The Elevation in Preoperative Procalcitonin Is Associated with a Poor Prognosis for Patients Undergoing Resection for Colorectal Cancer.

BACKGROUND: Procalcitonin (PCT) is a well-known marker for bacterial infection; however, the clinical significance of PCT in the long-term prognosis after colorectal cancer (CRC) surgery remains unclear. METHODS: This is a retrospective review of 277 patients that underwent CRC surgery to investigate the relationship between preoperative PCT, clinicopathological condition, cancer-specific overall survival (OS), and relapse-free survival (RFS). RESULTS: Median follow-up interval was 5.0 years in all patients. Thirty-six patients developed recurrence, and 46 patients died due to recurrences or metastases of CRC. Preoperative PCT levels were highest in Stage IV patients. The cancer-specific OS in patients with Stage IV/PCT ≤0.05 ng/mL was significantly higher than those with Stage IV/PCT >0.05 ng/mL (3 years survival; 42.3 vs. 14.3%, p = 0.0413). On multivariate analysis, gender, TNM classification, and PCT were identified as significant risk factors for cancer-specific OS in patients with Stage I-III CRC. The cancer-specific OS rate of these patients with PCT ≥0.08 ng/mL, compared with PCT <0.08 ng/mL, was significantly decreased (5 years survival; 59.1 vs. 92.7%, p < 0.0001). TNM classification was finally identified as an independent risk factor for cancer-specific RFS in these patients by multivariate analysis. CONCLUSION: High preoperative PCT values in CRC patients appeared to be associated with poor OS but not RFS following surgical treatments.

Involvement of TRPV1-containing peripheral sensory efferents in hemodynamic responses in a rat hemorrhagic shock model.

BACKGROUND: Mechanisms underlying hemodynamic disturbance in hemorrhagic shock are not completely understood. Transient receptor potential vanilloid 1-expressing afferents are involved in hemorrhagic shock pathology, and transient receptor potential vanilloid 1 antagonist, capsazepine, acts on the central nervous system to improve mortality in a rat hemorrhagic shock model. In contrast, transient receptor potential vanilloid 1-positive efferents promote vasoactive reactions through the release of neuropeptides, including calcitonin gene-related peptides. This study aimed to investigate whether transient receptor potential vanilloid 1-positive peripheral sensory efferents are involved in hemodynamic responses after hemorrhagic shock. METHODS: Male rats underwent hemorrhagic shock (mean arterial pressure 30 mm Hg for 90 min, followed by resuscitation for 30 min) and received capsazepine (5 µM/kg) 30 min after shock induction. A separate cohort of rats subjected to hemorrhagic shock received hCGRP8-37 (300 µg/kg), a calcitonin gene-related peptide receptor antagonist, at 30, 60, or 90 minutes after shock induction. The 24-hour survival rate, mean arterial pressure, heart rate, arterial blood gas, and plasma calcitonin gene-related peptide levels were measured. Tissue blood flow and oxygenation both in the mesentery and skeletal muscle were also assessed. RESULTS: Capsazepine treatment prevented the hemorrhagic shock-induced increase in plasma calcitonin gene-related peptide levels, and hCGRP8-37 treatment improved the 24-h survival rates after hemorrhagic shock at a time-dependent manner. The hCGRP8-37- or capsazepine-treated rats exhibited tissue oxygenation and metabolic conditions comparable to those in control rats at the end of the experiment. CONCLUSION: Transient receptor potential vanilloid 1 plays a crucial role in hemodynamic responses to hemorrhagic shock, partly via calcitonin gene-related peptide release, involved in its peripheral sensory-efferent functions. The hCGRP8-37 appears to improve peripheral circulatory failure, which may be useful as adjunct treatment after hemorrhagic shock.

ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan.

Irinotecan is a key drug for patients with advanced and recurrent colorectal carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as there is no useful marker to predict chemosensitivity to the drug. The aim of the present study was to evaluate whether the expression levels of adenosine triphosphate-binding cassette sub-family G (WHITE) member 2 (Junior blood group) (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using the resected primary tumor specimens of 189 patients with colorectal cancer, the association between the immunohistochemical expression of ABCG2 protein and the results of the collagen gel droplet embedded culture drug sensitivity test, performed to evaluate the chemosensitivity to SN-38 (an active metabolite of irinotecan), was investigated. Among the 189 patients, 17 received irinotecan-based chemotherapy, and their responses and progression-free survival (PFS) were analyzed. The tumors of patients with increased ABCG2 expression accounted for 60% of the tumors examined, and were significantly more resistant to SN-38, compared with patients with low ABCG2 expression (P<0.001). In a multivariate logistic regression analysis, increased expression of ABCG2 protein was an independent and significant predictor of resistance to SN-38, increasing the risk of resistance by 12-fold. Increased expression of ABCG2 and a low sensitivity to SN-38 was significantly associated with resistance to irinotecan-based chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with increased expression of ABCG2 was significantly shorter, compared with patients with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased immunohistochemical expression of ABCG2 in primary tumors may be a useful predictive biomarker of resistance to irinotecan-based chemotherapy for patients with recurrent or metastatic colorectal cancer.

Pyomyositis at the surgical site in a patient with chronic myeloid leukemia: a case report and literature review.

BACKGROUND: Pyomyositis is a rare, subacute, deep pyogenic infection of the muscle tissue. This disease has been previously described in patients that were immunocompromised due to a hematological malignancy. CASE PRESENTATION: A 68-year-old man with a history of chronic myeloid leukemia was treated with imatinib. He was diagnosed with ascending colon cancer and underwent curative surgery. His postoperative course was uneventful, and he was healthy at 6 months after surgery, allowing for reinitiation of imatinib therapy. After the reinitiation of therapy, a computed tomography (CT) scan revealed a mass shadow in the right iliopsoas muscle. This lesion was clinically diagnosed as recurrent colon cancer with an abscess, which was resected surgically. A pathological examination uncovered both edema and inflammation. Two months after the second surgery, imatinib therapy was reinitiated; however, he again developed painful swelling and erythema in his right thigh. A CT scan revealed a similar shadow as described previously. He was then diagnosed with pyomyositis; he underwent incisional drainage and was administered linezolid. Following the treatment for pyomyositis, there was no cancer recurrence or evidence of any recurrent pyomyositis. CONCLUSIONS: Findings from this case suggest that both undergoing surgery and receiving imatinib therapy may modulate an individual's immune response, whereby the surgical site becomes more prone to infection and may predispose an individual to pyomyositis. The case report is followed by a discussion of the literature regarding this disease, including potential risk factors and the underlying pathogenesis.

[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].

PURPOSE: We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS: We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS: We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).

Successful surgical approach for a patient with encapsulating peritoneal sclerosis after hyperthermic intraperitoneal chemotherapy: a case report and literature review.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). CASE PRESENTATION: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. CONCLUSION: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

A complete response to mFOLFOX6 and panitumumab chemotherapy in advanced stage rectal adenocarcinoma: a case report.

BACKGROUND: Pathological complete remission of advanced stage rectal adenocarcinoma by chemotherapy alone is rare. A case of advanced stage, low-lying rectal adenocarcinoma in which a complete response to treatment was obtained with mFOLFOX6 and panitumumab (Pmab) is reported. CASE PRESENTATION: A 53-year-old man was referred to Shiga University of Medical Science hospital Shiga, Japan, complaining of bloody stool. Gastrointestinal endoscopy was performed, and advanced stage rectal adenocarcinoma was diagnosed. Computed tomography (CT) revealed regional lymph node metastases in the mesorectum. Neoadjuvant chemotherapy (NAC) with mFOLFOX6 and Pmab was planned.Endoscopy following four courses of chemotherapy revealed that the rectal cancer had been markedly reduced, and the results of biopsies of the rectal tumor were negative for cancer. On CT, the mesorectal lymph node metastases had disappeared. Total intersphincteric resection (ISR) with a handsewn coloanal anastomosis was performed. Histological examination showed a complete response to mFOLFOX6 and Pmab in advanced stage rectal cancer. CONCLUSION: The result seen in this case suggests that short-term NAC with mFOLFOX6 and Pmab was effective for low-lying rectal adenocarcinoma.

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report.

In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was approved in Japan for clinical use against chemotherapy-refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC cases were administered immunohistochemistry with cetuximab as salvage monotherapy. The safety, side-effects and clinical efficacy of the treatment, including response rate, time to treatment failure, progression-free and overall survival, K-ras mutation status and impact on outcome, were investigated. The patient tumor growth control rate (TCR) was 38%, the mean time to progression (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2-12.4] and the mean overall survival (OS) was 49.4 weeks (95% CI, 30.1-68.8). The most common adverse reactions reported were skin reactions, including acne (67%), hand-foot syndrome (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the present single-center study demonstrated that cetuximab monotherapy is beneficial for the treatment of chemotherapy-refractory patients with mCRC and that it has an acceptable level of safety and manageable side-effects.

Differences in chemosensitivity between primary and metastatic tumors in colorectal cancer.

PURPOSE: We retrospectively evaluated the in vitro chemosensitivity of primary site and metastatic site tumors in colorectal cancer. METHODS: Various resected tumor samples (33 from lymph nodes, 42 from liver, six from lung, and 68 primary tumors) were assessed via a collagen gel droplet-embedded culture drug sensitivity test to determine chemosensitivity to a single agent or a combination of agents. RESULTS: Sensitivity to combination chemotherapy was significantly higher than that of monotherapy in the primary site group, lymph node group, and liver group. There was significant difference between chemosensitivity of primary site and that of liver metastasis in each agent (5-FU, p<0.001; SN38, p = 0.045; 5-FU/SN38, p<0.001; OHP, p = 0.037; 5-FU/OHP, p = 0.045). CONCLUSIONS: Tumors showed greater in vitro chemosensitivity to combination therapy when compared with monotherapy. Further, tumors that had metastasized to the liver were more resistant to chemotherapy when compared with matched primary tumors.

Clinical potential of the anticancer drug sensitivity test for patients with synchronous stage IV colorectal cancer.

PURPOSE: We retrospectively evaluated the clinical efficacy and feasibility of a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to guide therapy for patients with stage IV colorectal cancer (CRC). METHODS: We investigated 38 patients with stage IV CRC. All patients were younger than 85 years and had untreated evaluable metastatic lesions. The primary tumors were surgically resected, and the tissue samples were investigated by CD-DST. Patients treated with in vitro sensitive drugs were defined as Group A (n = 14), while those treated with in vitro non-sensitive drugs were defined as Group B (n = 24). We evaluated response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: RR was 85.71 % in Group A and 41.67 % in Group B (p = 0.0079). The median PFS was 696.5 days in Group A and 297.5 days in Group B (p = 0.0326). The median OS was 1,023.4 days in Group A and 518.5 days in Group B (p = 0.0061). CONCLUSIONS: The CD-DST can define chemoresistant and chemosensitive tumors. The use of CD-DST might be one of the tools to supplement informed consent prior to initiation of therapy.

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.

Safety and efficacy of panitumumab therapy after metastatic colorectal cancer progression with cetuximab: Experience at a single Japanese institution.

Panitumumab (Pmab) is generally considered to be ineffective after the failure of cetuximab (Cmab) therapy in metastatic colorectal cancer (mCRC) patients. However, a few studies have demonstrated that Pmab is an effective treatment for disease progression following Cmab-based regimens in the USA. In the present study, we evaluated the safety and efficacy of Pmab therapy following the failure of Cmab therapy in Japanese patients with mCRC. We performed a retrospective review of the treatment of 16 mCRC patients who tolerated Pmab with clinical benefits after the failure of Cmab therapy between August 2010 and September 2011 at Shiga University of Medical Science. Fourteen of the 16 patients were administered standard Pmab monotherapy (6 mg/kg) intravenously every 2 weeks and the remaining two patients received Pmab with mFOLFOX6 intravenously every 2 weeks. All patients received Pmab chemotherapy until the occurrence of disease progression. Partial radiographic responses (PR) were observed in 2 of the 16 patients and stable disease (SD) was observed in 5 patients. Nine patients had evidence of progressive disease (PD). According to the KRAS status, 7 of the 13 (53.8%) patients who had wild-type KRAS achieved a high disease control rate (PR + SD). The median progression-free survival (PFS) and overall survival (OS) in the wild-type KRAS patients was 96 and 245 days, respectively. Pmab may be an alternative treatment strategy for Japanese patients with mCRC who have experienced failure with standard Cmab-based therapeutic regimens.

Association between reduction of plasma adiponectin levels and risk of bacterial infection after gastric cancer surgery.

BACKGROUND AND PURPOSE: Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities. METHODS: We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ(2) test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility. RESULTS: Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively. CONCLUSION: T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection.

Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stage II-III colorectal cancer.

Clinically useful predictors of the efficacy of adjuvant chemotherapy following curative colorectal surgery remain to be determined. In the present study, we investigated the clinical utility of the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) as a predictor of the therapeutic response to 5-fluorouracil (5-FU)-based adjuvant chemo-therapy in patients with stage II-III colorectal cancer. CD-DST was conducted using tumor samples surgically obtained from 189 patients. The therapeutic effect of 5-FU-based regimens between high (high-group) and low (low-group) sensitivity groups and a group that did not receive chemotherapy [CTx(-) group] was compared. CD-DST was successfully performed in 151 out of the 189 patients (79.9%), 87 of whom received 5-FU-based adjuvant chemotherapy after surgery. Twenty-seven of these 87 patients (31.0%) were classified as the high-group and the remaining 60 (69.0%) as the low-group. The 5-year recurrence-free survival (RFS) in the high-group was significantly higher compared to that in the low- and the CTx(-) groups. No differences in the 5-year RFS were observed between the low- and CTx(-) groups. In conclusion, CD-DST appears to be useful for predicting the therapeutic response to 5-FU-based adjuvant chemotherapy in patients with stage II-III colorectal cancer.

Myeloid cells positive for CD10 at invasion front can predict poor outcome in stage II colorectal cancer.

BACKGROUND: Prediction of poor patient outcome as a effect of adjuvant therapy in stage II colorectal cancer (CRC) remains a matter of controversy. Tumor expression of CD10 and CD15 is reportedly related to poor outcome in CRC. In this study, we investigated whether the expression of CD10 and CD15 is a predictor of outcome and the effect of adjuvant therapy in stage II CRC. MATERIALS AND METHODS: Immunohistochemical analyses for CD10 and CD15 and some additional markers (CD11b, CD14, CD163, CD3, and CD20) were performed using paraffin sections of CRC specimens from 57 patients who had undergone curative surgical treatments between 1998 and 2004. Forty of these patients received postoperative adjuvant therapy. We distinguished between expression in tumor cells (tCD10 and tCD15), in stromal cells (sCD10), and infiltrating immune cells (iCD10 and iCD15). RESULTS: Expression of iCD10 was observed in 21.1% (12/57) of the specimens examined. Of all expression patterns, only iCD10 expression at the cancer invasion front was a useful predictor of a disease-free period and overall survival in stage II CRC. Adjuvant therapy improved the outcome of iCD10(+) patients. CD10(+) immune cells were heterogeneous in origin and partially overlapped the cells positive for myeloid lineage markers, including CD11b and CD15. CONCLUSIONS: iCD10 expression at the tumor invasion front is a useful marker for predicting a high risk of recurrence and mortality in stage II CRCs. CD10(+) immune cells appear to be of myeloid origin.

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.

Real-time magnetic resonance-guided microwave coagulation therapy for pelvic recurrence of rectal cancer: initial clinical experience using a 0.5 T open magnetic resonance system.

PURPOSE: This study aims to evaluate consecutive cases of recurrent rectal cancer in the pelvic cavity treated with microwave coagulation therapy using real-time navigation by an open magnetic resonance system. METHODS: Nine recurrent pelvic lesions in 8 patients after curative resection of rectal cancer were treated with real-time magnetic resonance-guided microwave coagulation therapy as a palliative local therapy to reduce tumor volume and/or local pain. Clinical and pathological data were collected retrospectively by reviewing medical records and clinical imaging results. RESULTS: Seven patients received other treatments before real-time magnetic resonance-guided microwave coagulation. Six patients had distant synchronous metastases. Three patients underwent surgery under lumbar anesthesia. Microwave coagulation was performed percutaneously in 5 lesions and under laparotomy in 4 lesions. Although adverse events related to microwave coagulation (skin necrosis and nerve injury) were observed, no fatal complications occurred. Local re-recurrence was observed in 2 of 9 ablated lesions. Except for 1 patient who died of chronic renal failure, the remaining 7 patients died of cancer. Median overall survival after microwave coagulation for all patients was 10 months (range, 4-37 mo). Median overall survival after discovery of pelvic recurrence in all patients was 22 months (range, 9-42 mo). CONCLUSIONS: The benefits of using an open magnetic resonance system in the pelvic cavity include the abilities to treat tumors that cannot be visualized by other modalities, to demonstrate internal architectural changes during treatment, to differentiate treated vs untreated areas, and to allow adjustments to the treatment plan during the procedure. Additional studies are required to clarify the efficacy of tumor coagulation for local control.

Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis.

BACKGROUND: Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, which increases the plasma APN concentration. MATERIALS AND METHODS: Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone. RESULTS: APN deficiency resulted in significant increases in the plasma levels of TNF-alpha, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-alpha, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis. CONCLUSION: These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.

Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality.

BACKGROUND: Adiponectin, a key substance in metabolic syndrome, is known to have anti-inflammatory properties. The relationship between adiponectin and sepsis in vivo is unclear. In this study, the possible involvement of adiponectin in polymicrobial sepsis was investigated using adiponectin-knockout (APN-KO) mice that underwent cecal ligation and puncture (CLP) and received the peroxisome proliferator-activated receptor gamma (PPAR-gamma) that increases the plasma adiponectin concentration. METHODS: APN-KO and wild-type (WT) mice underwent either CLP or a sham operation. The plasma adiponectin, endotoxin, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were determined before and at 2, 4, 6, 8, 12, 16, and 24 hours after the procedures, and the survival rates were compared. Mice were injected with rosiglitazone, a selective PPAR-gamma agonist, and compared survival rates after CLP with those without rosiglitazone. RESULTS: After CLP, APN-KO mice had a significantly higher mortality than WT mice. The plasma endotoxin, TNF-alpha, and IL-6 levels in APN-KO mice were significantly higher than those in WT mice 24 hours after CLP. Within 4 hours after CLP, the plasma adiponectin level in WT mice decreased to half of the initial levels. Pre-CLP treatment with PPAR-gamma was shown to increase the plasma adiponectin level and to improve significantly mortality of WT mice during sepsis; mortality among APN-KO mice did not improve. CONCLUSION: These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.