The invention of microwave surgical scissors for seamless coagulation and cutting.

PURPOSE: We developed a microwave energy-based scissors device (MWCX) that is capable of performing cutting and coagulation using 2.45 GHz microwave energy. This paper aims to present the concept of the device and assess the basic functions including the hemostasis, cutting, and sealing abilities. METHODS: Seven beagle dogs were used in our experiments. In six dogs, we measured the coagulation time (CT), lateral thermal injury (LTI), bursting pressure (BP). The dogs were then subjected to re-laparotomy 1 week later to allow us to investigate the results. In one dog, the same factors and the quantities of smoke and mist emitted were compared to those observed when using a Harmonic Focus (HF) device. RESULTS: At 60 W, the MWCX could cut and seal small (5 s, diameter 1-2 mm) and medium-sized (10 s, 3-4 mm) vessels with complete hemostasis. The liver (length 2 cm) was cut for 30 s. Harvested vessels were sealed for 10 s (artery, 17 times; vein, six times). The mean BP was 887. 8 ± 41.5 mmHg in the medium arteries and 457.2 ± 118.0 mmHg in veins, with a mean diameter of 4.5 ± 1.3 mm. In a comparative study, the MWCX showed similar results to the HF with regard to the CT, BP and LTI, and emitted less smoke and mist. CONCLUSION: The MWCX showed similar levels of functionality and safety to HF, as well as the advantages offered by the use of microwave energy. Microwave devices might be used in the majority of applications for which traditional energy devices are used.

Feasibility and safety of hyperthermic intraperitoneal chemotherapy using 5-fluorouracil combined with cisplatin and mitomycin C in patients undergoing gastrectomy for advanced gastric cancer.

BACKGROUND AND OBJECTIVES: We conducted a dose-finding study for 5-fluorouracil (5-FU) administered with cisplatin (CDDP) and mitomycin C (MMC) to find an improved regimen for hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (GC). METHODS: The appropriate HIPEC regimen previously determined in vitro was 5-FU (200 µg/mL), MMC (2 µg/mL), and CDDP (10 µg/mL) at hyperthermic conditions (42°C) for 30 min. This was a clinical study to determine the recommended dose of 5-FU in combination with MMC and CDDP at 42°C for 30 min and to evaluate HIPEC safety in patients at high risk of developing peritoneal metastases following GC surgery. RESULTS: Twelve patients were treated with surgery plus HIPEC using 5-FU at 0, 500, 750, and 1000 mg combined with MMC (10 mg) and CDDP (50 mg) in the perfusate (5 L). Dose-limiting toxicities did not develop until 1000 mg 5-FU was reached. Four patients experienced grade 1 or 2 adverse events. The recommended dose was 1000 mg 5-FU/5 L perfusate. Eight (66.7%) patients demonstrated no recurrence of peritoneal metastases; 5-year overall survival rate was 83.3%. CONCLUSION: Gastrectomy and HIPEC with MMC, CDDP, and 5-FU is feasible, safe, and may protect against peritoneal metastasis following surgery for advanced GC.

Minimally invasive surgery using the open magnetic resonance imaging system combined with video-assisted thoracoscopic surgery for synchronous hepatic and pulmonary metastases from colorectal cancer: report of four cases.

Simultaneous resection of hepatic and pulmonary metastases (HPM) from colorectal cancer (CRC) has been reported to be effective, but it is also considered invasive. We report the preliminary results of performing minimally invasive surgery using the open magnetic resonance (MR) imaging system to resect synchronous HPM from CRC in four patients. All four patients were referred for thoracoscopy-assisted interventional MR-guided microwave coagulation therapy (T-IVMR-MCT) combined with video-assisted thoracoscopic surgery (VATS). The median diameters of the HPM were 18.2 and 23.2 mm, respectively. The median duration of VATS and T-IVMR-MCT was 82.5 and 139 min, respectively. All patients were discharged without any major postoperative complications. One patient was still free of disease at 24 months and the others died of disease progression 13, 36, and 47 months without evidence of recurrence in the treated area. Thus, simultaneous VATS + T-IVMR-MCT appears to be an effective option as a minimally invasive treatment for synchronous HPM from CRC.

Initial experiences with MR Image-guided laparoscopic microwave coagulation therapy for hepatic tumors.

PURPOSE: Percutaneous thermal ablation is used for treating hepatic tumors. Recent advances in laparoscopy and imaging modalities have led to the development of a novel image-guided minimally invasive loco-regional treatment. The aim of this trial was to apply laparoscopic assistance to magnetic resonance (MR) image-guided thermoablation instead of ultrasonography, because of its various advantages. METHODS: Patients with hepatic tumors and liver cirrhosis underwent magnetic resonance (MR) image-guided laparoscopic microwave coagulation therapy using a borescope and endoscopic forceps. Six cases of laparoscopic microwave coagulation treatment using MR image guidance were successfully performed between January 2000 and December 2008. Tumors were detected, punctured, and ablated in an open-configured MR scanner. A total of nine hepatocellular carcinoma nodules were preoperatively identified in S3, S5 and S6 (mean diameter = 20.8 ± 5.4 mm). RESULTS: MR-guided microwave coagulation was laparoscopically achieved in all patients without any significant complications that required invasive treatment. The mean length of the operation was 275.3 ± 60.5 min, and the mean postsurgical hospital stay was 10.0 ± 2.3 days. Postoperative confirmation scanning was performed without moving the patients. CONCLUSION: MR-guided laparoscopic microwave coagulation therapy is an effective treatment for hepatic tumors adjacent to other organs, as it allows for more accurate detection of lesions and for tumors to be treated safely while avoiding adjacent organs. It is less invasive than conventional procedures, because the MR real-time guidance enabled continuous monitoring throughout the procedure.

Surgery-induced peritoneal cancer cells in patients who have undergone curative gastrectomy for gastric cancer.

BACKGROUND: Some patients who undergo curative gastrectomy with lymph node dissection (LND) for gastric cancer (GC) show subsequent peritoneal metastasis. The source of these metastatic cells remains unclear. METHODS: Curative gastrectomy with LND was performed in 102 patients with GC. Peritoneal washing was collected before and after gastrectomy. Cytology, reverse transcription-polymerase chain reaction, and cell culture were used to determine the presence of cancer cells. The proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. Peritoneal recurrence-free survival (RFS) and peritoneal recurrence rate (RR) were examined to determine the clinical relevance of detected cancer cells. RESULTS: Of 102 peritoneal washing samples obtained before gastrectomy, 57 showed no CEA or CK20 mRNA amplification. After gastrectomy, CEA or CK20 mRNA was detected in 35 of these 57 samples, and viable cancer cells were identified in 24. The viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells generated peritoneal nodules after spilling over the peritoneal cavity in NOD/ShiJic-scid mice in 4 cases. The peritoneal RFS of patients with CEA or CK20 mRNA amplification after gastrectomy was significantly poorer than that of patients with negative amplification (p < .05). The 24 patients with viable cancer cells in the peritoneal cavity after gastrectomy showed higher peritoneal RR than those without them (p = .033). CONCLUSIONS: Viable tumorigenic cancer cells spilled into the peritoneal cavity during surgery, indicating that surgery induces peritoneal metastasis.

Cell transplantation therapy for a rat model of secondary lymphedema.

BACKGROUND: Although lymphedema is a progressive and lifelong condition, substantial advances in therapeutic intervention are limited. The development of a novel therapy for lymphedema is urgent for those patients suffering from it. The aim of this study was to investigate the usefulness of a new cell transplantation therapy in the rat tail model of secondary lymphedema. MATERIALS AND METHODS: We prepared two cell sources, human dermal microvascular endothelial cells (HDMECs) and lymphatic endothelial cells (LECs), which were collected from the resected normal dermis of patients with breast cancer. After the animal model of secondary lymphedema of the nude rats' tails was established, phosphate-buffered saline, purified LECs, or unpurified HDMECs were injected in the rats' tails five times for more than 14 d. The evaluations were performed by measuring the circumference, fluorescence lymphography, and histologic analysis of the rats' tails between each group. RESULTS: The isolated cells by the simple immunomagnetic sorting from HDMECs were positive for a pan-endothelial marker (CD31) and lymphatic-specific markers (podoplanin, lymphatic vessel endothelial hyaluronan receptor-1 [LYVE-1], and prospero homebox 1 [Prox-1]), and were considered to be LECs. In the cell transplantation group, which was injected with human LECs, the circumference, lymphatic flow, and thickness of the skin of the rat tail became thinner than the groups injected with unpurified HDMECs or phosphate-buffered saline. Immunohistochemistry of the rat tails showed that the number of own lymphatic vessels was increased in the purified LEC transplantation group compared with the other groups. Furthermore, in the LEC transplantation group, some vessels were immunopositive for human-podoplanin or -LYVE-1 and the areas adjacent to the vessels were rat-podoplanin or -LYVE-1 immunopositive. CONCLUSIONS: Our findings indicate that cell transplantation therapy using human LECs improved the secondary lymphedema in the nude rat tail. This therapeutic strategy may merit clinical investigation in patients with lymphedema.

Resectable carcinoma developing in the remnant pancreas 7 years and 10 months after distal pancreatectomy for invasive ductal carcinoma of the pancreas: report of a case.

BACKGROUND: Pancreatic ductal adenocarcinoma, which represents 90% of pancreatic cancers, is one of the most lethal and aggressive malignancies. Operative resection remains the only treatment providing prolonged survival, however, recurrence of pancreatic ductal adenocarcinoma occurs in up to 80% of patients with pancreatic cancer within 2 years of a potential curative resection. There are few reports of pancreatic carcinoma recurrence (primary second cancer) in the remnant pancreas after pancreatectomy. CASE PRESENTATION: A 52-year-old woman underwent a distal pancreatectomy for pancreatic cancer in September 2004. Adjuvant chemotherapy was started after surgery and continued for 4 years. In March 2012, marked elevation of DUPAN-II was observed, followed by an irregular stenotic finding in the main duct. We performed an en bloc resection of the remnant pancreas in July 2012. Histologically, the tumor contained a second primary pancreatic carcinoma with lymph node metastasis. At follow-up 20 months after the second operation, the patient was alive without recurrence. Fourteen cases of resectable cancer developing in the remnant pancreas after a pancreatectomy for cancer have been reported; a minority of these was identified as second primary tumors. Therefore, our patient's primary second cancer is a rare event. CONCLUSION: The patient is considered to have shown a rare, unique pancreatic cancer recurrence. Persistent elevation of a tumor marker and extensive imaging led to proper diagnosis and treatment.

Transmembrane mucin MUC1 overexpression and its association with CD10⁺ myeloid cells, transforming growth factor-ß1 expression, and tumor budding grade in colorectal cancer.

The prognostic value of mucin expression has been reported in several studies. We examined the association between mucin expression and other previously reported prognostic factors, including infiltration of CD10⁺ myeloid cells, transforming growth factor-ß1 (TGF-ß1) expression, and tumor budding at invasion fronts. Immunohistochemical analysis of 206 colorectal samples was carried out to determine whether MUC1, MUC2, MUC4, and MUC5AC expression could predict the survival of colorectal cancer patients. Serial sections were stained for CD10, TGF-ß1, and pan-cytokeratin in order to detect tumor budding. As per multivariate analyses, MUC1 expression appeared to be the most significant predictor of both recurrence-free survival and overall survival. MUC4 was only significant to predict recurrence-free survival, and MUC5AC could be a good marker in stage IV colorectal cancers that require additional chemotherapy. MUC1 (CD227) expression was associated with infiltration of CD10⁺ myeloid cells, TGF-ß1 expression, and tumor budding grade. These findings suggest that MUC1 is indicative of poor prognoses that may be associated with immunosuppression and epithelial-mesenchymal transition. Furthermore, MUC1 expression appears to be a chemoattractant for CD10⁺ stromal cells.

Palliative stenting for malignant colorectal stenosis in the elderly.

Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.

Prognostic impact of postoperative infection after resection of biliary malignancy: A multicenter retrospective cohort study.

BACKGROUND: The aim of this study was to investigate the prognostic impact of postoperative infections in patients who underwent resection for biliary malignancy, including intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, gallbladder carcinoma, and carcinoma of the ampulla of Vater. METHODS: This study was conducted in an 11-center retrospective cohort study. Patients with biliary tract cancer who underwent curative resection between April 2013 and March 2015 at 11 institutions in Japan were enrolled. We analyzed the prevalence of postoperative infection, infection-related factors, and prognostic factors. RESULTS: Of the total 290 cases, 33 were intrahepatic cholangiocarcinoma, 60 were perihilar cholangiocarcinoma, 120 were distal cholangiocarcinoma, 55 were gallbladder carcinoma, and 22 were carcinoma of the ampulla of Vater. Postoperative infectious complications, including remote infection, were observed in 146 patients (50.3%), and Clavien-Dindo ≥III in 115 patients (39.7%). Postoperative infections occurred more commonly in the patients who received pancreaticoduodenectomy and bile duct resection. Patients with infectious complications had a significantly poorer prognosis than those without (median overall survival 38 months vs 62 months, P = .046). In a diagnosis-specific analysis, although there was no correlation between infectious complications and overall survival in intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, distal cholangiocarcinoma, and carcinoma of the ampulla of Vater, infectious complications were a significantly poor prognostic factor in gallbladder carcinoma (P = .031). CONCLUSION: Postoperative infection after surgery for biliary tract cancer commonly occurred, especially in patients who underwent pancreaticoduodenectomy and bile duct resection. Postoperative infection is relatively associated with the prognosis of patients with biliary malignancy, especially gallbladder carcinoma.

Survival impact of surgical site infection in esophageal cancer surgery: A multicenter retrospective cohort study.

Aim: This study was performed to evaluate the oncological impact of surgical site infection (SSI) and pneumonia on long-term outcomes after esophagectomy. Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 407 patients with curative stage I/II/III esophageal cancer at 11 centers from April 2013 to March 2015. We investigated the association of SSI and postoperative pneumonia with oncological outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: Ninety (22.1%), 65 (16.0%), and 22 (5.4%) patients had SSI, pneumonia, and both SSI and pneumonia, respectively. The univariate analysis demonstrated that SSI and pneumonia were associated with worse RFS and OS. In the multivariate analysis, however, only SSI had a significant negative impact on RFS (HR, 1.63; 95% confidence interval, 1.12-2.36; P = 0.010) and OS (HR, 2.06; 95% confidence interval, 1.41-3.01; P < 0.001). The presence of both SSI and pneumonia and the presence of severe SSI had profound negative oncological impacts. Diabetes mellitus and an American Society of Anesthesiologists score of III were independent predictive factors for both SSI and pneumonia. The subgroup analysis showed that three-field lymph node dissection and neoadjuvant therapy canceled out the negative oncological impact of SSI on RFS. Conclusion: Our study demonstrated that SSI, rather than pneumonia, after esophagectomy was associated with impaired oncological outcomes. Further progress in the development of strategies for SSI prevention may improve the quality of care and oncological outcomes in patients undergoing curative esophagectomy.

Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study.

Aim: To investigate the impact of postoperative infection (PI), surgical site infection, and remote infection (RI), on long-term outcomes in patients with colorectal cancer (CRC). Methods: The Japan Society for Surgical Infection conducted a multicenter retrospective cohort study involving 1817 curative stage I/II/III CRC patients from April 2013 to March 2015. Patients were divided into the No-PI group and the PI group. We examined the association between PI and oncological outcomes for cancer-specific survival (CSS) and overall survival (OS) using Cox proportional hazards models and propensity score matching. Results: Two hundred and ninety-nine patients (16.5%) had PIs. The 5-year CSS and OS rates in the No-PI and PI groups were 92.8% and 87.6%, and 87.4% and 83.8%, respectively. Both the Cox proportional hazards models and propensity score matching demonstrated a significantly worse prognosis in the PI group than that in the No-PI group for CSS (hazard ratio: 1.60; 95% confidence interval: 1.10-2.34; P = .015 and P = .031, respectively) but not for OS. RI and the PI severity were not associated with oncological outcomes. The presence of PI abolished the survival benefit of adjuvant chemotherapy. Conclusions: These results suggest that PI after curative CRC surgery is associated with impaired oncological outcomes. This survival disadvantage of PI was primarily derived from surgical site infection, not RI, and PI induced lower efficacy of adjuvant chemotherapy. Strategies to prevent PI and implement appropriate postoperative treatment may improve the quality of care and oncological outcomes in patients undergoing curative CRC surgery.

Safety and efficacy of 5-aminolevulinic acid phosphate/iron in mild-to-moderate coronavirus disease 2019: A randomized exploratory phase II trial.

BACKGROUND: 5-aminolevulinic acid (5-ALA), a natural amino acid that is marketed alongside sodium ferrous citrate (SFC) as a functional food, blocks severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proliferation in vitro and exerts anti-inflammatory effects. In this phase II open-label, prospective, parallel-group, randomized trial, we aimed to evaluate the safety and efficacy of 5-ALA in patients with mild-to-moderate coronavirus disease 2019. METHODS: This trial was conducted in patients receiving 5-ALA/SFC (250/145 mg) orally thrice daily for 7 days, followed by 5-ALA/SFC (150/87 mg) orally thrice daily for 7 days. The primary endpoints were changes in SARS-CoV-2 viral load, clinical symptom scores, and 5-ALA/SFC safety (adverse events [AE] and changes in laboratory values and vital signs). RESULTS: A total of 50 patients were enrolled from 8 institutions in Japan. The change in SARS-CoV-2 viral load from baseline was not significantly different between the 5-ALA/SFC (n = 24) and control (n = 26) groups. The duration to improvement was shorter in the 5-ALA/SFC group than in the control group, although the difference was not significant. The 5-ALA/SFC group exhibited faster improvement rates in "taste abnormality," "cough," "lethargy," and "no appetite" than the control group. Eight AEs were observed in the 5-ALA/SFC group, with 22.7% of patients experiencing gastrointestinal symptoms (decreased appetite, constipation, and vomiting). AEs occurred with 750/435 mg/day in 25.0% of patients in the first phase and with 450/261 mg/day of 5-ALA/SFC in 6.3% of patients in the second phase. CONCLUSION: 5-ALA/SFC improved some symptoms but did not influence the SARS-CoV-2 viral load or clinical symptom scores over 14 days. The safety of 5-ALA/SFC in this study was acceptable. Further evaluation using a larger sample size or modified method is warranted.

Needle Tip Detection Using Ultrasound Probe for Vertical Punctures: A Simulation and Experimental Study.

Current ultrasound-guided punctures are difficult to perform as they are performed at an angle to the ultrasound image of the affected area, resulting in longer puncture times, lower success rates, and higher unexpected injury rates. Vertical puncture techniques have also been investigated, but the principle of needle tip detection remains unclear. To optimize ultrasound probes for puncture, the principle of needle tip detection should be understood. This study aimed to verify the principle of needle tip detection and optimal measurement conditions for vertical puncture. Needle tip detection was performed in animal experiments using a probe with a central puncture slit. Moreover, the needle tip was detected at short distances using a puncture spacer. We also investigated the signal from the needle tip using a ring probe and confirmed the principle of needle tip detection, effect of needle tip angle, and insertion depth on needle tip detection through simulation and experiments. Needle tip detection using ultrasound-guided waves was described, and the relationship among needle tip angle, detection intensity, and phase change was verified. The needle tip can be detected by the leakage of the ultrasound-guided wave generated inside the needle tip.

Prognostic impact of postoperative infection in patients with pancreatic cancer: A multicenter cohort study.

BACKGROUND: Postoperative infection after pancreatectomy in patients with pancreatic cancer often leads to poor prognosis. The aim of this study was to determine the prognostic effect of postoperative infection in patients with pancreatic cancer. METHODS: A multicenter cohort study was performed using a common database of patients with pancreatic cancer who underwent curative pancreatic resections between April 2013 and March 2015 at 15 high-volume centers in Japan. The rate of postoperative infection was determined, and patient demographic characteristics, clinicopathologic factors, and prognostic factors for overall survival were analyzed. RESULTS: Of the 462 eligible patients who underwent curative pancreatectomy, postoperative infection occurred in 141 patients (31%), including 114 surgical site infections (25%), 50 remote infections (11%), and 23 combined infections (5%). Risk factors for postoperative infection included high body mass index, nondiabetes, and longer operation time. In the survival analysis, patients with postoperative infection had significantly worse overall survival than patients without postoperative infection. The median survival times were 21.9 and 33.0 months (P = .023), respectively, for patients with and without postoperative infection. According to the multivariate analysis for overall survival, lack of adjuvant therapy (P = .002), but not postoperative infection (P = .829), predicted poor prognosis. The multivariate analysis revealed that postoperative infection (P < .001) was an independent risk factor for lack of adjuvant therapy. CONCLUSION: Postoperative infection in patients with pancreatic cancer may indirectly worsen the prognosis by preventing timely adjuvant therapy.

Prognostic role of CD10⁺ myeloid cells in association with tumor budding at the invasion front of colorectal cancer.

The expression of CD10 in tumor cells has been reported to correlate with liver metastasis in colorectal cancer (CRC). However, fibroblasts and immune cells positive for CD10 at the tumor invasion front have not been comprehensively studied. We classified CD10 expression patterns into three types of cells, tumor cells (tCD10), stromal myofibroblasts (sCD10), and immune cells (iCD10), and investigated their correlation with the expression of transforming growth factor-ß (TGF-ß1) protein and tumor budding grade. Several cell surface markers were stained to detect the phenotype of iCD10(+) cells, including CD3, CD20, CD11b, CD14, CD15, and CD163. Specimens and follow-up data of 206 CRC patients were examined. In multivariate analysis, iCD10 could be an independent prognostic factor for both recurrence-free survival and overall survival in stage I-III CRC (hazard ratio, 2.522 [1.299-4.896], P = 0.006; 2.890 [1.357-6.157], P = 0.006, respectively). The expression of sCD10 and iCD10 was strongly correlated with TGF-ß1 expression in tumor cells and tumor budding grade. The phenotype of iCD10(+) cells was CD11b(+) and CD15(+) granulocytes. The infiltration of sCD10(+) fibroblasts and iCD10(+) granulocytes at the tumor invasion front might interact with TGF-ß1 protein expression and enhance tumor budding grade. The expression level of iCD10 at the tumor invasion front represented an independent prognostic biomarker in stage I-III CRC and could be integrated into a new staging system.

Expression of interleukin 1-like cytokine interleukin 33 and its receptor complex (ST2L and IL1RAcP) in human pancreatic myofibroblasts.

OBJECTIVE: Interleukin 33 (IL33) is a cytokine belonging to the IL1 family and it binds to a complex of the ST2L/IL1 receptor accessory protein (IL1RAcP). To define the role of IL33 in fibrogenesis of the pancreas, the expression of IL33, ST2L and IL1RAcP was examined in chronic pancreatitis tissues. The effects of IL33 on the functions of human pancreatic myofibroblasts were also investigated. METHODS: Tissue samples were obtained surgically. The expression of IL33, ST2L and IL1RAcP was evaluated by standard immunohistochemical procedures. Messenger RNA expression for IL33, ST2L and IL1RAcP was analysed by northern blotting and real-time PCR analyses, and protein expression was assessed by western blotting and ELISA. Cell proliferation and migration were assessed by a (3)H-thymidine incorporation assay and the modified Boyden chamber assay, respectively. RESULTS: IL33, ST2L and IL1RAcP were expressed by alpha-SMA-positive myofibroblasts in the fibrosis of chronic pancreatitis. In human pancreatic myofibroblasts, IL33 was weakly immunoexpressed without any stimuli, and this was markedly enhanced by IL1beta, tumour necrosis factor alpha (TNFalpha) and lipopolysaccharide (LPS) via the mitogen-activated protein kinase (MAPK)-dependent AP-1 activation pathway. ST2L mRNA was weakly detected in unstimulated cells, and IL4 and interferon gamma (IFNgamma) strongly enhanced ST2L expression via STAT6 and STAT1 signalling, respectively. IL33 rapidly induced the phosphorylation of MAPKs and IkappaBalpha, and enhanced the expression of inflammatory mediators (IL6, IL8, IP-10, Gro-alpha, Gro-beta and MCP-1) in IL4- or IFNgamma-pretreated cells. IL33 stimulated the proliferation and migration of pancreatic myofibroblasts. CONCLUSIONS: IL33 and its receptor complex (ST2L and IL1RAcP) constitute a novel signalling system which may play an important role in the pathogenesis of chronic pancreatitis.

Expression level of thymidylate synthase mRNA reflects 5-fluorouracil sensitivity with low dose and long duration in primary colorectal cancer.

OBJECTIVES: To investigate the prognostic marker for the adjuvant chemotherapy of primary colorectal carcinoma. METHODS: Primary colorectal cancer tissue from 24 patients was investigated to evaluate the relationship between the mRNA expression level of several 5-fluorouracil (5-FU)-related metabolic enzymes (thymidylate synthase, TS; dihydropyrimidine dehydrogenase, DPD; and thymidine phosphorylase, TP) and chemosensitivity to two different 5-FU doses and duration (1: 5-FU concentration 1.0 microg/mL (7.68 microM), 24 h exposure and 2: 5-FU concentration 0.3 microg/mL (2.30 microM), 144 h exposure). Chemosensitivity and mRNA expression levels were measured using collagen gel droplet embedded culture drug sensitivity tests and real-time quantitative reverse transcription-polymerase chain reaction. Clinicopathological features and chemosensitivity were also compared. RESULTS: The TS mRNA expression level was significantly higher in the 5-FU resistant group (T/C > 60%) compared with the 5-FU sensitive group (T/C < 60%) in both 5-FU regimens (1: 5.03 +/- 0.92 vs. 1.58 +/- 0.76, p < 0.01, 2: 4.88 +/- 0.91 vs. 0.96 +/- 0.20, p < 0.001). The group with the higher TS mRNA expression level (>3.83, the average) were more resistant to both 5-FU regimens than those with lower TS mRNA (<3.83) (1: T/C = 80 vs. 66%, p = 0.11, 2: T/C = 89 vs. 64%, p < 0.005). The TS mRNA expression level inversely correlated with the sensitivity to the latter 5-FU regimen (R = 0.577, p < 0.01). There were no relationships between chemosensitivity to 5-FU and the mRNA expression level of DPD and TP and clinicopathological factors. CONCLUSIONS: The TS mRNA expression level might be a good marker of chemosensitivity to 5-FU in primary colorectal cancer, especially the sensitivity to low dose 5-FU with a long duration.

Correlation between high field MR images and histopathological findings of rat transplanted cancer immediately after partial microwave coagulation.

PURPOSE: To investigate the immediate effects of microwave coagulation on rat tumors in various magnetic resonance (MR) images at high magnetic field strength using histopathological examinations as reference. MATERIALS AND METHODS: Tumors implanted in rat femurs were partially thermocoagulated by microwave. Immediately after, T1- and T2-weighted images, diffusion-weighted images (DWIs), and contrast-enhanced T1 weighted images (CE-T1WIs) were acquired with a 7-tesla MR scanner. After measurements, tumors were examined histopathologically with hematoxylin-eosin (HE) staining and histochemically for acid phosphatase activity. RESULTS: Without contrast, boundaries of coagulated areas were unclear on MR images, including apparent diffusion coefficient (ADC) maps. CE-T1WIs clearly showed immediate contrast enhancement of untreated areas of tumor, and the area of enhancement gradually enlarged in 5 min. Quantitative analyses were conducted by classifying tumor areas by contrast enhancement results. Signal intensities of the areas in the MR images showed no significant differences, but at the periphery, ADC values were significantly higher in areas with delayed enhancement than those with immediate enhancement. Compared with histopathological findings, with microwave thermocoagulation, increased ADC value seemed to derive from collection of extracellular fluid in the outer zone, where acid phosphatase activity was attenuated. CONCLUSION: ADC values in the areas with delayed enhancement of CE-T1WIs were higher than those in non-affected areas, but MR images could not show areas of coagulation within tumors. Clear detection of the boundaries of coagulated areas required contrast enhancement, even at magnetic field strength of 7T.