Several pathohistological classification systems exist for the diagnosis of gastric cancer.Many studies have investigated the correlation between the pathohistological characteristics in gastric ...cancer and patient characteristics,disease specific criteria and overall outcome.It is still controversial as to which classification system imparts the most reliable information,and therefore,the choice of system may vary in clinical routine.In addition to the most common classification systems,such as the Laurén and the World Health Organization(WHO)classifications,other authors have tried to characterize and classify gastric cancer based on the microscopic morphology and in reference to the clinical outcome of the patients.In more than 50 years of systematic classification of the pathohistological characteristics of gastric cancer,there is no sole classification system that is consistently used worldwide in diagnostics and research.However,several national guidelines for the treatment of gastric cancer refer to the Laurén or the WHO classifications regarding therapeutic decision-making,which underlines the importance of a reliable classification system for gastric cancer.The latest results from gastric cancer studies indicate that it might be useful to integrate DNA-and RNA-based features of gastric cancer into the classification systems to establish prognostic relevance.This article reviews the diagnostic relevance and the prognostic value of different pathohistological classification systems in gastric cancer.
For Siewert type II adenocarcinoma of the esophagogastric junction (AEG II), or similar tumors classified as Nishi EG, E=G, GE, the type of surgical resection and reconstruction should be ...individualized. Criteria for decision making mainly focus on the oral extent of esophageal infiltration, the cT and cN category and the functional status of the patient. For cT1/cT2 adenocarcinomas, which are non-poorly cohesive, intestinal type of Lauren Grading 1 or 2 without clinical signs of lymph node metastasis at the distal stomach, a limited transhiatal proximal gastrectomy with double tract reconstruction is recommended. For advanced adenocarcinomas, subtotal esophageal and proximal gastric resection with gastric pull-up or distal esophageal resection with total gastrectomy and esophagojejunostomy are competing procedures. Criteria for choosing the appropriate type of surgery are discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Objective Chylothorax is a major complication after esophagectomy. As recent studies refer to heterogeneous patient cohorts and surgical procedures, this study was conducted to report the ...incidence and evaluate the optimal management of chylous fistula in patients treated with transthoracic esophagectomy and two-field lymphadenectomy for esophageal cancer. Methods From 01/2005 to 12/2013 a total of 906 patients underwent transthoracic esophageal resection for esophageal carcinoma at our institution. En-bloc esophagectomy was performed with routine supradiaphragmatic ligation of the thoracic duct. The incidence of chylothorax, associated morbidity and mortality were analyzed and subsequent therapeutic management was reviewed. Results Chylothorax after Ivor Lewis esophagectomy could be observed in 17 patients (1.9%). Fifteen patients required surgical intervention with rethoracotomy and repeat duct ligation. Thoracic duct ligation was successful in all patients. Two patients died within 90 days after primary esophageal resection. Median time between initial tumor resection and rethoracotomy was 13 days. Average daily chest tube output at time of reoperation was 1900ml. In 2 patients pleural effusion did not exceed more than 1000 ml per day. In these cases conservative management with additional thoracic drainage and total parenteral nutrition led to complete resolution of chylous fistula. Conclusions Occurrence of chylothorax after prophylactic thoracic duct ligation during transthoracic esophagectomy for esophageal cancer is rare. In patients with high-output chylous fistula an early rethoracotomy with religation of the thoracic duct is safe and helps to shorten the recovery time. In the case of low volume drainage, a conservative approach is feasible.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of ...purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.
Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.
This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).
This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
Background and aims
Clinicopathological characteristics of gastric cancer (GC) are changing, especially in the West with a decreasing incidence of distal, intestinal-type tumours and the ...corresponding increasing proportion of tumours with Laurén diffuse or WHO poorly cohesive (PC) including signet ring cell (SRC) histology. To accurately assess the behaviour and the prognosis of these GC subtypes, the standardization of pathological definitions is needed.
Methods
A multidisciplinary expert team belonging to the European Chapter of International Gastric Cancer Association (IGCA) identified 11 topics on pathological classifications used for PC and SRC GC. The topics were debated during a dedicated Workshop held in Verona in March 2017. Then, through a Delphi method, consensus statements for each topic were elaborated.
Results
A consensus was reached on the need to classify gastric carcinoma according to the most recent edition of the WHO classification which is currently WHO 2010. Moreover, to standardize the definition of SRC carcinomas, the proposal that only WHO PC carcinomas with more than 90% poorly cohesive cells having signet ring cell morphology have to be classified as SRC carcinomas was made. All other PC non-SRC types have to be further subdivided into PC carcinomas with SRC component (< 90% but > 10% SRCs) and PC carcinomas not otherwise specified (< 10% SRCs).
Conclusion
The reported statements clarify some debated topics on pathological classifications used for PC and SRC GC. As such, this consensus classification would allow the generation of evidence on biological and prognostic differences between these GC subtypes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Immune checkpoint modulation in cancer has been demonstrated as a high-value therapeutic strategy in many tumor entities. VISTA is an immune checkpoint receptor regulating T-cell function. To the ...best of our knowledge, nothing is known about the expression and prognostic impact of VISTA on tumor infiltrating lymphocytes (TILs) in the tumor microenvironment of esophageal adenocarcinoma (EAC). We analyzed in total 393 EACs within a test-cohort (n = 165) and a validation-cohort (n = 228) using a monoclonal antibody (clone D1L2G). These data were statistically correlated with clinical as well as molecular data. 22.2% of the tumor cohort presented with a VISTA expression on TILs. These patients demonstrated an improved median overall survival compared to patients without VISTA expression (202.2 months vs. 21.6 months; p < 0.0001). The favorable outcome of VISTA positive tumors is significant in the entire cohort but mainly driven by the general better prognosis of T1/T2 tumors. However, in the pT1/2 group, VISTA positive tumors show a tremendous survival benefit compared to VISTA negative tumors revealing real long-term survivors in this particular subgroup. The survival difference is independent of the T-stage. This unique characteristic could influence neoadjuvant therapy concepts for EAC, since a profit of therapy could be reduced in the already favorable subgroup of VISTA positive tumors. VISTA emerges as a prognostic biomarker for long-term survival especially in the group of early TNM-stages. Future studies have to show the relevance of VISTA positive TILs within a tumor concerning response to specific immune checkpoint inhibition.
Residual tumor at the resection margins after surgery for gastric and gastroesophageal junction (GEJ) adenocarcinoma is a known prognostic factor. In this single-center, retrospective cohort study in ...a tertiary referral center, we aimed to evaluate the relevance of intraoperative pathology consultation (IOC) and consecutive extension of surgery on patient survival.
Of 737 consecutive patients undergoing (sub)total gastrectomy for gastric or GEJ adenocarcinoma, 679 cases with curative intent surgery between 05/1996 and 03/2019 were included. Patients were categorized into: i) R0 without further resection (direct R0), ii) R0 after positive IOC and extension of resection (converted R0) and iii) R1.
IOC was performed in 242 (35.6%) patients, in 216 (89.3%) at the proximal resection margin. Direct R0 status was achieved in 598 (88.1%), converted R0 in 26 (3.8%) of 38 (5.6%) patients with positive IOC and R1 in 55 (8.1%) patients. Median follow-up was 29 months for surviving patients. 3-year survival rate (3-YSR) was significantly higher for direct R0 compared to converted R0 with 62.3% compared to 21.8% (hazard ratio (HR)=0.298; 95%CI=0.186-0.477, P<0.001). 3-YSR was similar between converted R0 and R1 (21.8% vs. 13.3%; HR=0.928; 95%CI=0.526-1.636, P=0.792). In multivariate analysis, advanced T (P<0.001), N (P<0.001), R (P=0.003) and M1 status (P<0.001) were associated with worse overall survival (OS).
IOC and consecutive extended resection for positive resection margins in gastrectomy for proximal gastric and gastroesophageal junction does not achieve long-term survival benefits in advanced tumor stages.
Background
Esophagectomy with gastric tube reconstruction and extended transhiatal gastrectomy with Roux-en-Y reconstruction are alternative procedures in current therapeutic concepts for ...adenocarcinoma of the esophagogastric junction (AEG). The impact of these operations on long-term health-related quality of life (HRQL) is incompletely understood.
Methods
Patients with cancer-free survival of at least 24 months after esophagectomy (ESO) or extended gastrectomy (GAST) for AEG were identified from a prospectively maintained database. EORTC questionnaires were sent out to assess health-related general (QLQ-C30) and cancer-specific (OG-25) quality of life. Numeric scores were calculated for each conceptual area and compared with those of healthy reference populations.
Results
123 patients (ESO
n
= 71; GAST
n
= 52) completed the self-rated questionnaires. HRQL was consistently lower in surgical patients (GAST and ESO) compared with healthy reference populations. Also, there was a general trend for a better HRQL in GAST compared with ESO patients. This trend was statistically significant for physical function (
p
= 0.04), dyspnea (
p
= 0.02), and reflux (
p
= 0.03). Subgroup analysis revealed no significant differences between patients with or without prior neoadjuvant therapy.
Conclusions
After mid- and long-term follow-up, HRQL after extended gastrectomy with Roux-en-Y reconstruction is superior to that after esophagectomy and gastric tube reconstruction. Improved HRQL after gastrectomy is mainly due to less pulmonary and reflux-related symptoms. Our findings may influence the choice of the surgical strategy for patients with AEG.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality ...outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery.
Methods
In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996–2006) (pre-CTx) and b) after (2006–2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR).
Results
737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (
p
< 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (
p
= 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (
p
= 0.357), age (
p
= 0.379), pT category (
p
= 0.817), pN stage (
p
= 0.074), cM stage (
p
= 0.112), Laurén classification (
p
= 0.158), and SRs (3-YSR: 60.3% vs 59.4%;
p
= 0.898) between the MAGIC and FLOT regimens.
Conclusions
Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To prospectively assess the sensitivity (sens), specificity (spec), positive predictive value (ppv), negative predictive value (npv), and accuracy (acc) for clinical response evaluation by endoscopy, ...rebiopsy, and endoscopic ultrasound (EUS) to determine histomorphologic regression UICC T-category downstaging after neoadjuvant chemoradiation for esophageal cancer.
Histomorphologic regression is meanwhile established as objective parameter for response and prognosis after neoadjuvant chemoradiation for esophageal cancer.
Within a prospective observation trial, 80 patients with localized esophageal cancers (cT2-4,Nx,M0) received standardized neoadjuvant chemoradiation (cisplatin, 5-fluorouracil, 36 Gy) and were resected by transthoracic en bloc esophagectomy and two-field lymphadenectomy. Tumor regression was based on the percentage of vital residual tumor cells and classified in 4 categories as reported previously. Evaluation by endoscopy and EUS was performed based on WHO/UICC criteria before starting chemoradiation and before resection and rebiopsies were taken at the time of re-endoscopy.
Histomorphologic response was of significant (log rank) prognostic importance (P < 0.001), whereas clinical response evaluation by endoscopy (P = 0.1), rebiopsy (P = 0.34), and EUS (P = 0.35) was not. The results of the 3 diagnostic modalities to assess histomorphologic regression by endoscopy and rebiopsy UICC ypT-category downstaging for EUS are summarized: Endoscopy: sens 60%, spec 34%, ppv 49%, npv 44%, acc 47%. Rebiopsy: sens 36%, spec 100%, ppv 100%, npv 24%, acc 47%. EUS: sens 7%, spec 79%, ppv 18%, npv 57%, acc 50%.
Histomorphologic regression is an objective response parameter of significant prognostic importance. The diagnostic accuracy of endoscopy, rebiopsy, and EUS is inadequate for objective response evaluation after neoadjuvant chemoradiation and can be omitted for this purpose in the clinical practice.
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