Respiratory Disorder at the End of Surgery for Peritonitis Due to Colorectal Perforation Is a Critical Predictor of Postoperative Sepsis.

BACKGROUND/AIM: The aim of this study was to identify a critical predictor of postoperative sepsis in patients with peritonitis due to colorectal perforation. PATIENTS AND METHODS: Between 2009 and 2014, fifty-three patients who underwent emergency surgery for peritonitis due to colorectal perforation in our hospital were examined retrospectively to identify the critical predictor of postoperative sepsis. Between 2016 and 2017, twelve patients with peritonitis due to colorectal perforation were enrolled in a prospective study to validate the critical predictor obtained by the previous retrospective study. RESULTS: Mechanical ventilation for more than two days after surgery seemed to be a critical predictor of postoperative sepsis. In the prospective study, six patients who were withdrawn from mechanical ventilation within one day after surgery did not develop sepsis. CONCLUSION: Respiratory disorders at the end of surgery for peritonitis due to colorectal perforation seem to be a critical predictor of postoperative sepsis.

Usefulness of Fecoflowgram for Assessment of Defecation after Intersphincteric Resection.

AIM: We have developed an imaging functional assessment of defecation after partial intersphincteric resection (ISR) by fecoflowgram obtained by defecography. PATIENTS AND METHODS: Between January 2012 and December 2014, 6 patients with temporary ileostomy who underwent partial ISR for lower rectal cancer at our hospital were enrolled in this study. Defecography was performed 2 weeks after closure of the ileostomy. The defecation of all patients was evaluated by defecography and a fecoflowgram calculated from defecography. During the same period, the control group was comprised of 2 male and 2 female healthy volunteers. RESULTS: The descent of the perineum and linearization of the anorectal angle was observed relative to normal defecation in the healthy volunteers. All barium was discharged by a single abdominal pressure within 5 s in the controls. In patients after partial ISR, all barium could not be discharged by a single abdominal pressure. The time course of pressure distribution after ISR was lower than that of healthy volunteers, which could not be evaluated by defecography. Defecation time in patients following ISR was longer than that of healthy volunteers. CONCLUSION: Fecoflowgrams calculated from defecography seem to be useful for functional assessment of defecation after rectal resection.

Usefulness of TAS-102 as Third-line Chemotherapy for Metastatic Colorectal Cancer.

BACKGROUND/AIM: The feasibility and oncological outcomes of treatment with TAS-102, that is recommended as third-line chemotherapy for patients with metastatic colorectal cancer (mCRC), remain unknown. PATIENTS AND METHODS: Between 2013 and 2015, seven patients (five males, two females) with mCRC who were administered TAS-102 as third-line chemotherapy at our Institution were retrospectively studied. During the same period, seven patients with mCRC with Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type primary lesions who were administered irinotecan with panitumumab comprised the control group. RESULTS: The duration of third-line chemotherapy in the TAS-102 group was 217.0 (range=136-337) days compared to 226.9 (range=122-335) days in the control group, with no significant difference in the duration of administration between the two groups. No significant difference in overall survival was identified between the two groups No serious adverse effects were encountered in either group. CONCLUSION: TAS-102 may be suitable as third-line chemotherapy for patients with mCRC.

Lymphangiogenic factors are associated with the severity of hypersensitivity pneumonitis.

BACKGROUND: Antigen presenting cells play a pivotal role in the adaptive immune response in hypersensitivity pneumonitis (HP). It was hypothesised that lymphangiogenesis is involved in the pathophysiology of HP via cell transport. OBJECTIVE: To determine the clinical significance of lymphangiogenic factors in HP. METHODS: Levels of vascular endothelial growth factors (VEGF)-A, VEGF-C, VEGF-D and CCL21 in the serum and bronchoalveolar lavage fluid (BALF) were measured in 29 healthy volunteers, 14 patients with idiopathic pulmonary fibrosis (IPF) and 26 patients with HP by ELISA. Additionally, immunohistochemical analyses were performed using lung specimens of patients with HP (n=8) and IPF (n=10). RESULTS: BALF VEGF-D levels were significantly elevated in patients with HP compared to the other groups. BALF VEGF-D levels in patients with HP correlated significantly with the BALF total cell and lymphocyte counts (r=0.485, p=0.014 and r=0.717, p<0.0001, respectively). BALF VEGF-C and CCL21 levels were increased in patients with HP compared to healthy volunteers, but not patients with IPF. BALF CCL21 levels were negatively correlated with the forced expiratory volume in 1 s percentage and diffuse capacity of the lung for carbon monoxide (r=-0.662, p=0.007 and r=-0.671, p=0.024, respectively). According to the immunohistochemical analyses, CCL21 was expressed in the lymphatic endothelium in both conditions and CCR7(+) cells were aggregated around lymphatics in patients with HP, but not in patients with IPF. CONCLUSIONS: Lymphangiogenic factors might be associated with the inflammatory and functional severity of HP. The increased BALF VEGF-D levels were associated with lymphatic alveolitis intensity, and CCL21 with lung function impairment.

Heterogeneous characteristics of lymphatic microvasculatures associated with pulmonary sarcoid granulomas.

RATIONALE: Pulmonary sarcoidosis is a disorder characterized by noncaseating epithelioid granulomas that are anatomically distributed along lymphogenous routes. Currently, limited information is available about lymphangiogenesis in pulmonary sarcoidosis. OBJECTIVE: To clarify the characteristics of lymphangiogenesis in pulmonary sarcoidosis. METHODS: The concentrations of vascular endothelial growth factor (VEGF), VEGF-C, and VEGF-D in serum and bronchoalveolar lavage fluid from 65 patients with pulmonary sarcoidosis, 10 with idiopathic pulmonary fibrosis, and 29 healthy volunteers were measured by ELISA. Paraffin-embedded lung tissues obtained from 19 patients were used for immunohistochemical analyses, using primary antibodies against VEGF, VEGF-C, VEGF-D, podoplanin, VEGF receptor (VEGFR)-2, VEGFR-3, and CD73. RESULTS: The serum and bronchoalveolar lavage fluid concentrations of VEGF and VEGF-C were significantly increased in patients with pulmonary sarcoidosis. Immunohistochemical analysis showed that VEGF and VEGF-C were expressed in sarcoid granulomas. Immunostaining with anti-podoplanin antibody for the detection of lymphatic vasculatures showed the presence of usual lymphatics and atypical tubular structures around sarcoid granulomas. Atypical tubular structures were characterized by a thin membrane, with weak expression of podoplanin and a membrane deficit in a part of the borderline. The structures were observed in around 58.6% of the total of 193 granulomas, whereas usual lymphatics were limited in 15.6%. Atypical tubular structures were coexpressed with VEGFR-2, but not VEGFR-3, whereas VEGFR-3 was expressed in usual lymphatics. Part of the tubular structures was connected to CD73(+) afferent lymphatics. CONCLUSION: These results indicate the presence and the importance of heterogeneous lymphatic microvasculature around sarcoid granulomas in pulmonary sarcoidosis.

Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation.

BACKGROUND: Histamine is known to have immunoregulatory roles in allergic reactions through histamine receptor 1 (H1R), H2R, H3R and H4R. However, its role in goblet cell hyperplasia in the airways of asthma patients is yet to be clarified. OBJECTIVE: This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc-/- mice) with allergic airway inflammation. METHODS: Wild-type and Hdc-/- C57BL/6 mice were sensitized with ovalbumin (OVA). After a 2-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials and cytokines in BALF were analyzed. The mRNA levels of MUC5AC and Gob-5 gene were determined quantitatively. RESULTS: The number of eosinophils in BALF increased in both the sensitized wild-type mice and Hdc-/- mice with OVA inhalation. In addition, the numbers of alveolar macrophages and lymphocytes in BALF increased significantly in the sensitized Hdc-/- mice with OVA inhalation compared to the wild-type mice under the same conditions. The concentrations of Interleukin-4 (IL-4), IL-5, IL-13, Interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and IL-2 in the BALF all increased significantly in both groups compared to those exposed to saline. In particular, the concentration of TNF-alpha in the Hdc-/- mice exposed to OVA was significantly higher than that in the wild-type mice under the same conditions. The mRNA levels of Gob-5 and MUC5AC, and the ratio of the goblet cells in the airway epithelium significantly increased in Hdc-/- mice exposed to OVA compared to wild-type mice. CONCLUSIONS: These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.

[A case of increased resectability with preoperative chemotherapy FOLFOX4 for unresectable rectal cancer].

The patient was a 57-year-old man. The chief complaints were bleeding upon defecation and decreased body weight. He came to our department in May 2006 because the bleeding had been observed since summer 2005 and he had lost 7 kg in one year. A tumor was palpable on the rectum, approximately 5 cm proximal to the anal verge. Abdominal CT revealed a large tumor within the pelvis and enlarged paraaortic lymph nodes. CEA was 14.0 ng/mL. The patient underwent surgery in June 2006, but the tumor was firmly fixed anterior to the sacrum. We judged it unresectable and performed double-barrel descending colostomy. FOLFOX4 chemotherapy commenced following the surgery, and the tumor marker level normalized following three cycles. Abdominal CT following five cycles showed that the size of the tumor had reduced significantly. Later, the patient developed grade 2 nausea and decreased appetite as adverse events, and the chemotherapy was discontinued at his request. We considered resection possible and performed rectal resection in November 2006. The patient underwent radiotherapy following surgery and is currently receiving S-1. FOLFOX4 may be an effective preoperative chemotherapy for unresectable primary rectal cancer.

Progress in allergy signal research on mast cells: the role of histamine in goblet cell hyperplasia in allergic airway inflammation - a study using the Hdc knockout mouse.

Although histamine is a central mediator in the immediate allergic reaction, its role in goblet cell hyperplasia in the airway of asthma is not completely understood. This study was designed to examine the role of histamine in goblet cell hyperplasia using histamine-deficient mice (Hdc(-/-) mice) with allergic airway inflammation. Wild-type and Hdc(-/-) C57BL/6 mice were sensitized with ovalbumin (OVA). After two-week exposure to OVA, goblet cell hyperplasia was evaluated. Cell differentials in BALF were analyzed. The mRNAs level of MUC5AC and Gob-5 gene were quantitatively determined. The number of eosinophils in BALF increased in both the wild-type mice and Hdc(-/-) mice; however, their ratio in Hdc(-/-) mice was significantly lower than that in the wild-type mice. The mRNA levels of Gob-5 and MUC5AC and the ratio of the goblet cells in the airway epithelium were significantly increased in Hdc(-/-) mice exposed to OVA compared to the wild-type mice under the same condition. These results suggested that histamine may play a regulatory role in goblet cell hyperplasia in allergic airway inflammation.

[Multiple hepatic metastases of colon cancer responding to combined therapy with TS-1 and CPT-11--a case report].

We treated a patient with multiple liver metastases arising from colon cancer in whom the metastatic tumors were responsive to treatment with the combination of TS-1 and CPT-11. The patient was a 71-year-old woman with cancer of the ascending colon and metastatic hepatic tumors. She had undergone surgery on July 28, 2004, and abdominal contrast CT scans obtained after discharge from hospital revealed numerous LDA (low-density areas) in both lobes of the liver. The patient was given ambulatory chemotherapy with TS-1 (120 mg/day on days 1-14) and CPT-11 (100 mg/day on days 1 and 8). After completion of 2 courses of chemotherapy, abdominal contrast CT scans revealed that most of the LDAs in both lobes of the liver had disappeared, and the patient was judged to have achieved PR. No adverse reactions were observed except for a slight decrease of WBC, and her chemotherapy is being continued at present. This case suggests that the combination of TS-1 and CPT-11 may be an effective form of chemotherapy for the treatment of colon cancer with multiple hepatic metastases.

[Cytoprotective effects of heat shock protein-70 in bronchial epithelium against neutrophil elastase-induced cell injury].

BACKGROUND: Neutrophil releases several mediators during inflammation, including neutrophil elastase (NE) that impairs bronchial epithelial function. The stress response and stress proteins protect cells against a variety of cytotoxic conditions. Accordingly, we tested the hypothesis that bronchial epithelial heat shock protein (Hsp-70) would protect a NE-induced cell injury. METHODS: Bronchial epithelial cells (BECs) obtained by bronchial brushing under bronchoscopy were cultured and used for experiments. Expression of Hsp-70 in BECs was confirmed by Western blot and flowcytometric analysis. To test Hsp-70 in BECs, induction of Hsp-70 protein into BECs was carried out by liposome-based delivery system. Introduction of Hsp-70 into BECs were examined by direct fluorescence microscope examination and flowcytometric analysis. NE-induced cytotoxicity was evaluated by cell culture supernatant LDH assay and cell detachment assay. RESULTS: Higher expressions of Hsp-70 were observed in BECs, which were induced by sodium arsenite. Over expression of Hsp-70 in BECs reduced NE-induced cell injury. Introduction of Hsp-70 protein into BECs by liposomal delivery decreased LDH release, and inhibited necrosis and apoptosis of the cells by NE as compared to untreated control. CONCLUSION: These data suggested that Hsp-70 in BECs may inhibit NE-induced airway epithelial damage. Liposomal delivery of Hsp-70 into BECs may be a possible means of protecting bronchial epithelium against inflammatory airway diseases including acute and chronic bronchitis.

[Magnetoencephalographic responses to odor and non-odor by fast Fourier transformation analysis in humans].

Magnetoencephalographic (MEG) responses to odor (amyl-acetate) and non-odor stimuli for 1 second were recorded in 9 healthy volunteers (right handed) with a dual 37-channel SQUID (Magnes, Bti Co.) and evaluated by fast Fourier transformation analysis, with the following results: 1. On MEG analysis, the spectral density increase in the left mid-central region at a frequency of 7 Hz was significantly greater in response to odor than in response to non-odor stimuli. This greater increase is apparently related to the presence of the odor perception mechanism in the orbital frontal area, a major center of the olfactory system. 2. Both increased and decreased spectral density areas at a frequency of 8 Hz were observed over the right hemisphere when no stimuli was compared with non-odor and no stimulus compared with odor. These changes may reflect a high level of vigilance caused by stimulation. 3. When no stimulus was compared with non-odor stimulation, a significant spectral density increase at a frequency of 11 Hz was noted. Similar trends were observed at frequencies of 11 and 12 Hz when no stimulus was compared with odor. These findings indicated increased attention in response to random presentation of odor and non-odor. 4. Significant differences at frequencies from 14 to 24 Hz were noted in the contralateral hemisphere when no stimulus was compared with odor stimuli. MEG spectral densities at 21 and 22 Hz were also noted in the contralateral hemisphere when no stimulus was compared with non-odor stimulus. These differences apparently arise from the response of the somato-sensory cortex to non-odor stimuli and amyl-acetate. Alternation of MEG spectral densities at frequencies from 14 to 17 Hz and 23 to 24 Hz in the left hemisphere was noted when no stimulus was compared with non-odor and no stimulus was compared with odor. These results appear to be related to "emotions" of pleasantness and unpleasantness evoked by non-odor and odor.