Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

BACKGROUND: Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. METHODS: This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). CONCLUSIONS: One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

Short-term outcomes of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis (JCOG1704).

BACKGROUND: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. To assess the safety and efficacy of preoperative docetaxel, oxaliplatin, and S-1 (DOS), we conducted a multicenter phase II trial. METHODS: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky nodal (bulky N) involvement around major branched arteries or para-aortic node (PAN) metastases. Patients received three cycles of docetaxel (40 mg/m2, day 1), oxaliplatin (100 mg/m2, day 1), and S-1 (80-120 mg/body, days 1-14), followed by gastrectomy with D2 plus PAN dissection. Subsequently, patients underwent postoperative chemotherapy with S-1 for 1 year. The primary endpoint was major (grade ≥ 2a) pathological response rate (pRR) according to the Japanese Classification of Gastric Carcinoma criteria. RESULTS: Between October 2018 and March 2022, 47 patients (bulky N, 20; PAN, 17; both, 10) were enrolled in the trial. One patient was ineligible. Another declined any protocol treatments before initiation. Among the 45 eligible patients who initiated DOS chemotherapy, 44 (98%) completed 3 cycles and 42 (93%) underwent R0 resection. Major pRR and pathological complete response rates among the 46 eligible patients, including the patient who declined treatment, were 57% (26/46) and 24% (11/46), respectively. Common grade 3 or 4 toxicities were neutropenia (24%), anorexia (16%), febrile neutropenia (9%), and diarrhea (9%). No treatment-related deaths occurred. CONCLUSIONS: Preoperative chemotherapy with DOS yielded favorable pathological responses with an acceptable toxicity profile. This multimodal approach is highly promising for treating gastric cancer with ELM.

Importance of duodenal stump reinforcement to prevent stump leakage after gastrectomy: a large-scale multicenter retrospective study (KSCC DELICATE study).

BACKGROUND: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage. METHODS: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer. RESULTS: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality. CONCLUSIONS: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer.

Low skeletal muscle radiodensity is a risk factor for adjuvant chemotherapy discontinuation in colorectal cancer.

BACKGROUND: Previously, we reported SMR (skeletal muscle radiodensity) as a potential prognostic marker for colorectal cancer. However, there have been limited studies on the association between SMR and the continuation of adjuvant chemotherapy in colorectal cancer. METHODS: In this retrospective study, 143 colorectal cancer patients underwent curative surgery and adjuvant chemotherapy using the CAPOX regimen. Patients' SMRs were measured from preoperative CT images and divided into low (bottom quarter) and high (top three quarters) SMR groups. We compared chemotherapy cycles, capecitabine and oxaliplatin doses, and adverse effects in each group. RESULTS: The low SMR group had significantly fewer patients completing adjuvant chemotherapy compared to the high SMR group (44% vs. 68%, P < 0.01). Capecitabine and oxaliplatin doses were also lower in the low SMR group. Incidences of Grade 2 or Grade 3 adverse effects did not differ between groups, but treatment discontinuation due to adverse effects was significantly higher in the low SMR group. Logistic regression analysis revealed Stage III disease (odds ratio 18.09, 95% CI 1.41-231.55) and low SMR (odds ratio 3.26, 95% CI 1.11-9.56) as factors associated with unsuccessful treatment completion. Additionally, a higher proportion of low SMR patients received fewer than 2 cycles of chemotherapy (50% vs. 12%). CONCLUSION: The low SMR group showed higher treatment incompletion rates and received lower drug doses during adjuvant chemotherapy. Low SMR independently contributed to treatment non-completion in colorectal cancer patients.

Late complication after gastrectomy for clinical stage I cancer: supplementary analysis of JCOG0912.

BACKGROUND: Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients. METHODS: This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors. RESULTS: There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039-0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033-0.406, P < 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371-8.176, P = 0.008). The surgical approach was not a risk factor for any late complications. CONCLUSION: Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis.

Anatomical Position of the Pancreas as a Risk Factor for Pancreatic Fistula after Laparoscopic Gastrectomy for Gastric Cancer.

BACKGROUND: Laparoscopic gastrectomy is more frequently associated with postoperative pancreatic fistula than is open gastrectomy. We assumed that compression of the pancreas with various devices to obtain a proper operative view is associated with the higher incidence of PF in LG and that the extent of the compression differs depending on the anatomical position of the pancreas. The present study aimed to elucidate the correlation between the anatomical position of the pancreas and PF after LG for gastric cancer. METHODS: Patients who underwent LG for gastric cancer from 2005 to 2019 were retrospectively reviewed. Two anatomical parameters representing the height of the slope looking down the celiac artery from the top of the pancreas (P-A length) and the steepness of the slope (UP-CA angle) were measured in computed tomography sagittal projections. The correlation between PF and (1) P-A length, (2) UP-CA angle, and (3) other clinicopathological factors was analyzed using a logistic regression model. RESULTS: Among 3485 patients, grade ≥ II PF was observed in 140 (4.0%) patients. The UP-CA angle [odds ratio (OR), 2.472; 95% confidence interval (CI), 1.725-3.543; P < 0.001], a high BMI (OR 2.339; 95% CI 1.634-3.348; P < 0.001), and male sex (OR 2.602; 95% CI 1.590-4.257; P < 0.001) were independently correlated with grade ≥ II PF. CONCLUSIONS: The present study identified a significant correlation between anatomical position of the pancreas and PF after LG. High BMI and male sex were also significantly correlated with PF after LG.

Early administration of postoperative BCAA-enriched PPN may improve lean body mass loss in gastric cancer patients undergoing gastrectomy.

BACKGROUND: It has been reported that weight loss or lean body mass (LBM) loss after gastrectomy for gastric cancer is associated with prognosis and nutritional support alone is insufficient to prevent LBM loss. Branched-chain amino acids (BCAA) play an important role in muscle catabolism, however their clinical effects on suppression of LBM loss in gastric cancer patients undergoing gastrectomy remains elusive. In this current study, we investigated the effect of our original PPN regimen including BCAA (designated to BCAA-regimen) on LBM loss. METHODS: We conducted a randomized controlled trial (RCT) at a single institution where patients undergoing gastrectomy were assigned to either receive a five-day early postoperative course of the BCAA-regimen (BCAA group) or conventional nutrition. The primary endpoint was the % reduction in LBM at postoperative day 7. The secondary endpoints included the % reduction in LBM at 1 and 3 months postsurgery. RESULTS: At postoperative day 7, LBM loss in the BCAA group tended to be lower than in the control group (0.16% vs. 1.7%, respectively; P = 0.21), while at 1 month postsurgery, LBM loss in the BCAA group was significantly different to that of the control group (- 0.3% vs. 4.5%, respectively; P = 0.04). At 3 months postgastrectomy, however, LBM loss was similar between the BCAA and the control groups. CONCLUSION: Our RCT clinical trial clarified that early administration of the postoperative BCAA regimen improved LBM loss at 1 month after surgery in gastric cancer patients undergoing gastrectomy.

Pancreas-contactless gastrectomy for gastric cancer prevents postoperative inflammation.

BACKGROUND: Pancreas-related complications after laparoscopic gastrectomy (LG) for gastric cancer can be fatal. We developed a gastrectomy procedure with no pancreas contact to prevent such complications and herein report the surgical outcomes. METHODS: We retrospectively reviewed 182 consecutive patients with gastric cancer who underwent LG at Kitasato University Hospital from January 2017 to January 2020. These patients were divided into a pancreas-contact group (C group) and pancreas-contactless group (CL group) for comparison of postoperative complications, and inflammatory parameters such as body temperature (BT) and C-reactive protein (CRP). RESULTS: Postoperative complications of CDc grade ≧ IIIa were significantly fewer in the CL group than in the C group [0/76 (0%) vs. 6/106 (5.7%), P = 0.035]. The median drain amylase (drain-AMY) on postoperative day 1 (POD1) was significantly lower in the CL group than in the C group (641 vs. 1162 IU/L, P = 0.02), as was BT at POD1 (37.4 °C vs. 37.7 °C, P = 0.04), the patient group with a BT above 37.5 °C at POD3 [5/76 (6.5%) vs. 18/106 (17%), P = 0.037], and those showing a CRP above 20.0 mg/dL at POD3 [5/76 (6.5%) vs. 20/106 (19%), P = 0.018]. CONCLUSIONS: Our technique to prevent pancreas contact during supra-pancreatic lymph node dissection during LG could minimize the inflammatory response and prevent further postoperative complications. Further large-scale, prospective studies are now required.

Improved anastomotic technique for esophagojejunal anastomosis using circular stapler.

PURPOSE: In total gastrectomy, Roux-en-Y reconstruction with esophagojejunal anastomosis has been widely used in gastrointestinal reconstruction. In the case of anastomotic leakage of RY reconstruction, esophagojejunal anastomosis should be paid attention, and esophageal fragility is considered the reason for the leakage. Here, we introduce an atraumatic and innovative technique for esophagojejunostomy. METHODS: We prospectively performed routine novel esophagojejunal anastomosis using circular stapler device and reviewed the records of 14 consecutive patients with gastric cancer who underwent open total gastrectomy at Kitasato University Hospital from April 2019 to March 2020. By placing about 10 stay sutures around the entire esophageal stump, the esophageal stump can be opened to the maximum diameter. The forceps grasping the tissue was not necessary for these procedures, consequently preventing either tears the esophageal stump tissue or narrowing the esophageal lumen. RESULTS: These 14 cases were far advanced cases of gastric cancer, 6 cases of splenectomy and 3 cases of distal pancreatectomy. No technical problems such as esophageal tear were observed in all cases. Postoperative complications were observed in 6 patients (42.9%), and their contents varied. However, they all improved conservatively. Regarding anastomotic complications, anastomotic leakage of Clavien-Dindo-II was observed in one case, but it improved conservatively. CONCLUSION: Our new atraumatic anastomosis technique could abolish problems such as tear of esophagus wall due to introduce a larger-sized anvil, trauma of esophageal wall by grasping with forceps such as Alice or Babcock. Consequently, the atraumatic and innovative technique might make the esophagojejunostomy safe. This method might prevent anastomotic leakage and other complications effectively.

Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer.

The clinical efficacy of DNA cytology test (CY) in gastric cancer (GC) has been retrospectively proposed using cancer-specific methylation of cysteine dioxygenase type 1 (CDO1). We confirmed the clinical utility of DNA CY in a prospective cohort. Four hundred GC samples were prospectively collected for washing cytology (UMIN000026191), and detection of the DNA methylation of CDO1 was assessed by quantitative methylation-specific PCR in the sediments. Endpoint was defined as the match rate between conventional CY1 and DNA CY1 (diagnostic sensitivity), and the DNA CY0 rate (diagnostic specificity) in pStage IA. DNA CY1 was detected in 45 cases (12.5%), while CY1 was seen in 31 cases (8.6%) of 361 chemotherapy-naïve samples, where the sensitivity and specificity of the DNA CY in the peritoneal solutions were 74.2% and 96.5%, respectively. The DNA CY was positive for 3.5/0/4.9/11.4/58.8% in pStage IA/IB/II/III/IV, respectively (P < .01). In the multivariate analysis, DNA CY1 was independently correlated with pathological tumor depth (pT) (P = .0012), female gender (P = .0099), CY1 (P = .0135), P1 (P = .019), and carcinoembryonic antigen (CEA) (P = .036). The combination of DNA CY1 and P factor nearly all covered the potential peritoneal dissemination (P1 and/or CY1 and/or DNA CY1) (58/61:95.1%). DNA CY1 had a significantly poorer prognosis than DNA CY0 in GC patients (P < .0001). DNA CY1 detected by CDO1 promoter DNA methylation has a great value to detect minimal residual disease of the peritoneum in GC clinics, representing poor prognosis as a novel single DNA marker.

Safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal neoplasm: a retrospective multicenter study.

BACKGROUND: A delayed perforation can often occur after endoscopic treatment for duodenal neoplasms and may be fatal due to leakage of pancreatic and bile juices. We aimed to evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for duodenal neoplasms (D-LECS) in a multicenter, retrospective study. METHODS: The clinical characteristics and surgical outcomes of 206 patients with duodenal neoplasms in whom D-LECS had initially been attempted at one of 14 institutions were reviewed retrospectively. RESULTS: Of the 206 patients, 63 (30.6 %), 128 (62.1 %), and 15 patients (7.3 %) had lesions at the bulb, second portion, and third portion of the duodenum, respectively. The rates of en bloc and R0 resections during D-LECS were 96.1 % and 95.1 %, respectively. Intraoperative and delayed perforations occurred in 10 (4.9 %) and 5 patients (2.4 %), respectively. No cases of recurrence were observed. Surgical duration of ≥ 180 minutes was an independent risk factor for postoperative complications. CONCLUSIONS: The results revealed that D-LECS was performed with oncological safety and technical feasibility.

Intraoperative conversion from laparoscopic gastrectomy to an open procedure: a decade of experience in a Japanese high-volume center.

BACKGROUND: Although laparoscopic gastrectomy (LG) is a widely accepted treatment for gastric cancer, conversion to laparotomy is sometimes required. The current study aimed to review the time trends of intraoperative conversions to open procedures during the decade in which the LG procedure was being developed. METHODS: Cases in which LG was attempted at the Cancer Institute Hospital from 2005 to 2018 were retrospectively reviewed, and the details regarding conversions to open surgery were examined. RESULTS: Twenty-two (0.63%) of 3,498 patients required conversion to open surgery due to technical difficulties. The major reasons for conversions were difficulties in reconstruction (seven patients; 0.20%) and intraoperative bleeding (six patients; 0.17%). All conversions due to difficulties in reconstruction occurred in the introduction period of LG during the performance of esophagojejunostomy or esophagogastrostomy in laparoscopic total gastrectomy or proximal gastrectomy using a circular stapler. Five (71.4%) of the seven patients in whom conversion was performed due to difficulties in reconstruction developed postoperative severe complications. No conversions due to difficulties in reconstruction have been experienced since 2011, possibly due to the decrease in the number of laparoscopic total gastrectomy procedures and the introduction of the use of a linear stapler in esophagojejunostomy. To manage intraoperative bleeding in LG, hemostatic procedures were systematized and conversions were considered if visualization was not maintained following the procedures. None of the six patients who required laparotomy due to intraoperative bleeding required surgical or radiological intervention postoperatively. CONCLUSION: Over a decade of experience and procedural changes have markedly decreased the incidence of conversion to open surgery in LG. The main causes of conversion during the early period of LG introduction were difficulties in reconstruction and intraoperative bleeding; the incidences of these complications have been decreased by employing the appropriate procedures for LG.

Features of the complications for intracorporeal Billroth-I and Roux-en-Y reconstruction after laparoscopic distal gastrectomy for gastric cancer.

PURPOSE: Recently, the Roux-en-Y procedure (R-Y) and delta-shaped Billroth-I anastomosis (DB-I) have become prevalent as intracorporeal gastroenteric anastomosis methods after laparoscopic distal gastrectomy (LDG) for gastric cancer. However, the differences in postoperative outcomes between the two methods have not been clarified. Hence, this retrospective study aimed to reveal the features of the complications of the R-Y versus DB-I after LDG. METHODS: The study cohort comprised patients with gastric cancer who underwent DB-I or R-Y after LDG from January 2013 to May 2016. Patient characteristics and surgical and postoperative variables were analyzed. To compensate for intergroup differences in baseline characteristics, estimated propensity scores were used to perform one-on-one matching between the groups. RESULTS: A total of 564 patients were included, and propensity score matching created a matched cohort of 149 pairs in the DB-I and R-Y groups. The incidence of short-term complications such as gastrointestinal fistula classified as Clavien-Dindo grade IIIa or above was significantly greater in the DB-I group than the R-Y group (14.1% versus 4.7%, p=0.004). In contrast, the R-Y was associated with long-term complications such as internal hernia and tended to result in a slightly higher readmission rate in the R-Y group compared with the DB-I group (2.7% versus 6.0%, p=0.128). CONCLUSION: DB-I after LDG was associated with a significantly higher rate of short-term complications compared with the R-Y, whereas characteristic long-term complications tended to be observed after the R-Y. These differences should be considered during the selection of the reconstruction method and postoperative management of LDG.

Preoperative chemotherapy could modify recurrence patterns through postoperative complications in patients with gastric cancer.

PURPOSE: Postoperative infectious complications have a negative impact on survival outcomes in patients with gastric cancer. It is recently reported that preoperative chemotherapy may eliminate this negative impact. This study aimed to confirm whether preoperative chemotherapy can eliminate the negative impact of postoperative infectious complications (IC) on survival outcomes and elucidate the association between postoperative infectious complications and recurrence patterns. METHODS: We retrospectively reviewed data of 86 patients who received preoperative chemotherapy with docetaxel, cisplatin, and S-1 followed by R0 gastrectomy at the Kitasato University between 2006 and 2016. Patients who developed grade II or higher infectious complications during hospitalization were grouped into the IC group, while others were grouped into the non-IC (NIC) group. Survival outcomes and recurrence patterns were analyzed between the two groups. RESULTS: Infectious complications with Clavien-Dindo classification of grade II or higher were found in 12 patients (14.0%, IC group). The median observational period was 61 months. Overall survival and progression-free survival were similar in the IC and NIC groups. Recurrence occurred in 39 patients. The proportions of peritoneal and lymph node recurrences were not significantly different between the two groups. However, the proportion of distant metastasis in the IC group was significantly higher than that in NIC group (3/4 [75%] vs. 9/35 [17%], p = 0.04). CONCLUSIONS: Pathological stage after neoadjuvant therapy plays a stronger role in recurrence than postoperative complications. Lymph node and peritoneal metastasis may be suppressed by preoperative chemotherapy.

Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101).

BACKGROUND: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. METHODS: The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20-80 years old, (5) performance status of 0-2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. RESULTS: Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. CONCLUSION: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

Shorter Survival of Patients with Upper-Third Gastric Cancer Preoperatively Diagnosed as Stage IA Compared with Those with Middle to Lower Lesions.

BACKGROUND: Although preoperatively diagnosed stage IA (cT1N0) gastric cancer includes pathologically advanced disease, patients with cT1N0 middle- to lower-third gastric cancer (MLTG) experience favorable outcomes even if they undergo gastrectomy with limited lymph node dissection; however, whether this is true for upper-third gastric cancer (UTG) patients is unknown. In this study, we examined the survival of patients with cT1N0 UTG compared with patients with MLTG. METHODS: We retrospectively reviewed the data for 1707 consecutive patients with cT1N0 gastric cancer who underwent gastrectomy between 2006 and 2013. Patients were divided into the UTG or MLTG groups, and clinicopathological characteristics and survival were compared between the groups. Factors affecting survival were identified using multivariate analysis. Survival was calculated according to pathological findings. RESULTS: The patient group included 334 UTG patients and 1373 MLTG patients. The 5-year overall survival (OS) of UTG patients was significantly shorter than that of MLTG patients, and UTG was identified as an independent prognostic factor of cT1N0 gastric cancer. Among UTG cases, the OS of pT2-4 or pN1-3 was significantly shorter than that of pT1 or pN0 disease. No significant differences were found between such diseases in MLTG. All relapses in UTG were distant metastases. CONCLUSIONS: cT1N0 UTG with pT2-4 or pN1-3 are prognostic indicators of shorter OS, although MLTG of either disease is associated with favorable prognosis. Thus, UTG is an independent prognostic factor in cT1N0 gastric cancer; however, limited dissection is acceptable for cT1N0 UTG because relapses occur at distant sites.

CD33+ Immature Myeloid Cells Critically Predict Recurrence in Advanced Gastric Cancer.

BACKGROUND: It is elusive which subtypes of immune cells are pivotal in cancer progression and prognosis in gastric cancer (GC). The aim of this study is to clarify clinical impact of immature myeloid-derived immune cells in patients with GC who underwent curative gastrectomy with curative lymphadenectomy and treated with S-1 (tegafur/gimeracil/oteracil) postoperatively. METHODS: The prognostic impact of recruited CD33+ immature myeloid-derived cells were clinicopathologically analyzed in curatively resected stage II and III GC. Correlation of preoperative peripheral leukocyte fractions with recruited CD33+ immature cells was also assessed. RESULTS: Patients with high CD33+ cell counts in primary tumor showed dramatically worse prognosis (5-y recurrence-free survival 29.0%) than that of the counterparts (79.4%). High CD33+ cell counts independently predicted poor prognosis in stage II/III (hazard ratio, 4.34; P < 0.001). In analyses of each stage, high CD33+ cell count was pivotally associated with poor prognosis in both stages. There was no significant correlation of each peripheral leukocyte fraction with CD33+ cell recruitment. Of note, high CD33+ cell count was significantly correlated with hematogenous recurrence. CONCLUSIONS: Recruitment of CD33+ immature myeloid cells critically predict hematogenous recurrences in curatively resected advanced GC. These results give rational to focusing on CD33+ myeloid-derived cells as a novel approach to tackle advanced GC.

Prediction of Efficacy of Postoperative Chemotherapy by DNA Methylation of CDO1 in Gastric Cancer.

BACKGROUND: CDO1 is a presumed tumor suppressor gene in human cancers, the expression of which is silenced by promoter DNA methylation. Moreover, CDO1 harbors functionally oncogenic aspects through modification of mitochondrial membrane potential. We recently proposed that this oncogenic feature allows for the prediction of the efficacy of postoperative chemotherapy in colon cancer. The present study aims to elucidate the efficacy of prediction of success of postoperative chemotherapy in advanced gastric cancer to improve the treatment strategy of patients. MATERIALS AND METHODS: Forced expression of CDO1 in gastric cancer cell lines was assessed using the JC-1 assay. Promoter DNA methylation was investigated in quantitative TaqMan methylation-specific polymerase chain reaction in 321 pathological stage II/III advanced gastric cancer cases treated by curative gastrectomy with or without postoperative chemotherapy. RESULTS: (1) Forced expression of CDO1 led to increased mitochondrial membrane potential, accompanied by augmented survival in gastric cancer cells under anaerobic conditions. These results suggest that CDO1-expressing cancer cells survive more easily in anaerobic lesions which are inaccessible to anticancer drugs. (2) Intriguingly, in cases with the highest CDO1 methylation (ranging from 15% to 40%), patients with postoperative chemotherapy showed significantly better survival than those with no postoperative chemotherapy. (3) A robust prognostic difference was observed that was explained by differential recurrences of distant metastasis (P = 0.0031), followed by lymph node (P = 0.0142) and peritoneal dissemination (P = 0.0472). CONCLUSIONS: The oncogenic aspects of CDO1 can be of use to determine patients with gastric cancer who will likely respond to treatment of invisible systemic dissemination by postoperative adjuvant chemotherapy.

Conversion therapy for peritoneal lavage cytology-positive type 4 and large type 3 gastric cancer patients selected as candidates for R0 resection by diagnostic staging laparoscopy.

BACKGROUND: The long-term outcomes of type 4 and large type 3 gastric cancer patients with positive peritoneal lavage cytology (CY1) remain unsatisfying. We evaluated our treatment strategy of conversion therapy for CY1 patients without peritoneal dissemination (P0). METHODS: Diagnostic staging laparoscopy (DSL) was performed before treatment. Chemotherapy was applied for DSL-diagnosed P0CY1. The re-evaluation of peritoneal metastasis by staging laparoscopy (re-SL) was performed when a response to chemotherapy was identified by gastroscopy and/or CT. Gastrectomy with radical lymphadenectomy was applied as conversion therapy when peritoneal lavage cytology-negative (CY0) and P0 were diagnosed with re-SL, with the aim of achieving R0 resection. Chemotherapy was continued as palliative treatment in patients for whom re-SL was not applicable or when re-SL did not confirm P0CY0. The long-term outcomes were retrospectively evaluated. RESULTS: Between 2009 and 2015, 214 patients with type 4 and large type 3 gastric cancer underwent DSL in the Cancer Institute Hospital. Thirty-nine patients were initially diagnosed with P0CY1. Seven patients received palliative gastrectomy first due to outlet obstruction or other reasons. Thirty-two patients received chemotherapy first. Among them, 13 patients underwent gastrectomy as conversion therapy and 19 were treated with palliative chemotherapy. The 3-year survival rate of patients who underwent conversion therapy, palliative chemotherapy and palliative gastrectomy was 76.9% [95% confidence interval (CI) 47.8-92.4%], 10.5% (95% CI 1.9-42.3%), and 0%, respectively. CONCLUSION: Conversion therapy might be a promising treatment for P0CY1 type 4 and large type 3 gastric cancer patients. Re-SL was useful for selecting candidates for R0 resection.

Therapeutic value of splenectomy to dissect splenic hilar lymph nodes for type 4 gastric cancer involving the greater curvature, compared with other types.

BACKGROUND: Whether splenectomy for splenic hilar lymph node (No. 10) dissection in type 4 gastric cancer involving the greater curvature is necessary is not established. Patients with type 4 gastric cancer often experience peritoneal relapse, despite curative surgery, and total gastrectomy with splenectomy is frequently associated with infectious complications. METHOD: Patients with cT2-T4 gastric cancer in the upper or middle third of the stomach, or both, involving the greater curvature who underwent R0 total gastrectomy with splenectomy between 2006 and 2016 were selected. Clinicopathological findings, postoperative complications, the incidence of lymph node metastasis, and the therapeutic value index of each station were compared between type 4 and non-type 4 gastric cancer. RESULTS: We enrolled 50 patients with type 4 and 60 with non-type 4. The former had a significantly higher proportion of the undifferentiated type and larger and deeper tumors. The overall incidence of Grade III or higher complications was 20.9%. The incidence of No. 10 metastasis was 26.0% in type 4 and 31.7% in non-type 4. Although the therapeutic value index of the No. 10 was 13.7 in type 4 and 15.0 in non-type 4, the index of type 4 ranked just below several peri-gastric stations and seventh, while that in non-type 4 ranked second. CONCLUSION: Splenectomy for No. 10 dissection may be oncologically valid for type 4 gastric cancer involving the greater curvature. A safer procedure for No. 10 dissection should be established.