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OBJECTIVE: In this study we analyzed the impact of centralization on key metrics, outcomes and patterns of care at the Irish National Center. SUMMARY BACKGROUND DATA: Overall survival rates in esophageal cancer in the West have doubled in the last 25 years. An international trend towards centralization may be relevant, however this model remains controversial with Ireland, centralizing esophageal cancer surgery in 2011. STUDY DESIGN: All patients (n=1245) with adenocarcinoma of the esophagus or junction treated with curative intent involving surgery, including endoscopic surgery, were included (n= 461 from 2000-2011, and 784 from 2012-2022). All data entry was prospectively recorded. Overall survival was measured (i) for the entire cohort; (ii) patients with locally advanced disease (cT2-3N0-3); and (iii) patients undergoing neoadjuvant therapy. All complications were recorded as per Esophageal Complication Consensus Group (ECCG) definitions, and the Clavien Dindo (CD) severity classification. STATISTICAL ANALYSIS: Data were analyzed using GraphPad Prism (v.6.0) for Windows and SPSS (v.23.0) software (SPSS,Chicago,IL) RStudio (Rversion4.2.2). Survival times were calculated using log-rank test and a Cox-regression analysis, and Kaplan-Meier curves generated. RESULTS: Endotherapy for cT1a/IMC adenocarcinoma increased from 40 (9% total) to 245 (31% total) procedures between the pre-centralization (pre-C) and post-centralization (post-C) periods. A significantly (P<0.001) higher proportion of patients with cT2-3N0-3 disease in the post-C period underwent neoadjuvant therapy (66% vs 53%). Operative mortality was lower (P=0.02) post-C, at 2% vs 4.5%, and>IIIa CD major complications decreased from 33% to 25% (P<0.01). Recurrence rates were lower post-C (38% vs 53%, P<0.01). Median overall survival was 73.83 versus 47.23 months in the 2012-22 and 2000-11 cohorts respectively (P<0.001). For those who received neoadjuvant therapy, the median survival was 28.5 months pre-C and 42.5 months post-C (P<0.001). CONCLUSION: These data highlight improvements in both operative outcomes and survival from the time of centralization, and a major expansion of endoscopic surgery. Although not providing proof, the study suggests a positive impact of formal centralization with governance on key quality metrics, and an evolution in patterns of care.
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BACKGROUND: The presence at diagnosis, or development of, colorectal peritoneal metastases (CPM) is common in colorectal cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) show promising results in selected patients with CPM. The current study aimed to describe oncologic outcomes of patients with CPM, focusing on recurrence patterns and risk factors for adverse events. METHODS: We conducted a retrospective review of patients with CPM treated by CRS and HIPEC at a single institution between 2000 and 2021. RESULTS: A total of 555 patients were included, of whom 480 (86.5%) had complete cytoreduction, with a median age of 59 years and median Peritoneal Cancer Index (PCI) of 6. Following complete cytoreduction, 5-year overall survival (OS) and disease-free survival (DFS) were 51% and 31%, respectively. In multivariable Cox regression, PCI >6 (hazard ratio [HR] 2.25), pathological node positivity (pN+; HR 1.94), and perineural invasion (HR 1.85) were associated with decreased OS, while PCI >6, pN+, and previous systemic metastases resulted in reduced DFS. Overall, 284 (62%) patients developed recurrence, of whom 97 (34%) had local recurrence (LR), 100 (35%) had systemic recurrence (SR), and 87 (31%) had combined recurrence (5-year OS: 49.3%, 46%, and 37.4%, respectively). Mutated KRAS (mKRAS) was associated with lower 5-year OS (55.8%) and DFS (27.9%) compared with wild-type KRAS (wtKRAS; 70.7% and 37.6%, respectively). In multivariable analyses, mKRAS was related to decreased OS (HR 1.82), DFS (HR 1.55), and SR (OS 1.89), but not to LR. CONCLUSIONS: Complete cytoreduction results in good survival outcomes for patients with CPM. Burden of peritoneal disease and tumor biology are the main predictors of survival. Patients with mKRAS are a high-risk cohort, with increased probability of SR and reduced survival.
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BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.
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Consenso , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Neoplasias Peritoneais/terapia , Pseudomixoma Peritoneal/terapia , Terapia Combinada , Técnica Delphi , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mitomicina/administração & dosagem , Prognóstico , Hipertermia Induzida/métodosRESUMO
BACKGROUND: The role of gastrectomy to achieve complete cytoreduction (CCR) for pseudomyxoma peritonei (PMP) is controversial due to uncertain risk/benefit ratio. The outcomes of patients who gastrectomy over a twenty-year period in a high-volume unit are reported. METHODS: All patients requiring gastrectomy to achieve CCR for appendiceal PMP between 2000 and 2020 were reviewed. Demographics, disease, operative, complication, and survival data were analysed. The first and second decades were compared. RESULTS: A total of 2148 patients underwent CRS and HIPEC, of which 78% had CCR. Gastrectomy was performed in 7.1%. Median age was 55 years, and 52% were female. Among gastrectomy patients, 94.2% had ≥1 elevated tumour marker, and 18% had high-grade disease. Median PCI was 30, and 30% required subtotal colectomy. Clavien-Dindo III-IV complications occurred in 32%, and 90-day mortality was 1.75%. Median survival was 104 months, and 10-year OS was 47%. Comparing the two decades, total CRS cases almost tripled, with a greater proportion achieving CCR (82.2% vs. 67.8%) but fewer requiring gastrectomy (5.3% vs. 13.5%). In those who had gastrectomy, disease was more advanced (higher PCI, more high-grade disease, more colectomies) in the later period. However, on multivariable analysis, there was no difference in survival between decades. High-grade histology was the only predictor of survival. CONCLUSIONS: Gastrectomy can achieve good long-term survival with low mortality and acceptable morbidity and should not deter surgeons from achieving CCR. However, increasing experience shows CCR can be achieved, preserving the stomach in the majority of cases through careful consideration of the anatomy and gastric blood supply.
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BACKGROUND: The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL). METHODS: The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared. RESULTS: From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in 'tumor nodules' with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p < 0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p = 0.069]. CONCLUSIONS: The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in 'tumor nodules'. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.
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AIM: The clinical burden of pelvic exenteration (PE) for locally advanced rectal cancer (LARC) is nationally under-reported. The widespread use of pelvic MRI since 2005 has increased the accuracy of local staging and awareness of the need for 'beyond TME (total mesorectal excision)' surgery. The aim of this study was to assess the volume of patients undergoing PE within England, which factors affected survival outcomes and whether the use of MRI has influenced these outcomes. METHOD: The volume of patients undergoing PE and associated survival outcomes across England between 1995 and 2016 was evaluated from Public Health England Hospital Episode Statistics data. RESULTS: A total of 2996 patients were recorded as undergoing PE. The 5-year overall survival rate improved after 2005 compared with prior to 2005 (61.7% vs. 37%, p < 0.001), with no significant difference between cancer registries throughout England. After 2005, the volume of patients undergoing PE and undergoing preoperative MRI increased, as did the number of non-T4 cancers operated on. After 2005, age, preoperative MRI and preoperative radiotherapy were the significant factors influencing 5-year overall survival on multivariate analysis. CONCLUSION: This review of national data confirms that PE outcomes are under-reported. MRI staging aids with the identification of patients suitable for perioperative treatment, surgery or palliation and facilitates treatment planning. Since 2005, MRI, likely in combination with advances in surgery and perioperative treatment, has improved survival outcomes. It is imperative that detailed information from patients with LARC undergoing PE is captured and reported in order to optimize care and future service provision.
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BACKGROUND: The risk-benefit balance of prophylactic appendectomy in patients undergoing left colorectal cancer resection is unclear. The aim of this report is to assess the proportion of histologically abnormal appendices in patients undergoing colorectal cancer resection in a unit where standard of care is appendectomy, with consent, when left-sided resection is performed. METHODS: A retrospective study on a prospectively collected database was conducted in a single tertiary-care center. Overall, 717 consecutive patients undergoing colorectal cancer resection between January 2015 and June 2021 were analyzed. The primary outcome was the proportion of histologically abnormal appendix specimens at prophylactic appendectomy. The secondary outcome was complications from prophylactic appendectomy. RESULTS: Overall, 576/717 (80%) patients had appendectomy at colorectal cancer surgery. In total, 234/576 (41%) had a right-/extended-right hemicolectomy or subtotal colectomy which incorporates appendectomy, and 342/576 (59%) had left-sided resection (left-hemicolectomy, anterior resection or abdominoperineal excision) with prophylactic appendectomy. At definitive histology, 534/576 (92.7%) had a normal appendix. The remaining 42/576 (7.3%) showed abnormal findings, including: 14/576 (2.4%) inflammatory appendix pathology, 2/576 (0.3%) endometriosis, 8/576 (1.4%) hyperplastic polyp, and 18/576 (3.1%) appendix tumors, which encompassed six low-grade appendiceal mucinous neoplasms (LAMNs), three carcinoids, and nine serrated polyps. In the 342 patients who had prophylactic appendectomy, 10 (2.9%) had a neoplasm (two LAMN, three carcinoids, and five serrated polyps). There were no complications attributable to appendectomy. CONCLUSION: Occult appendix pathology in patients undergoing colorectal cancer resection is uncommon when prophylactic appendectomy was performed. However, approximately 3% of patients had a synchronous appendix neoplasm.
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Apendicectomia , Apêndice , Colectomia , Neoplasias Colorretais , Humanos , Apendicectomia/efeitos adversos , Apendicectomia/métodos , Feminino , Masculino , Estudos Retrospectivos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Pessoa de Meia-Idade , Idoso , Apêndice/patologia , Apêndice/cirurgia , Colectomia/efeitos adversos , Colectomia/métodos , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Adulto , Idoso de 80 Anos ou mais , Apendicite/cirurgia , Apendicite/patologiaRESUMO
Optimal pain control following esophagectomy remains a topic of contention. The aim was to perform a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) evaluating the analgesia strategies post-esophagectomy. A NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using Shiny and R. Fourteen RCTs which included 565 patients and assessed nine analgesia techniques were included. Relative to systemic opioids, thoracic epidural analgesia (TEA) significantly reduced static pain scores at 24 hours post-operatively (mean difference (MD): -13.73, 95% Confidence Interval (CI): -27.01-0.45) (n = 424, 12 RCTs). Intrapleural analgesia (IPA) demonstrated the best efficacy for static (MD: -36.2, 95% CI: -61.44-10.96) (n = 569, 15 RCTs) and dynamic (MD: -42.90, 95% CI: -68.42-17.38) (n = 444, 11 RCTs) pain scores at 48 hours. TEA also significantly reduced static (MD: -13.05, 95% CI: -22.74-3.36) and dynamic (MD: -18.08, 95% CI: -31.70-4.40) pain scores at 48 hours post-operatively, as well as reducing opioid consumption at 24 hours (MD: -33.20, 95% CI: -60.57-5.83) and 48 hours (MD: -42.66, 95% CI: -59.45-25.88). Moreover, TEA significantly shortened intensive care unit (ICU) stays (MD: -5.00, 95% CI: -6.82-3.18) and time to extubation (MD: -4.40, 95% CI: -5.91-2.89) while increased post-operative forced vital capacity (MD: 9.89, 95% CI: 0.91-18.87) and forced expiratory volume (MD: 13.87, 95% CI: 0.87-26.87). TEA provides optimal pain control and improved post-operative respiratory function in patients post-esophagectomy, reducing ICU stays, one of the benchmarks of improved post-operative recovery. IPA demonstrates promising results for potential implementation in the future following esophagectomy.
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Analgesia Epidural , Analgésicos Opioides , Esofagectomia , Metanálise em Rede , Dor Pós-Operatória , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Esofagectomia/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides/uso terapêutico , Analgesia Epidural/métodos , Feminino , Masculino , Medição da Dor , Pessoa de Meia-Idade , Idoso , Manejo da Dor/métodos , Analgesia/métodos , Tempo de Internação/estatística & dados numéricosRESUMO
BACKGROUND: Rural Australians typically encounter disparities in healthcare access leading to adverse health outcomes, delayed diagnosis and reduced quality of life (QoL) parameters. These disparities may be exacerbated in advanced malignancies, where treatment is only available at highly specialised centres with appropriate multidisciplinary expertise. Thus, this study aims to determine the association between patient residence on oncological, surgical and QoL outcomes following cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC). METHODS: A retrospective analysis was conducted on consecutive patients undergoing CRS and HIPEC at Royal Prince Alfred Hospital from January 2017 to March 2022. On the basis of their postcode of residence, patients were stratified into metropolitan and regional groups. Data encompassing demographics, oncological, surgical and QoL outcomes were compared. Statistical analysis included chi-square test, t-tests and Kaplan-Meier survival curves. RESULTS: Among the 317 patients, 228 (72%) were categorised as metropolitan and 89 (28%) as regional. Metropolitan patients presented higher rates of recurrence (61.8% versus 40.0%, p = 0.014) and shorter overall mean survival [3.8 years (95% CI: 3.44-4.09) versus 4.2 years (95% CI: 3.76-4.63), p = 0.019] compared with regional patients. No other statistically significant differences were observed in oncological, surgical and QoL outcomes. CONCLUSIONS: Most oncological, surgical and QoL parameters did not differ by geographical location of patients undergoing CRS and HIPEC for peritoneal malignancies at a high-volume quaternary referral centre. Observed differences in recurrence and survival may be attributed to the selective nature of surgical referrals and variable follow-up patterns. Future research should focus on characterising referral pathways and its influence on post-operative outcomes.
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População Australasiana , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Qualidade de Vida , Estudos Retrospectivos , AustráliaRESUMO
BACKGROUND: 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. METHODS: 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 and >65 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. RESULTS: During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were <45 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. CONCLUSION: 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.
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Neoplasias Colorretais , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Humanos , Idoso , Peritônio/patologia , Neoplasias Peritoneais/secundário , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução , Neoplasias Colorretais/patologia , Terapia Combinada , Irlanda/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de Sobrevida , Sistema de Registros , Reino Unido/epidemiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: 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). BACKGROUND: CRS and heated intraoperative peritoneal chemotherapy are effective treatments for many patients with PMP. In patients with extensive small bowel involvement or nonresectable recurrence, disease progression results in small bowel obstruction, nutritional failure, and fistulation, with resulting abdominal wall failure. METHODS: Between 2013 and 2022, patients with PMP who had a nutritional failure and were not suitable for further CRS underwent radical debulking and intestinal transplantation at our centre. RESULTS: Fifteen 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 7 patients underwent modified multivisceral transplantation. In addition, in 7 patients with significant abdominal wall tumor 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 6 months. CONCLUSION: Intestinal/multivisceral 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 the combined skills of both peritoneal malignancy and transplant teams.
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Hipertermia Induzida , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Humanos , Pseudomixoma Peritoneal/cirurgia , Pseudomixoma Peritoneal/patologia , Seguimentos , Qualidade de Vida , Neoplasias Peritoneais/cirurgia , Peritônio/patologia , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Estudos Retrospectivos , Terapia CombinadaRESUMO
BACKGROUND AND AIMS: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologiaRESUMO
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<0·0001) and 5-year overall survival (71% [62-78] vs 89% [84-92]; 2·59 [1·62-3·88]; p<0·0001). On multivariable analysis, NICE risk assessment was not associated with either disease-free survival or overall survival, whereas MRI criteria predicted disease-free survival (HR 2·74 [95% CI 1·80-4·17]; p<0·0001) and overall survival (HR 2·44 [95% CI 1·51-3·95]; p=0·00027). 139 NICE high-risk patients who were defined as low-risk based on MRI criteria had similar disease-free survival as 118 NICE low-risk patients; therefore, 37% (139 of 378) of patients in this study cohort would have been overtreated with NICE 2020 guidelines. Of the 130 patients defined as low-risk by NICE guidelines, 12 were defined as high-risk on MRI risk stratification and would have potentially been missed for treatment. INTERPRETATION: Compared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). FUNDING: None.
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Margens de Excisão , Neoplasias Retais , Estudos de Coortes , Extensão Extranodal , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Estudos RetrospectivosRESUMO
SUMMARY BACKGROUND DATA: MRI assessment of rectal cancer not only assesses tumor depth and surgical resectability but also extramural disease which affects prognosis. We have observed that nonnodal tumor nodules (tumor deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs). OBJECTIVE: We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers. METHODS: This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007 to October 2015. Data were obtained from electronic records and MRIs blindly rereported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen Kappa. RESULTS: On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival [hazard ratio (HR) 2.36 (1.54-3.61] for overall survival, 2.37 (1.47-3.80) for disease-free survival (both P < 0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31-0.80) P = 0.004 for overall survival, 0.60 (0.40-0.90) P = 0.014 for disease-free survival). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52-16.91) P ≤ 0.001) whereas T and N category were not. In a subgroup analysis of posttreatment MRIs in postchemoradiotherapy patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was k0.77 and k0.83. CONCLUSIONS: Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. Chemoradiotherapy may be a highly effective treatment strategy in mrTD/mrEMVI positive patients.
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Extensão Extranodal , Neoplasias Retais , Humanos , Imageamento por Ressonância Magnética/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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 ( P <0.01 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 Dindo >III 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P <0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42). CONCLUSIONS: 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.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Insuficiência Respiratória , Sarcopenia , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Monóxido de Carbono/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Feminino , Humanos , Masculino , Terapia Neoadjuvante/efeitos adversos , Insuficiência Respiratória/etiologia , Sarcopenia/complicações , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: The WHO classification of mucinous appendix neoplasms and pseudomyxoma peritonei (PMP) describes low- and high-grade histology and is of prognostic importance. The metastatic peritoneal disease grade can occasionally be different from the primary appendix tumor. This analysis aimed to report outcomes from a high-volume center in patients with pathological discordance. METHODS: This was a retrospective analysis of prospective data of patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP at a single institution between January 2016 and December 2020. Reporting was by pathologists with a special interest in peritoneal malignancy. Discordant pathology was classified as a low-grade primary appendix tumor with high-grade peritoneal disease, or a high-grade primary appendix tumor with low-grade peritoneal disease. Outcomes analyzed were overall and recurrence-free survival, and Kaplan-Meier survival curves and the log-rank test were used to analyze the outcomes. RESULTS: Between 2016 and 2020, 830 patients underwent CRS and HIPEC for PMP, of whom 37 (4.4%) had discordant pathology. The primary appendix tumors were low-grade in 23 patients and high-grade in 14 patients. The median Peritoneal Cancer Index (PCI) was significantly higher in patients with a low-grade primary tumor (31 vs. 16; p = 0.001), while complete cytoreduction (CC0/1) was achieved in 31/37 (83.8%) patients. The median follow-up was 19 months. Overall survival was worse in those with high-grade peritoneal disease (p = 0.029), whereas recurrence-free survival was similar in both groups (p = 0.075). CONCLUSION: In PMP with pathological discordance, the peritoneal disease grade influences prognosis and survival.
Assuntos
Neoplasias do Apêndice , Apêndice , Hipertermia Induzida , Pseudomixoma Peritoneal , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Apêndice/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Estudos Prospectivos , Pseudomixoma Peritoneal/patologia , Pseudomixoma Peritoneal/terapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: 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. OBJECTIVE: 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. DESIGN: This was a retrospective study using a prospectively collected database of patients discussed at the dedicated multidisciplinary team meeting. SETTINGS: This study was conducted in a single tertiary-care center. PATIENTS: Consecutive patients with significant polyps and early colorectal cancer were identified either through the Bowel Cancer Screening Program or colonoscopy for symptomatic patients. MAIN OUTCOME MEASURES: Proportions of patients who had organ preservation, and secondary treatment and recurrence rate served as outcome measures. RESULTS: 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. LIMITATIONS: This study was limited by its relatively small sample size and single-center setting. CONCLUSIONS: 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. MANEJO DE SPECC PLIPO COMPLEJO Y CNCER COLORRECTAL TEMPRANO ES OPTIMIZADO MEDIANTE LA IMPLEMENTACIN DE REUNIONES DE UN EQUIPO MULTIDISCIPLINARIO ESPECIALIZADOS LECCIONES APRENDIDAS DEL PROGRAMA NACIONAL DEL REINO UNIDO: 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).
Assuntos
Neoplasias Colorretais , Pólipos , Neoplasias Retais , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Humanos , Equipe de Assistência ao Paciente , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Reino UnidoRESUMO
BACKGROUND: Epithelial appendiceal neoplasms are uncommon peritoneal malignancies causing a spectrum of disease including pseudomyxoma peritonei (PMP). The optimal management is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete CRS (CCRS), recurrence develops in almost 45% of patients. No consensus exists for the optimal treatment of recurrent disease, with treatment strategies including repeat CRS, watch-and-wait, and palliative chemotherapy. This report aims to describe evolving management strategies for a large cohort with recurrence after CCRS. METHODS: This retrospective study analyzed a prospective database of patients with recurrence after CCRS for appendiceal neoplasms from 1994 to 2017 who had long-term follow-up evaluation with tumor markers and computed tomography (CT). RESULTS: Overall, 430 (37.6%) of 1145 PMP patients experienced recurrence at a median of 19 months. Of these 430 patients 145 (33.7%) underwent repeat CRS, 119 (27.7%) had a watch-and-wait approach, and 119 (27.7%) had palliative chemotherapy. The patients with recurrence had a median overall survival (OS) of 39 months, a 3-year survival of 74.6%, a 5-year survival of 57.4%, and a 10-year survival of 36.5%. In the multivariate analysis, the patients who had recurrence within 1 year after primary CRS (hazard ratio [HR], 3.55), symptoms at recurrence (HR, 3.08), a high grade of disease or adenocarcinoma pathology (HR, 2.94), signet ring cells (HR, 1.91), extraperitoneal metastatic disease (HR, 1.71), or male gender (HR, 1.61) had worse OS. The OS was longer for the patients who had repeat CRS (HR, 0.41). The patients who underwent repeat CCRS had a 3-year OS of 87.5%, a 5-year OS of 78.1%, and a 10-year OS of 67.9%. CONCLUSIONS: Dilemmas persist around the optimal management of patients with recurrence after CRS and HIPEC for appendiceal tumors. Selected patients benefit from repeat CRS, particularly those with favorable tumor biology and focal disease.
Assuntos
Neoplasias do Apêndice , Hipertermia Induzida , Pseudomixoma Peritoneal , Cirurgiões , Neoplasias do Apêndice/terapia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Masculino , Recidiva Local de Neoplasia/terapia , Pseudomixoma Peritoneal/tratamento farmacológico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
AIMS: Tumour deposits (TDs) are an important prognostic marker in colorectal cancer. However, the classification, and inclusion in staging, of TDs has changed significantly in each tumour-node-metastasis (TNM) edition since their initial description in TNM-5, and terminology remains controversial. Expert consensus is needed to guide the future direction of precision staging. METHODS AND RESULTS: A modified Delphi consensus process was used. Statements were formulated and sent to participants as an online survey. Participants were asked to rate their agreement with each statement on a five-point Likert scale and also to suggest additional statements for discussion. These responses were circulated together with anonymised comments, and statements were modified prior to carrying out a second online round. Consensus was set at 70%. Overall, 32 statements reached consensus. There were concerns that TDs were currently incorrectly placed in the TNM system and that their prognostic importance was being underestimated. There were concerns regarding interobserver variation and it was felt that a clearer, more reproducible definition of TDs was needed. CONCLUSIONS: Our main recommendations are that the number of TDs should be recorded even if lymph node metastases (LNMs) are also present and that nodules with evidence of origin [extramural venous invasion (EMVI), perineural invasion (PNI), lymphatic invasion (LI)] should still be categorised as TDs and not excluded, as TNM-8 specifies. Whether TDs should continue to be included in the N category at all is controversial, and did not achieve consensus; however, participants agreed that TDs are prognostically worse than LNMs and the N1c category is suboptimal, as it does not reflect this.
Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Técnica Delphi , Extensão Extranodal/diagnóstico , Extensão Extranodal/patologia , Neoplasias Colorretais/prevenção & controle , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
OBJECTIVES: To assess the individual treatment strategies among international experts in peritoneal carcinosis, specifically their decision-making in the process of patient selection for hyperthermic intraperitoneal chemotherapy (HIPEC) in women suffering from ovarian cancer, to identify relevant decision-making criteria, and to quantify the level of consensus for or against HIPEC. METHODS: The members of the executive committee of the Peritoneal Surface Oncology Group International (PSOGI) were asked to describe the clinical conditions under which they would recommend HIPEC in patients with ovarian cancer and to describe any disease or patient characteristics relevant to their decision. All answers were then merged and converted into decision trees. The decision trees were then analyzed by applying the objective consensus methodology. RESULTS: Nine experts in surgical oncology provided information on their multidisciplinary treatment strategy including HIPEC for patients with advanced ovarian cancer. Three of the total of 12 experts did not perform HIPEC. Five criteria relevant to the decision on whether HIPEC is performed were applied. In patients with resectable disease, a peritoneal cancer index (PCI) <21, and epithelial ovarian cancer without distant metastasis, consent was received by 75% to perform HIPEC for women suffering from recurrent disease. Furthermore, in the primary disease setting, consent was received by 67% to perform HIPEC according to the same criteria. DISCUSSION AND CONCLUSION: Among surgical oncology experts in peritoneal surface malignancy and HIPEC, HIPEC plays an important role in primary and recurrent ovarian cancer, and the PCI is the most important criterion in this decision.