The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not ...easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis.
ABSTRACT
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS‐induced lung injury and ...inflammation; however, its role in inflammation‐mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)–induced murine colitis and found inhibition of DSS‐induced inflammation in SMS2‐deficient (SMS2−/−) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2−/− colon tissue, and demonstrated attenuation of the elevation of both inflammation‐related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild‐type bone marrow, SMS2−/− mice also exhibited inhibition of DSS‐induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow–derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS‐induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS‐induced colitis and subsequent colitis‐associated colon cancer via inhibition of colon epithelial cell–mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic target for human colitis and colorectal cancer.—Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis‐associated colon cancer. FASEB J. 31, 3816–3830 (2017). www.fasebj.org—Ohnishi, Toshio, Hashizume, Chieko, Taniguchi, Makoto, Furumoto, Hidehiro, Han, Jia, Gao, Rongfen, Kinami, Shinichi, Kosaka, Takeo, Okazaki, Toshiro Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis‐associated colon cancer. FASEB J. 31, 3816–3830 (2017)
Background
The incidence of metachronous multiple gastric cancer (MMGC) after gastrectomy remains unclear. This study evaluated the incidences of MMGC according to specific gastrectomy types, ...including pylorus-preserving gastrectomy (PPG), proximal gastrectomy (PG), and function-preserving gastrectomy (FPG), which was categorized as segmental gastrectomy and local resection.
Methods
We conducted a questionnaire survey of the Japanese Society for Gastro-Surgical Pathophysiology members, who were asked to report their institutional numbers of radical gastrectomy cases for cancer between 2003 and 2012. The cases were categorized according to whether the remnant stomach’s status was followed for > 5 years, confirmation of MMGC, time to diagnosis, and treatment for MMGC. We calculated the “precise incidence” of MMGC by dividing the number of MMGC cases by the number of cases in which the status of remnant stomach was followed up for > 5 years.
Results
The responses identified 33,731 cases of gastrectomy. The precise incidences of MMGC were 2.35% after distal gastrectomy (DG), 3.01% after PPG, 6.28% after PG (
p
< 0.001), and 8.21% after FPG (
p
< 0.001). A substantial proportion of MMGCs (36.4%) was found at 5 years after the initial surgery. The rates of MMGC treatment using endoscopic submucosal dissection were 31% after DG, 28.6% after PPG, 50.8% after PG (
p
< 0.001), and 67.9% after FPG (
p
< 0.001).
Conclusions
The incidence of MMGC was 2.4% after DG, and higher incidences were observed for larger stomach remnants. However, the proportion of cases in which MMGC could be treated using endoscopic submucosal dissection was significantly higher after PG and FPG than after DG.
Complicated gastric lymphatic drainage potentially undermines the utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged by several favorable single-institution reports, we ...conducted a multicenter, single-arm, phase II study of SN mapping that used a standardized dual tracer endoscopic injection technique.
Patients with previously untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were eligible for inclusion in this study. SN mapping was performed by using a standardized dual tracer endoscopic injection technique. Following biopsy of the identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was performed according to current Japanese Gastric Cancer Association guidelines.
Among 433 patients who gave preoperative consent, 397 were deemed eligible on the basis of surgical findings. SN biopsy was performed in all patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of 57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99% (383 of 387). Only four false-negative SN biopsies were observed, and pathologic analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We observed no serious adverse effects related to endoscopic tracer injection or the SN mapping procedure.
The endoscopic dual tracer method for SN biopsy was confirmed as safe and effective when applied to the superficial, relatively small gastric adenocarcinomas included in this study.
Background
Lack of a suitable instrument to comprehensively assess symptoms, living status, and quality of life in postgastrectomy patients prompted the authors to develop postgastrectomy syndrome ...assessment scale (PGSAS)-45.
Methods
PGSAS-45 consists of 45 items in total: 8 items from SF-8, 15 items from GSRS, and an additional 22 items selected by 47 gastric surgeons. Using the PGSAS-45, a multi-institutional survey was conducted to determine the prevalence of postgastrectomy syndrome and its impact on everyday life among patients who underwent various types of gastrectomy. Eligible data were obtained from 2,368 patients operated and followed at 52 institutions in Japan. Of these, data from 1,777 patients were used in the current study in which symptom subscales of the PGSAS-45 were determined. We also considered the characteristics of the postgastrectomy syndrome and to what extent these symptoms influence patients’ living status and quality of life (QOL).
Results
By factor analysis, 23 symptom-related items of PGSAS-45 were successfully clustered into seven symptom subscales that represent esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation, and dumping. These seven symptom subscales and two other subscales measuring quality of ingestion and dissatisfaction for daily life, respectively, had good internal consistency in terms of Cronbach′s α (0.65–0.88).
Conclusion
PGSAS-45 provides a valid and reliable integrated index for evaluation of symptoms, living status, and QOL in gastrectomized patients.
Background
Proximal gastrectomy (PG) has become an increasingly preferred procedure for early cancer in the upper third of the stomach, owing to reportedly superior quality of life (QOL) after PG ...when compared with total gastrectomy. However, various methods of reconstruction have currently been proposed. We compared the postoperative QOL among the three different reconstruction methods after PG using the Postgastrectomy Syndrome Assessment Scale-45 (PGSAS-45) questionnaire.
Methods
Post Gastrectomy Syndrome Assessment Study (PGSAS), a nationwide multi-institutional survey, was conducted to evaluate QOL using the PGSAS-45 among various types of gastrectomy. Of the 2,368 eligible data from the PGSAS survey, data from 193 patients who underwent PG were retrieved and used in the current study. The PGSAS-45 consists of 45 items including 22 original gastrectomy specific items in addition to the SF-8 and GSRS. These were consolidated into 19 main outcome measures pertaining postgastrectomy symptoms, amount of food ingested, quality of ingestion, work, and level of satisfaction for daily work, and the three reconstruction methods (
n
= 193; 115 esophago-gastrostomy PGEG, 34 jejunal interposition PGJI, and 44 jejunal pouch interposition PGJPI) were compared using PGSAS-45.
Results
Size of the remnant stomach was significantly larger in PGEG, and significantly smaller in PGJI and PGJPI (
P
< 0.05). There was no difference in other patient background factors among the groups. EGJPI tended to be superior to PGEG in several of the 19 main outcome with marginal significance (
P
= 0.047–0.076).
Conclusion
PGJPI appears to be the most favorable of the three reconstruction methods after PG especially when the size of remnant stomach is rather small.
Trial registration number
UMIN-CTR #000002116 entitled as “A study to observe correlation between resection and reconstruction procedures employed for gastric neoplasms and development of postgastrectomy syndrome”
Background
Standard gastrectomy with systematic lymphadenectomy as an additional surgery after endoscopic resection (ER) causes a deterioration in long-term quality of life. If the sentinel lymph ...node (SN) basin concept can be applied in post-ER gastric cancer, minimal surgery can be applied without reducing the curability. This retrospective multicenter cohort study aimed to verify the validity of the SN basin concept in post-ER gastric cancer.
Patients and methods
Individual data of 132 patients who underwent SN mapping after ER were collected from 8 university hospitals in Japan from 2001 to 2016. Tracers were injected endoscopically in the submucosal layer at four sites around the post-ER scar. We compared the SN basin distribution of post-ER gastric cancer with that of 275 patients with non-ER gastric cancer.
Results
Two cases of SN were unidentified, both involving a single tracer (SN detection rate: 98.5%). Nine cases (6.8%) of lymph node metastasis were found, of which eight had a metastatic lymph node within the SNs and one had a non-SN metastasis within the SN basin. The diagnostic sensitivity of SN mapping for lymph node metastasis was 88.9% in post-ER group and 95.7% in non-ER group (
P
= 0.490); the accuracy was 99.2% and 99.6% (
P
= 0.539), respectively. Regarding the SN basin, no significant intergroup differences were found regardless of the primary tumor location.
Conclusions
Our findings clarified the feasibility of SN mapping based on the SN basin concept in patients with gastric cancer who previously underwent ER.
Abstract
This prospective multicenter non-randomized phase III study aims to evaluate the long-term outcome of sentinel node navigation surgery for early gastric cancer compared with conventional ...distal or total gastrectomy. Clinically diagnosed primary T1N0M0 gastric cancer patients with a single lesion (≤40 mm) and without previous endoscopic treatment will be enrolled in this study. Sentinel nodes are identified by dye and radioisotope tracers and are subjected to intraoperative rapid pathology. For patients with negative sentinel node metastasis, individualized surgery consisting of limited stomach resection and sentinel node basin dissection is performed, while standard gastrectomy with D2 lymph node dissection is employed for the positive sentinel node patients. A total of 225 patients will be accrued from 13 hospitals that have experience in sentinel node mapping. The primary endpoint is 5-year relapse-free survival. The secondary endpoints are overall survival, sentinel node detection rate, diagnostic accuracy for sentinel node, distribution of sentinel nodes and metastatic sentinel node/non-sentinel node, and postoperative quality of life.
This is a multicenter non-randomized phase III study to assess the non-inferiority of the long-term outcome of sentinel node navigation surgery to that of conventional gastrectomy in early gastric cancer.
Background
Although double tract reconstruction after proximal gastrectomy (PGDT) is commonly performed for proximal gastric or esophagogastric junction cancer, the impact of the procedure on ...postoperative quality of life (QOL) has not been clarified. We aimed to clarify the optimal PGDT procedure in terms of postoperative QOL.
Methods
Postoperative QOL was analyzed in 172 patients who underwent PGDT for proximal gastric cancer and were enrolled in the PGSAS-NEXT study, a multicenter cross-sectional study in Japan (UMIN000032221), in relation to the remnant stomach size, length of interposed jejunum between the esophagojejunostomy (E-J) and jejunogastrostomy (J-G), and size of the J-G.
Results
The remnant stomach size was approximately one-third in 13, half in 97, and two-thirds in 60 patients. Dissatisfaction scores for symptoms, diet, work, and daily life subscales were lower in patients with a larger stomach (
p
< 0.05). These patients also scored better in terms of weight loss (− 13.5%, − 14.0%, and − 11.2%, respectively) and amount of food ingested per meal (52%, 62%, and 66%). The length of the interposed jejunum was ≤ 10 cm in 62 and ≥ 11 cm in 97 patients. Weight loss (− 11.3% and − 13.8%) and dissatisfaction scores were better in the ≤ 10 cm group (
p
< 0.05). J-G size was ≤ 5 cm in 27 and ≥ 6 cm in 135 patients. The amount of food ingested (56%, 64%) and dissatisfaction scores were better in the > 6 cm group (
p
< 0.05).
Conclusions
Larger remnant stomach, shorter length of interposed jejunum, and longer J-G might contribute to better postoperative QOL after PGDT.
AIM To identify certain clinical factors other than the type of gastrectomy which affect the postoperative quality of life(QOL) of patients after gastrectomy.METHODS The postgastrectomy syndrome ...assessment scale(PGSAS)-45 was designed to assess the severity of symptoms, the living status and the QOL of gastrectomized patients. It consists of 45 items, of which 22 are original items while 23 were retrieved from the SF-8 and Gastrointestinal Symptoms Rating Scale questionnaires with permission. A nationwide surveillance study to validate PGSAS was conducted and 2368 gastric cancer patients who underwent various types of gastrectomy at 52 medical institutions were enrolled. Of these, 1777 patients who underwent total gastrectomy(TG) reconstructed with Roux-Y(n = 393), distal gastrectomy(DG) reconstructed with Billroth-I(n = 909), or DG reconstructed with Roux-Y(n = 475) were evaluated in the current study. The influence of the type of gastrectomy and other clinical factors such as age, sex, duration after surgery, the symptom severity, the degree of weight loss, dietary intake, and the ability for working on the postoperative QOL(i.e., dissatisfaction for daily life subscale, physical component summary and mental component summary of the SF-8) were examined by multiple regression analysis(MRA). In addition, importance of various symptoms such as esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation and dumping on the postoperative living status and QOL were also appraised by MRA.RESULTS The postoperative QOL were significantly deteriorated in patients who underwent TG compared to those after DG. However, the extent of gastrectomy was not an influential factor on patients’ QOL when adjusted by the MRA. Among various clinical factors, the symptom severity, ability for working, and necessity for additional meals were the most influential factorsto the postoperative QOL. As for the individual symptoms, meal-related distress, dumping, abdominal pain, and esophageal reflux significantly affected the postoperative QOL in that order, while the influence of indigestion, diarrhea and constipation was insignificant. CONCLUSION Several clinical factors such as the symptom severity(especially in meal-related distress and dumping), ability for working and necessity for additional meals were the main factors which affected the patients’ wellbeing after gastrectomy.
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