A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

Background: The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. Materials & methods: A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survival and individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation. The primary outcome was the cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were undertaken to investigate uncertainty. Results: Compared with BSC, T/T was associated with a cost per QALY gained of £37,907. Conclusion: T/T provides a cost-effective treatment option for mGC in the UK setting.

Assessment of Lymph Node Metastasis in Patients With Gastric Cancer to Identify Those Suitable for Middle Segmental Gastrectomy.

Importance: Segmental gastrectomy, a type of function-preserving surgery, is not broadly studied but can improve postoperative function and quality of life among patients with gastric cancer (GC). Objective: To establish an indication for middle segmental gastrectomy (MSG) as a treatment for middle-body (MB) and high-body (HB) GC. Design, Setting, and Participants: This cohort study analyzed patients with GC undergoing surgery between January 2000 and December 2015 in the National Cancer Center, Goyang, Korea, a high-volume cancer center with a structured database and accurate long-term follow-up. Inclusion criteria were age 18 to 85 year, histologically proven adenocarcinoma located in the HB or MB, cT1 to cT3 category cancers, curative resection with negative margins performed, and follow-up for at least 3 years. Exclusion criteria were Borrmann type 4 GC, T4 category cancer, neoadjuvant chemotherapy, and a history of other cancers. Data analysis was performed from December 2018 to May 2020. Exposures: Total or subtotal gastrectomy and LN dissection. Main Outcome and Measures: The primary outcome was the rate of metastasis at LN stations 2, 4sa, 5, 6, and 11d, which cannot be dissected during MSG. Results: Among 9952 patients who underwent surgery for GC, 8219 underwent either laparoscopic or open total or subtotal gastrectomy. Seven hundred seventy-three patients (mean [SD] age, 56.21 [12.16] years; 464 men [60.0%]) had GC in the MB or HB of the stomach. Among the 701 patients included in the final analysis after exclusion of the cN2/N3 carcinomas, the mean (SD) age was 56.35 (12.24) years, and 418 (59.6%) were men. The incidence of LN metastasis was 0% at station 5 for cT1-3N0/1M0 cancers, station 4sa for cT1-2N0/1M0 cancers, station 2 for cT1N0/1M0 cancers, station 6 for cT1N1M0 cancers, station 11d for cT1N1M0-cT2N0/1M0 cancers, and station 12a for cT1N0/1M0-T2N1M0 cancers, regardless of size and differentiation. The rates of LN metastasis for cT1N0M0 cancers were 0.3% (1 of 396 LNs) at station 6 and 0.8% (1 of 129 LNs) at station 11d. Tumors 4 cm or smaller were associated with a lower risk of LN metastasis compared with tumors 4.1 cm or larger (odds ratio, 2.10; 95% CI, 1.20-3.67; P = .009), and well-differentiated tumors were associated with lower risk of LN metastasis compared with poorly differentiated tumors (odds ratio, 2.88; 95% CI, 1.45-5.73; P = .002). Conclusions and Relevance: These findings suggest that MSG with dissection of stations 1, 3, 4sb, 4d, 7, 8a, 9, 11p, and 12a could be done for HB and MB cT1N0/1M0 gastric cancers 4 cm or smaller and well-differentiated cT2N0/1M0 cancers.

Cost-effectiveness of trifluridine/tipiracil (TAS102) for heavily pretreated metastatic gastric cancer.

BACKGROUND AND AIM: Trifluridine/tipiracil (TAS102), a novel oral cytotoxic chemotherapy, significantly improved overall survival compared with placebo in heavily pretreated advanced gastric cancer. This study aimed to evaluate the cost-effectiveness of TAS102 in the third-line or later treatment for this population from the US payer perspective. METHODS: A Markov model was developed to simulate advanced gastric cancer, including three health states: progression-free survival (PFS), progressive disease (PD) and death. Model inputs were derived from a randomised, double-blind, placebo-controlled, phase 3 trial (TAGS trial, NCT02500043). Utilities were extracted from public resources. Costs were calculated from an American payer perspective. Sensitivity analyses were conducted to explore the impact of uncertainty. RESULTS: From the US payer perspective, treatment with TAS102 for patients with heavily pretreated advanced gastric cancer was estimated to increase costs by $59,180 compared with the placebo, with a gain of 0.06 quality-adjusted life years (QALYs) for an incremental cost-effectiveness ratio (ICER) of $986,333 per QALY. The costs for progression-free survival of TAS102 group had the greatest impact on the ICERs, as well as the cost of TAS102. CONCLUSION: Trifluridine/tipiracil (TAS102) is not a cost-effective choice for patients with heavily pretreated metastatic gastric cancer from an American payer perspective.

Quantitative assessment of visual estimation of the infrared indocyanine green imaging of lymph nodes retrieved at sentinel node navigation surgery for gastric cancer.

BACKGROUND: Although the infrared indocyanine green (ICG) imaging is an effective method to identify sentinel lymph nodes (SLNs) of gastric cancer, its objectivity has not been verified. METHODS: We studied 563 lymph nodes under infrared light observation from the ICG-positive lymphatic basins of 36 patients who underwent SLN-navigated gastrectomy for clinically node-negative gastric cancer. First, the rate of SLN detection, the number of SLNs and sensitivities were compared between ordinary light observation and infrared light observation. Second, 563 lymph nodes were grouped into ICG-positive and -negative under infrared light observation. The intensities of the region of interest for each lymph node defined as the lymph node on which digital imaging was performed using an imaging-software, and the region of reference defined as its surrounding background, were compared and quantified. RESULTS: In the comparison of ordinary light observation with infrared light observation, the SLN identification rates were 28/36 (78 %) vs. 36/36 (100 %), the mean ± SD (minimum to maximum) number of SLNs was 3.4 ± 3.7 (0-16) vs. 9.2 ± 5.9 (2-25), and the sensitivities were 1/5 (20 %) vs. 5/5 (100 %). The ICG-positive group contained 358 lymph nodes with an intensity of 0.323 ± 1.56 (mean ± SD), and the ICG-negative group contained 205 lymph nodes with an intensity of 0.639 ± 1.93 (mean ± SD), demonstrating a significant difference between these two groups (P < 0.0001). CONCLUSIONS: The significant difference in the intensity as measured by an imaging-software between ICG-positive and ICG-negative lymph nodes would erase the concern about the objectivity of the infrared ICG method for SLN-navigated surgery for early gastric cancer.

Different lymph node staging systems in patients with gastric cancer from Korean: What is the best prognostic assessment tool?

To investigate whether the log odds of positive lymph nodes (LODDS) system is a more accurate prognostic tool than the number-based (pN) or ratio-based (rN) lymph node staging system in Korean patients with gastric cancer (GC).The LODDS is a recently proposed staging modality in surgical oncology. However, it is unclear whether LODDS is superior to the pN or rN system in terms of predicting the prognosis of GC patients who underwent radical gastrectomy with extended lymphadenectomy and had a greater number of retrieved lymph nodes.Clinicopathological data from 3929 patients who had undergone curative gastrectomy for GC were reviewed. In addition, overall survival rates according to pN and rN classification stratified by the LODDS were analyzed. A multivariate analysis of survival rate was performed using a Cox proportional hazard model.pN, rN, and LODDS were significantly correlated with 5-year survival rate. Spearman correlation test showed no correlation between LODDS and number of lymph nodes retrieved. The receiver operating characteristic (ROC) curves showed that the 3 staging systems had comparable prognostic accuracy (P < 0.05). Survival analysis according to pN and rN classification stratified by the LODDS staging system demonstrated that LODDS is superior to pN and rN.The LODDS is independently and significantly associated with the OS of Korean patients with GC, and its prognostic value is superior to that of the other lymph node staging systems in Korean patients.

Technique and assessment of sentinel lymph node biopsy usefulness in laparoscopy-assisted distal gastrectomy.

BACKGROUND: Recently, some studies have suggested that sentinel node biopsy also can be applied to gastric cancer. The authors apply sentinel lymph node biopsy in laparoscopy assisted distal gastrectomy to perform it as safe limited surgery. Limited surgery is a procedure in which the extent of lesion resection and lymph node dissection is reduced. The authors demonstrate that intraoperative diagnosis of lymph node metastasis is useful in this respect. METHODS: The study was conducted with 38 patients (29 men and 9 women) who had a preoperative diagnosis of T1 tumor invasion. The patients had a mean age of 66.2 years. Patent blue (1%) was injected submucosally into four or five different sites around the primary tumor at 1 ml per site. Blue-stained lymphatics and lymph nodes could be seen by turning over the greater omentum and the lesser omentum extraperitoneally. If blue nodes were found, biopsy was performed. RESULTS: The mean number of blue nodes dissected was 2.5 +/- 1.9. Intraoperative identification and biopsy of blue nodes could be performed for 35 (92.1%) of the 38 patients. Of the 35 patients in whom blue nodes were identified, 4 (9.7%) had metastases in blue nodes confirmed by intraoperative frozen-section diagnosis. Intraoperative frozen-section diagnosis was negative for blue node metastasis in 31 patients. Postoperative permanent section diagnosis also showed no evidence of lymph node metastasis in these 31 patients (100% accuracy, 0% false-negative rates). CONCLUSION: The reported method allows observation of blue-stained lymphatics up to 2 h after patent blue injection. Sentinel node biopsy was performed in laparoscopy assisted distal gastrectomy, making it technically equivalent to open gastrectomy. Sentinel node biopsy can serve as a method to determine the appropriate use of laparoscopy assisted distal gastrectomy for management of T1 gastric cancer.

[Fluorodeoxiglucose F18 positron emission tomography imaging (F18FDG) for the assessment of rising levels of serum CA 19-9 in pancreatic mucinous cystadenocarcinoma. Report of one case]. / Estudio de imágenes PET con Flúor18-Desoxiglucosa (F18FDG) en evaluación de elevación de marcador tumoral CA 19-9 en paciente con cistoadenocarcinoma mucinoso de páncreas.

We report a 38 year old female patient with a pancreatic mucinous cystadenocarcinoma. She presented at the onset with a peritoneal rupture that required emergency surgery. Five months later, the patient was subjected to a segmental pancreatectomy and splenectomy. One year later, the patient had a serious gastric bleeding secondary to a gastric ulcer. Due to a persistent increase in her CA 19-9 levels, a Positron Emission Tomography (PET) functional imaging with fluorine 18-deoxyglucose (F18FDG) was done. It showed an intense focal hypermetabolism in the gastric wall reported as a secondary tumour location. The patient was subjected to a total gastrectomy and Roux en Y anastomosis, with a good outcome. The pathological study confirmed the presence of a metastasis of an adenocarcinoma in the gastric wall. The relative value of CA 19-9 markers and FDG PET in pancreatic and gastric carcinomas is discussed.

[Tissue array technology for translational research. From gene discovery to application].

Large scale scanning of the human genome has become possible with the introduction of DNA microarray. The ability to survey the expression of up to 5000 to 50,000 genes in a single experiment provides significant new opportunities, as well as new challenge. It will be important to translate genomic scale information on cancer biology to functional or clinical application. This requires prioritization of hundreds of targets discovered, functional validation of these targets, as well as a thorough knowledge of the involvement of the candidate target genes in vivo in human tissue. We have developed a tissue array technology for genome scale expressional and clinical cancer research. This technology enables high-throughput molecular analysis of large number of specimens. Our tissue arrays are constructed by arranging the cylindrical biopsies of 2.0 mm diameter from 60 individual tumor tissues into a tissue array block, which is then sliced into 200 or more identical slides for probing RNA or protein targets. A single immunohistochemistry or in situ hybridization experiment provides information on all 60 specimens on the slides, while subsequent sections can be analyzed with other probes or antibodies. We produced gastric cancer tissue array slides with various kinds of subsets, including 600 subsequent cancer cases, 100 preneoplastic lesions, 60 metastatic lesions, 60 synchronous cancers, 60 metachronous cancers, 60 young age patients, and 120 familial cases. We searched the presence of Epstein-Barr virus in those cancer specimens. We also applied 10 antibodies in those samples and stratify the prognostic significance of these antibodies. Tissue array technology expand the scope of high-throughput molecular analysis of archival tissue specimens with multiple probes for specific genes or proteins for functional or clinical application.

Assessment of tumor cell kinetics by monoclonal antibody Ki-67.

The expression of Ki-67 antigen in 71 patients with advanced gastric cancer was studied by immunohistochemical technique. Immunohistochemical staining with Ki-67 produced clear labeling of a portion of tumor cell nuclei, and the nucleoli stained intensely. The Ki-67 labeling rates of the 71 specimens ranged from 7.7 to 70.5% (mean: 29.2%; standard deviation: 12.9%). There was no significant association between Ki-67 labeling rates and macroscopic type, peritoneal metastasis, or serosal invasion. The tumors showing high Ki-67 labeling rates (greater than 25%) are more likely to have liver metastasis and lymph node involvement. Larger tumors, with a diameter greater than 6 cm, more frequently showed high Ki-67 labelling rate than those with a diameter less than 6 cm. When the Ki-67 labeling rate and 9 clinicopathologic parameters, as conventional prognostic factors, were entered simultaneously into the regression model, nodal status and Ki-67 labeling rate emerged as independent prognostic factors. These results indicate that the in situ determination of the growth fraction by Ki-67 antibody may be a reliable prognostic marker of advanced gastric cancer.

[Sonographic imaging and assessment of stomach wall changes]. / Sonographische Darstellung und Beurteilung von Magenwandveränderungen.

By the use of a special method of investigation, the true value of percutaneous echography was investigated using 28 patients with primary gastric neoplasms and 3 patients with secondary infiltration of the gastric wall, for the proof and the judgement of the tumors, their extension and their metastases. Tumorous gastric wall thickening could be demonstrated in 87% (27/31), tumor invasion in neighbouring structures in 85% (12/14) and lymph nodes metastases in 66% (10/15). In all patients, who had liver metastases (4) or ascites (5) they were demonstrable. The sonographic appearance of the different gastric wall changes are described and discussed.

Comparison of 5- and 10-year survival rates in operated gastric cancer patients. Assessment of the 5-year survival rate as a valid indicator of postoperative curability.

To evaluate whether it is appropriate to estimate the postoperative curability of gastric cancer based on the 5-year survival rate, we compared 5- and 10-year survival rates in 477 primary gastric cancer patients who had undergone gastrectomy during the 8-year period from 1960-1967. In patients who had died more than 5 years after surgery, the cause of death was investigated. The 10-year survival rate of 315 curatively operated patients was 59.1%, 2.9% lower than the 5-year survival rate. Of 176 patients who survived more than 5 years postoperatively, only 9 (5.1%) died of cancer recurrence, suggesting that the 5-year survival rate adequately reflects the curative success of gastric cancer surgery. The postoperative curability of gastric cancer is usually estimated by the 5-year survival rate. However, even in patients who survived for more than 5 years postoperatively, cancer recurrence has been observed. Therefore, we deemed it useful to assess whether it is appropriate to estimate the postoperative curability of gastric cancer based on the 5-year survival rate. From this point of view, we compared the 5- and 10-year survival rates of operated primary gastric patients and investigated the cause of death in patients who died more than 5 years postoperatively. Furthermore, in patients with cancer recurrence more than 5 years postoperatively, the pathologic findings on the cancer in the originally resected specimen were re-evaluated.