[Show abstract][Hide abstract] ABSTRACT: Improvement in the prognosis of colorectal cancer (CRC) patients has led to increasing occurrences of multiple primary malignancies (MPMs) alongside CRC but little is known about their characteristics. This study was undertaken to clarify the clinical and pathological features of MPMs, especially those at extra colonic sites, in patients with CRC.
We reviewed 1,111 patients who underwent operations for primary sporadic CRC in Saitama Medical Center, Jichi Medical University between April 2007 and March 2012. Two patients with familial adenomatous polyposis, one with hereditary non-polyposis colorectal cancer, two with colitic cancer, and any patients with metastasis from CRC were excluded. We compared the clinicopathological features of CRC patients with and without MPMs. As a control, we used a database compiled of patients with gastric cancer (GC) detected by mass screening performed in the Saitama Prefecture in Japan 2010 and compared these with CRC patients with synchronous GC.
Multiple primary malignancies at extracolonic sites were identified in 117 of 1,111 CRC patients (10.5%). The median age was 68 (range, 29 to 96) versus 71 (50 to 92) (P < 0.001). The incidence of GC (44.4% (52 of 117)) was the highest of all MPMs. All CRC patients with GC were older than 57 years. Synchronous GC was detected in 26 patients. By contrast, out of 200,007 screened people, 225 people were diagnosed as having GC in the Saitama Prefecture. The age-standardized incidence of synchronous GC in CRC patients was significantly higher (0.53%) than in the control group (0.03%) (odds ratio, 18.8; 95% confidence interval, 18.6 to 19.0; P < 0.001).
Patients with CRC who were older than 50 years preferentially developed GC synchronously and metachronously. Thus, this patient group should undergo careful perioperative screening for GC.
World Journal of Surgical Oncology 12/2015; 13(1). DOI:10.1186/s12957-014-0432-2 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to present a retrospective review of 42 metastatic colorectal cancer (mCRC) patients treated using the XELIRI regimen as second-line chemotherapy during the period between 2010 and 2012. Patients were treated with capecitabine, 1,600 (≥65 years) or 2,000 mg/m(2) (<65 years), on days 1-15, 200 mg/m(2) irinotecan (CPT-11) on day 1, with or without 7.5 mg/kg bevacizumab on day 1 and every 21 days. A total of 21 patients underwent XELIRI and 21 underwent XELIRI plus bevacizumab treatment. Fifteen patients received continuous administration of bevacizumab in the first- and second-line settings [bevacizumab beyond progression (BBP)+], whereas 27 patients did not receive the treatment (BBP-). Forty patients (95.2%), including all the patients in the BBP+ group, received sequentially administered XELOX and XELIRI regimens from the first- to the second-line setting. The disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events were compared between the BBP- and BBP+ groups. The median relative dose intensity was similar (93.9% for capecitabine and 96.3% for CPT-11 in the BBP- group vs. 94.8% for capecitabine and 91.5% for CPT-11 in the BBP+ group). The DCR was 25.9% in the BBP- and 66.6% in the BBP+ groups (P=0.020). The median PFS was 3.5 months in the BBP- and 7.2 months in the BBP+ groups (P=0.028). The BBP+ group exhibited a higher median OS time compared to the BBP- group (12.5 months in the BBP- group vs. not reached in the BBP+ group; P=0.0267). The most common grade 3/4 adverse event (n≥20) was hypertension observed in the BBP+ group [three patients (20%)]: these three patients were well-controlled with a single antihypertensive drug. Treatment with sequentially administered XELOX and XELIRI regimens did not aggravate adverse events in the 40 patients. The results showed that the XELIRI regimen, involving continuous treatment with bevacizumab, was well-tolerated and effective as a second-line chemotherapy and sequentially administering XELOX and XELIRI was feasible and manageable for patients with mCRC.
Molecular and Clinical Oncology 09/2014; 2(5):827-832. DOI:10.3892/mco.2014.306
[Show abstract][Hide abstract] ABSTRACT: Approximately half of all patients with colorectal cancer develop local recurrence or distant metastasis during the course of their illness. Recently, the molecular detection of metastatic cancer cells in various types of clinical samples, such as lymph nodes, bone marrow, peripheral blood, and peritoneal lavage fluid, has been investigated as a potential prognostic marker. The prognostic value of molecular tumor cell detection was independent of the type of detection method used. As assays become more sensitive and quantitative, a more thorough assessment of the cancer status of patients will be based on molecular markers alone. At present, it is difficult to conclude that one specific molecular marker is superior to others. Comparative analyses are recommended to assess the prognostic impact of molecular analyses in the same patient and determine the biomarkers that provide the most accurate prognostic information.
[Show abstract][Hide abstract] ABSTRACT: Background
Recent work led to recognize sessile serrated adenomas (SSA) as precursor to many of the sporadic colorectal cancers with microsatellite instability (MSI). However, comprehensive analyses of DNA methylation in SSA and MSI cancer have not been conducted.
With an array-based methylation sensitive amplified fragment length polymorphism (MS-AFLP) method we analyzed 8 tubular (TA) and 19 serrated (SSA) adenomas, and 14 carcinomas with (MSI) and 12 without (MSS) microsatellite instability. MS-AFLP array can survey relative differences in methylation between normal and tumor tissues of 9,654 DNA fragments containing all NotI sequences in the human genome.
Unsupervised clustering analysis of the genome-wide hypermethylation alterations revealed no major differences between or within these groups of benign and malignant tumors regardless of their location in intergenic, intragenic, promoter, or 3′ end regions. Hypomethylation was less frequent in SSAs compared with MSI or MSS carcinomas. Analysis of variance of DNA methylation between these four subgroups identified 56 probes differentially altered. The hierarchical tree of this subset of probes revealed two distinct clusters: Group 1, mostly composed by TAs and MSS cancers with KRAS mutations; and Group 2 with BRAF mutations, which consisted of cancers with MSI and MLH1 methylation (Group 2A), and SSAs without MLH1 methylation (Group 2B). AXIN2, which cooperates with APC and β-catenin in Wnt signaling, had more methylation alterations in Group 2, and its expression levels negatively correlated with methylation determined by bisulfite sequencing. Within group 2B, low and high AXIN2 expression levels correlated significantly with differences in size (P = 0.01) location (P = 0.05) and crypt architecture (P = 0.01).
Somatic methylation alterations of AXIN2, associated with changes in its expression, stratify SSAs according to some clinico-pathological differences. We conclude that hypermethylation of MLH1, when occurs in an adenoma cell with BRAF oncogenic mutational activation, drives the pathway for MSI cancer by providing the cells with a mutator phenotype. AXIN2 inactivation may contribute to this tumorigenic pathway either by mutator phenotype driven frameshift mutations or by epigenetic deregulation contemporary with the unfolding of the mutator phenotype.
BMC Cancer 06/2014; 14(1):466. DOI:10.1186/1471-2407-14-466 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adenocarcinoma arising from an anal gland is extremely rare. Most anal canal cancers are squamous cell carcinoma, and adenocarcinoma is infrequently diagnosed. Diagnostic criteria and the standard treatment for adenocarcinoma of the anal canal have not been clearly defined, in part because of the rarity of this lesion.
An 84-year-old man who presented with a piece of tissue prolapsing from the anus. An incisional biopsy showed adenocarcinoma, and an abdomino-perineal resection was then performed. Cytokeratin 7 (CK7), cytokeratin 19 (CK19) stained positive in the specimen, suggesting that the tumor developed from an anal gland. The patient was discharged after surgery without any complications.
Exact diagnostic criteria for adenocarcinoma of the anal canal have not been previously described. In the present case, CK7 and CK19 were stained, and the tumor showed positivity for both of these markers, which is compatible with the staining patterns of anal gland origin cancer. Radical resection is recommended rather than local resection, because of the tumor's high recurrence rate. Some authors recommend combined modality treatment with preoperative or postoperative chemoradiotherapy because of the high rate of distant recurrence.
The preoperative diagnosis of adenocarcinoma arising from an anal gland is not easily established. However, it may be possible to suspect an anal glandular adenocarcinoma based on a meticulous physical examination, appropriate diagnostic studies and pathological findings on biopsy.
International Journal of Surgery Case Reports 03/2014; 5(5):234-236. DOI:10.1016/j.ijscr.2014.02.010
[Show abstract][Hide abstract] ABSTRACT: A randomized controlled trial to confirm the non-inferiority of laparoscopic surgery to open surgery in terms of overall survival was conducted, and short-term surgical outcomes are demonstrated.
The efficacy and safety outcome of laparoscopic surgery for clinical stages II/III colon cancer undergoing Japanese D3 dissection are still unclear.
Eligibility criteria included colon cancer; tumor located in the cecum, ascending, sigmoid, or rectosigmoid colon; T3 or T4 without involvement of other organs; N0-2; and M0. Patients were randomized preoperatively and underwent tumor resection with D3 dissection. Safety analyses were conducted by per-protocol set.
A total of 1057 patients were randomized between October 2004 and March 2009. By per-protocol set, 524 patients who underwent open surgery and 533 patients who underwent laparoscopic surgery were analyzed. D3 dissection was performed in 521 (99.4%) patients in the open surgery arm and 529 (99.2%) patients in the laparoscopic surgery arm. Conversion to open surgery was needed for 29 (5.4%) patients. Patients assigned to laparoscopic surgery had less blood loss (P < 0.001), although laparoscopic surgery lasted 52 minutes longer (P < 0.001). Laparoscopic surgery was associated with a shorter time to pass first flatus, decreased use of analgesics after 5 postoperative days, and a shorter hospital stay. Morbidity [14.3% (76/533) vs 22.3% (117/524), P < 0.001] was lower in the laparoscopic surgery arm.
Short-term surgical safety and clinical benefits of laparoscopic D3 dissection were demonstrated. The primary endpoint will be reported after the primary analysis, planned for 2014.
Annals of surgery 02/2014; 260(1). DOI:10.1097/SLA.0000000000000499 · 8.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Laparoscopic surgery for obstructive colorectal carcinoma is a controversial issue. Defining the obstructive carcinoma as colonoscopic impassability, the patients with obstructive carcinoma were managed according to the treatment algorithm, by which the indication of open or laparoscopic surgery was determined. As a result, 31 patients with obstructive colorectal carcinoma underwent laparoscopic surgery. The location of the tumor was in the right side in 10 patients and in the left in 21 patients. Preoperatively, all cases were managed by restriction of oral intake and/or decompression. Laparoscopic surgery was completed in 26 cases and colonic obstruction was the direct cause of the conversion in only 1 case. Regarding postoperative complications, there were 3 surgical site infections and 3 instances of postoperative prolonged ileus but no mortality. Oncologically, the primary tumor was completely resected in each case and lymph node harvest (26.6) was adequate.
[Show abstract][Hide abstract] ABSTRACT: A 71-year-old male patient was admitted to our hospital with dysphagia. Upper gastrointestinal endoscopy revealed severe stenosis between 26 and 36 cm from the incisors, and biopsy specimens taken from the stenotic lesion showed well-differentiated adenocarcinoma. A long-segment Barrett’s esophagus (LSBE) between 25 and 40 cm from the incisors was diagnosed. Subtotal esophagectomy with right thoracotomy was performed. Pleural tumor dissemination was seen 7 months later and was treated with chemotherapy. However, the patient died 14 months postoperatively. In Western countries, the incidence of adenocarcinoma in Barrett’s esophagus is high, but in Japan, the incidence is very low. In Japan, the incidence of short-segment Barrett’s esophagus is high, but that of LSBE is very low. We herein report esophageal adenocarcinoma in an exceedingly long LSBE of 15 cm.
[Show abstract][Hide abstract] ABSTRACT: The relationship between host factors and cancer cachexia was investigated. A single cell clone (clone 5 tumor) established from colon 26 adenocarcinoma by limiting dilution cell cloning methods was employed to eliminate the inoculation site-dependent differences in the composition of cell clones. Clone 5 tumor did not provoke manifestations of cancer cachexia when inoculated in subcutaneous tissue. However, when inoculated in the gastrocnemius muscle, the peritoneal cavity or the thoracic cavity of CD2F1 male mice, typical manifestations of cancer cachexia were observed in all groups of mice with intergroup variations. The blood levels of various cytokines, chemokines and hormones were increased but with wide intergroup variations. Analyses by stepwise multiple regression models revealed that serum interleukin-10 was the most significant factor associated with manifestations of cancer cachexia, suggesting the possible involvement of mechanisms similar to cancer patients suffering cancer cachexia. White blood cells, especially neutrophils, seemed to have some roles on the induction of cancer cachexia, because massive infiltrations and an increase in peripheral blood were observed in cachectic mice bearing clone 5 tumors. The amount of malonyl-CoA in liver correlated with manifestations of cancer cachexia, however the mRNA levels of spermidine/spermine N-1 acetyl transferase (SSAT) (of which overexpression has been shown to provoke manifestations similar to cancer cachexia) were not necessarily associated with cancer cachexia. These data suggest that the induction of cancer cachexia depends on the environment in which the tumor grows and that the infiltration of host immune cells into the tumor and the resultant increase in inflammation result in the production of cachectic factors, such as cytokines, leading to SSAT activation. Further, multiple factors likely mediate the mechanisms of cancer cachexia. Finally, this animal model was suitable for the investigation of the mechanisms involved in cachexia of cancer patients.
International Journal of Oncology 11/2013; 44(1). DOI:10.3892/ijo.2013.2180 · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High morbidity rates related to anastomotic leakage and other factors restrict the application of laparoscopic rectal excision. The aim of the present study was to assess the effect of left colonic artery (LCA) preservation on postoperative complications after laparoscopic rectal excision.
Data from 888 patients from 28 leading hospitals in Japan who underwent laparoscopic-assisted sphincter-preserving resection of middle and low rectal cancers between 1994 and 2006 were analyzed. The effects of LCA preservation were analyzed among all anterior resection (AR) cases (n = 888) and among AR cases with radical lymph node excision (n = 411).
Among all AR cases, the tumor size, number of lymph nodes collected with evidence of metastasis, TNM factor, and TNM staging were smaller in the LCA preservation group. Regarding complications, the rate of anastomotic leak was significantly higher in the LCA non-preservation group among all AR cases, as well as among AR cases with radical lymph node excision. Nevertheless, there was no difference in survival rate between LCA preservation group and non-preservation group, as measured by the Kaplan-Meier method.
Our data suggest that the preservation of the LCA in laparoscopic AR for middle and low rectal cancer is associated with lower anastomotic leak rates.
World Journal of Surgery 09/2013; 37(12). DOI:10.1007/s00268-013-2194-3 · 2.64 Impact Factor