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Study design: The present study is a single-center retrospective cohort study. Objective: The objective of the study is to verify the hypothesis that sharp elevation of systolic blood pressure at extubation is a risk factor for development of symptomatic epidural hematoma after spinal surgery. Summary of background data: Postoperative symptomatic epidural hematoma (she) after spine surgery is a rare but potentially serious complication that may result in paralysis unless removed at an early stage. Methods: The subjects were 2611 patients treated with decompression and decompression/fusion of the cervical, thoracic, and lumbar vertebrae at our hospital. Twelve of these patients developed postoperative SEH and removal of hematoma was performed. To investigate the risk factors in these patients, data were analyzed for age at the time of surgery, sex, preoperative complications, medical history, body mass index, preoperative platelet count, surgical procedure, microscope use, operative time, blood loss, surgical site, systolic blood pressure (SBP) at extubation, difference between resting and extubation SBP, ratio of SBP at extubation to that at rest, blood pressure at discharge from the operating room, and use of a drain. Results: There was a significantly higher rate of SBP ratio (extubation/rest) ≥1.3 in patients with SEH ( p = 0.021, Fisher’s exact test). Among the preoperative complications and medical histories, the frequency of cerebrovascular disorder tended to be higher in SEH cases than in non-SEH cases ( p = 0.073). There was no significant difference for all other parameters listed above. In multivariate logistic analysis, the odds ratios were 3.98 ( p = 0.018) for an SBP ratio (extubation/rest) ≥1.3 and 4.75 ( p = 0.055) for cerebrovascular disorder, suggesting effects of these two items. With simultaneous input into a multivariate model, SBP ratio ≥1.3 had a significant independent association with postoperative SEH ( p = 0.021) and cerebrovascular disorder showed a tendency for this association ( p = 0.072). Conclusion: The risk for symptomatic epidural hematoma is significant in patients with SBP at extubation that is more than 1.3 times that of SBP at rest.

Isolated avulsion fracture of the peroneus longus tendon insertion at the base of the first metatarsal without injury of the tarsometatarsal joint is very rare. Similar to most avulsion fractures, this type of injury is caused by strong tension exerted by the peroneus longus tendon. The mechanism leading to this lesion and treatment options are not clearly defined. Several surgical techniques have been advocated for this fracture, including excision of an avulsion fragment and open reduction for internal fixation through the medial aspect of the foot or minimal plantar incision. We have described a method of percutaneous fixing of the avulsion fracture at the plantar lateral base of the first metatarsal using the ZipTight Fixation System (Zimmer Biomet Warsaw, Indiana, USA), which offers the advantage of allowing a rigid fixation and minimal invasive surgical technique for a small fragment.

Summary Background Preoperative hypoalbuminemia is a well-known risk factor for anastomotic leakage after colorectal surgery, but the association between perioperative albumin level and anastomotic leakage has not been fully investigated in curative colorectal cancer (CRC) patients. Methods In total, 200 CRC patients (Stage I–III) undergoing curative laparoscopic surgery between January 2004 and December 2013 were enrolled in this study. We collected data on surgical factors, perioperative levels of serum albumin and inflammatory markers, and perioperative factors affecting hypoalbuminemia from 196 CRC patients to assess the relation to anastomotic leakage. Results Anastomotic leakage occurred in 11 cases (5.6%) and the frequency was higher in rectal cancer patients ( p = 0.0044). There was no significant difference of preoperative serum albumin level between the anastomotic leakage group (AL) and the nonanastomotic leakage group (NAL). Postoperative serum albumin levels in AL were significantly lower than in NAL [postoperative day (POD) 0, p = 0.0004; POD1, p = 0.0001; POD3, p = 0.0004; and POD7, p = 0.0021]. On multivariate analysis, lower average level of serum albumin on POD1 and POD3 {odds ratio (OR) [95% confidence interval (CI)] = 7.53 (1.60–55.80), p = 0.0095}, higher average level of serum white blood cells on POD1 and POD3 [OR (95% CI) = 7.24 (1.40–59.25), p = 0.0165], and surgery for rectal cancer [OR (95% CI) = 15.18 (3.26–93.99), p = 0.0004] were independent risk factors for anastomotic leakage. Conclusion Lower early postoperative serum albumin levels are a potentially valuable indicator of anastomotic leakage in CRC patients undergoing curative surgery.

Background/Aims: Pouchitis is one of the main complications after ileal pouch-anal anastomosis in patients with ulcerative colitis. The aim of this study was to determine whether the use of colonic histological criteria can predict the development of pouchitis. Methodology: We retrospectively reviewed 147 patients' clinical data and performed a histological evaluation of the resected total colon using Tanaka's criteria, which comprise the following 6 factors: ulceration (H1), crypt abscesses (H2), degree of mononuclear cell infiltration (MNCI) (H3), segmental distribution of MNCI (H4), eosinophil infiltration (H5), and extent of disease of resected colon (H6). Results: The development of pouchitis and chronic pouchitis within 3 years after restoration of gastrointestinal continuity was recognized in 52 (35.4%) and 26 (17.7%) of the 147 patients, respectively. Using various combinations of each score, the H3 + H4 - H5 scores of patients with pouchitis or chronic pouchitis were significantly higher than those of patients without. A H3 + H4 - H5 score of >0.4 was a statistically significant risk factor for the development of both pouchitis and chronic pouchitis. Conclusions: The combination of the degree of MNCI, segmental distribution of MNCI, and eosinophil infiltration from histological criteria has utility in predicting the future development of pouchitis, especially chronic pouchitis.

Aim To identify predictors of poor prognosis of patients with colon cancer (CC) who underwent surgery with curative intent, we investigated the association between the albumin to globulin ratio (AGR) with clinicopathological findings such as overall (OS) and disease-free (DFS) survival. Patients and methods We conducted a retrospective study of clinicopathological findings, including preoperative laboratory data, for 248 patients with stage I-III CC. Results Patients with low AGR had shorter DFS and OS compared to those with high AGR. Multivariate analyses identified low AGR as an independent variable independently associated with recurrence and poor prognosis of patients with CC who underwent surgery with curative intent regardless of lymphnode metastasis. Conclusion The preoperative AGR was an independent predictor of recurrence and poor prognosis of patients with CC who underwent surgery with curative intent. The AGR indicates that these patients may benefit from intensive adjuvant therapy.

Although patients with metastatic colorectal cancer (CRC) are often unable to undergo treatment after resection of primary tumors, identifying such patients before surgery is not easy. In this study, we evaluated the association among clinicopathological findings, survival outcomes, and ability to undergo multimodal therapy after primary tumor resection in patients with Stage IV CRC. We collected clinicopathological findings and preoperative laboratory data, including carcinoembryonic antigen (CEA) and systemic inflammatory response markers for 92 patients who were treated for Stage IV CRC between 2005 and 2014. We used multivariate analysis on factors that affect prognosis and ability to undergo postoperative treatment. Postoperative multimodal therapy improved overall survival (OS) significantly. Among serum markers, elevated CEA, neutrophil-to-lymphocyte ratio, and modified Glasgow prognosis score (mGPS) were significant indicators of shorter OS. In multivariate analysis, low performance status (P = 0.003), undifferentiated histology type (P = 0.019), and elevated mGPS (P = 0.042) were independent predictors of worse prognosis; and older age (P = 0.016), right-sided colon cancer (P = 0.043), and elevated mGPS (P = 0.031) were independent risk factors for difficulty of introducing postoperative multimodal therapy. Preoperative mGPS is a useful objective indicator for CRC patients with multiple metastases who are able to undergo primary site resection followed by postoperative multimodal therapy.

Familial adenomatous polyposis (FAP)-associated desmoid tumor (DT) is sometimes life threatening. However, the optimal treatment for DTs has not been established. The aim of this study was to analyze the outcomes of surgical and pharmacological treatments for DT in Japanese FAP patients.We retrospectively reviewed the data of 303 patients who underwent colectomy for FAP between 2000 and 2012. We analyzed 41 patients with DTs in which the location was apparent. The selection of treatment for intra-abdominal DTs was also evaluated according to Church's classification.Surgery was frequently used to treat extra-abdominal DTs. Multimodal treatments, including surgery, and the administration of non-steroidal anti-inflammatory drugs, hormonal therapy, and chemotherapy were widely used for intra-abdominal DTs. The most effective pharmacological treatment was cytotoxic chemotherapy, which was associated with a response rate of 45.5% and a disease control rate of 72.7%. After a median follow-up period of 53.0 months, the 5-year DT-specific survival rate in patients with stage IV disease was 71.4%; in contrast, the rate in patients with other stages was 100%. Four-stage IV patients died of DT due to uncontrollable rapid progression. No cytotoxic chemotherapy was administered; however, incomplete resection was performed in three cases.Our findings will provide clues that may help physicians in selecting the optimal strategy for this rare disease.

To assess the relationship of C-reactive protein/albumin ratio (CAR) to outcomes and surgical site infection (SSI) in gastric cancer (GC) treated with curative intent, we retrospectively assessed 384 patients with GC for CAR, SSIs, disease-free survival (DFS), overall survival (OS) and other factors. We found SSIs in 42 patients (10.9%). Pathological T-stage, TNM classification, body mass index, duration of surgery, blood loss and preoperative CAR were significantly associated with SSIs; in multivariate analyses, CAR [hazard ratio (HR)=2.98, p=0.003] and duration of surgery (HR=2.34, p=0.029) independently predicted SSI. Age, sex, T-and N-stages, tumor size and serum carcinoembryonic antigen (CEA) were associated with high CAR, and high CAR, CEA and CA19-9 combined was associated with shorter OS (p=0.0001) and DFS (p=0.0001). Multivariate analyses also linked high CAR to early recurrence (HR=2.21, p=0.011) and poor prognosis (HR=1.82, p=0.038). We show, for the first time to our knowledge, that a high CAR predicts SSI, early recurrence and poor prognosis in patients with GC treated with curative intent.

We used clinical data from Iga General Hospital to examine the association between polymorphisms in MTR (methionine synthase) A2756G (rs1805087), MTRR (methionine synthase reductase) His595Tyr (rs10380), MTHFR (methylenetetrahydrofolate reductase) C677T (rs1801133), MTHFR A1298C (rs1801131) and SHMT (serine hydroxymethyltransferase) C1420T (rs1979277), which are genes involved in folate metabolism, and the risk of weight loss in patients with gastrointestinal cancers, with the aim of establishing personalized palliative care for each patient based on genetic information. The data from 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic for cancer chemotherapy and palliative care at Iga General Hospital from December 2011 to August 2015 were analyzed. There was no significant association between the single nucleotide polymorphisms (SNPs) in the folate metabolizing genes examined and weight loss defined as weight loss of more than 5 percent or more than 10 percent during the first 6 months after initiation of chemotherapy. We did not detect any significant association between any of the SNPs examined and overall survival of patients. The present study indicated that these SNPs have relatively limited or no roles in the genesis of cachexia in patients with gastrointestinal cancers; however, further investigations into the roles of these folate metabolizing genes in the context of cancer palliative care, from clinical, biological and epidemiological viewpoints are warranted.

We defined small bowel obstruction occurring around the limbs of the ileostomy as stoma-related obstruction (SRO) and investigated the clinical characteristics and predictive factors of SRO. From January 2002 to March 2016, 309 consecutive patients who underwent ileal pouch–anal anastomosis (IPAA) for ulcerative colitis were enrolled. Two-stage IPAA with diverting ileostomy was analyzed. We assessed the possible associations between SRO and clinical factors. A total of 205 patients met the inclusion criteria. Fifty-three (25.8%) patients with SRO before ileostomy closure were identified for review. All patients with SRO were at least transiently resolved by intubation though orifice of ileostomy (98.1%) or nasally (3.7%). In 18 (33.9%) patients, the ileostomy was taken down ahead of schedule and the small bowel obstruction improved in all cases. Multivariate analysis revealed that age at surgery

BACKGROUND Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. PATIENTS AND METHODS Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. RESULTS Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC. CONCLUSIONS Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.

To investigate the incidence of colorectal cancer among familial adenomatous polyposis (FAP) patients by phenotype using the latest modalities. We collected data on 303 patients who underwent surgery for FAP at one of 23 institutions between 2000 and 2012. The incidence of colorectal cancer was investigated by phenotype. Colorectal cancer was diagnosed in 115 (38.0 %) of the 303 patients. Overall, colorectal cancer with the attenuated, sparse, and profuse phenotypes was diagnosed at 30, 31, and 28 years of age, respectively, in 10 % of the patients and at 59, 48, and 41 years of age, respectively, in 50 % of the patients (P = 0.013). The patients with colorectal cancer were older than those without colorectal cancer for all phenotypes. The optimal cut-off age for predicting the development of colorectal cancer in the attenuated, sparse, and profuse phenotypes was 46, 31, and 27 years, respectively. Patients with profuse and sparse phenotypes should undergo prophylactic proctocolectomy before their mid-to-late 20 s. On the other hand, the timing and type of surgery for patients with attenuated FAP (AFAP) should be decided individually with reference to the colonoscopic findings.

Excess body weight is associated with a risk of several malignancies, including colon cancer. However, the oncological significance of evaluating body mass index (BMI) preoperatively in colorectal cancer (CRC) patients undergoing curative surgery has not been fully evaluated. Clinicopathological findings including BMI and laboratory data [carcinoembryonic antigen (CEA) and neutrophil/lymphocyte ratio (NLR)] from 358 curative CRC patients (open surgery group: n = 157; laparoscopic surgery group: n = 201) were assessed as indicators of survival outcome. BMI

The coexistence of sarcopenia is associated with postoperative complications, including infection after abdominal surgery. We evaluated the association between sarcopenia and surgical site infection (SSI) after surgery for ulcerative colitis. The subjects of this retrospective study were 69 patients who underwent restorative proctocolectomy with perioperative abdominal computed tomography (CT). Sarcopenia was diagnosed by measuring the cross-sectional area of the right and left psoas muscles as the total psoas muscle area on CT images. We assessed whether sarcopenia was associated with SSI and clinical factors, including nutritional and inflammatory markers. The lowest quartiles defined as sarcopenia in men and women were 567.4 and 355.8 mm2/m2, respectively. According to this classification, 12 men and 6 women had sarcopenia. Patients with sarcopenia had a lower body mass index (p = 0.0004) and a higher C-reactive protein concentration (p = 0.05) than those without sarcopenia. SSIs were identified in 12 patients (17.3 %) and included six pelvic abscesses and seven wound infections. According to multivariate analysis, sarcopenia was an independent risk factor for SSI (odds ratio = 4.91, 95 % confidence interval 1.09–23.5, p = 0.03). Sarcopenia is predictive of SSI after pouch surgery for ulcerative colitis.

Afferent limb syndrome (ALS) is a type of small bowel obstruction (SBO) caused by obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis (IPAA). The aim of this study was to reveal the clinical features and management of ALS. Of 320 patients undergoing IPAA for ulcerative colitis, we analyzed data from patients presenting with SBO. Six of 19 patients with SBO were diagnosed with ALS. All patients with ALS presented with recurrent intermittent obstructive symptoms before admission, whereas 15 % of patients without ALS presented with these symptoms (P

Objectives: MicroRNA (miR)-503 is downregulated in several cancers and plays a tumor-suppressive role in carcinogenesis. However, the miR-503 expression pattern, its clinical significance and its molecular mechanism in colorectal cancer (CRC) have not been investigated. Methods: We analyzed miR-503 expression in normal mucosa (n = 20), adenoma (n = 27) and CRC (n = 20). We quantified miR-503 expression in an independent cohort (n = 191) and investigated the clinical significance of miR-503 in CRC. CRC cell lines were transfected with anti-miR-503 to assess its function and target gene. Results: miR-503 expression increased according to the adenoma-carcinoma sequence. High miR-503 expression was significantly associated with large tumor size, serosal invasion, lymphatic and venous invasion as well as lymph node metastasis. CRC patients with high miR-503 expression had significantly earlier relapse and poorer prognosis than those with low expression. miR-503 was an independent recurrence marker in stage I/II CRC. In vitro, attenuated miR-503 expression resulted in inhibition of proliferation, invasion and migration and acquisition of anoikis of CRC cells. The putative target gene (calcium-sensing receptor) was significantly upregulated after miR-503 attenuation. Conclusions: miR-503 acts as an ‘onco-miR' in CRC. High miR-503 expression is associated with early recurrence and poor prognosis in CRC.

A 56-year-old woman was diagnosed with rectal cancer and liver metastases(Stage IV), and underwent low anterior resection and laparoscopic partial hepatectomy. The patient received adjuvant chemotherapy(mFOLFOX6 for 24 weeks), but developed multiple lung metastases 11 months later. Before undergoing a pulmonary resection, the patient presented with acute small bowel obstruction. Abdominal computed tomography showed small bowel stenosis due to a tumor, and we suspected peritoneal metastases from the rectal tumor. We performed partial resection of the small intestine, and histopathological examination revealed a primary small bowel tumor. The patient was discharged to her home without complications, and later underwent pulmonary resections for bilateral lung metastases. We usually suspect that small bowel obstruction is due to peritoneal metastases in patients with advanced colorectal tumors, but must consider the rare possibility of a separate primary small bowel tumor, especially in patients with a solitary lesion. We report a rare primary small bowel tumor after FOLFOX treatment in a patient with Stage IV rectal cancer.

Epidermal growth factor receptor inhibitors (EGFRI), EGFR tyrosine kinase inhibitors (TKI) and anti-EGFR antibodies commonly develop skin toxicities including acneiform eruption (AfE). However, precise skin changes and risk factors for severe AfE are still unclear. The objective of the current study was elucidation of the useful parameters for early and sensitive detection of the skin changes by EGFRI. Transepidermal water loss (TEWL), skin surface hydration, skin surface lipid levels and erythema/melanin index were serially measured for 2 weeks in 19 EGFR-TKI afatinib/erlotinib-treated patients and for 8 weeks in 20 anti-EGFR antibody cetuximab-treated patients. The TEWL levels of the cheek in the patients who developed AfE of grade 2 and more (AfE ≥ Gr2) were already elevated at 7 days after the initiation of afatinib/erlotinib therapy compared with those before therapy as well as in patients with grade 1 or less (AfE ≤ Gr1). In patients treated with cetuximab, the skin surface hydration on the cheek in AfE ≥ Gr2 patients significantly decreased compared with that of AfE ≤ Gr1 patients at the 2nd and 6th week. Baseline skin surface lipid levels and erythema index on the cheek of patients with AfE ≥ Gr2 were significantly higher than those with AfE ≤ Gr1. The small sample size of the present study, especially for logistic regression analysis, is a limitation. In conclusion, instrumental evaluation declared rapid inflammatory changes of the skin by EGFRI and elucidated oily skin as a risk for severe AfE.

Combining in silico and in vitro systems reveals a mechanical feedback regulation of 3D tissue formation during organogenesis., Organogenesis is a self-organizing process of multiple cells in three-dimensional (3D) space, where macroscopic tissue deformations are robustly regulated by multicellular autonomy. It is clear that this robust regulation requires cells to sense and modulate 3D tissue formation across different scales, but its underlying mechanisms are still unclear. To address this question, we developed a versatile computational model of 3D multicellular dynamics at single-cell resolution and combined it with the 3D culture system of pluripotent stem cell–derived optic-cup organoid. The complementary approach enabled quantitative prediction of morphogenesis and its corresponding verification and elucidated that the macroscopic 3D tissue deformation is fed back to individual cellular force generations via mechanosensing. We hereby conclude that mechanical force plays a key role as a feedback regulator to establish the robustness of organogenesis.

To investigate the recent Japanese prevalence of thyroid cancer and its characteristics in familial adenomatous polyposis (FAP) patients, through the development of surveillance programs. The subjects of this study were 282 (93.1%) FAP patients for whom information on thyroid cancer was available, from among 303 patients registered in “the Retrospective Cohort Study of Familial Adenomatous Polyposis in Japan” database. We evaluated the prevalence and risk factors for thyroid cancer and integrated and/or compared our findings with those of previous reports, using a systematic review, including a meta-analysis. Thyroid cancer was diagnosed in 16 women (11.4%) and 2 men (1.4%), at 17–41 years and 39–57 years of age, respectively. The prevalence of thyroid cancer was 6.4%, with a female-to-male ratio of 8:1, which is comparable to reports from other countries. A young age of

Objective: The serum albumin-globulin ratio (AGR) is associated with malignancy outcomes. However, among patients with rectal cancer (RC) who undergo neoadjuvant chemoradiotherapy (nCRT), the clinical and prognostic significance of the pretreatment AGR is unclear. Methods: We investigated whether the pre-nCRT AGR can help predict oncological outcomes in patients with RC receiving nCRT. We analyzed 114 patients with RC who received nCRT followed by total mesorectal excision at our institution. Results: A lower AGR in pre-nCRT serum was significantly correlated with shorter overall survival and disease-free survival in patients with nCRT-treated RC. In multivariate analysis, a high carcinoembryonic antigen (CEA) level and a low AGR in pre-nCRT serum were independent predictors of a poor prognosis in these patients. Furthermore, combining the AGR with CEA provided a more accurate indicator of poor prognosis and early recurrence in these patients. In particular, a low pre-nCRT AGR was a stronger indicator of a poor prognosis and early recurrence in patients without than with pathological lymph node metastasis. Combining the pre-nCRT AGR with CEA could more precisely stratify patients’ oncological outcome risks. Conclusion: Assessment of the pretreatment AGR with or without CEA can guide postoperative treatment in patients with RC who undergo nCRT.

Severe malnutrition accompanied by sarcopenia and cachexia, is strongly associated with the surgical and oncological outcomes in cancer patients. The aim of the present study was to clarify the clinical significance of sarcopenia and its correlation with sarcopenia-associated miRNA in colorectal cancer (CRC). A total of 167 CRC patients were enrolled in the present study. We evaluated psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC). The expression of miR-21 in CRC tissues and preoperative serum was evaluated using quantitative PCR. Despite the lack of significant correlation between IMAC and disease-correlated factors, decreased PMI was significantly associated with well-established clinicopathological factors for disease progression. Decreased PMI was an independent prognostic factor for both overall survival and disease-free survival and was an independent risk factor for various types of metastasis. In contrast to the expression of tissue miR-21, the expression of serum miR-21 was significantly increased in CRC patients with low PMI. Furthermore, postoperative PMI was drastically improved compared with preoperative PMI in CRC patients with potentially curative resections. In conclusion, skeletal muscle mass may be a prognostic and predictive biomarker for distant metastasis in CRC patients and quantification of serum miR-21 expression could help clinicians make decisions regarding nutrition intervention strategies in CRC patients.

Colony‑stimulating‑factor‑1 (CSF‑1) is a hematopoietic growth factor that exerts its effects through the c‑fms/CSF‑1 receptor (CSF‑1R). The CSF‑1/CSF‑1R axis is thought to be involved in the development of several types of cancer. This study aimed to clarify the clinical and biological significance of the CSF‑1/CSF‑1R axis in gastric cancer (GC). For this purpose, we evaluated CSF‑1 and CSF‑1R expression in GC tissues from 148 patients by RT‑qPCR and immunohistochemistry. The biological roles of the CSF‑1/CSF‑1R axis were investigated by measuring the cell proliferation and migration, and anoikis resistance in a human GC cell line following treatment with recombinant human CSF‑1 and/or CSF‑1R inhibitor. The results revealed that an elevated expression of CSF‑1 or CSF‑1R significantly correlated with disease progression and with a poor overall survival (OS, P=0.037 and 0.016, respectively) and disease‑free survival (DFS, P

Background/aim This study aimed to clarify the potential of modified Glasgow Prognostic Score (mGPS) as a prognostic biomarker and reveal the significance of fish oil (FO)-enriched nutrition in colorectal cancer (CRC). Patients and methods A total of 738 CRC patients from three different patient cohorts, including 670 patients in the biomarker study and 68 patients in the nutrition-intervention study, were analyzed. Results High preoperative mGPS was significantly correlated with well-recognized disease progression factors and advanced UICC stage classification. In addition, high mGPS was an independent prognostic factor in both cohorts, especially in stage III and IV patients. These statuses were maintained in postoperative course and correlated with sarcopenia. Furthermore, FO-enriched nutrition suppressed systemic inflammatory reaction and improved skeletal muscle mass and prognosis, especially in CRC patients with mGPS 1 or 2. Conclusion Assessment of mGPS could identify patients with high-risk CRC, who might be candidates for FO-enriched nutrition.

Purpose Despite recent advances in colorectal cancer (CRC) treatment, the prognosis of patients suffering from this malignancy still remains substandard, and metastatic recurrence following curative surgery is the leading cause of mortality. Therefore, it is imperative to identify prognostic markers to predict the clinical outcome of CRC patients. Recent evidence revealed the new role of small nucleolar RNAs (snoRNAs) in oncogenesis. Herein, we systematically evaluated dysregulation of snoRNAs in CRC and clarified their biomarker potential and biological significance in CRC. Experimental design We analysed expression levels of 4 snoRNAs in 274 colorectal tissues from 3 independent cohorts and 6 colon cancer cell lines. The functional characterisation for the role of SNORA42 in CRC was investigated through a series of in vitro and in vivo experiments. Results In the screening phase, expression levels of all four snoRNAs were significantly elevated in CRC tissues than in corresponding normal mucosa. In the clinical validation cohort, increased SNORA42 expression was an independent prognostic factor for overall survival and disease-free survival, and was a risk factor for distant metastasis. SNORA42 expression negatively correlated with overall survival in an additional independent cohort and identified the patients with high risk for recurrence and poor prognosis in stage II CRC. Furthermore, in vitro and in vivo analyses showed that SNORA42 overexpression resulted in enhanced cell proliferation, migration, invasion, anoikis resistance and tumorigenicity. Conclusions SNORA42 appears to be a novel oncogene and could serve as a promising predictive biomarker for recurrence and prognosis in patients with CRC.

Aim The current trial was designed to study and compare the postoperative outcomes and systemic acute responses between patients undergoing laparoscopic-ileal pouch anal anastomosis (LAP-IPAA) and open IPAA for ulcerative colitis. Methods The clinical records of patients who underwent 89 restorative proctocolectomy procedures with IPAA were reviewed. After determining which patients underwent LAP-IPAA versus open IPAA, an equivalent number of controls matched for age and ulcerative colitis severity were selected. Results Twenty of 22 patients who underwent laparoscopic surgery met the inclusion criteria. Patients who underwent LAP-IPAA had significantly shorter times to first walking (P=0.021) and food intake (P=0.0003). The LAP-IPAA group had significantly lower interleukin-6 and interleukin-1ra levels soon after surgery (P=0.011 and P=0.0076). The LAP-IPAA group had significantly lower C-reactive protein levels on postoperative day 1 (P=0.0027). Conclusions LAP-IPAA is a less-invasive operative procedure than open IPAA with respect to the postoperative systemic inflammatory response and postoperative recovery.

CD26 is a transmembrane glycoprotein whose role in various types of malignancies, along with the potential therapeutic and diagnostic targets, has been evaluated. Preoperative chemoradiotherapy (CRT) is an effective tool for local control of rectal cancer, but the rate of disease recurrence remains high. The aim of this study was to clarify the association between CD26 expression and rectal cancer after preoperative CRT. A total of 85 patients with rectal cancer who had undergone preoperative CRT were enrolled in this study. We investigated CD26 expression in residual tumors and the surrounding stromal tissue using immunohistochemistry. Additionally, stromal CD26 gene expression was assessed by real-time quantitative polymerase chain reaction. Patients with high CD26 expression in cancer tissue more frequently had serosal invasion, vascular invasion, and a poor pathological response. High expression of CD26 in the tumor stroma was significantly correlated with histology and tumor recurrence. High CD26 expression in the stroma, but not the tumor itself, was significantly correlated with a poor prognosis. Patients expressing CD26 in the tumor stroma, based on transcriptional analysis, also had a significantly poorer prognosis than those without the expression. In multivariate analysis, lymph node metastasis and high stromal CD26 expression were identified as independent prognostic factors in patients with rectal cancer after neoadjuvant CRT. Stromal CD26 expression after preoperative CRT was significantly associated with tumor recurrence and prognosis in rectal cancer patients. Our data suggest that stromal CD26 plays an important role and is a potential therapeutic target in tumor relapse.

Metastasis is a major cause of death in patients with gastric cancer (GC). MicroRNAs (miRNAs) relating to the epithelial–mesenchymal transition (EMT) control GC progression and metastasis. The aim of this study was to evaluate serum EMT-associated miRNAs for metastatic and prognostic noninvasive biomarkers in GC. In the first step of this study (preliminary experiments), we selected candidate miRNAs associated with metastasis by analyzing the expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) and miR-203 in serum samples from stage I (n = 12) and stage IV (n = 12) GC patients. The second phase involved the independent validation of candidate miRNAs in serum specimens from 130 patients with GC and 22 controls. Based on the preliminary experiments, miR-203 was selected as the candidate serum miRNA that was most closely associated with metastasis. Validation analysis revealed that serum miR-203 levels were significantly lower in stage IV than stage I–III GC patients. Serum miR-203 expression was significantly lower in GC patients with a higher T stage, vessel invasion, and lymph node, peritoneal, and distant metastases. Low expression of serum miR-203 was significantly associated with poor disease-free and overall survival. Multivariate analysis revealed that low serum miR-203 expression was an independent predictive marker for lymph node, peritoneal, and distant metastases and a poor prognosis in patients with GC. Serum miR-203 has the potential to serve as a noninvasive biomarker for prognosis and to predict metastasis in patients with GC.

Preoperative serum systemic inflammatory response (SIR) in patients with colorectal cancer (CRC) has been reported to be a predictive biomarker of early recurrence. The molecular status of CRC, including microsatellite instability (MSI), BRAF and KRAS mutations, and tumor-infiltrating lymphocytes (TILs), has also been associated with recurrence in CRC patients treated with curative surgery. We investigated the impacts of SIR status, TILs, and MSI on recurrence in curative CRC patients. In this retrospective study, we enrolled 157 patients with stage I–III CRC undergoing curative surgery, for whom preoperative neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and C-reactive protein (CRP) data were available as indicators of SIR status. Molecular status was evaluated by counting TILs as the numbers of intratumoral Foxp3- and CD8-positive T cells by immunohistochemistry. MSI status was determined using five mononucleotide repeat microsatellite markers. Kaplan–Meier analysis of SIR indicators revealed that higher CRP, NLR, and PLR were associated with significantly poorer disease-free survival (DFS). Low levels of infiltrating CD8-positive T cells in CRC tissue was a significant predictor of poor DFS. Multivariate analysis showed that few infiltrating CD8-positive T cells and high serum CRP levels were independent predictive factors for recurrence. Furthermore, the combination of high CRP and few infiltrating CD8-positive T cells increased the predictive accuracy in these patients. The results of this study suggest that both CRP levels in preoperative serum and CD8 T cells in CRC tissue are useful biomarkers for predicting early relapse in CRC patients treated with curative surgery.

Although the safety of laparoscopic surgery for colon cancer has been reported in many randomized controlled trials, concerns about the difficulty of surgery for transverse colon cancer has not been fully resolved, mainly because of the variation in the vascular anatomy of mesenteric vessels, which leads to difficulty in determining the optimal operative procedure and the extent of lymph node dissection. We present the case of a patient with transverse colon cancer who underwent laparoscopic surgery after preoperative assessment using a combination of endoscopic clipping and three-dimensional computed tomography angiography (3DCTA). A 68-year-old man was diagnosed with transverse colon cancer, and laparoscopic surgery has been planned. 3DCTA showed right-middle and left-middle colic arteries arising independently from the superior mesenteric artery. The relationship between the clip and vessels showed that the right-middle colic artery was the feeding artery of the tumor. Operative findings were consistent with 3DCTA findings, and transverse colectomy with lymph node dissection was successfully performed.

Rac GTPase-activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation, invasive migration and metastasis. This study investigated the function and clinical significance of RacGAP1 expression in colorectal cancer (CRC). The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time PCR. Finally, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa and increased according to tumor node metastasis stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence and poor prognosis in CRC. Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.

Many studies have shown that hospital volume is significantly associated with short- and long-term outcomes in various diseases, including cancer. However, there have been no reports discussing the relationship between hospital volume and familial adenomatous polyposis (FAP). This study aimed to clarify whether hospital volume affects short- and long-term outcomes in FAP patients. We established a retrospectively collected database of FAP patients who underwent initial surgical treatment at 23 Japanese institutions during 2000–2012. Factors associated with short- and long-term outcomes were analyzed. The study cohort included 303 FAP patients. These patients were classified into tertile categories according to hospital volume: low (n = 31), middle (n = 72), and high volume (n = 200). The proportion of only adenoma/stage 0 was comparable among tertile categories. The adoption of operative procedure significantly differed among tertile categories; specifically, high-volume institutions preferred handsewn ileal pouch-anal anastomosis without diverting ileostomy (P

A 46-year-old woman was referred to our hospital because of nausea. Endoscopy revealed scirrhous gastric cancer, and abdominalcomputed tomography revealed peritonealdissemination. She was diagnosed with Stage IV gastric cancer and treated with S-1 plus CDDP combination chemotherapy. After 4 courses of chemotherapy, the primary tumor and peritoneal dissemination were considered clinically stable, but the uterus grew rapidly. She was diagnosed as having uterine metastasis based on cervicaland endometrialsmear class V cytology. As the chemotherapy was not effective for the uterine lesions, totalhysterectomy and bilateralsal pingo-oophorectomy were performed. Histological findings showed a poorly differentiated cancer with vascular emboli. Uterine metastases are an important consideration in women with scirrhous gastric cancer, and we recommend palliative hysterectomy for chemotherapy-resistant metastases if the primary tumor and other metastases are controlled.

Epithelial invagination is one of the fundamental deformation modes during morphogenesis, and is essential for deriving the three-dimensional shapes of organs from a flat epithelial sheet. Invagination occurs in an orderly manner according to the spatial pattern of the contractile cells; however, it remains elusive how tissue deformation can be caused by cellular activity in the patterned region. In this study, we investigated the mechanical role of the spatial patterns of the contractile cells in invagination of growing tissue using multicellular dynamics simulations. We found that cell proliferation and apical constriction were responsible for expanding the degree of tissue deformation and determining the location of the deformation, respectively. The direction of invagination depended on the spatial pattern of the contractile cells. Further, comparing the simulation results of surface and line contractions as possible modes of apical constriction, we found that the direction of invagination differed between these two modes even if the spatial pattern was the same. These results indicate that the buckling of the epithelial cell sheet caused by cell proliferation causes the invagination, with the direction and location determined by the configuration of the wedge-shaped cells given by the spatial pattern of the contractile cells.

Afferent limb syndrome (ALS) is caused by an obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis. Here, we describe the first case of ALS to be successfully treated by a laparoscopic approach. A 27-year-old man underwent ileal pouch-anal anastomosis for ulcerative colitis. He was subsequently diagnosed with ALS and underwent ileopexy with laparotomy at 33 years old. Then, 21 months after the first ileopexy, he underwent laparoscopic ileopexy for ALS recurrence. The operative findings revealed a shortened fixed portion of the afferent limb adhering to the right pelvic retroperitoneum, which was regarded as the cause of the acute angulation. The portion of the afferent limb fixed to the abdominal wall was extended under laparoscopic visualization by suturing above the level of the iliac crest. At the 12-month follow-up, the patient remained free of symptoms of obstruction. Laparoscopic ileopexy should be the procedure of choice for patients with ALS.

Solitary mediastinal lymph node metastasis of hepatocellular carcinoma (HCC) is rare. We report a case of metachronically solitary mediastinal metastases of HCC treated by video-assisted thoracic surgery (VATS) twice. A 66-year-old man underwent repeated laparoscopic radiofrequency ablation or trans-arterial catheter chemo-embolization against HCC for more than 10 years. The level of alpha fetoprotein protein was elevated, and radiological modalities including FDG-PET revealed solitary mediastinal tumor metachronically. VATS was performed bilaterally twice. The postoperative course was uneventful and there had no recurrence of extra-hepatic metastases and tumor markers are within normal limits at 18 months after second VATS. VATS is a minimally invasive and useful procedure for solitary mediastinal lymph node metastasis of HCC. If primary HCC was controlled and lymph node metastasis was solitary, mediastinum lymphadenectomy using VATS might give good short and long term results.

The management of postoperative rectovaginal fistula (RVF) after rectal cancer surgery is difficult and requires reconstruction of the anastomotic site and fistula. Though various surgical procedures have been reported for the repair of RVFs, the results of surgical repair are often unsatisfactory, and failure of the initial repair leads to difficulty in the later operations. Furthermore, it has been reported that cases associated with local infection result in low success rates. We report a case of an 80-year-old woman with a recurrent colonic J pouch-vaginal fistula after anoabdominal rectal resection with partial internal sphincteric resection, who achieved a good outcome following a repair using a puborectal sling interposition combined with seton drainage. It may be a useful option for RVF management in repair of such pouch-vaginal fistula after coloanal anastomosis with intersphincteric resection.

A 52-year-old woman was diagnosed with rectal hemangioma that had resulted in chronic bleeding. Klippel-Trenaunay syndrome was diagnosed by clinical examination. She was referred 30 years later because of progressive anemia. Colonoscopy revealed multiple bluish, polypoid nodules with severe vascular congestion and varicosis that had circumferentially spread along the wall from the dentate line to the rectosigmoid lesion. Selective abdominal angiography indicated that the hemangioma fed from the sigmoid artery and superior rectal artery. Doppler transrectal ultrasonography showed heterogeneous lesions with hypoechoic areas mostly in the submucosal layer, partly forming the mosaic pattern of the color flow signal in the intersphincteric layer on the oral side from the dentate line to 1 cm. Anterior resection and coloanal anastomosis with covering ileostomy was performed. Using a transanal approach, mucosectomy and intersphincteric resection were performed based on the Doppler transrectal ultrasonography results. There were no intraoperative complications, and her anemia resolved postoperatively.

The aims of this study were to reveal how using the antibiotics recommended by the 2010 Surgical Infection Society (SIS) and Infectious Disease Society of America (IDSA) guidelines can affect the therapeutic outcomes. We reviewed the cases of 53 patients with a postoperative intra-abdominal abscess without anastomotic leakage after gastrointestinal surgery who underwent image-guided percutaneous abscess drainage (PAD) and concomitant antibiotic therapy. The type of antibiotic initially administered was determined based on the surgeon’s judgment. A persistent abscess was defined as one or more PAD procedures resulting in complete resolution after 21 or more days. The recommended antibiotics were defined according to 2010 SIS/IDSA guidelines. All 53 patients had complete resolution without the need for surgery. The results of a multivariable analysis revealed that a C-reactive protein level ≥12 mg/dL and non-recommended antibiotics were significant risk factors for a persistent abscess (P = 0.042 and 0.013, respectively). With regard to a fever lasting more than 48 h, there was a significant difference between the recommended (45.1 %) and non-recommended (72.7 %) antibiotic groups (P = 0.046). Using the recommended antibiotics may shorten the time to defervescence and reduce the risk of a persistent abscess in patients undergoing PAD for a postoperative abscess after gastrointestinal surgery.

Interleukin-13 (IL-13) is an immunosuppressive cytokine produced by several immune cells and cancer cells. The aim of this retrospective study was to determine if serum IL-13 levels have an association with clinical outcome in patients with colorectal cancer. A total of 241 patients with colorectal cancer were enrolled in the present study. Preoperative serum IL-13 concentrations were measured by enzyme-linked immunosorbent assay. We analyzed the association of serum IL-13 levels with clinicopathological variables. Patients with lymph node metastasis, lymphatic invasion, vascular invasion, distant metastases or advanced stage of disease had significantly lower serum IL-13 levels. Low serum IL-13 was significantly associated with both poor recurrence-free and overall survival. Multivariate analysis showed that low IL-13 levels were an independent predictive marker for poor prognosis. In conclusion, our data suggest that low serum IL-13 levels may be a useful predictive marker for poor prognosis in colorectal cancer.

To evaluate the ability of epithelial-to-mesenchymal transition-related microRNAs (miRNAs) as serum biomarkers for prognosis and prediction of metastasis in patients with colorectal cancer (CRC).Epithelial-to-mesenchymal transition-related miRNAs drive CRC progression and metastasis. However, their potential as serum biomarkers in CRC has not been studied.This was a 3-phase study using 446 colorectal specimens. In the first phase, we selected candidate miRNAs associated with metastasis by analyzing the expression of 4 miR-200 family members (miR-200b, -200c, -141, and -429) in serum samples from 12 patients with stage I and IV CRC. The second phase involved independent validation of candidate miRNAs in serum from 182 patients with CRC and 24 controls. Finally, we analyzed expression in matched 156 tumor tissues from 182 patients with CRC and an independent set of 20 matched primary CRC and corresponding liver metastases to identify the source of circulating miRNAs.After initial screening, miR-200c was selected as the candidate serum miRNA best associated with metastasis. Validation analysis revealed that serum miR-200c levels were significantly higher in stage IV than in stage I-III CRCs. High serum miR-200c demonstrated a significant positive correlation with lymph node metastasis, distant metastasis, and prognosis (P = 0.0026, P = 0.0023, and P = 0.0064, respectively). More importantly, serum miR-200c was an independent predictor for lymph node metastasis (odds ratio: 4.81, 95% confidence interval: 1.98-11.7, P = 0.0005) and tumor recurrence (hazard ratio: 4.51, 95% confidence interval: 1.56-13.01, P = 0.005) and emerged as an independent prognostic marker for CRC (hazard ratio: 2.67, 95% confidence interval: 1.28-5.67, P = 0.01).Serum miR-200c has strong potential to serve as a noninvasive biomarker for CRC prognosis and predicting metastasis.

Rac GTPase activating protein 1 (RacGAP1) plays a regulatory role in cell growth, transformation and metastasis. The aim of this study was to clarify the association between RacGAP1 expression and clinical outcome in patients with gastric cancer. A total of 232 gastric cancer patients in our institute who underwent surgery without preoperative treatments were enrolled in this study. We investigated RacGAP1 expression using immunohistochemistry (IHC) and evaluated IHC scores calculated by the percentage of positive cells and intensity and its expression at the invasive front. RACGAP1 expression was also assessed. RacGAP1 expression was observed in the nuclei of gastric cancer cells. Evaluation by IHC score showed no significant correlations with clinicopathological variables except for histological differentiation. In transcriptional analyses, RACGAP1 expression was elevated in diffuse type gastric cancer than intestinal type without a significant difference. We observed significant correlations of RacGAP1 protein expression at the invasive front with older age, tumor size, lymph node metastasis, lymphatic invasion, vascular invasion and advanced stage. Patients with RacGAP1 protein expression at the invasive front had significantly poorer prognosis than those without it (P

We previously visualized in vivo responses to chemotherapy in a colorectal liver metastatic xenograft model using in vivo real-time and time-series intravital two-photon laser scanning microscopy (TPLSM). In this study, we established the method for evaluating the response of peritoneal xenografts to chemotherapy of metastatic gastric cancer using intravital TPLSM.Red fluorescent protein-expressing gastric cancer cells (NUGC4) were inoculated into the peritoneal cavity of green fluorescent protein nude mice.Laparotomy revealed that 2 weeks after inoculation, macroscopic peritoneal metastatic nodules were formed. The first intravital TPLSM session revealed that they were composed of red tumor cell clusters and green surrounding stroma. Paclitaxel was administered intraperitoneally after the first TPLSM three times a week for 7 days in the treatment group. At the second laparotomy, there were significantly fewer and smaller nodules in the treated mice than in the controls. The second intravital TPLSM session showed tumor cell fragmentation, swelling, and nuclear condensation in the metastatic nodules--a response to chemotherapy. There were multinuclear tumor cells in the paclitaxel-treated living mice.Our method may become a powerful tool for evaluating the efficacy of novel anti-gastric cancer drugs in a preclinical murine model with minimum interindividual variation.

To clarify whether the expression of nitrative and oxidative DNA damage markers in the rectal mucosa of patients with ulcerative colitis (UC) could be used to predict UC-associated neoplasia.A longer duration of UC can increase the risk of developing UC-associated cancer (UCAC). Effective diagnostic markers are being sought to provide more selective screening and treatment strategies for patients with long-standing UC.A total of 141 patients with UC who underwent a proctocolectomy were enrolled in this study. The expression of 8-nitroguanine (8-NG), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and inducible nitric oxide synthase (iNOS) in the rectal mucosa were evaluated using immunohistochemistry (IHC) and assessed relative to the pathogenesis of UC-associated neoplasia.Eighteen patients (12.8%) had UC-associated neoplasia including low-grade or high-grade dysplasia and UCAC. IHC scores of 8-NG in UC-associated neoplasia group was significantly higher than in non-neoplasia group (P0.0001). In contrast, IHC score of 8-oxodG in non-neoplasia group was significantly decreased compared with UC-associated neoplasia group (P=0.0028). In logistic regression analysis, duration of disease8 years, high IHC scores of 8-NG, and low 8-oxodG in the rectal mucosa were significantly associated with the development of UC-associated neoplasia (P0.01). The expression of 8-NG was more frequently observed in patients with UCAC than in patients with sporadic colorectal cancer (P0.01).These results suggest that evaluating the expression levels of 8-NG in the rectal mucosa may be a useful biomarker for detecting patients with UC-associated neoplasia.

Tissue morphogenesis in multicellular organisms is accompanied by proliferative cell behaviors: cell division (increase in cell number after each cell cycle) and cell growth (increase in cell volume during each cell cycle). These proliferative cell behaviors can be regulated by multicellular dynamics to achieve proper tissue sizes and shapes in three-dimensional (3D) space. To analyze multicellular dynamics, a reversible network reconnection (RNR) model has been suggested, in which each cell shape is expressed by a single polyhedron. In this study, to apply the RNR model to simulate tissue morphogenesis involving proliferative cell behaviors, we model cell proliferation based on a RNR model framework. In this model, cell division was expressed by dividing a polyhedron at a planar surface for which cell division behaviors were characterized by three quantities: timing, intracellular position, and normal direction of the dividing plane. In addition, cell growth was expressed by volume growth as a function of individual cell times within their respective cell cycles. Numerical simulations using the proposed model showed that tissues grew during successive cell divisions with several cell cycle times. During these processes, the cell number in tissues increased while maintaining individual cell size and shape. Furthermore, tissue morphology dramatically changed based on different regulations of cell division directions. Thus, the proposed model successfully provided a basis for expressing proliferative cell behaviors during morphogenesis based on a RNR model framework.

Laparoscopic adhesiolysis has been the focus of much recent attention; however, the role of single-port laparoscopic surgery for adhesive small bowel obstruction remains unclear. We report our experience of performing single-port laparoscopic surgery for adhesive small bowel obstruction through a retrospective review of 15 consecutive patients who underwent single-port laparoscopic surgery for single adhesive small bowel obstruction between 2010 and 2012. We analyzed data on patient demographics, operating time, conversion, and surgical morbidity. Surgery was completed successfully without conversion to laparotomy or the need for additional intraoperative ports in 14 patients, but the remaining patient had peritoneal dissemination from colon cancer. The median operative time was 49 (25-148) min, and the estimated blood loss was 19 (2-182) ml. There were no major postoperative complications. We conclude that single-port laparoscopic surgery is a technically feasible approach for selected patients with adhesive small bowel obstruction when preoperative imaging identifies a single adhesive obstruction.

Slug and Vimentin genes play a critical role in regulating epithelial-mesenchymal transition (EMT) via downregulation of epithelial markers and upregulation of mesenchymal markers. The present study evaluated the clinical significance of Slug and Vimentin expression as potential disease biomarkers in colorectal cancer (CRC). At first, the biological role of Slug in CRC was assessed by RNA interference in CRC cell lines to assess tumor progression, invasion and migration. Next, we analyzed Slug and Vimentin expression in surgical tissue specimens from 181 CRC patients (Cohort 1) by quantitative real-time reverse transcription-PCR and 208 patients (Cohort 2) by immunohistochemistry. Knockdown of Slug using small interfering RNA in CRC cell lines resulted in inhibition of EMT, reduced cell proliferation, invasion and migration in CRC cells. Interestingly, Slug and Vimentin expression in cancer tissues was significantly higher in patients with higher T stage, lymph node involvement, liver metastasis and advanced tumor node metastasis stages. A significant correlation was observed between Slug and Vimentin expression in CRC (messenger RNA: ρ = 0.546, protein: ρ = 0.405), and increased expression of Slug and Vimentin was significantly associated with poor prognosis. Furthermore, increased expression of Slug emerged as an independent prognostic factor and a predictive marker of lymph node metastasis in CRC patients. Our data provide novel evidence for the biological and clinical significance of Slug and Vimentin expression as potential predictive biomarkers for identifying patients with lymph node metastasis or poor prognosis in CRC.

Hyaluronan is a component of an anti-adhesive barrier and has been implicated in tumor growth and metastasis. We aimed to determine whether this anti-adhesive barrier was associated with rates of postoperative complications and duration of survival in patients with gastric cancer. We identified 415 consecutive patients with gastric cancer who underwent gastrectomy. Information about patients' demographics, medical history, surgical procedures, postoperative complications, disease stage, histology, and survival was collected from medical records. One hundred and ninety-six patients received intraoperative placement of an anti-adhesive barrier composed of hyaluronan–carboxymethylcellulose (HA-CMC) (HA-CMC group), and 219 did not (control group). The incidence of postoperative complications was significantly increased in the control group (22.8%) compared with the HA-CMC group (13.3%). However, there was no significant difference in overall survival between the HA-CMC and control groups. Our study suggests that the anti-adhesive barrier does not affect oncologic outcome, nor does it increase postoperative complications in patients undergoing surgery for gastric cancer.

With the recent advances in chemotherapy for colorectal cancer, the prognosis for patients with metastatic colorectal cancer has been significantly improved. The development of the implantable port system has also enabled patients to receive multiagent chemotherapy with a more satisfactory quality of life. Historically, chemotherapy using implantable port systems was begun to obtain an oncological benefit in the treatment of locoregional cancer. In the 1950s, there was an increasing interest in perfusion techniques for the application of chemotherapeutic agents, such as nitrogen mustard, in the locoregional treatment of metastatic cancer. Among them, the treatment of liver metastasis has interested oncologists for many years. On the other hand, implantable devices were developed during the intervening decades that have enabled patients with colorectal cancer with liver metastases to be treated effectively using hepatic arterial infusion; which became more common in the 1980s. The treatment of metastatic colorectal cancer increasingly requires a multimodal approach and multiple treatment options based not on convenience, but in terms of personalization and efficacy. Therefore, it is important to optimize the pharmacokinetics of chemotherapeutic agents. Implantable port systems for colorectal cancer patients have been essential for oncological practice, and the importance of these systems will remain unchanged in the near future.