Background
The aim was to define the pathological response in lymph nodes following neoadjuvant chemotherapy for oesophageal adenocarcinoma and to quantify any associated survival benefit.
Methods
...Lymph nodes retrieved at oesophagectomy were examined retrospectively by two pathologists for evidence of a response to chemotherapy. Patients were classified as lymph node‐negative (either negative nodes with no evidence of previous tumour involvement or negative with evidence of complete regression) or positive (allocated a lymph node regression score based on the proportion of fibrosis to residual tumour). Lymph node responders (score 1, complete response; 2, less than 10 per cent remaining tumour; 3, 10–50 per cent remaining tumour) and non‐responders (score 4, more than 50 per cent viable tumour; 5, no response) were compared in survival analyses using Kaplan–Meier and Cox regression analysis.
Results
Among 377 patients, 256 had neoadjuvant chemotherapy. Overall, 68 of 256 patients (26·6 per cent) had a lymph node response and 115 (44·9 per cent) did not. The remaining 73 patients (28·5 per cent) had negative lymph nodes with no evidence of regression. Some patients had a lymph node response in the absence of a response in the primary tumour (27 of 99, 27 per cent). Lymph node responders had a significant survival benefit (P < 0·001), even when stratified by patients with or without a response in the primary tumour. On multivariable analysis, lymph node responders had decreased overall (hazard ratio 0·53, 95 per cent c.i. 0·36 to 0·78) and disease‐specific (HR 0·42, 0·27 to 0·66) mortality, and experienced reduced local and systemic recurrence.
Conclusion
Lymph node regression is a strong prognostic factor and may be more important than response in the primary tumour.
Nodal response predicts survival
Peri-operative chemotherapy improves survival in patients with locally advanced oesophago-gastric adenocarcinoma. Two regimens with proven survival benefits are epirubicin, cisplatin plus ...capecitabine or fluorouracil (Medical Research Council Adjuvant Gastric Infusional Chemotherapy, MAGIC) and fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT). This study aimed to compare the effect of these regimens on survival (primary aim) and pathological response, surgical complications, adverse events and chemotherapy completion rates.
Cohort study including 946 patients treated with FLOT (n = 257) or MAGIC (n = 689) who underwent surgical resection for oesophageal (n = 743) or gastric (n = 203) adenocarcinoma between 2002 and 2021 at St Thomas’ Hospital or The Royal Marsden Hospital, London, UK. Survival analysis was performed using multivariable Cox regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, sex, clinical T-stage, clinical N-stage, tumour grade and presence of signet ring cells.
Patients treated with FLOT had better overall survival (HR = 0.69, 95% CI 0.50–0.94) and disease-free survival (HR = 0.75, 95% CI 0.58–0.98) than MAGIC. Patients treated with FLOT were more likely to have a complete pathological response (9.5% FLOT versus 5.5% MAGIC, p = 0.027) and were less likely to have a positive resection margin (19.1% FLOT versus 32.2% MAGIC, p < 0.001). The stratified analysis revealed similar results for oesophageal and gastric tumours. Rates of surgical complications, chemotherapy-associated adverse events and completion were similarly distributed between treatment groups.
Patients with oesophageal or gastric adenocarcinoma treated with peri-operative FLOT had better survival and pathological response than those treated with peri-operative MAGIC. Rates of surgical complications, adverse events and chemotherapy completion were comparable.
•Better survival in patients treated with fluorouracil plus leucovorin, oxaliplatin and docetaxel.•Better pathological and radiological response to chemotherapy with FLOT.•Higher rates of complete pathological response in patients treated with FLOT.•Patients treated with FLOT were less likely to have a positive resection margin.•Comparable rates of surgical complications, adverse events and chemo completion.
A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study ...examines survival and recurrence patterns in these patients.
Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.
Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1-3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16-0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (-16.3 vs -7.7 cm
, p = 0.033) with no significant difference between Mandard groups.
Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.
Background
The Tumor Location-Modified Laurén Classification (MLC) system combines Laurén histologic subtype and anatomic tumor location. It divides gastric tumors into proximal non-diffuse (PND), ...distal non-diffuse (DND), and diffuse (D) types. The optimum classification of patients with Laurén mixed tumors in this system is not clear due to its grouping with both diffuse and non-diffuse types in previous studies. The clinical relevance of the MLC in a Western population has not been examined.
Methods
A cohort study investigated 404 patients who underwent gastrectomy for gastric adenocarcinoma between 2005 and 2020. The classification of Laurén mixed tumors was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of clinicopathologic characteristics (chi-square). Survival analysis was performed using multivariable Cox regression.
Results
The ROC curve analysis demonstrated a slightly higher area under the curve value for predicting survival when Laurén mixed tumors were grouped with intestinal-type rather than diffuse-type tumors (0.58 vs 0.57). Survival, tumor recurrence, and resection margin positivity in mixed tumors also was more similar to intestinal type. Distal non-diffuse tumors had the best 5-year survival (DND 64.7 % vs PND 56.1 % vs diffuse 45.1 %;
p
= 0.006) and were least likely to have recurrence (DND 27.0 % vs PND 34.3 % vs diffuse 48.3 %;
p
= 0.001). Multivariable analysis demonstrated that MLC was an independent prognostic factor for survival (PND: hazard ratio HR, 1.64; 95 % confidence interval CI, 1.16–2.32 vs diffuse: HR, 2.20; 95 % CI, 1.56–3.09)
Conclusions
The MLC was an independent prognostic marker in this Western cohort of patients with gastric adenocarcinoma. The patients with PND and D tumors had worse survival than those with DND tumors.
Background
A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to ...establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma.
Methods
Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed.
Results
A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3–4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT‐assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c‐index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4–5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092).
Conclusion
The presence of advanced cT status, poor tumour differentiation, and CT‐assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.
Antecedentes
Un margen de resección circunferencial (circumferential resection margin, CRM) positivo se ha asociado con tasas más elevadas de recidiva locorregional y peor supervivencia en el cáncer de esófago. El objetivo de este estudio fue establecer si las variables clínico‐patológicas y radiológicas podrían predecir la positividad del CRM en el adenocarcinoma de esófago tras quimioterapia neoadyuvante antes de la cirugía.
Métodos
Se realizó un análisis multivariable de las características clínico‐patológicas y de la tomografía computarizada (computed tomography, CT) que se consideraron potencialmente predictivas de CRM en la estadificación inicial y tras la quimioterapia neoadyuvante. Se construyeron modelos de predicción. Se evaluó el área bajo la curva (area under curve, AUC) con el i.c. del 95% a partir de 1.000 muestras bootstrap.
Resultados
Se incluyeron 223 pacientes en el estudio. Una pobre diferenciación (razón de oportunidades, odds ratio, OR 2,84, i.c. del 95% 1,39‐6,01) y un estadio clínico T avanzado (T3‐4) (OR 2,93, i.c. del 95% 1,03‐9,48) se asociaron de forma independiente con un riesgo aumentado de CRM en el diagnóstico. La falta de respuesta en la CT (estable o enfermedad en progresión) tras la quimioterapia se correspondía de forma independiente con un riesgo aumentado de CRM positivo (OR 3,38, i.c. del 95% 1,43‐8,50). Además, la evidencia por CT de invasión local y un mayor volumen del tumor en CT (14 cm3) mejoraron el funcionamiento del modelo predictivo, incluyendo todos los parámetros previamente señalados; con AUC (índice c) de 0,76 (0,68‐0,83). Las variables asociadas de forma significativa con tasas más elevadas de recidiva locorregional fueron el estado de los ganglios linfáticos patológicos (P = 0,002), la invasión linfovascular (P = 0,007) y la respuesta pobre a la quimioterapia (Mandard 4 y 5 (P = 0,006)). La positividad del CRM se asoció con una tasa de recidiva locorregional más elevada pero sin alcanzar significación estadística (P = 0,09).
Conclusión
La presencia de un estadio clínico T avanzado, tumor pobremente diferenciado, falta de respuesta a la quimioterapia en la TC, mayor volumen del tumor en la TC e invasión local pueden ser utilizados para identificar pacientes en riesgo de un CRM positivo tras quimioterapia neoadyuvante.
A positive circumferential resection margin (CRM) has been shown to be an adverse prognostic indicator after oesophagectomy for adenocarcinoma. Clinical tumour status, tumour volume, poor differentiation, lack of response following chemotherapy and radiological assessment of invasion can be used to predict CRM positivity in oesophageal adenocarcinoma.
CRM assessment is still important
BACKGROUND:Discrimination between ulcerative colitis (UC) and Crohn disease (CD) may be difficult on ileo-colonoscopy alone because of a lack of definitive lesions. Retrospective studies show upper ...gastrointestinal endoscopy may be helpful in confirming diagnosis in such cases.
AIMS:To prospectively determine importance of upper gastrointestinal endoscopy in diagnosis of inflammatory bowel disease (IBD) and assess factors predictive of upper gastrointestinal involvement in IBD.
METHODS:All pediatric patients were enrolled prospectively and consecutively over a 2-year period and investigated with an ileo-colonoscopy and barium meal follow-through. Children with procto-sigmoiditis, later confirmed histologically to be typical of UC, were excluded from the study. The remainder underwent upper gastrointestinal endoscopy. The protocol and methodology were determined a priori.
RESULTS:65 children suspected of IBD underwent colonoscopy. Of the total, 11 had recto-sigmoiditis with typical macroscopic appearances of UC; once this was confirmed on histology these patients were excluded from the study. Of the 54 children (males, 31; median age, 11.1 years) remaining, 23 were initially diagnosed with CD on ileo-colonoscopy and 18 (33%) were diagnosed with UC. The diagnosis remained ambiguous in 13 (six colonic, four ileo-colonic, three normal colon) on clinical, radiologic and histologic grounds. Upper GI endoscopy helped to confirm CD in a further 11 (20.4%). Two patients were diagnosed with indeterminate colitis.Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Epigastric and abdominal pain, nausea and vomiting, weight loss and pan-ileocolitis were predictive of upper gastrointestinal involvement (P < 0.05). However, 9 children with upper gastrointestinal involvement were asymptomatic at presentation (31%). Overall upper gastrointestinal tract inflammation was most common in the stomach (67%), followed by the esophagus (54%) and duodenum (22%).
CONCLUSIONS:Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation.
.
Objectives:
Pigmented cells, that contain inert, submicron-sized dietary particles, are a consistent feature of the base of human Peyer’s patches (PP). We aimed (i) to phenotype these intestinal ...pigment cells (PC) in archival tissue specimens and (ii) to establish whether PC phenotype is altered in inflammatory conditions, especially Crohn’s disease (CD).
Methods:
PCs contained within PP were identified by routine haematoxylin and eosin (H&E) staining and dark field microscopy of archival ileal sections for: adenocarcinoma (n = 16), colonic CD (n = 23), non-CD colitis (n = 10). Paraffin-embedded serial sections were graded for microscopic inflammation and then investigated immunohistochemically with antibodies against CD68, MAC387, CD14, CD11b, CD15, CD1a, S100, HLA-DR, CD86 and Cathepsin D. Analyses were by light and confocal microscopies.
Results:
The majority of PCs were CD68 positive (circa 80%) with a minority (circa 20%) staining for MAC387. Microparticles were mainly identified within cathepsin D negative lysosomal compartments. Histological inflammatory grade and disease type had no influence on cell phenotype.
Conclusions:
The microparticle-containing PCs of the PP base are mainly mature macrophages (CD68) of low metabolic and immunological activity. There is no evidence of differential PC phenotype or activation in differing disease states, including CD.
Little is published about the local resection of oesophageal cancers. We adopted the principles of rectal cancer surgery, ie standard surgical dissection techniques as well as standard pathological ...processing and reporting, and assessed the feasibility of applying them to oesophagogastric junction (OGJ) cancer.
Over a two-year period consecutive patients with invasive cancers of the OGJ were studied. Following staging and neoadjuvant chemotherapy (NAC), a standard dissection defined as a total adventitial resection of the cardia (TARC) was performed. Standard histopathological processing involved external inking, photographing, transverse slicing and mounting of cut samples on megablocks. Hospital morbidity and mortality as well as survival at five years' follow-up were assessed.
Forty consecutive patients had a TARC for OGJ carcinoma. Of these, 32 were offered NAC. Introducing TARC did not result in increased morbidity or mortality. Twenty-seven patients (68%) had an R0 resection that was directly related to the tumour stage and significantly related to a response to chemotherapy. Sixteen patients (42%) were alive five years after their TARC operation.
Although the adventitia of the OGJ is not as well developed as that of the rectum, TARC can be performed safely as a standardised resection for OGJ cancers. Whereas the R0 rate for early stage tumours is very high, it remains disappointingly low for T3N1 tumours despite NAC. Improved long-term survival for these advanced tumours will only be achieved with better neoadjuvant and adjuvant therapies.
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