Bevacizumab plus Irinotecan,Fluorouracil,and Leucovorin for Metastatic Colorectal Cancer

Microwave Tumor Ablation: Mechanism of Action, Clinical Results and Devices

Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited.

Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS.

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Glutamine supplementation in cancer patients.

Pulmonary resection for colorectal metastases is well accepted. However, the main cause of death after pulmonary resection is recurrence in the lung. The aim of this study was to clarify whether a repeat pulmonary resection was warranted in patients with recurrent lung metastases. The records of 76 patients undergoing initial pulmonary resection, including 14 patients undergoing a repeat operation for lung metastases, were reviewed for survival, operative morbidity, and mortality. Overall, pulmonary resection was performed 96 times in this group of patients. The operative mortality was 0%, morbidity involved only one case of major postoperative hemorrhage associated with the first operation. The cumulative 5-year survival rate for the 76 patients was 32%. After the second pulmonary operation, recurrence was identified in 79% (11 of 14) of the patients. In 10 patients with isolated lung recurrence after a first pulmonary resection, who showed no extrapulmonary disease before or at the time of first thoracotomy, the 3-year, and 5-year-survival rate after the second pulmonary resection was 67%, and 33%, respectively, comparing favorably with the survival rate in those who underwent primary pulmonary resection. In contrast, all 4 patients with extrapulmonary disease before or at the time of thoracotomy had poor prognosis. Repeat pulmonary operation for isolated recurrent colorectal metastases to the lung yielded results comparable to those after the first pulmonary resection in terms of operative mortality and survival in the absence of hilar/mediastinal lymph node or extrathoracic involvement.

Repeat pulmonary resection for isolated recurrent lung metastases yields results comparable to those after first pulmonary resection in colorectal cancer.

Background

To determine the prognostic factors and to rationalize adjuvant therapy, the clinicopathologic data of patients with a stage II colon cancer were analyzed retrospectively.



Patients and Methods

A total of 392 patients underwent potentially curative resection at the Kurume University Hospital between 1982 and 2005. Postoperative adjuvant chemotherapy using oral fluoropyrimidines was administered in 163 patients, and the other 229 patients underwent surgery alone. Univariate and multivariate analyses for prognostic factors were carried out.



Results

Invasive type in gross features, elevated preoperative CEA level, and surgery alone were each an independently significant factor for shorter relapse-free survival, and tumor size <50 mm, invasive type in gross features, elevated preoperative CEA level, and surgery alone were each an independently significant factor for shorter overall survival. The relapse-free survival rate and overall survival rate in the patients who received postoperative adjuvant chemotherapy were significantly higher than those in the patients treated with surgery alone even after stratifying to the preoperative CEA level.



Conclusion

Patients with an elevated preoperative CEA may be candidates for adjuvant chemotherapy after curative resection in stage II colon cancer. These findings warrant clinical trials to test out the efficacy of adjuvant chemotherapy in stage II colon cancer with an elevated preoperative CEA. J. Surg. Oncol. 2009;99:65–70. © 2008 Wiley-Liss, Inc.

Elevated preoperative serum carcinoembrionic antigen level may be an effective indicator for needing adjuvant chemotherapy after potentially curative resection of stage II colon cancer.

Background : Since tumor-bearing rats are deficient in glutamine, we investigated whether (1) glutamine and glutathione deficiency occur in tumor-bearing rats, (2) glutamine supplementation caused an increase of glutathione levels in host tissues and tumor, (3) glutamine enhances protein synthesis in host tissues, and (4) glutamine stimulated the tumor to synthesize protein and DNA. Methods : Male Donryu rats were randomized into four groups : (1) non-tumor-bearing rat (NTB) + standard total parenteral nutrition (STPN) ; (2) NTB + glutamine-supplemented TPN (GTPN) ; (3) tumor-bearing rat (TB)+STPN ; (4) TB+GTPN. On day 0 AH109A rat hepatoma cells were subcutaneously injected into the backs of rats to induce tumor. The animals were maintained on TPN for 6 days from day 10 through day 15. On day 15, 1- 14 C-leucine was given by a 5-hour continuous infusion (2.0 μCi/h per rat) to determine the fractional synthesis rate and endogenous leucine production. The levels of glutamine and glutathione were measured by HPLC. The tumor DNA synthesis was estimated by bromodeoxyuridine labeling index. Results : Tumor development led to a significant weight loss, but this weight loss was significantly lessened by glutamine supplementation because of an increase in muscle protein synthesis. Glutamine did not enhance tumor weight, protein, and DNA synthesis in the tumor. Tumor development caused a significant reduction of glutathione in the muscle, jejunum, and liver, but supplemented glutamine increased the levels of glutathione in the jejunum. Conclusion: Glutamine supplementation is beneficial in preventing deficiencies of glutamine and glutathione and in improving protein metabolism in tumor-bearing rats.

Effect of Glutamine Supplementation on Protein Metabolism and Glutathione in Tumor-Bearing Rats

Background: The molecular and morphological alterations of the tight junctions in ulcerative colitis (UC)-associated colorectal cancer are still poorly understood. The possible involvement of claudin-1 (CL-1), one of the major tight junctional proteins, was investigated in the tumorigenesis of UC-associated CRC. Patients and Methods: A total of 39 patients with UC underwent surgical treatment from January 2001 until October 2009 at Kurume University Hospital in Fukuoka. CRC tissue specimens were analyzed to determine whether the expression of CL-1 correlates with clinicopathological factors and to determine the role of CL-1 and β-catenin in the alteration of tight junctions during tumorigenesis. Results: The operations were 30 of elective surgery and 9 of emergency surgery. Colectomy was performed in five patients (12.8%) because of UC-associated CRC, and in another patient (2.6 %) because of high-grade dysplasia. The immunostaining pattern of the high-grade dysplasia and UC-associated CRC for CL-1 showed much stronger and more diffuse staining in comparison to the normal or UC colonic mucosa. The expression of β-catenin was also positive or up-regulated in all of the UC-associated CRC and high-grade dysplasia tissue specimens. Conclusion: These observations suggested that CL-1 plays a pivotal role in the regulation of cellular morphology and behavior in UC. We speculate that increased CL-1 expression may be involved in the early stages of transformation in UC-associated neoplasia. CL-1 protein may therefore be a good candidate for surveillance of patients with UC.

Nobuya Ishibashi

Papers

Glutamine supplementation in cancer patients.

Repeat pulmonary resection for isolated recurrent lung metastases yields results comparable to those after first pulmonary resection in colorectal cancer.

Elevated preoperative serum carcinoembrionic antigen level may be an effective indicator for needing adjuvant chemotherapy after potentially curative resection of stage II colon cancer.

Effect of Glutamine Supplementation on Protein Metabolism and Glutathione in Tumor-Bearing Rats

Increased claudin-1 protein expression contributes to tumorigenesis in ulcerative colitis-associated colorectal cancer.