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Background Prokineticin family correlates with important roles in several biological processes, including homeostasis. We discovered novel functions of prokineticin1 (PROK1) in lymphangiogenesis and lymphnode metastasis in colorectal cancer. Materials and methods We examined changes in the number of lymphatic endothelial cells after PROK1 stimulation. PROK1 protein was stimulated with subcutaneously implanted in mice. Also a high-PROK1-expressing colorectal cancer cell line and anti-PROK1 antibody(Ab) were subcutaneously implanted in mice, and then examine lymphangiogenesis. PROK1 expression and the number of lymph vessels were examined in the primary lesion of 391 patients whose colorectal tumors had been resected. Results When PROK1 was used as a stimulus, the number of lymphatic cells increased compared to unstimulated cells. And the number of lymph vessels in the skin of mice increased compared to mice implanted without PROK1. The number of lymph vessels in the primary tumor tissue increased when PROK1 was highly expressed compared to cases with non-detectable PROK1 expression. When PROK1 was expressed in human colorectal tumors, the rate of lymphnode metastasis was significantly higher than that in cases with non-detectable PROK1 expression. Conclusions PROK1 is a lymphangiogenic factor involved in the formation of new lymph vessels and lymphnode metastasis in human colorectal cancer.

Immunogenic cell death (ICD), activated by damage-associated molecular patterns (DAMPs), is an apoptotic cell death process that elicits antitumor immunity. Although anticancer drugs that can induce ICD are promising for cancer treatment, the design strategy for ICD inducers remains unclear. In this study, we demonstrated the cell-penetrating redox phospholipid polymer poly(2-methacryloyloxyethyl phosphorylcholine-co-vinyl ferrocene) (pMFc) inducing ICD in murine colon cancer CT26 cells. pMFc produced oxidative stress by extracting electrons from CT26 cells and induced the release of DAMPs, such as calreticulin, adenosine triphosphate, and high-mobility group box 1. Moreover, the injection of pMFc-treated CT26 cells inhibited tumor formation in subsequently challenged CT26 cells, indicating that pMFc elicited antitumor immunity through ICD. Using in vivo therapy, intratumoral injections of pMFc induced complete tumor regression in 20% (1/5) of mice. These results suggested that the redox phospholipid polymer provides a new option for ICD-inducing anticancer polymers.

Spacers are widely used in membrane technologies to reduce fouling and concentration polarization. Fouling can start from the spacer surface and grow, thereby reducing flux, selectivity, and operation lifetime. Fluorescein isothiocyanate labeled bovine serum albumin was used for fouling studies and observed during cross-flow filtration operation for up to 144 h. Here, we mixed carbon nanotubes (CNTs) and polypropylene (PP) to make a spacer with better antifouling than plain PP spacers. The fouling process was observed by scanning electron microscopy and monitored in situ by fluorescence microscopy. Molecular dynamics simulations show that bovine serum albumin has a lower interaction energy with the nanocomposite CNTs/PP spacer than with the plain PP. The findings are relevant for the development of spacers to improve the operation lifetime of membranes in filtration technologies.

Reverse osmosis membranes typically suffer compaction during the initial stabilization stage due to the applied hydraulic pressure, altering the desalination performance. The elucidation of the underlying transformations during compaction is key for further development of new membranes and its deployment in real-world scenarios. Hydraulic compaction of amorphous carbon (a-C) based membranes under cross-flow operation for water purification and desalination has been observed experimentally, and analysed employing molecular dynamics simulations. The previous outstanding separation performance for carbon membranes, especially for the nitrogen-containing (a-C:N) type, has been studied during compaction using lab-scale cross-flow desalination membrane systems. Our results indicate that the high-water pressure induces an overall reduction in the interstitial spaces within the a-C structure. Remarkably, the compacted a-C:N membrane exhibits improved performance in salt rejection and water permeability, compared to the a-C based membrane. Our analysis shows that performance improvement can be related to the higher mechanical stability of the carbon structure due to the presence of nitrogen sites, which also promote water diffusion and permeability. These results show that a-C:N based membranes are a feasible alternative to conventional polymeric membranes.

The complexity of the supply chain, with a multiplicity of suppliers and organizations imposes challenges to its traceability, affecting the possibility of making it more sustainable. The declaration of Greenhouse Gas (GHG) by companies has been a response to pressures from stakeholders and regulations towards a sustainable supply chain management (SSCM). However, there are still some setbacks. The verification process of the inventories is a time-consuming task and the utilization of traditional renewable energy certificates can cause distortions in the perception of those who are consuming renewable energy but are not buying certificates. A blockchain-based application could address those problems by tracking transparent records of product history. Therefore, we propose a blockchain-based artifact in the form of a level 1 architecture diagram to improve the Brazil GHG Protocol Program inventory process on scope 2, which includes indirect carbon emissions from consumption of purchased electricity, heat or steam; main supply chain components. Using the Design Science Research (DSR) approach, we combine knowledge from business participants and environmental experts to understand the Program problems, propose and evaluate the artifact, and analyze its contributions. We find out that not all actors may want greater transparency in the supply chain and that traditional certificate issuers are expected to resist, while a new generation of blockchain-based certificates challenges the more traditional competitors. Additionally, the economic benefits observed in implementing blockchain points out that the organization and resistance of the actors, therefore, could be as important as costs in the implementation of new technologies in supply chains. There are two main contributions from this study. First, it introduces the discussion on blockchain adoption in the GHG Protocol Program. Second, it uses DSR as an instrument to both articulate a solution around a theoretical artifact and make its potential contribution understandable for actors not familiar with blockchain technologies. We propose that future studies could: (i) produce a proof-of-concept or a pilot implementation of this artifact; (ii) include other actors from the energy and trading certificates chain on the artifact, such as energy producers, regulators and the Brazilian Electricity Trading Chamber (CCEE); (iii) reproduce the same proposition focusing on GHG Protocol’s scope 3.

Gastric cancer is one of the most common malignancies in Asia, and the second most common cause of cancer-associated mortality in Japan. Colorectal metastases originating from gastric adenocarcinoma are extremely rare. The present study reports an unusual case of lymphogenous sigmoid metastasis of gastric adenocarcinoma occurring in a 58-year-old female patient. Endoscopic and radiological findings were indicative of 0-IIc+IIa early gastric cancer, and radical distal gastrectomy with D2 lymph node dissection was performed. The pathological diagnosis was stage IA gastric adenocarcinoma (T1bN0M0), according to the Japanese classification of gastric cancer. A follow-up examination at 18 months post surgery revealed a recurrence of paraaortic lymph node metastasis, detected by abdominal computed tomography (CT) and positron emission tomography (PET)/CT. The patient received chemotherapy with S-1 and cisplatin. Subsequently, radiotherapy was administered to the paraaortic lymph nodes at levels Th11-L3. Follow-up abdominal CT and PET/CT revealed an enlarged left ovary, and abnormal uptake in the left ovary and sigmoid colon. An oophorectomy and sigmoidectomy with D3 lymph node dissection were performed. The pathological diagnosis was metastatic adenocarcinoma; this was identical to the gastric pathology in the previous pathological report. The patient continued treatment with chemotherapy. Although sigmoid colonic metastasis from gastric cancer is extremely rare, metastasis from gastric cancer must be considered during the differential diagnosis of cases involving a colorectal mass and a previous history of gastric cancer.

The Prokineticin 2 (PROK2) is correlated with indispensable in maintaining the homeostasis of healthy human tissues. Herein, we examined the role of PROK2 in human colorectal cancer. After total RNA extraction from 6 colorectal cancer cell lines, we examined the expression of PROK2 mRNA. For investigating angiogenesis and tumor growth in mice, the PROK2 gene was transfected into colorectal cancer cell lines having low PROK2 mRNA expression. In addition, small interfering RNA (siRNA) was transfected into colorectal cancer cell lines having high PROK2 mRNA expression for investigation of angiogenesis and tumor growth in mice. From 6 colorectal cancer cell lines studied, PROK2 mRNA expression was increased in 3 cell lines. When the PROK2 gene was transfected into the colorectal cancer cell line with low PROK2 mRNA expression, angiogenesis and tumor growth in mice increased significantly compared to the cell line with the control vector. When PROK2 siRNA was transfected into colorectal cancer cell lines with high PROK2 mRNA expression, angiogenesis and tumor growth in mice were suppressed significantly compared to the cell line with siRNA (control). This is the first report of the association of PROK2 as an angiogenic growth factor in colorectal cancer.

In addition to the general surgical-site infection prevention measures in colorectal cancer surgery, we performed a simple subcutaneous scrubbing procedure with gauze at the time of abdominal closure, which reduced the incidence of wound infections. There are 289 patients whose primary colon cancer lesions were removed by elective surgeries. They were divided into Group A (74 patients with no wound infection prevention measures who were treated from 2002 to 2003), Group B (76 patients with wound infection prevention measures who were treated from 2007 to 2008), and Group C (139 patients with subcutaneous scrubbing with gauze plus the measures in Group B who were treated from 2009 to 2012). The incidence in Group A was 23%, while the corresponding values in Group B and Group C were 14.5% and 2.9%, respectively. The incidence of wound infections was substantially reduced by additional subcutaneous scrubbing with a saline solution and gauze during closure of a surgical incision. This very simple procedure was considered useful for surgical site infection prevention.

Introduction Herein we report our retrocolic Roux-en-Y anastomosis for laparoscopic distal gastrectomy and its feasibility. Materials and Surgical Technique After laparoscopic distal gastrectomy with lymphadenectomy, the gastric remnant was fixed through the mesentery of the transverse colon. The gastrojejunostomy was performed with linear stapling devices at an angle that allowed for easy application. The jejunojejunostomy was also performed with linear stapling devices. All spaces between the mesentery were hand-sewn closed. This procedure was performed laparoscopically without additional incisions in all 34 patients. The median operative time was 365 min and the median blood loss was 50 mL. All patients started liquid intake the day after gastrectomy. There were three cases of Grade 1 complications and one Grade 2 complication per the Clavien-Dindo Classification. Patients’ weights after surgery were stable at the 36-month follow-up. Discussion The advantages of Roux-en-Y reconstruction have been reported to include less frequent anastomotic leakage, less gastritis and less bile reflux over the long term. The retrocolic reconstructions were performed in a manner similar to open surgery but under a laparoscopic view. The mesentery closure stitches to prevent internal herniation did not require as many stitches as the antecolic route and were easier to place. Our anastomosis for laparoscopic distal gastrectomy showed acceptable short-term results, with patients maintaining up to 91.0% of their preoperative weight and nutritional input. By fixing the remnant stomach to the mesentery of the transverse colon before the anastomosis, we easily completed the retrocolic Roux-en-Y anastomosis under laparoscopic view.

Background and Purpose Two distinct α1-adrenoceptor phenotypes (α1A and α1L) have recently been demonstrated to originate from a single α1A-adrenoceptor gene. Here, we examined the agonist profiles of recombinant α1A and α1L phenotypes and of lower urinary tract (LUT) α1-adrenoceptors. Experimental Approach A series of drugs (A61603, Ro 115–1240, NS-49 , MK017 and ESR1150) originally developed for stress urinary incontinence (SUI) therapy were used to stimulate recombinant α1A- and α1L-adrenoceptor phenotypes, and their potencies and intrinsic activity estimated from Ca2+ responses. Agonist-induced contractions were also examined in LUT tissues of rats and humans and in human mesenteric artery and rat tail artery. Key Results All the drugs were potent agonists of the α1A-adrenoceptor compared with the α1L-adrenoceptor phenotype. Among them, Ro 115–1240 was shown to be an α1A-specific partial agonist that produced partial contractions through α1A-adrenoceptors in rat prostate and tail artery, but not in the other LUT tissues and human mesenteric artery. In contrast, P-come 102 showed full agonist activity at α1A- and α1L-adrenoceptors, but was less selective than noradrenaline for α1A-adrenoceptors. Like noradrenaline, P-come 102 was highly potent at inducing contractions in all of the LUT tissues tested. However, the potency and intrinsic activity of P-come 102 were significantly lower than those of noradrenaline in human mesenteric artery. Conclusions and Implications The α1A- and α1L-adrenoceptor phenotypes and LUT α1-adrenoceptors were demonstrated to have distinct agonist profiles. As adrenergic contractions in LUT are predominantly mediated through α1L-adrenoceptors, the development of α1L-selective agonists may provide clinically useful drugs for SUI therapy.

// Youhei Kimura 1 , Takanori Goi 1 , Toshiyuki Nakazawa 1 , Yasuo Hirono 1 , Kanji Katayama 1 , Takeshi Urano 2 , Akio Yamaguchi 1 . 1 First Department of Surgery, University of Fukui, Fukui, Japan. 2 Department of Biochemistry, Shimane University School of Medicine, Izumo, Japan, Japan. Correspondence: Takanori GOI, email: // Keywords : colon cancer, CD44 variant exon, stem cells, Cancer initiating cells Received : May 22, 2013 Accepted : June 4, 2013 Published : June 6, 2013 Abstract Cancer stem cells(cancer initiating cells) have become increasingly important in the treatment of malignant tumors. CD44 in particular has been identified as a marker for stem cells in colon cancer, which is a high-morbidity tumor. However, many details remain unknown, including identification of the relevant exon. The elucidation of these details could lead to the development of new therapies and improvements in prognosis. We report our findings on the importance of CD44 variant exon 9(v9) of stem cells in colon cancer. Using the anti-CD44 standard form(s) antibody, as well as antibodies for each of the CD44 variant exons, we studied colon cancer cell lines by examining stained images of stem cells in the crypt of normal colon mucosa. Using the anti-CD44v9 antibody that fits the normal colon mucosa stem cells, we screened cells using flow cytometry to examine colony formation, resistance to anticancer drugs, and tumor mass formation after subcutaneous implantation in mice. The stem cell–containing region in the crypt of normal colon mucosa was negative for anti-Ki67 antibody staining; only the anti-CD44 v9 antibody stain was expressed. As for colony formation, resistance to anticancer drugs, and tumor mass formation, cells positive both for anti-CD44s and anti-CD44v9 antibody stains was significantly more frequent than those positive for anti-CD44s antibody stain and negative for anti-CD44v9 antibody stain and those negative both for anti-CD44s and anti-CD44v9 antibody stains. CD44 variant exon 9 plays an important role in colon cancer stem cells.

We report two cases of successful laparoscopic surgery for splenic artery aneurysm. In case 1, a 59-year-old man who had hypertension was admitted to the hospital with complaints of slight back pain. CT scan showed a winding splenic artery and an aneurysm behind the pancreas body. In case 2, a 71-year-old woman with hypertension consulted us and was diagnosed with splenic artery aneurysm. Her aneurysm increased from 1.2 mm to 20 mm at the 1-year follow-up. In both cases, we performed laparoscopic splenectomy, using the left lateral approach, to resect the aneurysm. Splenectomy was performed after the spleen had changed color. The operating times were 210 and 259 min, respectively and the bleeding was 60 and 100 mL, respectively. The postoperative course was uneventful. By using the lateral approach from the left side, we were able to precisely resect the splenic artery aneurysm under a stable laparoscopic view.

We present a rare case of rapidly enlarging inflamematory hepatocellular adenoma (IHCA) in a 60-year-old Japanese man. Screening abdominal computed tomography (CT) for the fatty liver patient revealed a 1.7-cm liver mass in the anterior segment of the liver. After 19 months, the lesion had rapidly enlarged to 6 cm in diameter and the patient was referred to our hospital. On perflubutane microbubble contrast-enhanced ultrasonography, the tumor showed a characteristic centripetal filling pattern in the vascular phase. We performed hepatic anterior segment resection because we could not rule out malignant tumor. Histopathological examination showed hyperplasia of mildly atypical hepatocytes and sinusoidal dilatation with marked inflammatory cell infiltration. Immunohistological staining revealed positive staining for serum amyloid A and C-reactive protein; therefore, we diagnosed this tumor as IHCA. The patient remains alive 42 months after operation without evidence of recurrence.

Pancreatic fistula after pancreatoduodenectomy (PD) is not uncommon, but few reports describe a stricture after pancreatogastrointestinalstomy. We investigated the clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy after PD. The subjects of this prospective cohort study were 132 patients who underwent PD or pylorus-preserving PD. We reviewed the relationships between pancreatic duct dilatation of the remnant pancreas and several risk factors. We also compared pancreatic duct dilatation with pancreatic atrophy and analyzed nutrient parameters in the first postoperative year. Patients with a preoperative pancreatic duct diameter less than 3 mm had a significantly dilated postoperative pancreatic duct diameter (p = 0.0001). The average atrophy rate of the remnant pancreas was 26.3 %, with the lowest atrophy rate (7.3 %) seen in patients without pre- or postoperative pancreatic duct dilation. A normal pancreas in which pancreatic duct dilatation developed postoperatively had a high atrophy rate (34.9 %). Moreover, only patients without pre- or postoperative pancreatic dilatation gained body weight (3.9 %). This study shows a significant correlation between pancreatic atrophy rate and weight loss. Atrophy of the remnant pancreas caused by anastomotic stricture influences the exocrine function of patients after PD. The anastomotic method must be improved to prevent pancreatic duct dilatation and allow for early diagnosis and management of stenotic lesions.

Procedures of our H-HIPEC and cytoreductive surgery (CRS) for patients with peritoneal metastases from colorectal cancer and appendiceal pseudomyxoma (PMP) are reported.

The protein-bound polysaccharide K (PSK) is used as a non-specific immunotherapeutic agent for the treatment of colon cancer. Little research, however, has been conducted on its association with angiogenesis, which is a prognostic factor markedly correlated with hematogenous metastases. We therefore decided to investigate the action of PSK on angiogenic growth factors, angiogenesis inhibitors and angiogenesis in colon cancer cells. Reverse transcription-polymerase chain reaction (RT-PCR) was used to investigate changes in HIF-1α mRNA expression. PCR array was used to investigate changes in angiogenic growth factors and angiogenesis inhibitors, as well as the expression of related genes. Colon cancer cells were cultured with or without PSK for 48 h. The following day, cells were cultured for two days at 37°C in new complete media. The resulting culture medium was placed in the chamber of a tube formation system in order to investigate tube formation. Investigation of HIF-1α mRNA expression in colon cancer cell lines and in cells cultured under identical conditions with added PSK revealed a significant decrease in expression, as well as a decrease in angiogenic growth factors and related genes in PSK-treated colon cancer cell lines. By contrast, levels of angiogenesis inhibitors and related genes were higher in the PSK-treated colon cancer cell lines. Investigation of tube formation revealed that elongation was inhibited in the medium of the PSK-treated colon cancer cell lines in comparison to the medium of the non-treated colon cancer cell lines. PSK suppresses angiogenic growth factors and related genes, enhances angiogenesis inhibitors and related genes and ultimately suppresses angiogenesis in colon cancer cells.

Atypical carcinoid tumors of the uterine cervix represent rare neuroendocrine tumors and are highly aggressive, showing early lymphatic invasion and hematogenous distant metastases. Because of the small number of cases, there are currently no recommendations regarding treatment, and little is known about the response to chemotherapeutic agents. A 39-year-old woman was diagnosed with a primary atypical carcinoid of the uterine cervix with numerous metastases to the liver. After radical hysterectomy, she underwent hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil. Complete response was achieved in numerous liver metastases. At the 2-year follow up of chemotherapy, the patient remains alive. Treatment for atypical carcinoid tumors remains elusive, however hepatic arterial chemoembolization with streptozotocin and 5-fluorouracil was effective in the present primary atypical carcinoid with liver metastases. A review of the previous reports is also presented.

大腸癌における再発巣の部位では腟転移は非常に稀である．今回，我々は直腸癌（Ra）術後2年に腟転移を認めた症例を経験したので，再発経路など文献的考察をふまえて報告する．症例は77歳女性．2007年7月直腸癌に対し当科で直腸低位前方切除術+リンパ節郭清（D3）を行った．術後フッ化ピリミジン経口抗がん剤内服にて補助療法を行った．術後経過良好であったが，術後2年のフォローアップCTにて傍大動脈リンパ節の腫脹を認めた．次いでFDG-PET検査を行ったところ，同部位と外陰部に強い集積を認めた．外陰部異常所見に対し，産婦人科にて精査を行ったところ腟に粘膜病変を認め，生検でAdenocarcinomaと診断された．直腸癌術後腟転移，傍大動脈リンパ節転移再発と診断し，中心静脈カテーテルポートを用いた化学療法（mFOLFOX6）と腟転移巣の切除を行った．現在転移再発治療開始後1年7カ月経過しており治療を継続している．

We report the case of a patient with colon cancer accompanied by multiple unresectable liver metastases who showed complete response (CR) to modified TEGAFIRI (mTEGAFIRI) (tegafur-uracil/leucovorin+irinotecan) chemotherapy. The patient was a 58-year-old Japanese male with cancer of the descending colon accompanied by multiple unresectable liver metastases. Following resection of the sigmoid colon cancer, mTEGAFIRI chemotherapy was administered. Abdominal computed tomography performed upon completion of 12 courses of chemotherapy showed that the unresectable liver metastatic lesions had disappeared, indicating CR. The only adverse drug reactions (ADRs) experienced to date have been stomatitis (grade 1) and neutropenia (grade 1). Anticancer therapy has thus been continued, and CR has been maintained for 15 months. The present patient achieved CR in response to mTEGAFIRI chemotherapy, a regimen that has not previously been reported, while experiencing only mild ADRs and maintaining a good quality of life. mTEGAFIRI chemotherapy is convenient to administer and is thought to be a potentially useful treatment option for patients with unresectable, recurrent colon cancer.