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The diagnosis of strangulated bowel obstruction (SBO) is sometimes difficult. We attempted to create and verify a discriminant formula for use as a diagnostic aid for the early diagnosis of SBO. This retrospective study included 97 patients who underwent an operation for SBO from January 2007 to September 2018. First, a discriminant analysis was performed for 73 patients who underwent an operation from January 2007 to December 2015 in order to obtain a formula. Next, we analyzed 34 patients who underwent an operation from January 2016 to September 2018 to verify the formula. The risk factors for SBO included ascites, signs of preperitoneal irritation, and lactate > 1.16 mmol/L. The discriminant formula is as follows: 1.954 × collection of ascites (1 or 0) + 1.239 × peritoneal irritation sign (1 or 0) + 0.378 × lactate − 2.331 (1: positive, 0: negative). The predictive value was as follows: sensitivity, 87.5%; specificity, 64.7%; and predictive accuracy, 73.5%. In patients who presented within 24 h of the onset, the sensitivity was 92.3%, the specificity was 75.0%, and the predictive accuracy was 85.7%. Our discriminant formula seems useful for the rapid diagnosis of SBO.

Benign neural tumors or tumor-like lesions are rarely detected in the gastrointestinal tract. In this article, we present the case of a neural lesion of the sigmoid colon, which was incidentally detected in a 68-year-old man treated with laparoscopic low anterior resection for an advanced carcinoma of the rectosigmoid junction. Within the resected specimen, a submucosal tumor-like protruding lesion was found in the sigmoid colon. Histologically, the growth was composed of mucosal neurofibromatous and submucosal ganglioneuromatous lesions, between which there was transition. Immunohistochemical analysis revealed a rupture of the perineurium in the area of transition, along with a proliferation of Schwann cells and supporting cells extending into the deep mucosa. This transition indicated that the mucosal and submucosal lesions comprised a single lesion, and that a diagnosis of neurofibroma or ganglioneuroma would be inadequate in this case. Because we could not classify it as an established single entity, we diagnosed the mass as an unclassifiable colonic neurogenic lesion. In summary, we report the case of an extremely rare occurrence of an unclassifiable colonic neurogenic lesion comprising an admixture of transitioning mucosal neurofibromatous and submucosal ganglioneuromatous lesions.

We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients. The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24–36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up. The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event. It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC. The UMIN Clinical Trials Registry number was UMIN000018633.

Nodal metastatic foci of colorectal carcinoma are usually solid nodules. Serous inclusions are occasionally found in lymph nodes, particularly in female patients, and they occasionally form cysts. An 86-year-old woman was treated with laparoscopic low anterior resection and D3 lymph node dissection for advanced rectal carcinoma. A cyst with serous fluid and no necrotic debris was found within one of the dissected pararectal lymph nodes. Histologically, the cyst was lined by low columnar-to-cuboid epithelium with mild nuclear atypia, mimicking a serous inclusion cyst. Immunohistochemically, the epithelial cells were positive for caudal type homeobox 2 and negative for Wilms’ tumor suppressor gene1. Immunohistochemistry for p53 showed a diffuse strong positivity, indicating a mutant TP53 as seen in primary rectal carcinoma. Thus, the nodal cystic lesion was confirmed to be a metastatic lesion. It is important to carefully assess a nodal cystic lesion to confirm whether it is benign or malignant.

In addition to the direct power of anticancer drugs, the effectiveness of anticancer therapy depends on the host immune function. The present study investigated whether or not the reduction rate and histological response of preoperative chemotherapy were related to the immune microenvironment surrounding a primary tumor of the rectum. Sixty-five patients received preoperative chemotherapy followed by resection from 2012 to 2014; all of these patients were retrospectively analyzed. CD3, CD8, and FoxP3 were immunohistochemically examined as markers for T lymphocytes, cytotoxic T lymphocytes, and regulatory T lymphocytes (Treg), respectively. The correlation between the tumor-infiltrating lymphocyte composition and the tumor reduction rate and histological response to neoadjuvant chemotherapy was investigated. The average tumor reduction rate was 41.5% ± 18.8%. According to RECIST, 47 patients (72.3%) achieved a partial response (PR), and 1 patient (1.5%) achieved a complete response (CR). Eight patients (12.3%) showed a grade 2 histological response, and 2 (3.1%) showed a grade 3 response. A multivariate analysis demonstrated that a low Treg infiltration in stromal cell areas was significantly associated with the achievement of a PR or CR [odds ratio (OR) 7.69; 95% confidence interval (CI) 1.96–33.33; p

A 40-year-old man with no previous history of abdominal surgery or noteworthy family history presented to our hospital because of a palpable abdominal mass. Abdominal CT revealed a 9 cm diameter mass in the mesocolon. The differential diagnosis included desmoid tumor, and right hemicolectomy with partial resection of the pancreas head and duodenum was performed. Pathologically, the tumor cells were negative for S-100, c-kit, CD34, and desmin but partially positive for a-SMA and slightly for b-catenin. From these findings, desmoid tumor of the mesocolon was diagnosed. Invasion of the pancreas was also found. Desmoid tumor is pathologically benign, but because of its malignant-like characteristics, such as direct invasion and local recurrence, it is treated as a malignant tumor. Desmoid tumors are associated with familial adenomatous polyposis coli and Gardner syndrome, or they arise in patients who have a history of laparotomy or antecedent trauma. In this paper, we report a rare case of resected sporadic desmoid tumor in the mesocolon with pancreatic invasion, together with a review of the literature.

Background Surgical site infection (SSI) is a common morbidity in patients undergoing colorectal surgery, and the focus of previous studies has primarily been on incisional SSI. Most reports thus far have focused on open surgery rather than on laparoscopic colorectal surgery (Lap CR). Therefore, the aim of the present study was to identify the risk factors for incisional SSI in patients undergoing elective Lap CR. Methods This retrospective study was conducted to evaluate the occurrence and risk factors of incisional SSI for elective Lap CR. From January 2008 to June 2018, 1825 consecutive patients with a preoperative diagnosis of colorectal cancer who underwent Lap CR were analyzed at a single institution. Results Incidence of incisional SSI was 3.3%. Postoperative hospital stay (days) was significantly longer in the incisional SSI group than in the non‐incisional SSI group (8 [6‐12] vs 10 [8‐19], P

Cancer of unknown primary (CUP) is metastatic disease without a known primary and therefore very difficult to identify effective therapy. Previously, we demonstrated partial efficacy of Salmonella typhimurium A1-R (S. typhimurium A1-R) alone and carboplatinum alone (CAR) on a CUP patient tumor in the patient-derived xenograft (PDOX) model. The aim of the present study was to investigate the efficacy of S. typhimurium A1-R combined with CAR on the CUP PDOX model. The CUP tumors were implanted orthotopically into the left supraclavicular fossa of nude mice to match the site from which they were resected from the patient. CUP PDOX models were divided randomly into the following 4 groups after the tumor volume reached 100 mm3: G1: untreated group; G2: CAR (30 mg/kg, i.p., weekly, 2 weeks); G3: S. typhimurium A1-R (5x107 CFU/body, i.v., weekly, 2 weeks).; G4: S. typhimurium A1-R combined with CAR (S. typhimurium A1-R; 5x107 CFU/body, i.v., weekly, 2 weeks; CAR, 30 mg/kg, i.p., weekly, 2 weeks). Each group comprised 7 mice. All mice were sacrificed on day 15. Tumor volume and body weight were measured twice a week. S. typhimurium A1-R and CAR moderately inhibited tumor growth compared to the untreated group on day 15 (P

Gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit is a rare type of sarcoma. The aim of this study was to determine drug sensitivity for a regionally-recurrent case of GIST using a patient-derived orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o., daily, for 3 weeks); G4, regorafenib (p.o., daily, for 3 weeks); G5, pazopanib (p.o., daily, for 3 weeks). All mice were sacrificed on day 22. Tumor volume was evaluated on day 0 and day 22 by laparotomy. Body weight were measured 2times per week. Though regorafenib is third-line therapy for GIST, it was the most effective drug and regressed the tumor significantly (p < 0.001). Sunitinib suppressed tumor growth compared to the control group (p = 0.002). Imatinib, first-line therapy for GIST, and pazopanib did not have significant efficacy compared to the control group (p = 0.886, p = 0.766). The implications of this result is discussed for GIST patients.

The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm3: untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient.

Laparoscopic surgery has been widely accepted for the treatment of colorectal cancer; however, long-term outcomes in elderly patients remain controversial. The midterm results of a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer are presented. This was a randomized trial comparing open surgery with laparoscopic surgery in elderly patients with colorectal cancer. The primary outcome was complication rate, and secondary outcomes included 3-year recurrence-free survival and overall survival. A total of 200 patients were randomly assigned to open surgery or laparoscopic surgery between 2008 and 2012. The main study objective was to compare the midterm outcomes of open surgery with those of laparoscopic surgery in elderly patients with colorectal cancer. This trial is registered with Clinical Trials.gov (NCT01862562). There were no differences between the laparoscopic surgery group and open surgery group in the 3-year overall survival rate (91.5% for laparoscopic surgery vs. 90.6% for open surgery, p = 0.638) or the 3-year recurrence-free survival rate (84.8% for laparoscopic surgery vs. 88.2% for open surgery, p = 0.324). The local recurrence rate was significantly higher in the laparoscopic surgery group than in the open surgery group in rectal cancer (13.8% for laparoscopic surgery vs. 0% for open surgery, p = 0.038). In subgroup analysis according to tumor location, there were no significant differences in the 3-year overall survival rate or 3-year recurrence-free survival rate between the two treatment groups. The midterm outcomes of laparoscopic surgery are similar to those of open surgery in elderly patients with colorectal cancer.

Capeox is widely used as an adjuvant chemotherapy regimen of colorectal cancer that does not require central vein catheter insertion. However, oxaliplatin-related vascular pain with peripheral administration is a major adverse event. We assessed the preventive effect of Celecoxib on oxaliplatin-related vascular pain. A multicenter study of the Yokohama Clinical Oncology Group (YCOG) in Japan. This study was an open label, randomized non-comparative phase II study between Capeox without Celecoxib (C+ Group) and with it (C− group). The primary endpoint was the appearance frequency of grade ≥ 2 vascular pain according to the Verbal Rating Scale (VRS). Between October 2012 and February 2014, 81 patients were recruited to this study and randomly divided into 2 groups: 38 patients in the C− group and 39 patients in the C+ group. Four cases were excluded at the analysis stage because they had not received the allocated intervention. The rate of grade ≥ 2 vascular pain was 55.3% in the C− group and 53.8% in the C+ group (p = 1.000). Celecoxib was unable to prevent oxaliplatin-related vascular pain in this study. However, it may be able to decrease the vascular pain that patients already have.

Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration [p.o.], daily, for 3 weeks); G3, S. typhimurium A1-R group (intravenous [i.v.] injection, weekly, for 3 weeks). All mice from each group were sacrificed on day 22. Relative tumor volume was estimated by laparotomy on day 0 and day 22. Body weight of the mouse was evaluated 2 times per week. We found that S. typhimurium A1-R significantly reduced tumor growth in contrast to the untreated group (P = 0.001). In addition, we found that S. typhimurium A1-R was more effective compared to imatinib (P = 0.013). Furthermore, Imatinib was not significantly effective compared to the control group (P = 0.462). These results indicate that S. typhimurium A1-R may be new effective therapy for imatinib-resistant GIST and therefore a good candidate for clinical development of this disease.

Cancer of unknown primary (CUP) is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy. CUP consists of diverse malignancy groups, making personalized precision therapy essential. The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft (PDOX) model. This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S. typhimurium A1-R with first-line chemotherapy using the CUP PDOX model. The present study is the first to use a CUP PDOX model, which was able to precisely distinguish the chemotherapeutic course. We found that a carboplatinum (CAR)-based regimen was effective for this CUP patient. We also demonstrated that S. typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy. Our results indicate that S. typhimurium A1-R has clinical potential for CUP, a resistant disease that requires effective therapy.

We report here a color-coded imaging model in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche. J. Cell. Biochem. 116: 2730–2734, 2015. © 2015 Wiley Periodicals, Inc.

Cancer of unknown primary (CUP) is a recalcitrant disease with poor prognosis because it lacks standard first-line therapy. CUP consists of diverse malignancy groups, making personalized precision therapy essential. The present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft (PDOX) model. This paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of S. typhimurium A1-R with first-line chemotherapy using the CUP PDOX model. The present study is the first to use a CUP PDOX model, which was able to precisely distinguish the chemotherapeutic course. We found that a carboplatinum (CAR)-based regimen was effective for this CUP patient. We also demonstrated that S. typhimurium A1-R was more effective against the CUP tumor than first-line chemotherapy. Our results indicate that S. typhimurium A1-R has clinical potential for CUP, a resistant disease that requires effective therapy., Cancer therapeutics: Mouse model reveals best treatments for resistant cancer The genetically-engineered strain of Salmonella A1-R effectively targets human metastatic cancers of unknown primary (CUP) in a mouse model. In up to 5% of advanced cancer diagnosis the primary site of cancer growth cannot be identified. In these cases, prognosis is poor as the most appropriate therapies are determined by the cancer’s tissue of origin. A study led by US researchers Shree Ram Singh, Fritz C. Eilber and Robert M. Hoffman examined the effect of four standard chemotherapeutic drugs and Salmonella A1-R on CUP progression in mice implanted with a lymph node tumor resected from a patient’s neck. To mimic the tumor microenvironment in the patient, the tumor was placed in the corresponding anatomical site in mice. This model showed that only carboplatinum and Salmonella A1-R were able to suppress CUP tumor growth.

Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration [p.o.], daily, for 3 weeks); G3, S. typhimurium A1-R group (intravenous [i.v.] injection, weekly, for 3 weeks). All mice from each group were sacrificed on day 22. Relative tumor volume was estimated by laparotomy on day 0 and day 22. Body weight of the mouse was evaluated 2 times per week. We found that S. typhimurium A1-R significantly reduced tumor growth in contrast to the untreated group (P = 0.001). In addition, we found that S. typhimurium A1-R was more effective compared to imatinib (P = 0.013). Furthermore, Imatinib was not significantly effective compared to the control group (P = 0.462). These results indicate that S. typhimurium A1-R may be new effective therapy for imatinib-resistant GIST and therefore a good candidate for clinical development of this disease.

Background The fecal occult blood test (FOBT) is widely accepted as the most economic and non‐invasive screening method for colorectal cancer (CRC). However, the FOBT is inconvenient because it requires a fecal sample and shows limited accuracy. Alternatively, we hypothesized that fecal gas compounds from bowel movements may be a non‐invasive biomarker for CRC. Methods Gas compounds were collected from the bowel movements of 30 patients with CRC and from 26 healthy controls. The patient group comprised 17 males and 13 females, and the average age was 68 years. Additionally, 22 patients had colon cancer, and eight patients had rectal cancer. Gas compounds were analyzed using gas chromatography and compared with those from healthy controls. Results In the gas analysis, methyl mercaptan was significantly higher in the CRC group than in the control group. Hydrogen was significantly lower in the CRC group than in the control group and was correlated with tumor depth and advanced disease stage. Sensitivity, specificity, and accuracy of detection by a discriminant formula were 90%, 57.7%, and 75%, respectively. Conclusion Gas compounds from defecation constitute a promising, novel non‐invasive approach for CRC screening. (UMIN000028256), This study analyzed the gas compounds of colorectal cancer (CRC) patients and healthy controls at defecation in toilet using an extremely non‐invasive technique. The volatile organic compounds from defecation are different compared with CRC patients and healthy controls. The sensitivity, specificity, and accuracy of the discriminant formula for colorectal cancer were 90%, 57.7%, and 75%, respectively. We concluded that gas compounds from defecation constitute a promising, novel non‐invasive approach for CRC screening.

The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing’s sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing’s sarcoma PDOX, but not doxorubicin, similar to the patient’s resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing’s sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm3: untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician’s request and were used for third-line therapy of the patient.

Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm3 : G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma.

We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

The aim of this study is to determine the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on pancreatic cancer patient-derived orthotopic xenografts (PDOX). The PDOX model was originally established from a pancreatic cancer patient in SCID-NOD mice. The pancreatic cancer PDOX was subsequently transplanted by surgical orthotopic implantation (SOI) in transgenic nude red fluorescent protein (RFP) mice in order that the PDOX stably acquired red fluorescent protein (RFP)-expressing stroma for the purpose of imaging the tumor after passage to non-transgenic nude mice in order to visualize tumor growth and drug efficacy. The nude mice with human pancreatic PDOX were treated with A1-R or standard chemotherapy, including gemcitabine (GEM), which is first-line therapy for pancreatic cancer, for comparison of efficacy. A1-R treatment significantly reduced tumor weight, as well as tumor fluorescence area, compared to untreated control (P = 0.011), with comparable efficacy of GEM, CDDP, and 5-FU. Histopathological response to treatment was defined according to Evans's criteria and A1-R had increased efficacy compared to standard chemotherapy. The present report is the first to show that A1-R is effective against a very low-passage patient tumor, in this case, pancreatic cancer. The data of the present report suggest A1-1 will have clinical activity in pancreatic cancer, a highly lethal and treatment-resistant disease and may be most effectively used in combination with other agents.

The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC 50 values of stem-like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC 50 values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1-R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P = 0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The results of the present report indicate A1-R is a promising therapy for chemo-resistant pancreatic cancer stem-like cells.

The effects of subcutaneous closed-suction Blake drain for preventing incisional surgical site infections (SSIs) after colorectal surgery have never been evaluated in a randomized controlled trial (RCT). Thus, we performed a RCT to evaluate the clinical benefits of using a subcutaneous closed-suction Blake drain in patients undergoing colorectal surgery. Consecutive patients who underwent colorectal surgery were enrolled in this study. Patients were randomly assigned to the subcutaneous closed-suction drainage arm or the control (no subcutaneous drainage) arm. The primary endpoint was incidence rate of incisional SSIs. And, we performed logistic regression analysis to detect predictive factors for incisional SSIs after colorectal surgery. From November 2012 to September 2014, a total of 240 patients were enrolled in this study. One-hundred-seventeen patients who were treated by the control arm and 112 patients by the subcutaneous drainage arm were judged to be eligible for analysis. The incidence of incisional SSIs rate was 8.7 % in the overall patients. The incidence of incisional SSIs rate was 12.8 % in the control arm and 4.5 % in the subcutaneous drainage arm. There was significantly reduction of the incidence in the subcutaneous drainage arm than in the control arm (p = 0.025). Logistic regression analysis demonstrated that thickness of subcutaneous fat >3.0 cm, forced expiratory volume in 1 s as percent of forced vital capacity (FEV1.0 %) >70 %, and subcutaneous drain were independent predictors of postoperative incisional SSIs (p = 0.008, p = 0.004, and p = 0.017, respectively). The results of our RCT suggest that a subcutaneous Blake drain is beneficial for preventing incisional SSIs in patients undergoing colorectal surgery.

The effect of UVC irradiation was investigated on a model of brain cancer and a model of experimental brain metastasis. For the brain cancer model, brain cancer cells were injected stereotactically into the brain. For the brain metastasis model, lung cancer cells were injected intra-carotidally or stereotactically. The U87 human glioma cell line was used for the brain cancer model, and the Lewis lung carcinoma (LLC) was used for the experimental brain metastasis model. Both cancer cell types were labeled with GFP in the nucleus and RFP in the cytoplasm. A craniotomy open window was used to image single cancer cells in the brain. This double labeling of the cancer cells with GFP and RFP enabled apoptosis of single cells to be imaged at the subcellular level through the craniotomy open window. UVC irradiation, beamed through the craniotomy open window, induced apoptosis in the cancer cells. UVC irradiation was effective on LLC and significantly extended survival of the mice with experimental brain metastasis. In contrast, the U87 glioma was relatively resistant to UVC irradiation. The results of this study suggest the use of UVC for treatment of superficial brain cancer or metastasis.

Integrins play a role in tumor growth and metastasis. However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. The 143B human osteosarcoma cell line, expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus, was established. Such double-labeled cells enable imaging of apoptosis and mitosis and other nuclear-cytoplasmic dynamics. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged. The anti-β1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung (experimental metastasis) while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth, possibly due to inhibition of lung seeding of the cancer cells as imaged in the experimental metastasis study. AIIB2 treatment also increased survival of mice with orthotopically growing 143B-RFP.

We report here a color-coded imaging model of breast cancer-metastatic niche formation in which metastatic niches in the lung and liver of breast cancer can be identified. The transgenic green fluorescent protein (GFP)-expressing nude mouse was used as the host. The GFP nude mouse expresses GFP in all organs. However, GFP expression is dim in the liver parenchymal cells. Mouse mammary tumor cells (MMT 060562) (MMT), expressing red fluorescent protein (RFP), were injected in the tail vein of GFP nude mice to produce experimental lung metastasis and in the spleen of GFP nude mice to establish a liver metastasis model. Niche formation in the lung and liver metastasis was observed using very high resolution imaging systems. In the lung, GFP host-mouse cells accumulated around as few as a single MMT-RFP cell. In addition, GFP host cells were observed to form circle-shaped niches in the lung even without RFP cancer cells, which was possibly a niche in which future metastasis could be formed. In the liver, as with the lung, GFP host cells could form circle-shaped niches. Liver and lung metastases were removed surgically and cultured in vitro. MMT-RFP cells and GFP host cells resembling cancer-associated fibroblasts (CAFs) were observed interacting, suggesting that CAFs could serve as a metastatic niche.