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
Following neoadjuvant chemotherapy for operable gastroesophageal cancer, lymph node metastasis is the only validated prognostic variable; however, within lymph node groups there is still ...heterogeneity with risk of relapse. We hypothesized that gene profiles from neoadjuvant chemotherapy treated resection specimens from gastroesophageal cancer patients can be used to define prognostic risk groups to identify patients at risk for relapse.
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial (n = 202 with high quality RNA) samples treated with perioperative chemotherapy were profiled for a custom gastric cancer gene panel using the NanoString platform. Genes associated with overall survival (OS) were identified using penalized and standard Cox regression, followed by generation of risk scores and development of a NanoString biomarker assay to stratify patients into risk groups associated with OS. An independent dataset served as a validation cohort.
Regression and clustering analysis of MAGIC patients defined a seven-Gene Signature and two risk groups with different OS hazard ratio (HR) 5.1; P < 0.0001. The median OS of high- and low-risk groups were 10.2 95% confidence interval (CI) of 6.5 and 13.2 months and 80.9 months (CI: 43.0 months and not assessable), respectively. Risk groups were independently prognostic of lymph node metastasis by multivariate analysis (HR 3.6 in node positive group, P = 0.02; HR 3.6 in high-risk group, P = 0.0002), and not prognostic in surgery only patients (n = 118; log rank P = 0.2). A validation cohort independently confirmed these findings.
These results suggest that gene-based risk groups can independently predict prognosis in gastroesophageal cancer patients treated with neoadjuvant chemotherapy. This signature and associated assay may help risk stratify these patients for post-surgery chemotherapy in future perioperative chemotherapy-based clinical trials.
Summary
Recent national audit has shown that levels of minimally invasive esophagectomy for cancer have increased to around 45% in the UK. The hybrid approach is the most common, with a laparoscopic ...abdominal phase and an open thoracic dissection. A number of centers have now adopted a two-phase Ivor–Lewis minimally invasive esophagectomy using a laparoscopic abdominal phase, followed by a thoracoscopic chest phase with a mini-thoracotomy to extract the specimen. The two-phase nature of the procedure lengthens the operative time and makes returning to the abdominal cavity difficult. The thoracotomy incision can also be painful and may reduce respiratory function post operatively. This report describes a novel single-phase minimally invasive left-sided technique with a mini-laparotomy for specimen extraction. This method offers excellent hiatal exposure, avoids a thoracotomy, and shortens the procedure time. Minimally invasive left-sided esophagectomy is a new useful approach for tumors located at the gastroesophageal junction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Transhiatal and transthoracic oesophagectomy in patients with oesophageal cancer have similar survival rates. Whether these approaches differ in health‐related quality of life (HRQoL) is ...uncertain and was examined in this study.
Methods
Patients undergoing transhiatal or transthoracic surgery for lower‐third oesophageal or gastro‐oesophageal junctional cancer between 2011 and 2015 were selected from an institutional database. HRQoL outcomes were measured at 6 and 12 months after surgery using validated written questionnaires (European Organisation for Research and Treatment of Cancer QLQ‐C30 and QLQ‐OG25). Linear mixed models provided mean score differences (MSDs) with 95 per cent confidence intervals, adjusted for preoperative HRQoL, age, physical status (ASA fitness grade), tumour location, tumour stage, neoadjuvant therapy, adjuvant therapy and postoperative complications. MSD values of 10 or more were regarded as clinically relevant.
Results
Some 146 patients underwent transhiatal (86, 58·9 per cent) or transthoracic (60, 41·1 per cent) oesophagectomy. The HRQoL questionnaires were returned by 111 patients at 6 months and 74 at 12 months. At 6 months, transthoracic oesophagectomy was associated with worse role function (MSD –12, 95 per cent c.i. –23 to 0; P = 0·046). At 12 months, patients in the transthoracic group had more nausea and vomiting (MSD 11, 0 to 22; P = 0·045), dyspnoea (MSD 13, 1 to 25; P = 0·029) and constipation (MSD 20, 7 to 33; P = 0·003) than those in the transhiatal group.
Conclusion
Transhiatal oesophagectomy seems to offer better HRQoL than transthoracic oesophagectomy 6 and 12 months after surgery.
Favours transhiatal
Summary Surgeons frequently sustain needlestick injuries when operating. The aim of this study was to evaluate the incidence and reporting rate of needlestick injuries at one institution. A ...questionnaire was distributed anonymously to 69 surgeons of all grades and specialties in a district general hospital in the UK. The questionnaire was returned by 42 surgeons (60.9%). There were 840 needlestick injuries over two years, of which 126 caused bleeding. Senior surgeons who spent more hours operating per week had a higher rate of needlestick injuries compared with junior surgeons (29.1 vs 6.59 injuries per surgeon over two years). Of the total number of injuries, 19 (2.26%) were reported to Occupational Health according to the surgeons questioned, but only six reported incidents were found in the Occupational Health records. Junior surgeons were significantly more likely to report needlestick injuries than senior surgeons (9.82% vs 1.10% of injuries reported, P = 0.0000045). The main reasons for failure to report needlestick injuries were due to the lack of time and excessive paperwork. Seventy-three percent of surgeons did not routinely use double gloves when operating, mainly because of decreased hand sensation. The rate of needlestick injury reporting by surgeons at this institution is extremely low. Previous studies have shown a higher reporting rate suggesting that, despite awareness of blood-borne infections, surgeons are still not following recommended protocols.
Neoadjuvant chemotherapy is established in the management of most resectable esophageal and esophagogastric junction adenocarcinomas. However, assessing the downstaging effects of chemotherapy and ...predicting response to treatment remain challenging, and the relative importance of tumor stage before and after chemotherapy is debatable.
We analyzed consecutive resections for esophageal or esophagogastric junction adenocarcinomas performed at two high-volume cancer centers in London between 2000 and 2010. After standard investigations and multidisciplinary team consensus, all patients were allocated a clinical tumor stage before treatment, which was compared with pathologic stage after surgical resection. Survival analysis was conducted using Kaplan-Meier analysis and Cox regression analysis.
Among 584 included patients, 400 patients (68%) received neoadjuvant chemotherapy. Patients with downstaged tumors after neoadjuvant chemotherapy experienced improved survival compared with patients without response (P < .001), and such downstaging (hazard ratio, 0.43; 95% CI, 0.31 to 0.59) was the strongest independent predictor of survival after adjusting for patient age, tumor grade, clinical tumor stage, lymphovascular invasion, resection margin status, and surgical resection type. Patients downstaged by chemotherapy, compared with patients with no response, experienced lower rates of local recurrence (6% v. 13%, respectively; P = .030) and systemic recurrence (19% v. 29%, respectively; P = .027) and improved Mandard tumor regression scores (P = .001). Survival was strongly dictated by stage after neoadjuvant chemotherapy, rather than clinical stage at presentation.
The stage of esophageal or esophagogastric junction adenocarcinoma after neoadjuvant chemotherapy determines prognosis rather than the clinical stage before neoadjuvant chemotherapy, indicating the importance of focusing on postchemotherapy staging to more accurately predict outcome and eligibility for surgery. Patients who are downstaged by neoadjuvant chemotherapy benefit from reduced rates of local and systemic recurrence.
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
The optimal surgical approach to tumours of the oesophagus and oesophagogastric junction remains controversial. The principal randomized trial comparing transhiatal (THO) and transthoracic ...(TTO) oesophagectomy showed no survival difference, but suggested that some subgroups of patients may benefit from the more extended lymphadenectomy typically conducted with TTO.
Methods
This was a cohort study based on two prospectively created databases. Short‐ and long‐term outcomes for patients undergoing THO and TTO were compared. The primary outcome measure was overall survival, with secondary outcomes including time to recurrence and patterns of disease relapse. A Cox proportional hazards model provided hazard ratios (HRs) and 95 per cent confidence intervals (c.i.), with adjustments for age, tumour stage, tumour grade, response to chemotherapy and lymphovascular invasion.
Results
Of 664 included patients (263 THO, 401 TTO), the distributions of age, sex and histological subtype were similar between the groups. In‐hospital mortality (1·1 versus 3·2 per cent for THO and TTO respectively; P = 0·110) and in‐hospital stay (14 versus 17 days respectively; P < 0·001) favoured THO. In the adjusted model, there was no difference in overall survival (HR 1·07, 95 per cent c.i. 0·84 to 1·36) or time to tumour recurrence (HR 0·99, 0·76 to 1·29) between the two operations. Local tumour recurrence patterns were similar (22·8 versus 24·4 per cent for THO and TTO respectively). No subgroup could be identified of patients who had benefited from more radical surgery on the basis of tumour location or stage.
Conclusion
There was no difference in survival or tumour recurrence for TTO and THO.
Surgical approach makes little difference to long‐term outcomes
Background
The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often ...used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins.
Methods
Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence‐free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score‐matched analysis was also performed.
Results
Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence‐free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non‐responders (Mandard tumour regression grade 4–5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score‐matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence‐free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment.
Conclusion
Adjuvant therapy may improve overall survival and recurrence‐free survival after margin‐positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non‐responders to neoadjuvant chemotherapy.
Antecedentes
El papel del tratamiento adyuvante en pacientes con adenocarcinoma esofagogástrico tratados con quimioterapia neoadyuvante es polémico. En la práctica del Reino Unido, el estado del margen de resección quirúrgico se utiliza a menudo para identificar a los pacientes que reciben tratamiento adyuvante. El objetivo de este estudio fue evaluar el beneficio en la supervivencia del tratamiento adyuvante en pacientes con márgenes de resección positivos (R1).
Métodos
Se combinaron dos bases de datos de instituciones del Reino Unido que recogen información de forma prospectiva para identificar pacientes elegibles. Se utilizaron análisis de regresión de Cox ajustados para comparar la supervivencia global y la supervivencia libre de recidiva según el tratamiento adyuvante. Los patrones de recidiva se evaluaron como resultado secundario. También se realizó un análisis de emparejamiento por puntaje de propensión.
Resultados
De 616 pacientes incluidos en la base de datos combinada, se incluyeron en el estudio 242 pacientes con resección R1. De estos pacientes, 112 (46%) recibieron quimiorradioterapia adyuvante, 46 (19%) pacientes fueron tratados con quimioterapia adyuvante y 84 (35%) pacientes no recibieron ningún tratamiento. En el análisis ajustado, la quimiorradioterapia adyuvante mejoró la supervivencia libre de recidiva (cociente de riesgos instantáneos, hazard ratio, HR 0,59, i.c. del 95% 0,38‐0,94; P = 0,026) con un beneficio tanto para la recidiva local (HR 0,48, i.c. del 95% 0,24‐0,99; P = 0,047) como para la sistémica (HR 0,56, i.c. del 95% 0,33‐0,94; P = 0,027). Cuando los pacientes se clasificaron según la respuesta tumoral a la quimioterapia neoadyuvante, los no respondedores (Mandard Grado 4/5) tratados con quimiorradioterapia adyuvante obtuvieron un beneficio en la supervivencia (HR 0,61, i.c. del 95% 0,38‐0,97; P = 0,037). En el análisis por emparejamiento por puntaje de propensión, se observó un beneficio en la supervivencia global (HR 0,62, i.c. del 95% 0,39‐0,98; P = 0,042) y en la supervivencia libre de recidiva (HR 0,51.i.c. del 95% 0,30‐0,87; P = 0,004) con la quimiorradioterapia adyuvante frente a no recibir tratamiento adyuvante.
Conclusión
El tratamiento adyuvante puede mejorar la supervivencia global y la supervivencia libre de recidiva en pacientes con margen de resección positivo. Este patrón parece más pronunciado con la quimiorradioterapia adyuvante en pacientes que no responden a la quimioterapia.
In UK practice, surgical resection margin status is often used to stratify patients for receipt of adjuvant treatment. This cohort study suggested both an overall and recurrence‐free survival benefit following adjuvant therapy in patients with positive margins, who had undergone neoadjuvant chemotherapy and resectional surgery for oesophageal adenocarcinoma. The benefit seemed greater with adjuvant chemoradiotherapy and in poor responders to neoadjuvant chemotherapy.
Decreases recurrence and improves survival
OBJECTIVE—Rapid thrombus recanalization reduces the incidence of post–thrombotic complications. This study aimed to discover whether adenovirus-mediated transfection of the vascular endothelial ...growth factor gene (ad.VEGF) enhanced thrombus recanalization and resolution.
METHODS AND RESULTS—In rats, thrombi were directly injected with either ad.VEGF (n=40) or ad.GFP (n=37). Thrombi in SCID mice (n=12) were injected with human macrophages transfected with ad.VEGF or ad.GFP. Thrombi were analyzed at 1 to 14 days. GFP was found mainly in the vein wall and adventitia by 3 days, but was predominantly found in cells within the body of thrombus by day 7. VEGF levels peaked at 4 days (376±299 pg/mg protein). Ad.VEGF treatment reduced thrombus size by >50% (47.7±5.1 mm to 22.0±4.0 mm, P=0.0003) and increased recanalization by >3-fold (3.9±0.69% to 13.6±4.1%, P=0.024) compared with controls. Ad.VEGF treatment increased macrophage recruitment into the thrombus by more than 50% (P=0.002). Ad.VEGF-transfected macrophages reduced thrombus size by 30% compared with controls (12.3±0.89 mm to 8.7±1.4 mm, P=0.04) and enhanced vein lumen recanalization (3.39±0.34% to 5.07±0.57%, P=0.02).
CONCLUSION—Treatment with ad.VEGF enhanced thrombus recanalization and resolution, probably as a consequence of an increase in macrophage recruitment.
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