To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer.
Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival ...benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive.
We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%.
Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (<1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025).
In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.
Backgrounds
No confirmatory randomized controlled trials (RCTs) have evaluated the efficacy of laparoscopy-assisted distal gastrectomy (LADG) compared with open distal gastrectomy (ODG). We performed ...an RCT to confirm that LADG is not inferior to ODG in efficacy.
Methods
We conducted a multi-institutional RCT. Eligibility criteria included histologically proven gastric adenocarcinoma in the middle or lower third of the stomach, clinical stage I tumor. Patients were preoperatively randomized to ODG or LADG. This study is now in the follow-up stage. The primary endpoint is relapse-free survival (RFS) and the primary analysis is planned in 2018. Here, we compared the surgical outcomes of the two groups. This trial was registered at the UMIN Clinical Trials Registry as UMIN000003319.
Results
Between March 2010 and November 2013, 921 patients (LADG 462, ODG 459) were enrolled from 33 institutions. Operative time was longer in LADG than in ODG (median 278 vs. 194 min,
p
< 0.001), while blood loss was smaller (median 38 vs. 115 ml,
p
< 0.001). There was no difference in the overall proportion with in-hospital grade 3–4 surgical complications (3.3 %: LADG, 3.7 %: ODG). The proportion of patients with elevated serum AST/ALT was higher in LADG than in ODG (16.4 vs. 5.3 %,
p
< 0.001). There was no operation-related death in either arm.
Conclusions
This trial confirmed that LADG was as safe as ODG in terms of adverse events and short-term clinical outcomes. LADG may be an alternative procedure in clinical IA/IB gastric cancer if the noninferiority of LADG in terms of RFS is confirmed.
Background
Neoadjuvant chemotherapy (NAC) followed by radical surgery is a promising strategy to improve survival of patients with stage III gastric cancer, but is associated with the risk of ...preoperative overdiagnosis by which patients with early disease may receive unnecessary intensive chemotherapy.
Methods
We assessed the validity of a preoperative diagnostic criterion in a prospective multicenter study. Patients with gastric cancer with a clinical diagnosis of T2/T3/T4, M0, except for diffuse large tumors and extensive bulky nodal disease, were eligible. Prospectively recorded clinical diagnoses (cT category, cN category) were compared with postoperative pathological diagnoses (pT category, pN category, and pathological stage). The primary endpoint was the proportion of pathological stage I tumors among those diagnosed as cT3/T4, which we expected to be 5% or less.
Results
Data from 1260 patients enrolled from 53 institutions were analyzed. The proportion of pathological stage I tumors in those with a diagnosis of cT3/T4 (primary endpoint) was 12.3%, which was much higher than the prespecified value. The positive predictive value and the sensitivity for pathological stage III tumors were 43.6% and 87.8% respectively. The sensitivity and specificity of contrast-enhanced CT for lymph node metastasis were 62.5% and 65.7% respectively. After exploring several diagnostic criteria, we propose, for future NAC trials in Japan, a diagnosis of “cT3/T4 with cN1/N2/N3,” by which inclusion of pathological stage I tumors was reduced to 6.5%, although its sensitivity for pathological stage III tumors decreased to 64.5%.
Conclusion
Clinical diagnosis of T3/T4 tumors was not an optimal criterion to select patients for intensive NAC trials because more than 10% of patients with pathological stage I disease were included. We propose the criterion “cT3/T4 and cN1/N2/N3” instead.
Background
To evaluate the feasibility and accuracy of diagnosis using sentinel node (SN) biopsy in T1 gastric cancer, a multicenter trial was conducted by the Japan Clinical Oncology Group (JCOG).
...Methods
Sentinel node biopsy with indocyanine green (ICG) was performed in patients with T1 gastric cancer. Green-stained nodes (GNs), representing SNs, were removed first, and gastrectomy with lymphadenectomy was then performed. GNs in one plane (with the largest dimension) were histologically examined intraoperatively by frozen section with hematoxylin and eosin (H&E) stain. All harvested lymph nodes (GNs and non-GNs) were histologically examined by paraffin section after surgery. The primary endpoint was to determine the proportion of false negatives, which was defined as the number of patients with negative GNs by frozen section divided by those with positive GNs and/or positive non-GNs by paraffin section. The sample size was set at 1,550, based on the expected and threshold value as 5 and 10 % in the proportion of false negatives.
Results
Accrual was suspended when 440 patients were enrolled because the proportion of false negatives was high. In the primary analysis, the proportion of false negatives was 46 % (13/28) after a learning period with 5 patients for each institution. Seven of 13 patients had nodal metastases outside the lymphatic basin. False negatives remained at 14 % (4/28) even by examining additional sections of GNs by paraffin section.
Conclusions
The proportion of false negatives was much higher than expected. Intraoperative histological examination using only one plane is not an appropriate method for clinical application of SN biopsy in gastric cancer surgery.
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
Billroth-I (BI) and Roux-en-Y (RY) are well-known reconstruction methods that are conducted following distal gastrectomy. However, the relative merits of these 2 methods are not well ...documented. The newly developed Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 is an integrated questionnaire consisting of 45 items, including 8 items from the 8-Item Short-Form Health Survey (SF-8), 15 items from the Gastrointestinal Symptom Rating Scale, and 22 items selected by gastric surgeons. Postoperative QOL ratings were evaluated for each reconstruction method using PGSAS-45.
Methods
The PGSAS-45 questionnaire was distributed to 2,922 patients who underwent gastrectomies at 52 medical institutions. Among the questionnaires distributed, 2520 (86 %) were retrieved and 2368 (81 %) met eligibility requirements. Statistical analyses were conducted to compare 1,384 of the eligible questionnaires, including responses from patients who underwent BI (
n
= 909) and RY (
n
= 475) procedures.
Results
BI procedures were associated with significantly longer postoperative periods, a significantly greater size of gastric remnants, and a higher frequency of laparoscopic approaches and celiac branch preservation. Postoperative QOL analysis indicated that BI procedures resulted in significantly lower postoperative weight loss and significantly higher esophageal reflux symptoms than RY procedures. There was no significant difference between the two groups on other outcome measures.
Conclusions
Although weight loss was significantly lower following BI procedures, esophageal reflux symptoms were significantly higher. Either BI or RY procedures may be recommended based on the individual patient’s condition after distal gastrectomy. The newly developed QOL questionnaire, PGSAS-45 and changes in body weight proved useful for evaluation of QOL following gastrectomy.
A Phase III study was started in Japan to evaluate the non-inferiority of overall survival of laparoscopy-assisted distal gastrectomy with open distal gastrectomy in patients with clinical IA (T1N0) ...or IB T1N1 or T2(MP)N0 gastric cancer. This study followed the previous Phase II study to confirm the safety of laparoscopy-assisted distal gastrectomy (JCOG0703) and began in March 2010. A total of 920 patients will be accrued from 33 institutions within 5 years. The primary endpoint is overall survival. The secondary endpoints are relapse-free survival, proportion of laparoscopy-assisted distal gastrectomy completion, proportion of conversion to open surgery, adverse events, short-term clinical outcomes, postoperative quality of life. Only a credentialed surgeon can be responsible for both open distal gastrectomy and laparoscopy-assisted distal gastrectomy.
Background
To compare irinotecan-alone, paclitaxel-alone, and each combination chemotherapy with S-1 in patients with advanced gastric cancer (AGC) that is refractory to S-1 or S-1 plus cisplatin ...(SP).
Methods
Patients with AGC after first-line chemotherapy with S-1 or SP, or patients during adjuvant chemotherapy or within 26 weeks after adjuvant chemotherapy completion with S-1 with confirmed disease progression were eligible. Patients were randomly divided into four groups based on treatment: irinotecan-alone (irinotecan; 150 mg/m
2
, day 1, q14 days), paclitaxel-alone (paclitaxel; 80 mg/m
2
, days 1, 8, 15, q28 days), S-1 plus irinotecan (irinotecan; 80 mg/m
2
, days 1, 15, S-1; 80 mg/m
2
, days 1–21, q35 days), and S-1 plus paclitaxel (paclitaxel; 50 mg/m
2
, day1, 8, S-1; 80 mg/m
2
, days 1–14, q21 days). The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), response rate, and safety.
Results
From July 2008 to March 2012, 127 patients were enrolled. No difference in median OS was observed in the irinotecan vs. paclitaxel groups or in the monotherapy groups vs. the S-1 combination therapy groups. Median PFS was longer in the paclitaxel group compared with the irinotecan group (4.1 vs. 3.6 months,
p
= 0.035), although no difference was observed when comparing monotherapy vs. S-1 combination. The most common grade 3 to 4 hematological adverse events were neutropenia with no difference in incidence rate across the treatment groups.
Conclusions
There was no difference in OS between irinotecan and paclitaxel no in OS prolongation of S-1 combination therapy in second-line chemotherapy.
Introduction
After D2 gastrectomy for advanced gastric cancer, patients with a high drainage fluid amylase level (d-AMY) on the first postoperative day (1POD) have an especially high risk of severe ...abdominal infectious complications (AICs), which could be fatal. On the hypothesis that prolonged antibiotic administration could reduce the incidence of severe AICs, we conducted a randomized phase II study to evaluate the optimal treatment duration of prophylactic antibiotics for patients who underwent D2 gastrectomy and had elevated d-AMY on 1POD.
Methods
Patients whose d-AMY was >3000 IU/L on 1POD after D2 gastrectomy for gastric cancer were randomly assigned to normal prophylactic antibiotic treatment given only on the day of surgery (Group A) or to prolonged antibiotic treatment given for 1 week after surgery (Group B). The primary endpoint was the incidence of severe AICs (Clavien–Dindo grade IIIa or higher). This trial was registered as UMIN000012152.
Results
This study was started in December 2013 and stopped in February 2019 because of poor patient accrual. Finally, 35 and 37 patients were assigned to groups A and B, respectively. The incidences of AICs were 22.9% (eight of 35) in group A and 13.5% (five of 37) in group B. One-sided P value of the Fisher exact test was 0.234. No adverse reactions to antibiotic prophylaxis were observed in any of the patients.
Conclusions
Prolonged prophylactic antibiotic administration had a marginal benefit in preventing grade III or higher AICs and caused no treatment-related morbidities.
Background
In the ABSOLUTE trial, weekly nanoparticle albumin-bound paclitaxel (w-nab-PTX) showed non-inferiority to weekly solvent-based paclitaxel (w-sb-PTX) for overall survival (OS). Thus, ...w-nab-PTX might be an option for second-line chemotherapy in advanced gastric cancer (AGC). However, predictive factors for efficacies of these agents have not been evaluated.
Methods
Patients previously enrolled in the ABSOLUTE trial were divided into apparent peritoneal metastasis group (PM group) and no apparent peritoneal metastasis group (no PM group) based on baseline imaging evaluated by RECIST ver. 1.1 criteria and amount of ascites. OS, progression-free survival, and overall response rate were compared between two arms in each group.
Results
This study included 240 and 243 patients in the w-nab-PTX and w-sb-PTX arms, respectively. In the PM group, the w-nab-PTX arm (
n
= 88) had longer OS than the w-sb-PTX arm (
n
= 103), and median survival time (MST) of 9.9 and 8.7 months hazard ratio (HR) 0.63; 95% CI 0.45–0.88;
P
= 0.0060, respectively. In the no PM group, the w-nab-PTX arm (
n
= 140) had shorter OS than the w-sb-PTX arm (
n
= 152), and MST of 11.6 and 15.7 months (HR 1.40; 95% CI 1.06–1.86;
P
= 0.0180), respectively. After adjusting for prognostic factors, the HR for OS in the w-nab-PTX arm versus the w-sb-PTX arm was 0.59 (95% CI 0.42–0.83;
P
= 0.0023; PM group) and 1.34 (95% CI 1.01–1.78;
P
= 0.0414; no PM group), with significant interaction between treatment efficacy and presence of peritoneal metastasis (
P
= 0.0003).
Conclusions
The presence of apparent peritoneal metastasis might be a predictive factor for selecting w-nab-PTX for pretreated AGC patients.
Trial registration number
JapicCTI-132059.
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