Small Molecules with Thiourea Skeleton Induce Ethylene Response in Arabidopsis.

Ethylene is the only gaseous plant hormone that regulates several aspects of plant growth, from seedling morphogenesis to fruit ripening and organ senescence. Ethylene also stimulates the germination of Striga hermonthica, a root parasitic weed that severely damages crops in sub-Saharan Africa. Thus, ethylene response stimulants can be used as weed and crop control agents. Ethylene and ethephon, an ethylene-releasing compound, are currently used as ethylene response inducers. However, since ethylene is a gas, which limits its practical application, we targeted the development of a solid ethylene response inducer that could overcome this disadvantage. We performed chemical screening using Arabidopsis thaliana "triple response" as an indicator of ethylene response. After screening, we selected a compound with a thiourea skeleton and named it ZKT1. We then synthesized various derivatives of ZKT1 and evaluated their ethylene-like activities in Arabidopsis. Some derivatives showed considerably higher activity than ZKT1, and their activity was comparable to that of 1-aminocyclopropane-1-carboxylate. Mode of action analysis using chemical inhibitors and ethylene signaling mutants revealed that ZKT1 derivatives activate the ethylene signaling pathway through interactions with its upstream components. These thiourea derivatives can potentially be potent crop-controlling chemicals.

Surgical experience of using the endoscope manipulator robot EMARO in totally extraperitoneal inguinal hernia repair: A case report.

Robot-assisted surgery has advanced rapidly since the 1980s. However, new equipment is still needed to overcome problems in conventional endoscopic surgery, including unique risks, such as camera shake and communication difficulties between the operator and the scopist. EMARO, an endoscope manipulator robot, is the world's first pneumatically driven endoscope-holder robot that can operate flexibly and smoothly with the use of air pressure. We herein report the surgical experience of using EMARO in totally extraperitoneal inguinal hernia repair. A 77-year-old Japanese man presented with bulging in the right groin area. After we diagnosed a right inguinal hernia, endoscopic inguinal hernia repair was performed. We selected the totally extraperitoneal approach with EMARO. The endoscopic procedure time was 100 minutes, and no intraoperative complications occurred. EMARO brings together features of smooth motion and good manipulation performance. This operation was performed safely and was comparable to a conventional operation completed with human assistants. Solo surgery with EMARO was beneficial in this inguinal hernia patient.

Effect of early oral feeding on length of hospital stay following gastrectomy for gastric cancer: a Japanese multicenter, randomized controlled trial.

PURPOSE: This multicenter, randomized controlled study evaluates the safety of early oral feeding following gastrectomy, and its effect on the length of postoperative hospital stay. METHODS: The subjects of this study were patients who underwent distal gastrectomy (DG) or total gastrectomy (TG) for gastric cancer between January 2014 and December 2015. Patients were randomly assigned to the early oral feeding group (intervention group) or the conventional postoperative management group (control group) for each procedure. We evaluated the length of postoperative hospital stay and the incidence of postoperative complications in each group. RESULTS: No significant differences in length of postoperative stay were found between the intervention and control groups of the patients who underwent DG. The incidence of postoperative complications was significantly greater in the DG intervention group. In contrast, the length of postoperative stay was significantly shorter in the TG intervention group, although the TG group did not attain the established target sample size. CONCLUSION: Early oral feeding did not shorten the postoperative hospital stay after DG. The higher incidence of postoperative complications precluded the unselected adoption of early oral feeding for DG patients. Further confirmative studies are required to definitively establish the potential benefits of early oral feeding for TG patients.

Technical Feasibility and Oncological Legitimacy of Enucleation of Intraductal Papillary Mucinous Neoplasm Located at the Pancreatic Head or Uncinate Process.

BACKGROUND: Surgical indications and strategies for branch duct (BD)-intraductal papillary mucinous neoplasm (IPMN) at the pancreatic head (PH) are controversial issues. We investigated the technical feasibility and oncological legitimacy of enucleation for IPMN of the PH. PATIENTS AND METHODS: The clinicopathological parameters of 11 patients with IPMN who underwent conventional pancreaticoduodenectomy (PD, n=7) or enucleation (n=4) during the same period were evaluated. RESULTS: The mean operative time (442 vs. 280 min, p<0.05) and blood loss (864 vs. 93 ml, p<0.05) were significantly better in the enucleation group. The final pathological diagnosis (low-/intermediate-/high-grade dysplasia) in the PD and enucleation groups was 4/2/1 and 3/1/0, respectively. The incidence of grade B pancreatic fistula and Clavien III complications was 14% vs. 0% and 43% vs. 25%, respectively. No recurrent pancreatitis or exocrine or endocrine dysfunction was noted in the enucleation group; however, de novo or exacerbated diabetes mellitus developed in three patients in the PD group. All patients were alive and no disease recurrence was noted at a mean follow-up of 1,059 days. CONCLUSION: Enucleation of BD-IPMN at the PH is a technically feasible and oncologically acceptable procedure which should be justified in patients with IPMNs with a low risk of malignancy.

Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for vascular invasion and patient outcomes.

The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %) was significantly related to tumor location, cancer invasion depth, vascular and lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall survival rates of patients with high tumoral C5aR expression were significantly lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver metastasis was significantly higher in patients with high tumoral C5aR expression (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR expression at liver metastatic sites was associated with the C5aR expression status at the primary site (P = 0.0004), vascular invasion at the primary site (P = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in gastric cancer was associated with cancer progression, liver metastasis, and poor prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic target in gastric cancer.

Laparoscopy-assisted distal gastrectomy for early gastric cancer poses few limitations for selected elderly patients: a single-center experience.

BACKGROUND: The safety and efficacy of laparoscopy-assisted distal gastrectomy (LADG) for early gastric cancer have been demonstrated in clinical studies. The aim of this study was to clarify the safety and efficacy of LADG in patients ≥80 years of age with early gastric cancer, an American Society of Anesthesiologists (ASA) classification of 1-2, and a performance status (PS) of 0-1. CASE PRESENTATION: From April 2009 to July 2011, 12 elderly patients aged ≥80 years and 43 younger patients underwent LADG for early gastric cancer. Seven of the 55 patients underwent LADG and simultaneous surgery including surgery for colorectal cancer, cholecystectomy, or other conditions. Forty-eight of the 55 patients who underwent only LADG were studied. Demographics and postoperative outcomes were compared. RESULTS: The postoperative complication rate, time to first ambulation, time to first flatus, time to first fluid intake, and postoperative hospital stay were similar in these two groups. Nutritional status as assessed by body weight, serum albumin, and total protein at 1 and 3 months after surgery was also similar in these two groups. CONCLUSIONS: Postoperative outcomes were acceptable in the elderly patients included in the study. LADG for early gastric cancer is a safe and effective treatment in elderly patients aged ≥80 years with an ASA status of 1-2 and PS of 0-1.

Uracil-Tegafur and Oral Leucovorin Combined With Bevacizumab in Elderly Patients (Aged ≥ 75 Years) With Metastatic Colorectal Cancer: A Multicenter, Phase II Trial (Joint Study of Bevacizumab, Oral Leucovorin, and Uracil-Tegafur in Elderly Patients [J-BLUE] Study).

BACKGROUND: We previously reported that uracil-tegafur with oral leucovorin (UFT/LV) treatment for elderly patients (aged ≥ 75 years) was well-tolerated in a phase II study. In the present study, the efficacy and safety of a modified (1-week shorter administration period) UFT/LV schedule combined with bevacizumab for a similar population are reported. PATIENTS AND METHODS: The present study was a single-arm, open-label, multicenter, cooperative group clinical trial. The key eligibility criteria included age ≥ 75 years, Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ function. Patients received UFT 300 mg/m(2)/d and LV 75 mg/d on days 1 to 21 and intravenous bevacizumab 5 mg/kg on days 1 and 15. Treatment was repeated every 28 days. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Of the 55 patients enrolled from 15 Japanese institutions, 52 eligible patients were evaluated. Their median age was 80 years (range, 75-87 years), and 73% had an ECOG performance status of 0. The median PFS was 8.2 months (95% confidence interval [CI], 6.2-10 months). The ORR was 40% (95% CI, 27%-55%). The median OS was 23 months (95% CI, 12-33 months). The most common grade 3 and 4 treatment-related adverse events were hypertension (12%), fatigue (8%), anemia (8%), nausea (6%), and diarrhea (6%). Treatment-related death occurred in 2 patients. CONCLUSION: UFT/LV (3 weeks of therapy and 1 week without) combined with biweekly bevacizumab is a tolerable and effective treatment option for elderly patients (aged ≥ 75 years) with metastatic colorectal cancer.

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

BACKGROUND: The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. PATIENTS AND METHODS: We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. RESULTS: Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. CONCLUSIONS: To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

The short term feasibility of abdominoperineal resection with prostatectomy for locally advanced rectal cancer: open and laparoscopic cases report.

Total pelvic exenteration is often selected for advanced rectal cancer with prostatic invasion. The aim of this study was to evaluate the short term feasibility of the abdominoperineal resection with prostatectomy for locally advanced rectal cancer. We performed abdominoperineal resection with prostatectomy for 3 patients with locally advanced rectal cancer, including 2 patients by totally laparoscopic procedure. Patients' background, intra- and postoperative factors and short-term prognosis were evaluated. All patients underwent complete resection of primary tumor with negative surgical margins. We could perform the surgery by both open and laparoscopic procedure in collaboration with urologist. There was no operation related mortality. One patient who was treated by open procedure had urinary anastomotic leakage. No patient had recurrenced, but one patient died of other disease. Our experience suggests that open or laparoscopic abdominoperineal resection with prostatectomy could be an alternative to total pelvic exenteration for the patients with rectal cancer invading the prostate. The collaboration with the urologist would be important to perform quality-controlled surgery.

Laparoscopic and Open Resection of Gastrointestinal Stromal Tumors of the Stomach.

INTRODUCTION: Laparoscopic resection has been reported as reasonable for patients with gastrointestinal stromal tumors (GISTs). In this study, we report the feasibility of the laparoscopic approach for GIST of the stomach. We also discuss the laparoscopic approach for GIST larger than 5 cm, which is reported to be difficult to treat by laparoscopic surgery. MATERIALS AND METHODS: We retrospectively reviewed 22 patients with GIST of the stomach resected by laparoscopic or open procedures between January 2006 and February 2014. RESULTS: Laparoscopic resections were performed in 9 patients and open resections in 13 patients. Curative resections with negative resection margins were successfully completed for all patients. Although the size of the tumors was greater in open surgery cases than in laparoscopic patients (P = 0.03), the loss of blood was lower and the hospital stay was shorter in laparoscopic cases (P = 0.01 and 0.003, respectively). Laparoscopic resection was performed for 2 patients with GISTs larger than 5 cm. Both were located at greater curvature, and curatively resected without any complications or recurrence. DISCUSSION: Our experience suggests that laparoscopic surgery for GISTs of the stomach, including those larger than 5 cm, may be feasible after careful deliberation of its indications. Laparoscopic resection for GIST was associated with lower loss of blood and shorter hospital stay in comparison with open resection.

Phase II study of first-line chemotherapy with uracil-tegafur plus oral leucovorin in elderly (≥75 years) Japanese patients with metastatic colorectal cancer: SGOSG-CR0501 study.

BACKGROUND: Oral uracil-tegafur and leucovorin (UFT/LV) therapy for elderly patients with metastatic colorectal cancer (mCRC) requires careful handling in Western countries because of a high incidence (≥20 %) of grade 3 diarrhea. However, its efficacy and safety for elderly Asian patients have not been investigated. METHODS: In this multicenter cooperative phase II study, the eligibility criteria were: age of 75 years or older, no prior chemotherapy, and histologically confirmed colorectal cancer with one or more measurable lesions. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally for 28 days followed by a 7-day rest period. RESULTS: Twenty-one patients were enrolled in this study (prior to study termination after approval of bevacizumab), and all patients were eligible for efficacy and safety analysis. The median age was 79 years (range, 75-83 years). The majority of patients (95 %) had ECOG Performance Status 0 or 1. The overall response rate was 33 % (95 % confidence interval [CI], 18-53 %). The median progression-free and overall survivals were 5.3 months (95 % CI 4.0-7.9 months) and 18 months (95 % CI 13-21 months), respectively. Grade 3 or greater adverse events included anorexia (10 %), diarrhea (10 %), and leukopenia (5 %). These results were compatible with those seen in Japanese patients in a previous bridging study between Japan and the US, in which patients under 75 years old were evaluated. CONCLUSIONS: UFT/LV therapy was safe and feasible in elderly Japanese patients with mCRC, and further study of UFT/LV therapy in combination with bevacizumab is warranted.

Liver resectability of advanced liver-limited colorectal liver metastases following mFOLFOX6 with bevacizumab (KSCC0802 Study).

BACKGROUND/AIM: The Kyushu Study group of Clinical Cancer (KSCC) conducted phase II trials (KSCC0802-UMIN000001308) concerning liver resectability after first-line treatment of advanced liver-limited colorectal metastases (CRLM) by a prospective, multi-center study. PATIENTS AND METHODS: Patients received 6 cycles of mFOLFOX6 with bevacizumab followed by evaluating liver resectability. The primary end-point was liver resection rate. RESULTS: The 40 patients enrolled from September 2008 to August 2010. The median number of administration cycles was 6 (range=1-7). The liver resectability cases were 16/40 (40.0 %) and the number of R0 cases was 10 patients (25.0%). An overall response rate was 30.0% (95% CI=15.2%-44.8%). Median progression-free and overall survival of all patients was 9.7 months and 33.0 months), respectively. CONCLUSION: mFOLFOX6 with bevacizumab regimen is safe and effective for advanced liver-limited CRLM and might lead to high liver resectability.

Phase II study of docetaxel and S-1 (DS) as neoadjuvant chemotherapy for clinical stage III resectable gastric cancer.

BACKGROUND: We conducted a phase II trial to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel (DTX) plus S-1 for resectable advanced gastric cancer. PATIENTS AND METHODS: A total of 47 patients from 14 centers were centrally registered. Patients received DTX (35 mg/m(2)) on days 1 and 15, and daily oral administration of S-1 (80 mg/m(2)/day) for days 1-14 every 4 weeks for two courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). This study was registered in the UMIN clinical trial registry (UMIN000000875). RESULTS: The primary endpoint pRR was 47 % (90 % confidence interval (CI), 34-60 %; p < 0.0001). The response rate to preoperative chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) was 34 %. Forty-six patients (98 %) underwent surgery, and curative resection was performed in 44 patients. Thirty-seven patients completed the protocol treatment. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42 %), febrile neutropenia (4 %), grade 2 anorexia (21 %), and fatigue (15 %). Treatment-related death and operative mortality was not observed in this study. CONCLUSIONS: The combination of docetaxel and S-1 was well tolerated. This is promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.

Indications for emergency surgery for perforated diverticulitis in elderly Japanese patients ≥80 years of age.

PURPOSE: Perforated diverticulitis (PD) remains a serious acute abdominal condition. The aim of this study was to evaluate indications for emergency surgery in patients ≥80 years of age with PD. METHOD: Twenty patients ≥80 years of age and 28 younger patients who underwent emergency surgery for PD from January 2002 to December 2011 were studied. The demographics and postoperative outcomes were compared. RESULTS: The preoperative characteristics, mortality rate, and postoperative complications were similar between these two groups. All seven patients ≥80 years of age with an American Society of Anesthesiologists (ASA) score of 2 survived after surgery. All five patients with a Mannheim peritonitis index (MPI) score of ≥26 in the elderly group died after surgery. There were significant associations between the mortality, the MPI and ASA score in patients ≥80 years of age. CONCLUSIONS: Best supportive care may be an alternative for patients ≥80 years of age with PD, an ASA score of ≥3 or an MPI score of ≥26.

A randomized phase-II trial comparing sequential and concurrent paclitaxel with oral or parenteral fluorinated pyrimidines for advanced or metastatic gastric cancer.

BACKGROUND: The purpose of this study was twofold: (1) to compare S-1 with infusional 5-fluorouracil (FU) to determine which would be a better partner of paclitaxel (PTX), and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice. METHODS: The 161 eligible patients were randomized into four arms to receive the following regimens: A (sequential), intravenous 5-FU at 800 mg/m(2) for 5 days every 4 weeks followed by weekly PTX at 80 mg/m(2); B (sequential), S-1 at 80 mg/m(2) for 4 weeks and 2-week rest followed by PTX; C (concurrent), intravenous 5-FU at 600 mg/m(2) for 5 days and weekly PTX at 80 mg/m(2) every 4 weeks; and D (concurrent), S-1 for 14 days and PTX at 50 mg/m(2) on days 1 and 8 every 3 weeks. The primary endpoint was the overall survival (OS) rate at 10 months. RESULTS: The ten-month OS rates in arms A, B, C, and D were 63, 65, 61, and 73%, respectively. The OS was best in the concurrent S-1/PTX arm, with a mean survival time of 15.4 months, but no significant difference was observed between the four arms. Response rates were higher in the concurrent arms than in the sequential arms. CONCLUSION: Our study did not show sufficient prolongation of survival with the concurrent strategy to proceed to a phase-III trial; however, the sequential arms showed survival comparable to that in the concurrent arms, with less toxicity. In patients who are ineligible for cisplatin (CDDP), sequential treatment starting with S-1 and proceeding to PTX would be a good alternative strategy, considering quality of life (QOL) and the cost-benefits of an oral agent as first-line treatment.

[A case of capecitabine-resistant recurrent breast cancer found to be responsive to S-1].

Thirteen months following surgery, local recurrence and multiple lung metastases occurred. Hormone therapy was continued following the recurrence but was found to be ineffective, so the patient was referred to our hospital 9 months after the recurrence. Capecitabine-based chemotherapy was administered but found to be ineffective; 3 months later, the anti-cancer drug was changed to S-1. After 3 months of S-1 administration, a CT scan showed a marked reduction in sites of recurrence and metastasis, making it possible to control progression of the disease over a longer period. No critical adverse reactions were observed, suggesting that S-1 can be useful and safe for the treatment of capecitabine-resistant recurrent breast cancer.

Two Arabidopsis cyclin A3s possess G1 cyclin-like features.

A-type cyclins (CYCAs) are a type of mitotic cyclin and are closely related to cyclin B. Plant CYCAs are classified into three subtypes (CYCA1-CYCA3), among which CYCA3 has been suggested to show a biased expression during the G1-to-S phase. We characterised Arabidopsis CYCA3s (CYCA3;1-CYCA3;4) in terms of expression pattern and protein function. CYCA3;1 and CYCA3;2 transcripts were highly accumulated at the G1/S phase, whereas CYCA3;4 was constantly expressed during the cell cycle. Expressions of CYCA3;1 and CYCA3;2 were observed in actively dividing tissues, such as root and shoot apical meristems and lateral root primordia. Overexpression of CYCA3;1 or CYCA3;2 distorted apical dominance in Arabidopsis, indicating that they have critical functions in shoot meristems. In insect cells, CYCA3;1 formed an active kinase complex with CDKA;1, an orthologue of the yeast Cdc2/Cdc28p, and phosphorylated retinoblastoma-related protein, a key regulator in the transition from the G1 to the S phase. Our results suggest that Arabidopsis CYCA3;1 and CYCA3;2 are distinct members of the G1 cyclin family that play an important role in meristematic tissues.

Coexistence of mucinous cystic neoplasm occurring in the head of the pancreas with annular pancreas: report of a case.

Mucinous cystic neoplasms (MCN) of the pancreas are rare tumors that are almost exclusively located in the body or the tail of the pancreas. A 60-year-old woman with no history of pancreatic disease was referred to our hospital with a chief complaint of dull pain in the upper abdomen. Abdominal computed tomography showed a multilocular cystic mass of 7.0 cm in the head of the pancreas, and endoscopic retrograde cholangiopancreatography showed no communication between the cystic mass and the main pancreatic duct. A pancreatoduodenectomy was performed for the complete resection of the tumor, and an annular pancreas was discovered by accident. The pathological examination of the tumor led to a definitive diagnosis of MCN with ovarian-type stroma. To our knowledge this is the first documented case of MCN occurring in the head of the pancreas and associated with annular pancreas.

Phase II study of biweekly docetaxel and S-1 combination therapy for advanced or recurrent gastric cancer.

OBJECTIVE: This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer. METHODS: Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m(2) on days 1 and 15, and oral S-1 80 mg/m(2)/day on days 1-14 every 4 weeks. The primary endpoint was objective response. RESULTS: Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1-19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24-56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3-4 toxicities were neutropenia (23%) and leukocytopenia (15%). CONCLUSION: Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic.