NAFLD, defined as ≥5% macrovesicular steatosis. Postoperative complications were recorded prospectively, including Clavien-Dindo grade (CD) and comprehensive complications index (CCI). Liver function tests were monitored in the first postoperative week, with hepatocellular dysfunction defined as a transaminase rise ≥3-times the upper limit of normal. Multivariable logistic and Cox proportional hazards regression were utilised to determine independent predictors of operative and oncologic outcome. The study was registered on clinicaltrials.gov (NCT04152044). Results NAFLD was evident in 62 patients (47.7%) who had biopsies, with a mean (SD) score of 10.1(9.3)%. NAFLD was associated with metabolic syndrome (41.9 vs 25%, P = 0.04), obesity (44.1 vs 11.9%, P Conclusion A marker of metabolic dysregulation in obesity-associated carcinogenesis, NAFLD is prevalent among patients with esophageal cancer. Liver dysfunction post esophagectomy is common, and although temporary, is associated with worse oncologic outcomes. Baseline NAFLD did not incur an adverse long-term oncologic outcome.

The peritoneal cavity is the second commonest site of mesothelioma after the pleural cavity. There are five histological types of peritoneal mesothelioma with variable symptomatology, clinical presentation and prognosis. Cystic mesothelioma is a borderline malignant neoplasm with a favourable prognosis, well-differentiated papillary mesothelioma is generally a low-grade malignancy, and all other varieties such as epithelioid, sarcomatoid and biphasic mesothelioma are highly malignant types of peritoneal mesothelioma with poor prognosis. Malignant peritoneal mesothelioma was considered inevitably fatal prior to the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in selected cases where long-term survival and cure could be achieved. However, the survival benefits following CRS and HIPEC mainly depend on completeness of cytoreduction, which come at the cost of high morbidity and potential mortality. Using the acronym ‘PAUSE’, we aimed at describing the key imaging findings that impact surgical decision-making in patients with peritoneal mesothelioma. PAUSE stands for peritoneal cancer index, ascites and abdominal wall disease, unfavourable sites of involvement, small bowel and mesenteric disease and extraperitoneal disease. Reporting components of ‘PAUSE’ is crucial for patient selection. Despite limitations of CT in accurately depicting the volume of disease, describing findings in terms of PAUSE plays an important role in excluding patients who might not benefit from CRS and HIPEC.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery (CRS) for peritoneal metastases (PM). Apart from the Peritoneal Cancer Index (PCI), completeness of cytoreduction and tumour grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy (SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilisation of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilisation of these factors in clinical decision making and the extent of peritoneal resection performed for different tumours. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors.Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy-proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a prespecified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumour nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centres will be studied.Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27 July, 2020) and Lyon-Sud ethics committee (A15-128).Trial registration numberCTRI/2020/09/027709; Pre-results.

The coronavirus disease 19 (COVID-19) pandemic has become the focus of attention worldwide, and herein we seek to highlight the potential problem of ‘collateral mortality’ from delayed or deferred treatments in patients with cancer. We propose potential solutions to ensure continuity of care in the field of surgical oncology.

Background Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. Objectives To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. Methods FORMA‐05 was an off‐label single‐center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0‐4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4‐point scales and adjudicated by an independent committee. Results One hundred percent of patients receiving HFC (95% confidence interval: 83.9‐100.0, n = 21) or cryoprecipitate (84.6‐100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P = .0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line ...

Mini: A radiological, anatomic distinction between the rectum and sigmoid colon was agreed by consensus of international experts in rectal cancer using the Delphi Technique. Use of this landmark, “the sigmoid take-off,” may harmonize efforts in research and clinical practice to improve patient outcomes. Background: The wide global variation in the definition of the rectum has led to significant inconsistencies in trial recruitment, clinical management, and outcomes. Surgical technique and use of preoperative treatment for a cancer of the rectum and sigmoid colon are radically different and dependent on the local definitions employed by the clinical team. A consensus definition of the rectum is needed to standardise treatment. Methods: The consensus was conducted using the Delphi technique with multidisciplinary colorectal experts from October, 2017 to April, 2018. Results: Eleven different definitions for the rectum were used by participants in the consensus. Magnetic resonance imaging (MRI) was the most frequent modality used to define the rectum (67%), and the preferred modality for 72% of participants. The most agreed consensus landmark (56%) was “the sigmoid take-off,” an anatomic, image-based definition of the junction of the mesorectum and mesocolon. In the second round, 81% of participants agreed that the sigmoid take-off as seen on computed tomography or MRI achieved consensus, and that it could be implemented in their institution. Also, 87% were satisfied with the sigmoid take-off as the consensus landmark. Conclusion: An international consensus definition for the rectum is the point of the sigmoid take-off as visualized on imaging. The sigmoid take-off can be identified as the mesocolon elongates as the ventral and horizontal course of the sigmoid on axial and sagittal views respectively on cross-sectional imaging. Routine application of this landmark during multidisciplinary team discussion for all patients will enable greater consistency in tumour localisation.

BACKGROUND: The interest and adoption of transanal total mesorectal excision (TaTME) is growing worldwide, but evidence on nationwide implementation and short-term outcomes is scarce. This study aims to evaluate national results for this relatively new technique in the UK. METHODS: A l l TaTME procedures performed in the UK and recorded on the international TaTME registry between January 2013 and January 2018 were analyzed. Surgeons who received training on TaTME in the UK were sent a survey regarding their experience with implementation of TaTME in their unit. Primary endpoint was a composite for "optimal pathology" (free resection margin (R0) and TME specimen with no major defects and no rectal wall perforations). Sec¬ ondary outcomes included 30-day clinical course and survey outcomes. RESULTS: Forty-two hospitals entered 513 cases over a 5-year period; 28 of 42 hospitals (66.7%) performed ten cases or less. The indication for surgery was cancer in 364 (71.0%) cases. Optimal pathology was achieved in 295 (92.8%), with an involved resection margin (R1) rate of 13 of 513 (4.1%). A Clavien-Dindo >III within 30 days was 13.4% (N.=45) and 6.8% (N.=10) in the cancer and benign groups, respectively. Based on the survey (response rate 68 of 86; 79%), 76.1% of the surgeons implemented TaTME in their unit after receiving training, all of whom experienced difficulties with performing TaTME. CONCLUSIONS: This study reports acceptable nationwide short-term outcomes of TaTME. However, adoption oc¬ curred in a rapid and non-standardized manner. A structured TaTME training program is therefore recommended.

AIMS Patients with abdominal cancer requiring major surgical intervention are at high risk of venous thromboembolic events (VTE), particularly pulmonary emboli (PE). A proportion of patients with cancer can present with, or have had, major VTEs prior to definitive surgical treatment. Preoperative percutaneous inferior venal caval filters (IVCF) may reduce the risk of PE. The aim of this study was to assess the indications, complications, retrieval rates, and long-term outcome of IVCFs in patients undergoing major abdominal surgery. METHODS This was a retrospective analysis of a prospective IVCF database between 2007 and 2018 of all patients with IVCF insertion prior to major abdominal surgery. The indications for an IVCF, procedural complications and surgical interventions were recorded. RESULTS Overall, 111 patients had IVCF insertion. IVCF placement failed in one patient with gross abdominal disease. Indications for an IVCF were: prior PE in 65/111 (59%) and major vein thrombus in 42 (38%). Overall, 26/111 (23%) had the IVCF removed at a median of 91 days. In two patients IVCF removal failed. At follow-up of the 85 patients who had the IVCF left in situ, six developed filter-related thrombus and 13 a deep vein thrombosis (DVT). Four patients had a PE with an indwelling IVCF. CONCLUSION Preoperative IVCF may reduce perioperative PE in patients at high risk of thrombosis undergoing major abdominal surgery where early anticoagulation is contraindicated. Long-term follow-up of retained IVCF suggests that major problems are infrequent, though further thrombosis may occur and long-term anticoagulation may be needed.

Background Classification of pelvic local recurrence (LR) after surgery for primary rectal cancer is not currently standardized and optimal imaging is required to categorize anatomical site and plan treatment in patients with LR. The aim of this review was to evaluate the systems used to classify locally recurrent rectal cancer (LRRC) and the relevant published outcomes. Methods A systematic review of the literature prior to April 2020 was performed through electronic searches of the Science Citation Index Expanded, EMBASE, MEDLINE and CENTRAL databases. The primary outcome was to review the classifications currently in use; the secondary outcome was the extraction of relevant information provided by these classification systems including prognosis, anatomy and prediction of R0 after surgery. Results A total of 21 out of 58 eligible studies, classifying LR in 2086 patients, were reviewed. Studies used at least one of the following eight classification systems proposed by institutions or institutional groups (Mayo Clinic, Memorial Sloan-Kettering – original and modified, Royal Marsden and Leeds) or authors (Yamada, Hruby and Kusters). Negative survival outcomes were associated with increased pelvic fixity, associated symptoms of LR, lateral compared with central LR and involvement of three or more pelvic compartments. A total of seven studies used MRI with specifically defined anatomical compartments to classify LR. Conclusion This review highlights the various imaging systems in use to classify LRRC and some of the prognostic indicators for survival and oncological clearance based on these systems. Implementation of an agreed classification system to document pelvic LR consistently should provide more detailed information on anatomical site of recurrence, burden of disease and standards for comparative outcome assessment.

Objective: To determine the relationship between body composition (BC), specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. Background: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however evidence is lacking in emergency surgery. Methods: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using pre-operative CT images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modelling. Results: Six hundred and ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs. 45.1%, p = 0.028; 57.5% vs. 42.6%, p = 0.014), 30-day (9.5% vs. 3.6%, p = 0.010; 14.9% vs. 3.4%, p < 0.001), and 1-year mortality (27.4% vs. 11.5%, p < 0.001; 29.7% vs.12.5%, p < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia (OR 2.56 (95%CI 1.12-5.84), p = 0.026) and myosteatosis (OR 4.26 (2.01-9.06), p < 0.001), similarly at 1-year (OR 2.66 (95%CI 1.57-4.52), p < 0.001; OR 2.08 (95%CI 1.26-3.41), p = 0.004). BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95%CI 0.835-0.84). Conclusion: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.

IntroductionDespite optimal patient selection and surgical effort, recurrence is seen in over 70% of patients undergoing cytoreductive surgery(CRS) for peritoneal metastases (PM). Apart from the peritoneal cancer index(PCI), completeness of cytoreduction and tumor grade, there are other factors like disease distribution in the peritoneal cavity, pathological response to systemic chemotherapy(SC), lymph node metastases and morphology of PM which may have prognostic value. One reason for the underutilization of these factors is that they are known only after surgery. Identifying clinical predictors, specifically radiological predictors, could lead to better utilization of these factors in clinical decision making and the extent of peritoneal resection performed for different tumors. This study aims to study these factors, their impact on survival and identify clinical and radiological predictors. Methods and analysisThere is no therapeutic intervention in the study. All patients with biopsy proven PM from colorectal, appendiceal, gastric and ovarian cancer and peritoneal mesothelioma undergoing CRS will be included. The demographic, clinical, radiological, surgical and pathological details will be collected according to a pre-specified format that includes details regarding distribution of disease, morphology of PM, regional node involvement and pathological response to SC. In addition to the absolute value of PCI, the structures bearing the largest tumor nodules and a description of the morphology in each region will be recorded. A correlation between the surgical, radiological and pathological findings will be performed and the impact of these potential prognostic factors on progression-free and overall survival determined. The practices pertaining to radiological and pathological reporting at different centers will be studied. Ethics and disseminationThe study protocol has been approved by the Zydus Hospital ethics committee (27th July, 2020) and Lyon-sud ethics committee (A15-128). It is registered with the clinical trials registry of India (CTRI/2020/09/027709).The results will be published in peer-reviewed scientific journals.Strength and limitationsA prospective correlation between the radiological, surgical and pathological findings in patients undergoing CRS will be performed which has not been done before.Being prospective in nature it will also enable us to evaluate the impact of the current treatment practices on the clinical end-pointsThere is fixed protocol for radiological and pathological evaluation for which there are no specific guidelinesThe data collection format will capture all the relevant data but this may affect compliance.Despite the large sample size planned for each primary site, the heterogeneity of treatment protocols may be a limiting factor while evaluating the impact on survival.

Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.