Prognostic value of the combination of pre- and postoperative C-reactive protein in colorectal cancer patients.

PURPOSE: Inflammation is closely related to cancer development and progression. This retrospective study investigated the prognostic value of the combination of pre- and postoperative C-reactive protein (CRP) levels in patients with colorectal cancer (CRC). METHODS: The subjects of this study were 406 patients who underwent surgery for CRC. RESULTS: Based on receiver-operating characteristic analysis, patients were divided into the following groups: those with a preoperative CRP of ≥ 0.5 mg/dL (pre-CRPHigh), those with a preoperative CRP of < 0.5 mg/dL (pre-CRPLow), those with a postoperative CRP of ≥ 17.0 mg/dL (post-CRPHigh), and those with a postoperative CRP of < 17.0 mg/dL (post-CRPLow). They were then allocated to one of the following three groups: Group A, comprised of those in the pre-CRPHigh and post-CRPHigh groups; Group B, comprised of those in either the pre-CRPHigh and post-CRPLow or pre-CRPLow and post-CRPHigh groups; and Group C, comprised of those in the pre-CRPLow and post-CRPLow groups. The disease-specific 5-year survival rates were 53.8%, 72.8%, and 87.2% in Groups A, B, and C, respectively, and these differences were significant. Finally, multivariate analysis revealed that the combination of pre- and postoperative CRP levels was an independent prognostic indicator. CONCLUSIONS: The combination of pre- and postoperative CRP was predictive of the prognosis of CRC patients.

Inflammation-based prognostic scores and nutritional prognostic index in patients with locally-advanced unresectable colorectal cancer.

BACKGROUND: Unresectable colorectal cancer has a poor prognosis. However, some patients survive intensive chemotherapy, and complete resection of primary and metastatic tumors may even be possible. In the present study, we examined the prognostic factors associated with survival after intensive chemotherapy in patients with unresectable colorectal cancer. METHODS: This retrospective study enrolled 61 patients diagnosed with unresectable locally advanced colorectal cancer between January 2004 and December 2013. Among the prognostic parameters, we found that the prognoses of patients with abnormal performance status (PS) of 2 or 3, high Glasgow Prognostic Score (GPS) of 1 or 2, high neutrophil/lymphocyte ratio (NLR) >5, and low prognostic nutritional index (PNI) <40 were poor. Thus, we scored each patient according to our scoring system (abnormal PS, 2 or 3 = +1; high GPS, 1 or 2 = +1; high NLR, >5 = +1; and low PNI, <40 = +1). If the patient showed abnormalities in every parameter, the score would be +4. RESULTS: Sixteen patients had a score of 0, 17 scored +1, 10 scored +2, 17 scored +3, and one scored +4. The median survival time (MST) of the 61 patients was 9 months. Patients were divided into two groups, a low-score group (0 and +1) and a high-score group (+2, +3, and +4). The MST of the 33 patients in the low-score group was significantly longer than that of the 28 patients in the high-score group (15 months versus 4 months, P < 0.001). Also, conversion chemotherapy was performed in 4.9% (3/61) of patients. And these 3 patients were in a low-score group. CONCLUSIONS: This new prognostic scoring system may help to select patients with unresectable advanced colorectal cancer who are able to survive through intensive chemotherapy.

Topoisomerase I expression in tumors as a biological marker for CPT-11 chemosensitivity in patients with colorectal cancer.

Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an objective response to CPT-11 and the drug has severe toxicities, such as delayed-onset diarrhea, neutropenia, nausea, and vomiting. It is important to select patients who will demonstrate sensitivity to CPT-11 treatment to avoid unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. This article reviews the possibility of assessing Topo I protein expression in tumors as a biological marker for CPT-11 treatment in CRC.

Advanced cancer with situs inversus totalis associated with KIF3 complex deficiency: report of two cases.

Situs inversus totalis (SIT) is a relatively rare congenital anomaly, occurring at an incidence of 1 in 10 000-50 000 live births. Although there are some case reports of SIT with the presence of cancer, there are few reports on the relationship between SIT and cancer. However, the recent phylogenetic investigations of this condition suggest that this may be linked to the development and progression of cancer on the molecular level. The key elements are one of the intracellular motor proteins, the KIF3 complex, and the cell-adhesion factors N-cadherin and beta-catenin. We herein present the cases of advanced gastric cancer and lung cancer with SIT, and review the relationship between SIT and the development and progression of cancer.

Resection of rectal cancer resembling submucosal tumor that was preoperatively diagnosed with endoscopic ultrasound-guided biopsy.

BACKGROUND: Colorectal cancer (CRC) resembling submucosal tumor (SMT; CRC/SMT) is very rare. Because its biopsy is challenging, accurate preoperative diagnosis is also very rare. CASE PRESENTATION: A 55-year-old woman with a high serum carcinoembryonic antigen level underwent a computed tomography colonoscopy, which showed extrinsic rectum compression. A coronal magnetic resonance image showed a 4-cm low-intensity tumor between her rectum and sacrum. Endoscopic ultrasound (EUS) showed a 30-mm low-echoic lesion originating from the rectum. Pathological examination of specimen obtained with EUS-guided fine-needle aspiration biopsy (EUS-FNAB) revealed adenocarcinoma. Immunohistochemical staining showed the tumor to be positive for both CK20 and CDX2 and negative for CK7, indicating that it was a rectal cancer. We performed a laparoscopy-assisted low-anterior resection with dissection of the regional lymph nodes after eight chemotherapy cycles. Macroscopically, tumor was completely covered by normal rectal mucosa, but showed a 2-mm bulge on the mucosa. Histological examination revealed a moderately differentiated adenocarcinoma, mainly located at the subserosal layer and severely invaded to lymphatic and blood vessels. The mucosal layer was not exposed to the cancer components, and her postoperative course was uneventful. CONCLUSION: EUS-FNAB was useful in preoperative accurate diagnosis of this very rare tumor. We also review the literature and discuss CRC/SMT.

Traumatic Gastric Perforation Associated with Cardiopulmonary Resuscitation: A Case Report.

Sternal and rib fractures are well-known complications of cardiopulmonary resuscitation (CPR). We experienced a rare case of traumatic gastric perforation associated with CPR that required emergency laparotomy. In this case, we examined whether surgery is essential for gastric perforation associated with CPR. A 67-year-old man experienced cardiopulmonary arrest in the workplace, and bystander CPR was performed by his colleagues. He was then transported by ambulance to our hospital. A large amount of free air was found in the peritoneal cavity on computed tomography at presentation, and perforation of the gastrointestinal tract was suspected. During emergency laparotomy, a 2-cm serosal-muscular layer tear was found in the gastric lesser curvature. The damaged stomach wall was repaired, the abdominal cavity was lavaged, and surgery was completed by placing a drainage tube. The patient's postoperative course was good and he was discharged on the 26th postoperative day. Emergency laparotomy has been performed frequently for traumatic gastric perforation associated with CPR. However, emergency laparotomy may be avoided by conservative treatment in some cases. Traumatic gastric perforation associated with CPR is a serious complication; however, the life prognosis of cardiopulmonary arrest patients depends on the original disease and the success of CPR. Traumatic gastric perforation associated with CPR is rarely fatal, and bystanders should not hesitate to initiate CPR.

Hepatobiliary cystadenoma with mesenchymal stroma in a patient with chronic hepatitis C.

Hepatobiliary cystadenoma was suggested to be uncommon and it is often difficult to make a differential diagnosis. We report a case of a 65-year-old woman who presented with changes in the structure of a cyst that had been observed for the previous 10 years. Diagnostic imaging revealed a 7-cm-diameter cystic lesion with internal septations and papillary projections in her liver. All laboratory test results were normal; however, cystic fluid carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were raised, at 160 ng/ml andover 200,000 U/ml, respectively. Owing to changes in the structure of the cyst and the difficulty of differential diagnosis from cystadenocarcinoma, a complete surgical excision was performed. The histological findings indicated that the tumor consisted of a multilocular cyst lined by glandular cells (with cuboidal or tall columnar cystoplasm), which were immunohistochemically positive for cytokeratin, CEA, epithelial membrane antigen, and CA 19-9. The underlying stroma was composed of proliferating primitive spindle cells which were immunoreactive for vimentin, alpha-smooth muscle actin, muscle-specific actin, and desmin, and resembled ovarian stroma. From these findings, this tumor was diagnosed as hepatobiliary cystadenoma with mesenchymal stroma. Even though the tumor was previously diagnosed as a simple liver cyst, it was necessary to pay special attention to the changes in the structure of the cyst, using ultra sonography and/or computed tomography, bearing in mind hepatobiliary cystadenoma with mesenchymal stroma. The malignant potential of this tumor is stressed, and complete surgical resection is the recommended therapy.

Neoangiogenesis in patients with gastric carcinoma in relation to the expression of vascular endothelial growth factor and thymidine phosphorylase.

BACKGROUND: We investigated the prognostic significance of microvessel density and the relationship between the expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP), and angiogenesis in patients with gastric carcinoma. MATERIALS AND METHODS: The expression of VEGF and TP, and the microvessel density were examined by immunohistochemistry in patients with gastric carcinoma invading the serosa. RESULTS: The prognosis of patients with low microvessel density in the cancerous tissue was significantly better than that of patients with high microvessel density. A multivariate analysis showed that microvessel density, lymph node metastasis and tumor size were independent prognostic indicators. VEGF was expressed in tumor cells and TP was expressed in both tumor cells and infiltrating cells. VEGF expression in tumor cells and TP expression in infiltrating cells significantly correlated with microvessel density. However, microvessel density was not correlated with TP expression in tumor cells. Combined analysis based on VEGF expression in tumor cells and TP expression in infiltrating cells revealed that microvessel density was the highest in VEGF-positive and TP-positive tumors and the lowest in VEGF-negative and TP-negative tumors. Microvessel density is an independent prognostic indicator in patients with gastric carcinoma invading the serosa. CONCLUSION: VEGF expression in tumor cells and TP expression in infiltrating cells may indicate the microvessel density.

Lymph node metastasis of gastric cancer: comparison of Union International Contra Cancer and Japanese systems.

BACKGROUND: The pN classification of gastric cancer (GC) in the Japanese system (Japanese Gastric Cancer Association; JGCA) is based on the site and distance of metastatic nodes from the primary tumour. Union International Contra Cancer (UICC) has recently proposed a classification system based on the number of nodes involved (TNM-1997). The aim of the present study is to assess which classification system is more suitable for providing a prognosis in advanced GC with lymph node metastasis. METHODS: A total of 224 patients who underwent curative gastrectomy (R0: UICC-TNM and Resection A and B: JGCA) and D2 lymphadenectomy between 1990 and 1999, and diagnosed as pT2, pT3 and pT4 GC were enrolled. Patients were followed until the end of 2002. The disease-free survival rates of patients were compared between the two-stage systems (UICC-TNM and JGCA). RESULTS: Using the JGCA system, there was a significant difference between the two survival curves (pN0 and pN1, P = 0.025; pN1 and pN2, P < 0.001; pN2 and pN3, P = 0.031), but the 5-year survival rate of 27 pN2 patients (32.7%) was not significantly different from that of 14 pN3 patients (34.3%, P = 0.994) using the UICC-TNM. In 47 patients with JGCA pN2, the 5-year survival rate of 18 patients with UICC-TNM pN1 (42.9%) was not significantly different from that of 18 patients with UICC-TNM pN2 (25.2%, P = 0.422) or from that of 11 patients with UICC-TNM pN3 (24.2%; P = 0.383). CONCLUSIONS: The JGCA system is more suitable for estimating the prognosis of Japanese patients with advanced GC than the UICC-TNM.

Scoring of prognostic parameters in patients with unresectable advanced or recurrent colorectal cancer undergoing chemotherapy.

BACKGROUND: Suitable chemotherapy is needed to prolong the survival of patients with unresectable advanced or recurrent colorectal cancer. We scored the periodical changes of several prognostic markers during chemotherapy in patients with this type of cancer to discern the effectiveness of chemotherapy. METHODS: Twenty consecutive patients with unresectable advanced or recurrent colorectal cancer were enrolled. All patients underwent combination chemotherapy with oxaliplatin or irinotecan plus 5-fluorouracil/leucovorin. Neutrophil/lymphocyte ratio (NLR), serum C-reactive protein (CRP), serum carcinoembryonic antigen (CEA) and serum albumin (ALB) were compared between the two periods (before chemotherapy and 3 months after it was started) in each patient. The scoring system was as follows: points are added when a patient shows a decrease of NLR, CRP and CEA and an increase of ALB at 3 months after the start of chemotherapy with a possible final score of +4. On the other hand, points are reduced if a patient shows an elevation of NLR, CRP and CEA and a decrease of ALB at 3 months after the start of chemotherapy with a possible final score of -4. RESULTS: At 3 months after the start of first line chemotherapy, 13 patients showed positive scores but 7 patients showed zero or minus scores. According to our scoring system, we found the mean survival time (MST) of the 13 patients with plus scores was 34 months and this was significantly better than that of the 7 patients who showed zero or minus scores (P = 0.0008). CONCLUSION: Our new scoring system is useful but when we find that first line chemotherapy is ineffective, we need to change it to second line chemotherapy as soon as possible. That may be the best treatment for patients with unresectable advanced or recurrent colorectal cancer.

Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer.

Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) or irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) has become a standard regimen for advanced or recurrent colorectal cancer. Numerous studies have reported that long-term use of FOLFOX or FOLFIRI leads to better survival for these patients. Thus, control of the toxicity of these drugs may be crucial to prolonging survival. Fucoidan is one of the major sulfated polysaccharides of brown seaweeds and exhibits a wide range of biological activities. In the present study, we analyzed the effect of fucoidan on suppressing the toxicity of anti-cancer drugs. A total of 20 patients with unresectable advanced or recurrent colorectal cancer scheduled to undergo treatment with FOLFOX or FOLFIRI were randomly allocated into a fucoidan treatment group (n=10) and a control group without fucoidan treatment (n=10). Results showed that fucoidan regulated the occurrence of fatigue during chemotherapy. Chemotherapy with fucoidan was continued for a longer period than chemotherapy without fucoidan. Additionally, the survival of patients with fucoidan treatment was longer than that of patients without fucoidan, although the difference was not significant. Thus, fucoidan may enable the continuous administration of chemotherapeutic drugs for patients with unresectable advanced or recurrent colorectal cancer, and as a result, the prognosis of such patients is prolonged.

The expression of RCAS1 and tumor infiltrating lymphocytes in patients with T3 gastric carcinoma.

BACKGROUND: This study aimed to assess the prognostic value of receptor binding cancer antigen expressed on SiSo cells (RCAS1) expression and host immune response in gastric carcinomas. METHODS: We investigated the relationship between RCAS1 expression, density of tumor-infiltrating lymphocytes (TIL), and clinicopathological findings in 129 patients with T3 gastric carcinoma who underwent curative surgery. RESULTS: RCAS1 immunoreactivity was detected in the membrane and cytoplasm of tumor cells. Positive immunoreactivity for RCAS1 was detected in 70 patients (54.3%) and high expression levels of RCAS1 were found in 33 patients (25.6%). The expression of RCAS1 significantly correlated with the histological type of carcinoma and lymph node metastasis. Apoptotic rates in TILs showed marginally higher significance in patients with high RCAS1 expression than in those with low expression. The 5-year survival rates were 77.9% in patients with low RCAS1 expression and 48.4% in those with high RCAS1 expression. Although there was no significant difference in survival between the patients with marked and slight infiltration of TILs, frequent apoptosis in TILs indicated significantly worse prognosis. Patients with low RCAS1 expression survived significantly longer than those with high RCAS1 expression, as did those patients with a high rate of apoptosis in TILs. Multivariate analysis revealed that RCAS1 expression, as well as tumor size and lymph node metastasis, was an independent prognostic factor. CONCLUSIONS: The expression of RCAS1 was significantly correlated with poor prognosis in patients with T3 gastric carcinoma. RCAS1 protein may play an important role in the evasion of tumor cells from immunological defense mechanisms in human gastric carcinoma.

Expression of Mcl-1 and p53 proteins predicts the survival of patients with T3 gastric carcinoma.

BACKGROUND: The expression of myeloid cell leukemia 1 (Mcl-1) and p53 proteins was investigated for clinicopathological and prognostic significance in patients with gastric carcinoma. METHODS: Mcl-1 protein was immunohistochemically examined in 182 patients with gastric carcinoma. The overexpression of p53 was also analyzed in T3 gastric carcinomas. RESULTS: The expression of Mcl-1 was detected in 127 (69.8%) patients with gastric carcinoma. Mcl-1 was detected significantly more frequently in the undifferentiated type ( P < 0.05) and in the advanced stage of disease ( P < 0.05). The prognosis of patients with an Mcl-1-positive tumor was significantly worse than that of those with an Mcl-1-negative tumor ( P < 0.05). Multivariate analysis revealed that the expression of Mcl-1 was an independent prognostic factor, as were lymph node metastasis and tumor size. There was no significant relationship between the expression of Mcl-1 and p53. In patients with T3 gastric carcinoma who underwent curative surgery; however, Mcl-1(-)/p53 (-) tumor demonstrated the best postoperative survival rate, whereas Mcl-1(+)/p53(+) tumor had the worst. CONCLUSION: The expression of Mcl-1 is an indicator of tumor progression and postoperative recurrence in patients with gastric carcinoma. Combined analysis of Mcl-1 and p53 proteins may accurately predict the survival of patients with T3 gastric carcinoma.

Gene expression levels of cytokines in peritoneal washings from patients with gastric cancer.

Peritoneal seeding is frequently detected in patients with gastric cancer. The peritoneal cavity is a compartment in which the immunologic host-tumor interaction can occur. Here, we investigated the gene expression levels of cytokines, and compared these gene expressions with the progression of gastric cancer. Total RNA was extracted from 50 ml of peritoneal washings from 78 patients with gastric cancer and 11 noncancerous patients. The gene expression levels of transforming growth factor-beta (TGF-beta), interleukin (IL)-2, IL-6 and IL-12 were analyzed by real-time reverse transcription-polymerase chain reaction. The gene expression levels of TGF-beta and IL-12 in 16 patients with peritoneal seeding (peritoneal metastasis or free cancer cells) did not differ from those in controls (n = 11) and stage I and II (n = 43) patients. However, the relative gene expression level of IL-2 in patients with peritoneal seeding (0.9) was lower than that in controls (1.4, p = 0.066) and stage I and II patients (1.4, p = 0.036). In contrast, the relative gene expression level of IL-6 in patients with peritoneal seeding (3.3) was higher than that in control (2.4, p = 0.064) and stage I and II patients (2.6, p = 0.065). Low IL-2 gene and high IL-6 gene expressions in the peritoneal cavity may correlate with cancer development in the peritoneal cavity in patients with gastric cancer.