Proximal bowel necrosis after high ligation of the inferior mesenteric artery in colorectal surgery.

BACKGROUND AND AIMS: High ligation of the inferior mesenteric artery may jeopardize blood supply to the proximal bowel. We undertook this study to review the clinical features and outcomes of patients who developed proximal bowel necrosis after high ligation of the inferior mesenteric artery, and to assess the incidence and the risk factors for this complication. MATERIALS AND METHODS: A retrospective analysis of patients undergoing high or low ligation for sigmoid colon and rectal cancer with a primary anastomosis between April 2004 and March 2009 was performed. Patient and tumor characteristics and the incidence of bowel necrosis were reviewed. RESULTS: Four hundred and nine patients were included to the analysis. Six out of 302 patients (2.0%) with high ligation developed proximal bowel necrosis, while the remaining 107 patients with low ligation did not suffer from this complication. All patients who developed proximal bowel necrosis underwent secondary surgery with resection of necrotic bowel. The pathological examination of the resected specimen revealed mucosal to transmural ischemic necrosis without the evidence of vascular thrombosis or embolic occlusion. Univariate analysis revealed that advanced age, cerebrovascular disease, and hypertension were significantly associated with proximal bowel necrosis. Multivariate analysis demonstrated that cerebrovascular disease was an independent predictor of this complication. Of these six patients, two died from associated complications. CONCLUSIONS: Proximal bowel necrosis after high ligation is potentially fatal, and this report provides a warning in clinical settings where high ligation is indicated. Further studies are warranted to evaluate its distinct relationship with high ligation and to clarify whether low ligation would be a safeguard.

DNA demethylation in normal colon tissue predicts predisposition to multiple cancers.

Some colon cancer (CC) patients present synchronous cancers at diagnosis and others develop metachronous neoplasms, but the risk factors are unclear for non-hereditary CC. We showed previously that global DNA demethylation increased with aging and correlated with genomic damage in CC, and we show now that preferentially associates to CCs with wild-type p53. This study aimed to elucidate the extent of DNA hypomethylation in patients with single and multiple CC, its relationship with aging, and its potential as predictive tool. We compared by real-time methylation-specific PCR the relative demethylation level (RDL) of long interspersed nucleotide element-1 (LINE-1) sequences in matched cancer tissues and non-cancerous colonic mucosa (NCM) from patients with single and multiple right-sided CCs. Although no RDL difference was found in NCM from single CC patients and healthy volunteers (P=0.5), there was more demethylation (higher RDL) in NCM from synchronous cancer patients (P=1.1 × 10(-5)) multiple CCs also were more demethylated than single CCs (P=0.0014). High NCM demethylation was predictive for metachronous neoplasms (P=0.003). In multivariate logistic regression analyses RDL was the only independent predictor for metachronous (P=0.02) and multiple (P=4.9 × 10(-5)) tumors. The higher LINE-1 demethylation in NCM from patients with multiple (synchronous and metachronous) tumors (P=9.6 × 10(-7)) was also very significant in patients with tumors without (P=3.8 × 10(-6)), but not with (P=0.16) microsatellite instability. NCM demethylation increased with aging in patients with single tumors, but decreased in those with multiple tumors. Moreover, the demethylation difference between patients with single vs multiple tumors appeared higher in younger (P=3.6 × 10(-4)) than in older (P=0.0016) patients. These results predict that LINE-1 hypomethylation in NCM can be used as an epigenetic predictive biomarker for multiple CC risk. The stronger association of demethylation in NCM with multiple CC risk from younger patients also suggests an inherited predisposition for the apparent field cancerization effect of somatic demethylation.

Laparoscopic adrenalectomy by general surgeons familiar with laparoscopic surgical skills: experiences of a single center.

INTRODUCTION: Laparoscopic adrenalectomy (LA) is still considered an advanced procedure requiring a high level of skills with potentially lethal pitfalls. We report our clinical outcomes of 50 cases of LA, and discuss whether a general surgeon is suitable to perform LA, and the effect of mentor-initiated training on improving outcomes. METHODS: Patients' age and sex, size of tumor, preoperative diagnosis, procedure details, intra- and postoperative complications, operation time, final histological diagnosis, and length of stay of 50 consecutive cases of LA were collected through a review of hospital charts. These cases were divided into two equal consecutive groups. The first 25 cases were named Group A, and the latter 25 cases were named Group B, and two groups were compared. RESULTS: Median operation time in Group B (110 min) was significantly shorter than that in Group A (125 min) (P=0.021). Mean postoperative hospital stay in Group B (7.0 ± 2.8 days) was significantly shorter than that in Group A (10.9 ± 8.8 days) (P=0.019). Only one case (Group B) of 50 LA (2%) required a conversion to open adrenalectomy because of failure to control bleeding during dissection. CONCLUSION: Under mentor-initiated training, general surgeons with experience of more than 50 cases of laparoscopic cholecystectomies can attain favorable clinical outcomes in LA.

The Endoscopic Surgical Skill Qualification System for gastric surgery in Japan.

INTRODUCTION: Laparoscopic surgery has been increasing in popularity in recent years. In 2004, the Japan Society for Endoscopic Surgery developed its Endoscopic Surgical Skill Qualification System (ESSQS) to assess surgeons. METHODS: To earn the ESSQS accreditation, applicants must submit an unedited operative video in which they perform either a distal gastrectomy or pylorus-preserving gastrectomy with lymph node dissection for gastric cancer. The videos are assessed by two separate judges based on detailed criteria for common and procedure-specific technical-grade slips. Common criteria from all fields of gastrointestinal and general surgery are used to evaluate the basic laparoscopic surgical skills and autonomy of the operator. The target organ determines the procedure-specific criteria are set to assess whether or not adequate oncological clearance has been achieved. RESULTS: Between 2004 and 2009, 154 (44.6%) out of 345 applicant surgeons assessed under the ESSQS for gastric surgery have been accredited. Interrater agreement was acceptable and ranged between 0.21 and 0.59. CONCLUSION: The ESSQS system may facilitate improvement in surgical technique and the standardization of laparoscopic surgery in Japan.

Distribution of the first metastatic lymph node in colon cancer and its clinical significance.

INTRODUCTION: The pattern of distribution of lymph node metastasis in resected specimens of colon cancer has been rarely reported in the English literature. The aim of this study was to determine the location of the first metastatic lymph node, giving insight into the drainage pattern of colon cancer lymphatics. METHOD: All lymph nodes in the mesentery of the resected specimen were carefully harvested and their precise locations documented. Patients with a single metastatic node in the resected specimen were included in the study. RESULTS: Ninety-three patients with only one metastatic lymph node found on histology were studied. The mean number of lymph nodes per specimen was 22.3 (range: 8-72). The patients' first metastatic node was not directly below the tumour in 48% of cases. The first metastatic node was found in the region either along the feeding vessels (skipping the pericolic nodes) or in the pericolic area outside 5 cm on either side of the tumour edge in 18% of cases. No factors were found to be predictive for lymph node metastasis occurring elsewhere other than in the pericolic region just below the tumour. CONCLUSION: Although there has been recent resurgence of interest in using sentinel node biopsy to limit surgical dissection to facilitate minimally access and natural orifice surgery, the present study is a warning that this may compromise oncological clearance. Radical surgery should remain standard practice for colorectal cancer.

Multimedia article. Transanal endoscopic resection of the rectum with high ligation on a swine model--a novel type of natural orifice endoscopic surgery.

We present the video of a transanal radical resection of the rectum on a swine model (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A4). The equipment used included simple instruments used in perianal surgery and a flexible endoscope with diathermy. The equipment and skill set required for this technique is easily accessible and reproduced. The potential exists to further develop this procedure with the ultimate aim of performing an incisionless and painless radical resection of the rectum in humans.

Sushi-roll wrap of Seprafilm for ileostomy limbs facilitates ileostomy closure.

BACKGROUND: Sodium hyaluronate and carboxymethylcellulose membrane (Seprafilm) reduced postoperative intraabdominal adhesion. In this study, we examined whether Seprafilm reduces operative difficulties in ileostomy closure. PATIENTS AND METHODS: During the creation of the ileostomy, Seprafilm was cut in half and used to wrap both the ileum and mesentery. Patients who underwent ileostomy closure before February 2008 (without Seprafilm, Group T, n = 18) and after March (with Seprafilm, Group S, n = 18) were enrolled in this study. All operations were performed by surgical residents. Operative time and perioperative complications were analyzed. RESULTS: The mean operative time of Group S (106.88 min) was significantly less than that of Group T (120.6 min). The amount of intraoperative bleeding in Groups S and T was not significantly different and there were no major complications. CONCLUSION: Seprafilm applied to the two limbs of the ileostomy and mesentery facilitate ileostomy closure done by non-expert surgeons.

Colorectal surgery in octogenarian patients--outcomes and predictors of morbidity.

INTRODUCTION: Surgery for elderly patients pose a constant challenge. This study aims to review the outcome and find predictors of adverse outcome in octogenarians undergoing major colorectal resection for cancer. METHODS: A review of 121 octogenarians who underwent colorectal cancer surgery between September 1992 and May 2008 was performed. Comorbidities were quantified using the weighted Charlson Comorbidity Index and ASA classification. CR-POSSUM scores and ACPGBI scores and the predicted mortality rates were calculated. Outcome measures were morbidity rates and 30-day mortality rates. RESULTS: The patients had a mean age of 83.5 years (range, 80-99). The mean index of comorbidity was 3.1 (2-7) and 12.5% of patients were classified ASA III and above. The mean predicted mortality rate based on CR-POSSUM and ACPGBI scoring models were 11.2% and 5.4% respectively. The overall observed morbidity rate was 30.7% and 30-day mortality was 1.6. Factors found on bivariate analysis to be significantly associated with an increased risk of morbidity were tumor presenting with complication, comorbid coronary heart disease, serum urea levels, ASA classification > or =3 and comorbidity index 3 of 5 > or = 5. Multivariate analysis revealed the latter two factors to be independent predictors of morbidity. CONCLUSION: Octogenarians undergoing major colorectal resection have an acceptable perioperative morbidity and mortality rate and survival rate and should not be denied surgery based on age alone. Comorbidity index scores and ASA scores are useful tools to identify poor risk patients.

Frequent reduced expression of alpha-1B-adrenergic receptor caused by aberrant promoter methylation in gastric cancers.

Recent studies have suggested that epigenetic inactivation of tumour-related genes by promoter methylation participates in the development of gastric cancer. We newly identified the frequently aberrant promoter methylation of alpha-1B-adrenergic receptor (ADRA1B) in colorectal cancer by methylation-sensitive representational difference analysis (MS-RDA) and examined the methylation status of the ADRA1B promoter in 34 paired samples of colorectal cancer and surrounding epithelial tissue, and 34 paired samples of gastric cancer and surrounding epithelial tissue. In colorectal cancers, only four of 34 (11.8%) tumours showed ADRA1B promoter methylation. In contrast, ADRA1B promoter methylation was detected in 24 of 34 (70.6%) gastric cancers and in 14 of 34 (41.2%) surrounding epithelial tissues. The frequency of ADRA1B promoter methylation was higher in gastric epithelial tissues with intestinal metaplasia (41.6%) than in those without intestinal metaplasia (25.0%). Reverse transcription-PCR detected reduced ADRA1B expression in 12 of 18 (66.7%) gastric cancers, and its promoter methylation was detected in 11 of these 12 (91.7%) gastric cancers with reduced ADRA1B expression. Thus, ADRA1B promoter is frequently methylated in gastric cancer. Our results suggest that the ADRA1B gene is an important tumour-related gene frequently involved in the development and progression of gastric cancer.

Promoter hypermethylation of tumor-related genes in sporadic colorectal cancer in young patients.

Sporadic colorectal cancer (SCRC) occurring in young patients represent a subset with a higher proportion of advanced tumors and a poor prognosis, however, the genetic basis of SCRCs has not yet been sufficiently studied. We assigned 16 SCRC patients aged 40 years or less to group 1, and 30 SCRCs patients aged 65 years or more to group 2. The methylation status in the promoter of 7 tumor suppressor genes regarding these two groups was then examined. The average number of hypermethylated tumor-related genes per sample in group 1 was 1.50 +/- 0.07, which was significantly lower than that in group 2 of 2.73 +/- 1.24 (p = 0.0040). The frequencies of the promoter hypermethylation of hMLH1, p15INK4b, p16INK4a, and RASSF1A in group 1 were 12.5%, 12.5%, 12.5%, 6.3%, and 0.0%, which were substantially less frequent than those same rates observed in group 2. In contrast, the frequencies of the promoter hypermethylation of APC, MGMT, p14ARF, in group 1 were 43.8%, 37.5%, and 31.3%, which were as frequent as those seen in group 2. The promoter hypermethylation of APC, MGMT, and pl4ARF is therefore considered to be closely related to the development of SCRCs in young patients, regardless of aging.

Frequent involvement of ras-signalling pathways in both polypoid-type and flat-type early-stage colorectal cancers.

The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways, but the roles of their aberrations in colorectal carcinogenesis remain unclear. The authors studied mutations of the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously showed any combination of K-ras mutations, BRAF mutations, and RASSF1A promoter methylation. Three of the 73 tumors (4.1%) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenoma or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4%), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.

A multicenter study on laparoscopic surgery for colorectal cancer in Japan.

BACKGROUND: Laparoscopic colectomy for malignant disease technically is feasible but not widely accepted because there are no large-series studies or data on long-term outcomes. A retrospective, multicenter study investigating a large series of patients was conducted in Japan to evaluate preliminary long-term results of laparoscopic surgery for colorectal cancer. METHODS: The study group comprised 2,036 patients who underwent laparoscopic colorectal resection April 1993 to August 2002 in 12 participating surgical units (Japanese Laparoscopic Surgery Study Group). RESULTS: Of the 1,495 patients with colon cancer, 781 (59%) had International Union Against Cancer (UICC) stage I, 248 (19%) had stage II, and 284 (22%) had stage III disease. Cancer recurred for 61 (4.1%) of 1,367 curatively treated patients (median follow-up period, 32 months; range, 6-125 months). The 5-year survival rate was 96.7% for stage I, 94.8% for stage II, and 79.6% for stage III disease. Of the 541 patients with rectal cancer, 220 (56%) had stage I, 62 had (16%) stage II, and 108 (28%) had stage III disease. Cancer recurred for 30 (5.6%) of 476 curatively treated patients (median follow-up period, 25 months; range 6-102 months). The 5-year survival rate was 95.2% for stage I, 85.2% for stage II, and 80.8% for stage III disease. CONCLUSIONS: The findings indicate that laparoscopic surgery for colorectal cancer yields an oncological outcome as good as that reported for conventional open surgery in the Japanese Registry for all disease stages.

Natural history of a patient with malignant nonfunctioning islet cell tumor associated with unresectable multiple liver metastases.

Islet cell tumors of the pancreas are uncommon. Approximately 15% of islet cell tumors are nonfunctioning and have a higher malignancy rate than their functioning counterparts. Though, because of the rarity of malignant nonfunctioning islet cell tumors, the natural history of a patient with this tumor has not been clearly defined. We describe a young patient with unresectable malignant nonfunctioning islet cell tumor associated with multiple liver metastases. He was treated with palliative therapies to improve his quality of life, but did not undergo surgical removal of tumors or systemic chemotherapy. He survived for 46 months since laparotomy for histological diagnosis. Our findings may represent the natural history of patients with unresectable malignant nonfunctioning islet cell tumor, and suggest that palliative therapy may contribute not only to the improvement of a patients' quality of life but also the prolongation of survival.

Flat and depressed lesions of the colon and rectum: Pathogenesis and clinical management.

INTRODUCTION: It is not clear whether flat lesions play a role in the pathogenesis of colorectal carcinoma. Flat lesions are being increasingly recognised with new colonoscopic techniques. MATERIALS AND METHODS: A total of 10,939 consecutive colonoscopies were performed over a 9-year period. After bowel preparation with polyethylene glycol electrolyte lavage solution, high-resolution video colonoscopy and indigocarmine spraying were performed to detect flat lesions. All lesions suggesting neoplastic change were removed by polypectomy or surgery. Cancers invading beyond the submucosal layer were excluded from this analysis. The gross appearance of flat-type lesions was classified as flat elevated type or flat depressed type based on the presence or absence of central depression. RESULTS: A total of 5408 neoplastic lesions were index lesions, including 5035 adenomas and 373 carcinomas (124 with submucosal invasion). The prevalence of flat depressed and flat elevated lesions were 2.8% and 18.1%, respectively. Submucosal invasion rates were 17.1% in the flat depressed, 0.8% in the flat elevated, 1.6% in the sessile, 4.0% in pedunculated lesions and 9.3% in creeping lesions. The submucosal invasion rate in the flat depressed lesions was significantly higher than in any others, except for creeping lesions (P = 0.06). The percentage of flat elevated and flat depressed carcinomas among all carcinomas invading the submucosa was 6.5% and 21.0%, respectively. CONCLUSION: Flat lesions were common during routine colonoscopy. One-quarter of colorectal cancers may be derived from flat lesions. Training in dye spray technique may result in a higher detection rate of flat colonic lesions.

Runme Shaw Memorial Lecture 2002. Modern management of colorectal polyps: Are they all premalignant?

There are various types of polyps in the colon and rectum. Most colorectal polyps in the colon and rectum are either adenomas or hyperplastic polyps. In general, adenomas are considered to be premalignant. Adenoma-carcinoma sequence is an established theory of carcinogenesis in the large bowel in Western countries. However, small adenomas are ubiquitous phenomena, and it is questionable whether they are actually precancerous. Most small adenomas did not become larger in our colonoscopic follow-up study of small adenomas measuring 5 mm or less. It was considered safe to leave such small adenomas behind, particularly in a situation in which follow-up examination is periodically performed, such as in patients who have undergone colorectal cancer surgery before. In Japan, small flat carcinomas have been reported as an important precursor of advanced colorectal carcinoma. They are also found in Western population. The malignancy rate of small flat and depressed lesions was significantly higher than that of polypoid lesions. Although small flat carcinomas are less frequently seen than polypoid-type carcinomas in the early stages, they are considered to be an important precursor of advanced colorectal cancer.