Short-Term Outcomes from a Randomized Screening Phase II Non-inferiority Trial Comparing Omentectomy and Omentum Preservation for Locally Advanced Gastric Cancer: the TOP-G Trial.

BACKGROUND: Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP-G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short-term findings regarding the trial's secondary endpoints. METHODS: The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/ : UMIN000005421). The key eligibility criteria were histologically confirmed cT2-4a and N0-2 gastric adenocarcinoma. Short-term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum-preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non-inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients. RESULTS: A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and < 10% in both groups (8% vs. 9%, p = 1.000). There was no mortality in either group. CONCLUSIONS: Operative risk was generally similar between omentectomy and omentum-preserving surgery for locally advanced gastric cancer.

[A Case of Neuroendocrine Tumor G1 of the Ileum with Multiple Liver Metastases].

A 74-year-old man was admitted to our hospital with multiple liver tumors detected by routine ultrasonography. Colonoscopy showed a type 2 tumor measuring approximately 25mm in diameter at the terminal ileum. The biopsy specimen showed neuroendocrine tumor(NET)G1. The patient was diagnosed with NET G1 of the ileum with multiple liver metastases. Thus, he underwent ileocecal resection with lymph node dissection and liver(S2)biopsy. A tumor was observed at the terminal ileum with serosal invasion, and the mesenteric lymph nodes were enlarged. Multiple liver metastatic tumors were observed in S2, S5, and S8. The patient was diagnosed with NET G1 of the ileum, T4N1M1, Stage Ⅳ. He is receiving octreotide therapy and has maintained stable disease for about 24 months.

[Gallbladder Malignant Lymphoma Diagnosed after Surgery for Acute Cholecystitis - A Case Report].

An 84-year-old man visited our hospital with epigastralgia.Levels of hepatic and biliary enzymes and CRP were elevated, as detected by a blood test.On a CT scan, a swollen gallbladder with stones was detected.The patient was admitted to the hospital with a diagnosis of Grade I acute cholecystitis.Conservative treatment was continued with antibiotic administration and the patient was discharged from the hospital with improvement on day 6 after admission.Three months later, the patient underwent laparoscopic cholecystectomy.In the gallbladder, a 45×45 mm tumor was found.Upon pathological examination, diffuse proliferation of lymphocyte-like heterotypic cells and subserosal invasion were observed.Immunohistochemistry results were negative for MUM1 and positive for CD10 and Bcl6 markers.A malignant diffuse large B-cell lymphoma was diagnosed.We experienced a case of malignant lymphoma of the gallbladder diagnosed after surgery for acute cholecystitis, which we herein report with literature consideration.

[The Case of HER2 Positive Advanced Gastric Cancer with Para-Aorta Lymph Node Recurrence Responding to Capecitabine plus CDDP plus Trastuzumab Chemotherapy].

We report the case of a 69-year-old man diagnosed with gastric cancer.The patient underwent distal gastrectomy(D2) and Billroth I reconstruction in March, 2010. Postoperative histopathological examination indicated M, Ant, Type 5, 100×50 mm, pap>por2>sig, T4aN3M0, pStage III C.We performed S-1 therapy as adjuvant chemotherapy.Abdominal CT showed para-aortic lymph node recurrence in February, 2015. Since HER2 protein was overexpressed in primary tumor immunostaining, he was treated with capecitabine plus CDDP plus trastuzumab therapy.After the chemotherapy, CEA levels decreased to the normal range and the enlarged lymph node was remarkably decreased in size in May, 2015.T he patient is alive 24 months after the chemotherapy with no evidence of recurrence.

[The Outcomes of Laparoscopy-Assisted Surgery in Elderly Patients with Colorectal Carcinoma].

AIM: To evaluate short-term outcomes of laparoscopy-assisted colectomy (LAC) in elderly patients with colorectal carcinoma. METHODS: A total of 289 colorectal cancer patients underwent LAC between 2008 and 2013. They were divided into an elderly group (<80 years of age, group E), and a younger group (<80 years of age, group Y). The treatment results, including the surgery-related factors, the perioperative course, and the pre- and postoperative complications, were retrospectively analyzed. RESULTS: There were 49 patients in group E, and 240 patients in group Y. There was no significant difference between the 2 groups considering the operative time, blood loss, rate of transfusion, post-operative hospital stay, rate of conversion to open surgery, or rate of complications, except for the number of patients with an ASA classification of greater than Grade 2 and the degree of lymph node dissection. CONCLUSIONS: LAC in elderly patients was found to be relatively safe because it was associated with a reduction in damage to the abdominal wall, and with an early recovery from surgery. These results suggest that the indications of LAC could be expanded for elderly patients.

[Clinicopathological Features and Outcomes of Treatment for HER2 Positive Gastric Cancer].

In March 2011, trastuzumab was approved for treating human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer (AGC) in Japan. Therefore, all patients with AGC should be evaluated for HER2 status. In this study, we analyzed the clinicopathological features and current status of treatment in HER2 positive gastric cancer. One hundred 6 gastric cancer patients were examined for HER2 expression in our hospital between March 2011 and August 2014. Sixteen patients (15.1%) were HER2 positive. There was no correlation between HER2 status and age, sex, and location of tumor; however, HER2 positivity was significantly more frequent in patients with intestinal type tumors and had a tendency towards being more frequent in patients with macroscopic types 0, 1 or 2. Trastuzumab was administered to 10 patients with HER2 positive AGC. The total number of doses of trastuzumab was 1 to 44 (median 7.5), and the therapeutic effect of trastuzumab combination chemotherapy was 1 patient with a complete response and 4 with a partial response. Adverse events due to trastuzumab were not observed. The incidence of HER2 over-expression was 15.1%, and trastuzumab combination chemotherapy was relatively safe and effective.

Impact of overexpression of Sushi repeat-containing protein X-linked 2 gene on outcomes of gastric cancer.

BACKGROUND AND OBJECTIVES: Sushi repeat-containing protein X-linked 2 (SRPX2) was first described as a downstream target gene for E2A-HLA, which causes pro-B acute leukemia. SRPX2 is considered to promote cellular migration and adhesion in cancers. Our objective was to evaluate the relative expression of the SRPX2 gene and to determine whether such expression correlates with outcomes in patients with gastric cancer. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa obtained from 227 patients with previously untreated gastric cancer were examined. SRPX2 mRNA expression levels of cancer tissue and adjacent normal mucosa were measured by quantitative real-time polymerase chain reaction. We evaluated the clinicopathological significance of the relative expression of SRPX2 in patients with gastric cancer. RESULTS: SRPX2 expression was higher in cancer tissue than in adjacent normal mucosa (P < 0.001). On analysis of the relations between gene expression and clinicopathological factors, SRPX2 expression correlated with tumor size and distant metastasis. Overall survival was significantly lower in patients whose tumors had high SRPX2 expression than in those who had low SRPX2 expression (P = 0.003). Multivariate analysis showed that high SRPX2 expression was an independent predictor of survival (HR = 2.028, 95% CI = 1.265-3.251). CONCLUSIONS: SRPX2 expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa, and overexpression of the SRPX2 gene is considered a useful independent predictor of outcomes in patients with gastric cancer.

Vitamin E deficiency begins within 6 months after gastrectomy for gastric cancer.

BACKGROUND: To clarify factors related to vitamin E malabsorption after gastric surgery, we evaluated serum vitamin E levels in patients who had undergone gastrectomy for gastric cancer. METHODS: We studied 39 patients (26 men, 13 women; mean age, 61.7 years) who underwent gastrectomy for early gastric cancer. Surgical procedures included 24 subtotal gastrectomies and 15 total gastrectomies. We measured serum levels of vitamin E before and 3, 6, 9, and 12 months after gastrectomy. A level of less than 0.75 mg/dl was defined as a low vitamin E level. RESULTS: Serum vitamin E levels decreased to less than 0.75 mg/dl in 6 (15.4%) of the 39 patients within 6 months after gastrectomy and in 7 (17.9%) of the 39 patients within 1 year after gastrectomy. The proportion of patients with a low serum vitamin E level was significantly higher in the total gastrectomy group (p = 0.002). A low vitamin E level was significantly associated with a low total cholesterol level. Total cholesterol levels in low vitamin E levels patients were lower than normal vitamin E levels patients. None of the patients with a low vitamin E level had neuropathy. CONCLUSIONS: The type of operation performed (total vs. subtotal gastrectomy) may be the major cause of vitamin E malabsorption after gastrectomy for gastric cancer. Vitamin E deficiency probably begins within 6 months after gastrectomy for gastric cancer.

Visualization of blood supply route to the reconstructed stomach by indocyanine green fluorescence imaging during esophagectomy.

BACKGROUND: Ensuring an adequate blood supply is essential to the safe performance of an anastomosis during esophagectomy and the prevention of anastomotic leakage. Recently, indocyanine green (ICG) fluorescence imaging has been used to visualize the blood supply when anastomosis is performed in vascular surgery. We used ICG fluorescence imaging to visualize the blood supply for reconstruction during esophagectomy. METHODS: Since January 2009, we have performed ICG fluorescence imaging in 33 patients with thoracic esophageal cancer who underwent thoracic esophagectomy. After pulling up the reconstructed stomach, 2.5 mg of ICG was injected as a bolus. ICG fluorescence imaging was performed with a near-infrared camera, and the images were recorded. RESULTS: ICG fluorescence was easily detected in all patients 1 min after injection. Vascular networks were well visualized in the gastric wall and omentum. The blood supply route was located in the greater omentum beside the splenic hilum in 22 (66.7%) of the 33 patients. CONCLUSIONS: ICG fluorescence can be used to evaluate the blood supply to the reconstructed stomach in patients undergoing esophagectomy for esophageal cancer. On ICG fluorescence imaging, the splenic hiatal vessels were the major blood supply for the anastomosis in most patients.

Perivascular epithelioid cell tumor of the rectum: report of a case and review of the literature.

We report a case of perivascular epithelioid cell tumor arising in the rectum of a 55-year-old woman. The tumor was treated by transanal endoscopic microsurgery. After 1 year follow-up, the patient is alive with no radiologic or endoscopic evidence of recurrence. Perivascular epithelioid cell tumor is a rare mesenchymal tumor characterized by co-expression of melanocytic and smooth muscle markers. This rare tumor can arise in various organs, including the falciform ligament, uterus, uterine cervix, liver, kidney, lung, breast, cardiac septum, pancreas, prostate, thigh, and gastrointestinal tract. Perivascular epithelioid cell tumor of the gastrointestinal tract is very rare, with only 23 previously reported cases. We review the literature on perivascular epithelioid cell tumors arising in the gastrointestinal tract.

[The role of staging laparoscopy in clinical stage III/IV gastric cancer].

We investigated the significance of staging laparoscopy (SL) for clinical Stage III/IVgastric cancer.SL was performed in 60 patients with clinical Stages III/IV gastric cancer.Pre -SL Stages were T3/4a/4b in 3/49/8 patients, N1/2/3 in 14/21/25, M0/ 1 in 38/22, and IIIA/IIIB/IIIC/IV in 16/13/9/22 patients, respectively.After SL, 11 patients were downstaged from T4a to T3, and 3 patients were downstaged from T4b to T4a.Moreover, 14 patients of P0 were identified as P1 or CY1, and 1 patient of H0 was identified as H1 after SL.As a result, post-SL Stages were IIB/IIIA/IIIB/IIIC/IV in 3/17/9/2/29 patients, respectively. In Stage III patients, staging was changed in 17 patients (44.7%) and the treatment strategies were changed in 9 patients (23.7%).In Stage IV cases, none of the patients changed staging and treatment strategies after SL.In conclusion, SL is useful for accurate staging and determining the treatment strategies in Stage III gastric cancer; however, re-evaluation is needed for the indication of SL in Stage IV gastric cancer.

[Clinical Impact of adjuvant chemotherapy in patients with T1N2/3 Gastric cancer].

The ACTS-GC trial showed the efficacy of S-1 adjuvant chemotherapy in patients with pathological Stage II/III gastric cancer who had undergone D2 gastrectomy; however, T1 patients were excluded from this trial.In this study, we compared the prognosis of T1N2/3 gastric cancer with the outcomes of ACTS-GC.From 2000 to 2009, out of 480 patients with resected T1 gastric cancer, 27 patients(5.6%) were pN2/3.Six patients received S-1 adjuvant chemotherapy (group S), whereas 21 patients did not(group N).The 3-year overall survival rates of T1N0/1 and T1N2/3 were 91.7% and 71.3%, respectively. Among T1N2/3 gastric cancer patients, the 3-year survival rate and relapse-free survival rate were 100%/100% in group S and 72.7%/71.1% in group N, respectively. The prognosis of group N was poorer than that of the surgery-alone group in Stage II of ACTS-GC.Furthermore, 5 patients (23.8%) of group N had recurrences; the primary sites of recurrences were lymph nodes in 4 cases, and lymph nodes and liver in 1 case.The prognosis of T1N2/3 gastric cancer is poor; we should, therefore, consider evaluating the efficacy of adjuvant chemotherapy in T1N2/3 gastric cancer patients.

[Outcomes of laparoscopic surgery after preoperative metallic stent placement for obstructive colorectal cancer].

AIM: To assess the outcomes of preoperative colonic stent placement for obstructive colorectal cancer. PATIENTS AND METHODS: A total of 30 patients with colorectal cancer were treated after preoperative colonic metallic stent placement between July 2012 and March 2014. We reviewed their medical records to assess the usefulness of stent placement and the clinical course. The effects of various clinicopathological variables on post-operative complications were analyzed statistically. RESULTS: Stent insertion was effective in 93% of the 30 patients with obstructive colorectal cancer. Preoperative colonoscopy or enema for proximal colonic survey was possible in 70% of the patients after stent placement; colonic lesions requiring simultaneous resection were noted in 5 patients (24%). The mean interval between stent insertion and operation was 19 days, and 23%of the patients underwent laparoscopic surgery. Statistical analysis revealed that the occurrence of complications was associated with laparoscopic surgery and the amount of operative blood loss. CONCLUSION: Preoperative stent placement in patients with obstructive colorectal cancer is feasible and laparoscopic surgery can be selected after stent placement.

Clinical significance of SPARC gene expression in patients with gastric cancer.

PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is one of the first known matricellular proteins that modulates interactions between cells and extracellular matrix. Recent studies investigated the clinical significance of SPARC gene expression in the development, progression, and metastasis of cancer. The present study examined the relations of the relative expression of the SPARC gene to clinicopathological factors and overall survival in patients with gastric cancer. METHODS: We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 227 patients with previously untreated gastric cancer. The relative expression levels of SPARC mRNA in cancer tissue and in adjacent normal mucosa were measured by quantitative real-time, reverse-transcription polymerase chain reaction. RESULTS: The relative expression level of the SPARC gene was higher in cancer tissue than in adjacent normal mucosa. High expression levels of the SPARC gene were related to serosal invasion (P = 0.046). Overall survival at 5 years differed significantly between patients with high SPARC gene expression and those with low expression (P = 0.006). CONCLUSIONS: Overexpression of the SPARC gene may be a useful independent predictor of outcomes in patients with gastric cancer.

A randomized phase II trial of omentum-preserving gastrectomy for advanced gastric cancer.

This randomized Phase II trial is being conducted to evaluate the impact of omentectomy for advanced gastric cancer on patient survival. The primary endpoint is the 3-year relapse-free survival rate and the secondary endpoints are 5-year overall survival, intraoperative blood loss, length of the operation and postoperative morbidity (especially postoperative ileus). The planned sample size is 250 patients (125 for complete removal of the omentum and 125 for preservation of the omentum) to determine whether omentum-preserving gastrectomy may be a candidate procedure for a Phase III trial in a randomized Phase II setting.

[Curative resection of a case of advanced gastric cancer with peritoneal dissemination responding well to combination chemotherapy of docetaxel,cisplatin and S-1].

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

[The clinical outcomes of endoscopic stent placement for patients with malignant gastric outlet obstruction - a comparison with gastrojejunostomy].

Owing to its less invasiveness, endoscopic stent placement is a potential treatment option for gastric cancer patients with gastric outlet obstruction( GOO). We compared the clinical outcomes of stent placement with gastrojejunostomy( GJ) bypass in terms of postoperative oral intake status, duration of oral intake, and overall survival. Thirty-eight patients who had unresectable gastric cancer with GOO were enrolled in this study. The stent placement group was divided into 2 subgroups: group P comprising 9 patients who received palliative treatment; and group A comprising 12 patients who received aggressive chemotherapy. Stent placement was performed for almost all the patients who had massive peritoneal metastasis and poor performance status. Improvement in oral intake was achieved in 19( 90.5%) of 21 patients after stent placement. Moreover, oral intake improved significantly in patients who underwent chemotherapy after stent placement. The median duration of oral intake and median overall survival was shorter in group P (1.8 and 2.8 months, respectively) and group A (3.2 and 4.8 months, respectively) than in group GJ( 11.8 and 12.7 months, respectively). In conclusion, endoscopic stent placement is effective in improving the oral intake status; however, it may be insufficient to improve the duration of oral intake. Thus, further studies are needed to clarify the clinical benefit of stent placement.

Usefulness of multidisciplinary therapy combining neoadjuvant chemotherapy with S-1 plus cisplatin and postoperative sequential chemotherapy in patients with scirrhous gastric cancer.

BACKGROUND/AIMS: The outcomes of patients with scirrhous gastric cancer (SGC) remain poor. We retrospectively compared outcomes according to historically different treatments for SGC and studied the therapeutic usefulness of NAC with S-1 plus cisplatin followed by postoperative sequential chemotherapy. METHODOLOGY: We studied 93 patients with SGC. Between 1995 and 2000, 29 patients did not receive NAC and were instead given conventional anti-cancer drugs. Between 2000 and 2003, 20 patients received 4 weeks of NAC with low-dose cisplatin plus 5-fluorouracil (5-FU) followed by postoperative sequential treatment with new anticancer agents (neoadjuvant low-dose FP group). Between 2003 and 2006, 44 patients received 2 courses of NAC with S-1+cisplatin followed by postoperative sequential administration of new anticancer agents (neoadjuvant S-1+cisplatin group). Response rates and overall survival were compared among the treatment groups. RESULTS: The rates of response to NAC were 15% in the neoadjuvant low-dose FP group and 36% in the neoadjuvant S-1+cisplatin group. Overall survival was significantly longer in the neoadjuvant S-1+cisplatin group than the other groups. CONCLUSIONS: Our results suggest that multidisciplinary therapy combining NAC with S-1+cisplatin and postoperative sequential administration of new anticancer drugs is therapeutically useful in patients with SGC.

Relationship between RegIV gene expression to outcomes in colorectal cancer.

BACKGROUND: Regenerating islet-derived family members (Reg) are superfamily of calcium-dependant lectins that are expressed in the proximal gastrointestinal tract and ectopically at other sites in the setting of tissue injury. The regenerating islet-derived family member 4 (RegIV) gene has been reported in various cancers, associating with diverse functions. This study examined the relation of the relative expression of RegIV gene to clinicopathological factors and outcomes in patients with colorectal cancer (CRC). METHODS: We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated CRC. The relative expression levels of RegIV mRNA in cancer and in normal adjacent mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. RESULTS: RegIV gene expression was higher in cancer tissue than in adjacent normal mucosa. The multivariate analysis of clinicopathological factors for 5-year overall survival showed a higher level of RegIV gene expression was a significant independent predictor. Overall survival at 5 years differed significantly between patients with high RegIV gene expression and those with low expression. CONCLUSIONS: Overexpression of the RegIV gene is considered a useful independent predictor of outcomes in patients with CRC.

Primary placement technique of jejunostomy using the entristar™ skin-level gastrostomy tube in patients with esophageal cancer.

BACKGROUND: We developed a skin-level jejunostomy tube (SLJT) procedure for patients undergoing esophagectomy using a skin-level gastrostomy tube (G-tube) (Entristar™; Tyco Healthcare, Mansfield, Mass), in order to improve their nutrition status and quality of life (QOL). We describe the procedure and the adverse effects of SLJT in patients with esophageal cancer (EC). METHODS: Over a 24-month period (March 2008 to March 2010), there were 16 patients (mean age: 61.8 years; age range: 49-75 years; 15 men, 1 woman) who had Stage II or III EC. Primary jejunostomy was performed under general anesthesia during esophagectomy. The technical success and the immediate and delayed complications of the procedure were recorded. JEJUNOSTOMY TECHNIQUES: SLJT placement using the G-tube (20Fr) was performed 20 cm from the Treitz ligament on the side opposing the jejunal mesenterium. The internal retention bolster was exteriorized through an incision in the abdominal wall. A single purse string suture using a 4-0 absorbable suture was performed. The internal retention bolster was then inserted into the jejunal lumen via the small incision. The intestine adjacent to the tube was anchored to the peritoneum using a single stitch. RESULTS: The SLJT was successfully inserted in all 16 patients. No early complications were documented. Follow-up for a median of 107 days (range, 26-320 days) revealed leakage to the skin in four patients, including superficial wound infections in two patients. There were no cases of obstruction of the tube or procedure-related death. CONCLUSIONS: This SLJT placement technique using the G-tube is a safe procedure in patients with EC and allows the creation of a long-term feeding jejunostomy.