INTRODUCTION: The UK Medical Research Council CLASICC trial assessed the safety and efficacy of laparoscopically assisted surgery in comparison with open surgery for colorectal cancer. The results of the 5-year follow-up analysis are presented. METHODS: Five-year outcomes were analysed and included overall and disease-free survival, and local, distant and wound/port-site recurrences. Two exploratory analyses were performed to evaluate the effect of age (70 years or less, or more than 70 years) on overall survival between the two groups, and the effect of the learning curve. RESULTS: No differences were found between laparoscopically assisted and open surgery in terms of overall survival, disease-free survival, and local and distant recurrence. Wound/port-site recurrence rates in the laparoscopic arm remained stable at 2.4 per cent. Conversion to open operation was associated with significantly worse overall but not disease-free survival, which was most marked in the early follow-up period. The effect of surgery did not differ between the age groups, and surgical experience did not impact on the 5-year results. CONCLUSION: The 5-year analyses confirm the oncological safety of laparoscopic surgery for both colonic and rectal cancer. The use of laparoscopic surgery to maximize short-term outcomes does not compromise the long-term oncological results. REGISTRATION NUMBER: ISRCTN74883561 (http://www.controlled-trials.com).

Five‐year follow‐up of the Medical Research Council CLASICC trial of laparoscopically assisted versus open surgery for colorectal cancer

Background The risk factors for anastomotic leak (AL) after anterior resection have been evaluated in several studies and remain controversial as the findings are often inconsistent or inconclusive Objective To analyze the risk factors for AL after anterior resection in patients with rectal cancer Design Retrospective analysis Setting The Nationwide Inpatient Sample 2006 to 2009 Patients A total of 72 055 patients with rectal cancer who underwent elective anterior resection Main Outcome Measures To build a predictive model for AL using demographic characteristics and preadmission comorbidities, the lasso algorithm for logistic regression was used to select variables most predictive of AL Results The AL rate was 1368% The AL group had higher mortality vs the non-AL group (178% vs 074%) Hospital length of stay and cost were significantly higher in the AL group Laparoscopic and open resections with a diverting stoma had a higher incidence of AL than those without a stoma (1597% vs 1325%) Multivariate analysis revealed that weight loss and malnutrition, fluid and electrolyte disorders, male sex, and stoma placement were associated with a higher risk of AL The use of laparoscopy was associated with a lower risk of AL Postoperative ileus, wound infection, respiratory/renal failure, urinary tract infection, pneumonia, deep vein thrombosis, and myocardial infarction were independently associated with AL Conclusions Anastomotic leak after anterior resection increased mortality rates and health care costs Weight loss and malnutrition, fluid and electrolyte disorders, male sex, and stoma placement independently increased the risk of leak Laparoscopy independently decreased the risk of leak Further studies are needed to delineate the significance of these findings

https://jamanetwork.com/journals/jamasurgery/articlepdf/1358216/sps120007_65_71.pdf

Risk Factors for Anastomotic Leakage After Anterior Resection for Rectal Cancer

Objective Several large randomized controlled trials on laparoscopic resection for colon and rectosigmoid cancer have recently been published. There is a need to provide an up-to-date systematic review in this subject.



Methods  A literature search of all published randomized trials in English between January 1991 and September 2005 was obtained, from Ovid MEDLINE, EMBASE, CINAHL, and All EBM Reviews (Cochrane Central Register of Controlled Trial, Cochrane Database of Systemic Review, and Database of Abstracts of Reviews of Effects), including e-links to the related articles. Two independent assessors reviewed the trials using a standardized protocol. Where means and standard deviations were available, meta-analysis was performed using the Forest plot review. Studies where medians and ranges were presented were separately analysed.



Results  A total of 17 randomized controlled trials with 4013 procedures were reviewed. The conversion rate varied widely between studies and was lowest in single-Centre trials. There were no significant differences in overall and surgical complication rate, anastomotic leak rate, re-operation rate and oncological clearance. However, laparoscopic resection has a significantly lower peri-operative mortality (odds ratio 0.33; P = 0.005), lower wound complications (odds ratio 0.65; P = 0.01), less blood loss (weighted mean difference 0.11 l; P < 0.00001) and reduced postoperative pain scores by 12.6% with reduction of requirements for narcotic analgesia by 30.7%. After laparoscopic surgery, patients passed flatus 38.8% earlier (weighted mean difference 27.6 h; P < 0.00001) and had bowel movement 21.0% earlier (weighted mean difference 23.9 h; P < 0.00001) and resumed oral diet 28.3% sooner than patients in the open group (weighted mean difference 27.3 h; P < 0.00001). Patients were discharged 19.1% earlier after laparoscopic surgery than open surgery (weighted mean difference 1.7 days; P < 0.00001). Laparoscopic resection took 28.7% longer (weighted mean difference 40.1 min; P < 0.00001) to perform.



Conclusions  Laparoscopic resection for colon and rectosigmoid cancer is feasible, safe and has many short-term benefits.

Systematic review on the short-term outcome of laparoscopic resection for colon and rectosigmoid cancer.

Every colorectal surgeon during his or her career is faced with anastomotic leakage (AL); one of the most dreaded complications following any type of gastrointestinal anastomosis due to increased risk of morbidity, mortality, overall impact on functional and oncologic outcome and drainage on hospital resources. In order to understand and give an overview of the AL risk factors in laparoscopic colorectal surgery, we carried out a careful review of the existing literature on this topic and found several different definitions of AL which leads us to believe that the lack of a consensual, standard definition can partly explain the considerable variations in reported rates of AL in clinical studies. Colorectal leak rates have been found to vary depending on the anatomic location of the anastomosis with reported incidence rates ranging from 0 to 20%, while the laparoscopic approach to colorectal resections has not yet been associated with a significant reduction in AL incidence. As well, numerous risk factors, though identified, lack unanimous recognition amongst researchers. For example, the majority of papers describe the risk factors for left-sided anastomosis, the principal risk being male sex and lower anastomosis, while little data exists defining AL risk factors in a right colectomy. Also, gut microbioma is gaining an emerging role as potential risk factor for leakage.

Predictive factors for anastomotic leakage after laparoscopic colorectal surgery.

The purpose of this study was to evaluate the impact of laparoscopic colorectal resection on short-term postoperative outcome in elderly patients. A series of 535 patients with colorectal disease who had been randomly assigned to laparoscopic (n = 268) or open (n = 267) resection was analyzed. A total of 201 patients (37.6 percent) were elderly (aged 70 years or older) and 334 patients (62.4 percent) were younger than aged 70 years. Follow-up for postoperative morbidity was performed for 30 days after hospital discharge. Elderly patients had a higher American Society of Anesthesiologists score compared with younger patients in both the laparoscopic and open groups (P = 0.0001). In the open group, elderly patients had higher morbidity rate (37.5 vs. 23.9 percent; P = 0.02) and longer length of hospital stay (13 vs. 10.6; P = 0.007) compared with younger patients. In the laparoscopic group, morbidity rate (20.2 vs. 15.1 percent) and length of hospital stay (9.5 vs. 9.1) were similar in elderly and younger patients. In elderly patients, the laparoscopy-reduced morbidity rate (20.2 vs. 37.5 percent; P = 0.01) and length of hospital stay (9.5 vs. 13; P = 0.001) compared to the open approach. In younger patients, the advantages of the laparoscopic approach on morbidity rate (15.1 vs. 23.9 percent; P = 0.06) and length of stay (9.1 vs. 10.6; P = 0.004) were less pronounced. Laparoscopy improved short-term postoperative outcome more in elderly than in younger patients. Advanced age was associated with higher morbidity and longer length of stay only in patients who underwent open colorectal surgery.

Benefits of Laparoscopic Colorectal Resection Are More Pronounced in Elderly Patients

AIM: Laparoscopic surgery, especially laparoscopic rectal surgery, for colorectal cancer has been developed considerably. However, due to relatively complicated anatomy and high requirements for surgery techniques, laparoscopic right colectomy develops relatively slowly. This study was designed to compare the outcomes of laparoscopic right hemicolectomy (LRH) with open right hemicolectomy (ORH) in the treatment of colon carcinoma.

METHODS: Between September 2000 and February 2003, 30 patients with colon cancer who underwent LRH were compared with 34 controls treated by ORH in the same period. All patients were evaluated with respect to surgery-related complications, postoperative recovery, recurrence and metastasis rate, cost-effectiveness and survival.

RESULTS: Among 30 LRH, 2 (6.7%) were converted to open procedure. No significant differences were observed in terms of mean operation time, blood loss, post-operative complications, and hospital cost between LRH and ORH groups. Mean time for bowel movement, hospital stay, and time to resume early activity in the LRH group were significantly shorter than those in the ORH group (2.24±0.56 vs 3.25±1.29 d, 13.94±6.5 vs 18.25±5.96 d, 3.94±1.64 vs 5.45±1.82 d respectively, P<0.05). As to the lymph node yield, the specimen length and total cost for operation and drugs, there was no significant difference between the two groups. Local recurrence rate and metachronous metastasis rate had no marked difference between the two groups. Cumulative survival probability at 40 mo in LRH group (76.50%) was not obviously different compared to the ORH group (74.04%).

CONCLUSION: LRH in patients with colon cancer has statistically and clinically significant advantages over ORH. Thus, LRH can be regarded as a safe and effective procedure.

Laparoscopic versus open right hemicolectomy with curative intent for colon carcinoma

Background: Up to now, there is still no ideal tumor marker in early diagnosis and effective monitoring, especially for surgical resection of colorectal cancer (CRC). The aim of the present study was to evaluate the application of urinary normal and modified nucleosides in diagnosis and surgery monitoring of CRC.

Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring.

AIM: To analyze the clinical manifestations and risk factors of complications in laparoscopic low anterior resection (LAR) for rectal cancer patients.

METHODS: A series of 132 consecutive patients who received laparoscopic LAR for rectal cancer in our center were included. The etiology, diagnosis, treatment and prevention of rectal cancer were studied among the patients with surgery-related complications using both univariate and multivariate regression analysis.

RESULTS: No conversion to open surgery was observed and 5 cases converted to hand-assisted laparoscopic operation. The overall morbidity rate was 20.5%. Complications occurred during the operation in 7 patients (5.3%), within 30 postoperative days in 24 patients (18.2%), and within 3 mo in 2 patients (1.5%). The most significant complications were anastomotic leakage (9.1%) and anastomotic hemorrhage (5.3%). Size and location of tumor, pathological staging and preoperative nutrition were significant factors associated with LAR complications, while gender, age and pathological type showed no relevance. Binary logistics regression showed that the size and location of tumor, and pathological staging were independent factors of laparoscopic LAR. All the complications were treated during their onset of clinical manifestations by interventional or conservative therapy.

CONCLUSION: Anastomotic leakage is a major complication in laparoscopic LAR. The complications may be associated with tumor size and site, and pathological stage. Interventional therapies are of value in the management of laparoscopic LAR complications.

Laparoscopic low anterior resection for rectal carcinoma: Complications and management in 132 consecutive patients

Background and aims: Elderly patients have a high incidence of colorectal cancer, which may be associated with increased morbidity and mortality due to complex comorbidity and diminished cardiopulmonary reserves. The aims of this study were to compare the outcomes of laparoscopic colorectal cancer surgery with those observed in traditional open surgery in patients aged over 70 years. Methods: Between January 2003 and October 2004, 51 patients aged over 70 years with colorectal cancer, who underwent laparoscopic surgery (LAP group), were evaluated and compared with 102 controls (also over 70 years old) treated by traditional open surgery (OPEN group) in the same period. All patients were evaluated with respect to the American Society of Anesthesiologists (ASA) classification, surgery-related complications, and postoperative recovery. Results: No surgery-related death was observed in the LAP group, whereas two deaths occurred in the OPEN group for severe post-operative pulmonary infection and anastomotic leak, respectively. No pneumoperitoneum-related complications were observed in the LAP group; 2 (3.9%) patients required conversion to open surgery, because of the unexpectedly bulky tumor and severe adhesions in the abdominal cavity. With the increase in patients’ age, increased ASA classification was observed. No significant differences were observed in gender, Dukes’ staging or types of procedures between LAP and OPEN groups. The overall morbidity in the LAP group was significantly less than that of the OPEN group [17.6% (9/51) vs 37.3% (38/102), p=0.013]. Mean blood loss, time to flatus passage, and time to semi-liquid diet in the LAP group were significantly shorter than those of the OPEN group (90.7±49.9 vs 150.3±108.7ml, 2.4±1.2 vs 3.5±2.9 d, 5.0±1.8 vs 5.9±1.2 d, respectively, p<0.05). No significant differences were observed in terms of mean operation time or hospital stay between LAP and OPEN groups. Conclusion: Laparoscopic colorectal cancer surgery in elderly patients with colon cancer has clinically significant advantages over traditional open surgery, and appears to be the ideal surgical choice for the elderly.

Clinical advantages of laparoscopic colorectal cancer surgery in the elderly.

Background and Aim:  Recent evidence suggests that the human kallikrein 10 (KLK10) gene is differentially regulated in endocrine-related tumors and has potential as diagnostic and/or prognostic marker; however, KLK10 expression has never been investigated in gastrointestinal cancers. The aims of this study were to demonstrate expression and single nucleotide polymorphisms of KLK10 in colorectal cancer (CRC) and gastric cancer (GC), and to correlate the relative KLK10 expression level with clinicopathological factors of CRC and GC.



Methods:  Between March 2004 and January 2005, 63 patients with histologically confirmed CRC and 36 with GC were recruited into the study. Using quantitative real-time (qRT) RT–PCR and Western blot, KLK10 expression in tumor and non-tumor colorectal and gastric tissues was determined at the mRNA and protein levels. KLK10 protein was localized by immunohistochemistry. The KLK10 genomic DNA from 16 cases of paired normal/cancerous colorectal tissues was PCR-amplified and examined for single nucleotide polymorphisms by direct sequencing.



Results:  KLK10 mRNA expression was detected by qRT in 61 of 63 (96.8%) CRC specimens and in all GC specimens. KLK10 expression was much higher in tumor tissue than in the corresponding normal mucosal tissue at the mRNA and protein levels (P < 0.01). The KLK10 mRNA expression level significantly correlated with lymphatic invasion (P = 0.034) and clinical stage of CRC (P = 0.025). The KLK10 mRNA expression level significantly correlated with the depth of GC invasion (P = 0.018), clinical stage (P = 0.045), patient sex (P = 0.027) and Lauren type of gastric cancer (P = 0.028). No mutations or polymorphisms were detected in exon 1, 2 and 5 of KLK10 gene in CRC. Single nucleotide polymorphisms were identified in codon 50 of exon 3, GCC (alanine) to TCC (serine). The genetic changes of exon 4 were located at codon 106 [GGC (glysine) to GGA (glysine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and codon 149 [CCG (proline) to CTG (leucine)]. All were identical in tumor and corresponding normal tissue DNA from the same individuals.



Conclusion:  KLK10 expression is up-regulated in CRC and GC and higher expression of KLK10 closely correlates with advanced disease stage, which predicts a poorer prognosis; however, further follow-up study is needed.

Jian-Wen Li

Papers

Laparoscopic versus open right hemicolectomy with curative intent for colon carcinoma

Normal and modified urinary nucleosides represent novel biomarkers for colorectal cancer diagnosis and surgery monitoring.

Laparoscopic low anterior resection for rectal carcinoma: Complications and management in 132 consecutive patients

Clinical advantages of laparoscopic colorectal cancer surgery in the elderly.

Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.