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.

[Case of Spindle Cell Carcinoma of the Breast Resistant Neoadjuvant Chemotherapy].

We report a rare case of spindle cell carcinoma of the breast which grew rapidly during neoadjuvant chemotherapy. A 72- year-old female was presenting with chief complaint of a mass in the right breast; a tumor about 20 mm in size. Core needle biopsy of tumor revealed invasive ductal carcinoma and fine needle aspiration cytology of axillary lymph node was Class Ⅴ. So she was diagnosis breast cancer as cT2N1M0, cStage ⅡB. The tumor subtype was triple negative breast cancer (TNBC). She received the neoadjuvant chemotherapy by FEC100. After FEC 4 courses, we detected a huge and rapid growing breast mass of 40 mm by CT. She was administered received mastectomy and axillary lymph node dissection after 4 months from initial contact. Pathological finding was spindle cell carcinoma of the breast. Postoperatively, she was treated with weekly PTX for a total of 12 courses and radiation therapy for a right chest wall and supraclavicular fossa. Although the tumor was resistant for neoadjuvant chemotherapy, she is alive and well without metastasis for more than 3 years.

[The Efficacy of D3 Lymph Node Dissection in Elderly Patients with Colorectal Cancer].

The effectiveness of lymph node dissection tends to be reduced clinically in elderly patients with colorectal cancer because of physical limitations, such as comorbidities and organ dysfunction. We investigated the influence of the level of lymph node dissection on the prognosis of elderly patients with colorectal cancer. A total of 137 patients with pT2 or more-advanced tumors or lymph node metastasis were retrospectively studied. The 5-year overall survival(OS)andrelapse free survival(RFS) rates were 74.1% and 63.9%, respectively. Lymph node dissection was an independent prognostic factor in the examination of prognostic factors of OS. In the propensity-matchedcohort, the 5-year OS rates were 87.2% and5 8.2%(p=0.02), and the 5-year RFS rates were 77.8% and4 6.4%(p=0.03)in the D3 andred ucedgroups, respectively. The D3 group hada significantly better prognosis than the reduced group. D3 lymph node dissection might contribute to the improvement of prognosis in elderly people with colorectal cancer.

[Four Cases of Appendiceal Mucinous Neoplasm Treated with Laparoscopic Surgery].

Appendiceal mucinous neoplasm has a risk for pseudomyxoma peritonei caused by appendiceal perforation.It has been reported that laparoscopic surgery is more risky than open surgery.We investigated 4 patients who underwent laparoscopic surgery for appendiceal mucinous neoplasm.The median age was 69.5(49-85).There were 3 males and 1 female.Three cases of partial laparoscopic resection of the cecum and 1 case of ileocecal resection with lymph node dissection were performed. The pathology was low-grade mucinous neoplasm in all cases.The median hospital stay was 6 days, and there were no postoperative complications(CD Grade 3 or higher)or hospital death.As for long-term results, peritoneal pseudomyxoma developed in 1 case, which had already ruptured at the time of surgery.There were no recurrences in other cases.This result suggests that laparoscopic surgery for appendiceal mucinous neoplasm is safe with optimal selection of the procedure and a protective technique.

[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.

[A Case of Solitary Adrenal Metastasis from Rectal Cancer Treated by Adrenalectomy after Preoperative Chemotherapy].

Adrenal metastasis from colorectal cancer occurs in the presence of multiple synchronous metastases at other sites. We report a case of heterochronous solitary adrenal metastasis from rectal cancer. A 55-year-old man underwent anterior resection with D3 lymph node dissection for rectal cancer. The pathological stage of the tumor was III b, and adjuvant chemotherapy with mFOLFOX6 was administered for 6 months. Eighteen months after surgery, abdominal computed tomography(CT) revealed right solitary adrenal metastasis. His tumor marker levels were considerably elevated; therefore, he received preoperative chemotherapy with FOLFIRI plus bevacizumab(BV). After preoperative chemotherapy, his tumor marker levels decreased, and CT and FDG-PET/CT did not uncover any other metastatic lesions. The patient was diagnosed with solitary adrenal metastasis, and right adrenalectomy was performed. Histological examination confirmed the tumor to be adrenal metastasis from rectal cancer, and the histopathological Grade was 2. The patient received adjuvant chemotherapy with mFOLFOX6, and he is alive 7 months after adrenalectomy without evidence of recurrence. Adrenalectomy is recommended for solitary adrenal metastasis from colorectal cancer. Additionally, adrenalectomy after preoperative chemotherapy is an effective strategy for patients with solitary adrenal metastasis and high tumor marker levels.

[A case of intractable fistula after low anterior resection repaired by transsacral direct suture].

We report a case of an intractable fistula repaired by transsacral direct suture. A 65-year-old man underwent low anterior resection for rectal cancer. He subsequently underwent ileostomy due to anastomosis leakage. The fistula of the anastomosis persisted 3 months after surgery. He underwent surgery to repair the fistula using a transsacral approach. After removing the coccyx, the fistula in the postrectal space was exposed directly. The presence of the fistula was confirmed by an air leak test and was closed by direct suture. After 33 days, the patient underwent ileostomy closure.

Gallbladder herniation into the lesser sac through the foramen of Winslow: report of a case.

We report a case of gallbladder hernia into the lesser sac through the foramen of Winslow. The patient was a 90-year-old woman, admitted to hospital with obstructive jaundice. Computed tomography (CT) showed a left-deviated and remarkably enlarged gallbladder dragging the liver, and a dilated intrahepatic bile duct. The deviated gallbladder was thought to compress the common bile duct, causing the obstruction. Laparoscopic examination revealed gallbladder herniation into the lesser sac without a floating gallbladder; thus, we performed laparoscopic cholecystectomy. Herniation of the gallbladder is the rarest of all internal hernias and most reported cases have involved a floating gallbladder. The case we report here is therefore considered especially unusual.

[A case of gastric cancer with intensive peritoneal dissemination treated with long-term chemotherapy and surgery].

A 45-year-old man was transferred to our hospital because of advanced gastric cancer and peritoneal dissemination. After he received an S-1 plus cisplatin( CDDP) regimen for 6 courses, the primary lesion and ascites had disappeared. However, the primary lesion recurred, and he underwent treatment with 16 courses of an S-1 plus docetaxel regimen. He subsequently developed peripheral neuropathy, and was switched to the irinotecan (CPT-11) regimen. As he experienced appetite loss, it was impossible to continue the chemotherapy. Therefore, he underwent a salvage surgery and an R0 resection was performed. However, 9 months after the surgery, he experienced paraaortic lymph node recurrence and peritoneal dissemination. The patient died 13 months after the surgery.

[A case of rectal stenosis due to peritoneal dissemination from gastric cancer that was treated with chemoradiation therapy].

An 82-year-old man underwent total gastrectomy(D2 lymph node dissection)in August 2006. The pathological findings indicated T4a, N3, M0, Stage IIIC gastric cancer, but adjuvant chemotherapy was not initiated. In October 2009, he presented to the hospital with dyschezia. During colonoscopy, the scope could not pass through the colon, thus indicating rectal stenosis. The biopsy findings indicated the presence of signet ring cell carcinoma, which was determined to be due to the peritoneal dissemination from the gastric cancer. To avoid the need for creating a stoma, radiation therapy(2 Gy×20; total dose, 40 Gy)and chemotherapy(weekly paclitaxel and S-1)were initiated. Rectal stenosis was improved and complete remission was maintained until May 2013.

[Feasibility of bevacizumab for elderly patients with metastatic colorectal cancer].

The feasibility of treatment containing bevacizumab (BV) for elderly patients is not well established. We investigated the safety of treatment containing BV for advanced or metastatic colorectal cancer in elderly patients. From June 2008 to December 2010, 22 patients were treated with BV in our hospital. We classified them into three groups: less than 65 years (group A: 8 patients), 66-75 years (group B: 9 patients), and more than 76 years (group C: 5 patients). Then, we compared the adverse events involving BV. The patient median age was 71. 5 (range 45-84)years old; 10 patients were treated in first-line therapy and 12 patients in second-line therapy or beyond. The number of patients with hypertension was one (12. 5%) in group A, 3 (33. 3%)in group B, and 3 (60%) in group C. Treatment was continued in 4 patients, and discontinued in 18. The reasons for discontinuing BV treatment were tumor progression in 14 patients, toxicities in 3 patients, and degradation of performance state in one patient. BV-associated adverse events had a tendency to become severe with aging, and patients for whom BV treatment was discontinued because of toxicities were all in group C. Severe adverse events of rectal bleeding, cerebral hemorrhage and cerebral infarction were observed in three patients. These patients had risk factors for BV-associated adverse events such as hypertension or a history of radiation therapy, besides the risk factor of age. It is suggested that BV-associated adverse events are highly frequent and severe in elderly patients. Especially in patients over 76 years old, risk factors such as hypertension and severe adverse events were observed. The administration of BV for elderly patients should be considered very carefully.

[A case of rectal hemorrhage during chemotherapy with bevacizumab for local recurrence of rectal cancer].

Chemotherapy with bevacizumab(BV)has been one of the standard treatments for patients with metastatic colorectal cancer. However, emergent treatments are sometimes required because of severe adverse events associated with it. We experienced a case of massive rectal hemorrhage during BV treatment, and interventional radiology(IVR)successfully controlled it. An 81-year-old male visited our hospital, suffering from local recurrence of rectal cancer. He underwent colostomy for fecal diversion, and chemoradiation therapy was performed. Systemic chemotherapy with XELOX+BV was performed for the residual tumor. On the 27th day after the first administration of BV, the patient was hospitalized because of anal bleeding and a state of shock. The colonoscopic examination showed a dimple caused by tumor shrinkage, which was closed by clipping. However, a state of shock was caused by intermittent hemorrhages again afterwards. The hemorrhagic point was identified as the oral side of the dimple by angiography, and coil embolization led to immediate hemostasis. The colonoscopic examination revealed nothing abnormal besides the dimple. It is therefore suspected that the cause of rectal hemorrhage might be induced by BV. During combination chemotherapy with BV, bleeding is one of the severe adverse events requiring an emergent treatment regardless of BV dose. IVR may be an effective treatment when bleeding can not be controlled by endoscopic hemostasis. Therefore, we should construct a system for emergency hemostasis including IVR.

Optimal temperature of graft preservation after ex vivo gene transfer in lung isografts.

The aim of this study was to determine the optimal temperature of graft preservation after ex vivo gene transfer to rat lung isografts. Left lungs were harvested and infused with cationic lipid/LacZ-DNA complex via the pulmonary artery, and the grafts were stored for 4h. The grafts (n7) were allocated into groups I-IV according to the storage temperature:4, 10, 16, and 23, respectively. Forty-eight h after orthotopic transplantation, the arterial blood gas was analyzed and the peak airway pressure (PAP) and the level of LacZ protein production in the grafts were measured by reverse transcription polymerase chain reaction. After reperfusion, the grafts were stained with hematoxylin and eosin. The grafts in groups III and IV showed more deterioration as evidenced by decreased arterial oxygen tension, increased PAP, and predominant infiltration of inflammatory cells compared with groups I and II. The level of LacZ production was significantly lower in group I than in groups II-IV. The optimal temperature of lung graft preservation after ex vivo gene transfer was determined to be 10, balancing considerations of lung injury and efficiency of transgene expression.

Addition of a neutrophil elastase inhibitor to the organ flushing solution decreases lung reperfusion injury in rat lung transplantation.

BACKGROUND: Neutrophil elastase plays an important role in ischemia-reperfusion injury. We hypothesized that the addition of sivelestat, a specific neutrophil elastase inhibitor, to the organ flushing solution would decrease reperfusion injury in a rat single left-lung transplant model. METHODS: All donor lungs were flushed with 25 ml low-potassium dextran-glucose solution and stored for 16 h at 4 degrees C. Rats were divided into three experimental groups (n=10) that received donor lungs washed in either normal flushing solution (group 1), or flushing solution containing 20mg sivelestat (group 2) or 40 mg sivelestat (group 3). Graft function was assessed 48 h after reperfusion using five measurements: isolated graft oxygenation, wet/dry ratio, peak airway pressure, tissue myeloperoxidase activity, and serum lipid peroxides level. Histological examination of lung grafts was also performed. RESULTS: Group 3 showed better oxygenation (groups 1, 2, and 3: 133.9+/-113.5, 254.0+/-84.6, and 378.7+/-77.6 mmHg, respectively; p<0.0001 vs group 1, p=0.0052 vs group 2), lower peak airway pressure (groups 1, 2, and 3: 28.7+/-6.1, 26.0+/-5.8, and 21.5+/-5.3 mmHg, respectively; p=0.0385 vs group 1), lower wet/dry ratio (groups 1, 2, and 3: 6.74+/-0.78, 5.77+/-0.52, and 4.90+/-0.16, respectively; p=0.0010 vs group 1), and lower myeloperoxidase activity (groups 1, 2, and 3: 0.304+/-0.081, 0.178+/-0.053, and 0.106+/-0.029 DeltaOD/mg/min, respectively; p<0.0001 vs group 1, p=0.0319 vs group 2). No significant differences in arterial PaCO(2) and serum lipid peroxide levels were observed between the three groups. CONCLUSIONS: Addition of sivelestat to the organ flushing solution ameliorated ischemia-reperfusion injury in a lung transplant model.

[A case of breast metastasis of gastric cancer].

We report a rare case of breast metastasis of gastric cancer in a 61-year-old female. She was diagnosed as primary gastric cancer with peritoneal dissemination and received systemic chemotherapy after distal gastrectomy for a primary lesion. A tumor developed in her right breast 4 years after the surgery, and was confirmed to be the metastasis from gastric cancer by aspiration cytology. In Japan, there are 25 reports of breast metastasis from gastric cancer. Two possible pathways from gastric lesion were lymphatic and one vascular, but the mechanism of breast metastasis has remained controversial.

Feasibility study of biweekly CPT-11 plus CDDP for S-1- and paclitaxel-refractory, metastatic gastric cancer.

BACKGROUND: To confirm the feasibility and efficacy of biweekly irinotecan (CPT-11) plus cisplatin (CDDP) as third-line chemotherapy, the response rate (RR), overall survival and toxicity were evaluated in patients who had been treated with S-1 as a first-line and paclitaxel as a second-line chemotherapy for metastatic gastric cancer. PATIENTS AND METHODS: The eligibility criteria of our study were: i) pathologically-confirmed adenocarcinoma of the stomach, ii) primary non-resectable or recurrent tumors, iii) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or less, iv) age less than 75 years, v) adequate hepatic, renal and bone marrow functions and vi) patients had received S-1 as a first-line and paclitaxel as a second-line chemotherapy and both regimens had failed. The treatment consisted of CPT-11 (60 mg/m2) and CDDP (30 mg/m2) on day 1 and day 15, repeated every 4 weeks. RESULTS: Twenty-six patients were enrolled in this study. All the treatment was administered at the out-patient clinic except the first course for the initial 4 patients. The overall RR was 23.1% in all and 30.0% in the patients with target tumors (6 partial response, 11 stable disease, 7 progressive disease, 2 non-evaluable). Overall grade 3/4 toxicity was observed in 5 patients (19.2%) including pancytopenia, neutropenia, anemia, anorexia and elevation of AST/ALT. The time-to-treatment failure and the median survival time were 95 and 299 days, respectively. CONCLUSION: Biweekly CPT-11 plus CDDP was feasible for S-1- and paclitaxel-refractory metastatic gastric cancer, with moderate activity and favorable toxicity. This regimen was safely performed at the out-patient clinic as third-line chemotherapy.

Easy method for fixation of the anvil using a one-handed sliding-knot technique after laparoscopic total gastrectomy.

INTRODUCTION: When esophagojejunostomy is performed using a circular stapler after laparoscopic total gastrectomy, fixing the anvil to the end of the esophagus is challenging. We describe an easy method for fixation of the anvil using a one-handed sliding-knot technique after the anvil has been inserted into the esophagus. MATERIALS AND SURGICAL TECHNIQUE: After removing the stomach, the main operator makes a whip stitch at the end of the esophagus using a long piece of monofilament string. Both ends of the string are pulled out from the port. A knot is then made and brought close the esophagus twice (sliding granny knots). After inserting the anvil into the esophagus, the main operator pulls the main standing string with one hand, applying vibration only. This causes the knots to tighten the anvil. Then, one or two knots are added to make sure that the anvil is firmly fixed in place. In addition, we routinely add one more ligation with a ready-made ligating loop. DISCUSSION: This method is easy and reliable, and does not require special devices or skills when performing reconstruction after laparoscopic total gastrectomy. Because of these factors, it has the potential to be widely used to perform esophagojejunostomy.

Significance of volume-reduction surgery for far-advanced gastric cancer during treatment with novel anticancer agents.

BACKGROUND: We retrospectively assessed the survival benefit of novel anticancer agents (NACA) after volume-reduction surgery for far-advanced gastric cancer (FAGC). METHODS: From 1995 to 2005, 41 patients with FAGC underwent chemotherapy after volume-reduction surgery. Those treated since 2000 who received NACA were referred to as group A, and those treated before 2000, who received anticancer agents other than NACA, were referred to as group B. In addition, 21 patients with unresectable gastric cancer treated since 2000 who received NACA were referred to as group C. We investigated the significance of volume-reduction surgery during treatment with NACA. RESULTS: The median survival time (MST) was significantly prolonged in group A (626 days) compared to group B (364 days; P = 0.0156). Multivariate analysis showed that having one noncurative factor (NCF), and the use of NACA, were factors that contributed to survival time. Comparison between the subgroup of group A that had one NCF and the subgroup that had two or more NCFs revealed MSTs of 700 days and 180 days, respectively, with a significantly longer MST among the patients with one NCF (P = 0.0021). In addition, no difference from the MST of 333 days in group C was seen among the group A patients with two or more NCFs. CONCLUSION: The postoperative survival time of patients with one NCF was prolonged by the advent of NACA, but no significant prolongation was observed in the patients with two or more NCFs.

Transintestinal systemic oxygenation using perfluorocarbon.

PURPOSE: Perfluorocarbons have an excellent oxygen- and carbon dioxide-carrying capacity. This prompted us to investigate the feasibility of transintestinal systemic oxygenation using perfluorocarbon. METHODS: A rat hypoventilation model (room air, 20 breaths/min and a tidal volume of 10 ml/kg) was thus established, and FC-77 (Sumitomo-3M, Osaka, Japan) was used as a perfusate. Oxygenated FC-77 was perfused through the small intestine for 4 h. The rats were allocated into three groups as follows. Group 1 (n = 6): hypoventilation only; Group 2 (n = 6): saline was perfused instead of FC-77; Group 3 (n = 6): FC-77 was perfused. Arterial blood samples were drawn from the common iliac artery every 30 min until the end of perfusion. A standard blood gas analysis was performed. RESULTS: The PaO2 level in Group 3 was significantly higher than in Groups 1 or 2 (P = 0.006: at the end of perfusion, Group 1 = 58.6 +/- 14.5 mmHg, Group 2 = 65.2 +/- 29.4 mmHg, Group 3 = 84.0 +/- 35.5 mmHg). The PaCO2 level in Group 3 was significantly lower than that in Groups 1 or 2 (P = 0.014: at the end of perfusion, Group 1 = 56.8 +/- 8.5 mmHg, Group 2 = 52.6 +/- 5.7 mmHg, Group 3 = 44.4 +/- 11.1 mmHg). CONCLUSION: Our findings indicate that transintestinal systemic oxygenation is indeed possible and could therefore become a useful new modality for respiratory assist.

The efficacy of gastrectomy for large gastric cancer.

BACKGROUND: Large gastric cancer (LGC) is frequently associated with extended disease, and the role of surgical resection has been debated. We investigated the efficacy of surgical treatment for LGC. METHODS: The size of LGC was defined as 8 cm or greater. Four hundred and fifteen patients with LGC who underwent gastrectomy were included. The clinicopathological features, the status of the residual tumor, the incidence and patterns of relapse, and the survival were analyzed. RESULTS: Macroscopically, diffuse-type tumors were dominant (60%). The numbers of patients with tumors of T3 or greater, lymph node involvement, and peritoneal metastases were 356 (86%), 359 (87%), and 126 (30%), respectively. One hundred and eighty-eight patients (45%) underwent incomplete tumor resection (R2). The R2/R0 (no residual tumor) ratio was greater than 1 in patients with type 4 tumors and N1 or greater metastasis and in those with type 3 tumors and N2 or greater metastasis. In contrast, T2, type 2, and type 5 tumors were more likely to be completely resected. The 5-year survival for all 415 patients was 26%. The survival rates were inversely related to the tumor type, size, and lymph node metastasis. In the 216 patients with R0, the 5-year survivals of those with pN (International Union Against Cancer [UICC] classification) 0, 1, 2, and 3 were 66%, 56%, 36%, and 5%, respectively (P = 0.001). In 96 of these 216 patients (44%) the tumor recurred, and peritoneal metastasis was the most frequent mode of recurrence (48%). By Cox's proportional hazard model, the tumor size was an independent prognostic factor. CONCLUSION: The chance of achieving R0 resection for LGC is low, except for T2, type 2, or type 5 tumors. Primary resection should be avoided for other types of LGC.