Wim C. J. Hop

Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial.

BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable. The multicentre COLOR (COlon cancer Laparoscopic or Open Resection) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon. METHODS 627 patients were randomly assigned to laparoscopic surgery and 621 patients to open surgery. The primary endpoint was cancer-free survival 3 years after surgery. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, metastasis, overall survival, and blood loss during surgery. Analysis was by intention to treat. Here, clinical characteristics, operative findings, and postoperative outcome are reported. FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection (median 100 mL [range 0-2700] vs 175 mL [0-2000], p<0.0001), although laparoscopic surgery lasted 30 min longer than did open surgery (p<0.0001). Conversion to open surgery was needed for 91 (17%) patients undergoing the laparoscopic procedure. Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups. Laparoscopic colectomy was associated with earlier recovery of bowel function (p<0.0001), need for fewer analgesics, and with a shorter hospital stay (p<0.0001) compared with open colectomy. Morbidity and mortality 28 days after colectomy did not differ between groups. INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right, left, and sigmoid colon.

Long-term follow-up of a randomized controlled trial of suture versus mesh repair of incisional hernia.

Objective:The objective of this study was to determine the best treatment of incisional hernia, taking into account recurrence, complications, discomfort, cosmetic result, and patient satisfaction. Background:Long-term results of incisional hernia repair are lacking. Retrospective studies and the midterm results of this study indicate that mesh repair is superior to suture repair. However, many surgeons are still performing suture repair. Methods:Between 1992 and 1998, a multicenter trial was performed, in which 181 eligible patients with a primary or first-time recurrent midline incisional hernia were randomly assigned to suture or mesh repair. In 2003, follow-up was updated. Results:Median follow-up was 75 months for suture repair and 81 months for mesh repair patients. The 10-year cumulative rate of recurrence was 63% for suture repair and 32% for mesh repair (P < 0.001). Abdominal aneurysm (P = 0.01) and wound infection (P = 0.02) were identified as independent risk factors for recurrence. In patients with small incisional hernias, the recurrence rates were 67% after suture repair and 17% after mesh repair (P = 0.003). One hundred twenty-six patients completed long-term follow-up (median follow-up 98 months). In the mesh repair group, 17% suffered a complication, compared with 8% in the suture repair group (P = 0.17). Abdominal pain was more frequent in suture repair patients (P = 0.01), but there was no difference in scar pain, cosmetic result, and patient satisfaction. Conclusions:Mesh repair results in a lower recurrence rate and less abdominal pain and does not result in more complications than suture repair. Suture repair of incisional hernia should be abandoned.

Survival after laparoscopic surgery versus open surgery for colon cancer : long-term outcome of a randomised clinical trial

BACKGROUND Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. METHODS Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. FINDINGS During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). INTERPRETATION Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial

BACKGROUND Laparoscopic surgery as an alternative to open surgery in patients with rectal cancer has not yet been shown to be oncologically safe. The aim in the COlorectal cancer Laparoscopic or Open Resection (COLOR II) trial was to compare laparoscopic and open surgery in patients with rectal cancer. METHODS A non-inferiority phase 3 trial was undertaken at 30 centres and hospitals in eight countries. Patients (aged ≥18 years) with rectal cancer within 15 cm from the anal verge without evidence of distant metastases were randomly assigned to either laparoscopic or open surgery in a 2:1 ratio, stratified by centre, location of tumour, and preoperative radiotherapy. The study was not masked. Secondary (short-term) outcomes-including operative findings, complications, mortality, and results at pathological examination-are reported here. Analysis was by modified intention to treat, excluding those patients with post-randomisation exclusion criteria and for whom data were not available. This study is registered with ClinicalTrials.gov, number NCT00297791. FINDINGS The study was undertaken between Jan 20, 2004, and May 4, 2010. 1103 patients were randomly assigned to the laparoscopic (n=739) and open surgery groups (n=364), and 1044 were eligible for analyses (699 and 345, respectively). Patients in the laparoscopic surgery group lost less blood than did those in the open surgery group (median 200 mL [IQR 100-400] vs 400 mL [200-700], p<0·0001); however, laparoscopic procedures took longer (240 min [184-300] vs 188 min [150-240]; p<0·0001). In the laparoscopic surgery group, bowel function returned sooner (2·0 days [1·0-3·0] vs 3·0 days [2·0-4·0]; p<0·0001) and hospital stay was shorter (8·0 days [6·0-13·0] vs 9·0 days [7·0-14·0]; p=0·036). Macroscopically, completeness of the resection was not different between groups (589 [88%] of 666 vs 303 [92%] of 331; p=0·250). Positive circumferential resection margin (<2 mm) was noted in 56 (10%) of 588 patients in the laparoscopic surgery group and 30 (10%) of 300 in the open surgery group (p=0·850). Median tumour distance to distal resection margin did not differ significantly between the groups (3·0 cm [IQR 2·0-4·8] vs 3·0 cm [1·8-5·0], respectively; p=0·676). In the laparoscopic and open surgery groups, morbidity (278 [40%] of 697 vs 128 [37%] of 345, respectively; p=0·424) and mortality (eight [1%] of 699 vs six [2%] of 345, respectively; p=0·409) within 28 days after surgery were similar. INTERPRETATION In selected patients with rectal cancer treated by skilled surgeons, laparoscopic surgery resulted in similar safety, resection margins, and completeness of resection to that of open surgery, and recovery was improved after laparoscopic surgery. Results for the primary endpoint-locoregional recurrence-are expected by the end of 2013. FUNDING Ethicon Endo-Surgery Europe, Swedish Cancer Foundation, West Gothia Region, Sahlgrenska University Hospital.

Immunophenotyping of blood lymphocytes in childhood: Reference values for lymphocyte subpopulations

OBJECTIVE Immunophenotyping of blood lymphocytes is an important tool in the diagnosis of hematologic and immunologic disorders. Because of maturation and expansion of the immune system in the first years of life, the relative and the absolute size of lymphocyte subpopulations vary during childhood. Therefore we wished to obtain reference values for the relative and the absolute size of all relevant blood lymphocyte subpopulations in childhood. STUDY DESIGN We used the lysed whole blood method for analysis of lymphocyte subpopulations in 429 blood samples from neonates (n = 20), healthy children (n = 358), and adults (n = 51). The following age groups were used: 1 week to 2 months (n = 13), 2 to 5 months (n = 46), 5 to 9 months (n = 105), 9 to 15 months (n = 70), 15 to 24 months (n = 33), 2 to 5 years (n = 33), 5 to 10 years (n = 35), and 10 to 16 years (n = 23). RESULTS Our results show that the absolute number of CD19+ B lymphocytes increases twofold immediately after birth, remains stable until 2 years of age, and subsequently gradually decreases 6.5-fold from 2 years to adult age. The CD3+ T lymphocytes increase 1.5-fold immediately after birth and decrease threefold from 2 years to adult age. The absolute size of the CD3+/CD4+ T-lymphocyte subpopulation follows the same pattern as the total CD3+ population, but the CD3+/CD8+ T lymphocytes remain stable from birth up to 2 years of age, followed by a gradual threefold decrease toward adult levels. In contrast to B and T lymphocytes, the absolute number of natural killer cells decreases almost threefold in the first 2 months of life and remains stable thereafter. Our study also showed that changes in the absolute size of lymphocyte subpopulations are not always consistent with changes in their relative size. This demonstrates that the relative counts of lymphocyte subsets do not reflect their actual size and are therefore of limited value. CONCLUSION On the basis of this study we strongly recommend that immunophenotyping of blood lymphocytes for the diagnosis of hematologic and immunologic disorders be based on the absolute rather than on the relative size of lymphocyte subpopulations. Our data can be used as age-matched reference values for blood lymphocyte immunophenotyping.

Blood Transfusions and Prognosis in Colorectal Cancer

BACKGROUND Blood transfusions may adversely affect the prognosis of patients treated surgically for cancer, although definite proof of this adverse effect has not been reported. METHODS We carried out a randomized trial to investigate whether the prognosis in patients with colorectal cancer would be improved by a program of autologous blood transfusion as compared with the current practice of allogeneic transfusion. Patients in the autologous-transfusion group were required to donate two units of blood before surgery. RESULTS A total of 475 patients were evaluated. We found no significant difference in prognosis between the allogeneic-transfusion group (236 patients) and the autologous-transfusion group (239 patients); colorectal cancer-specific survival rates at four years were 67 percent and 62 percent, respectively (P = 0.39). Among the 423 patients who underwent curative surgery, 66 percent of those in the allogeneic-transfusion group and 63 percent of those in the autologous-transfusion group had no recurrence of colorectal cancer at four years (P = 0.93). We also found that the risk of recurrence was significantly increased in patients who received blood transfusions, either allogeneic or autologous, as compared with patients who did not require transfusions; the relative rates of recurrence were 2.1 (P = 0.01) and 1.8 (P = 0.04), respectively; these rates did not differ significantly from each other. CONCLUSIONS The use of autologous blood as compared with allogeneic blood for transfusion does not improve the prognosis in patients with colorectal cancer. Regardless of their type, transfusions are associated with poor prognosis, probably because of the circumstances that necessitate them.

Controlled clinical trial of selective decontamination for the treatment of severe acute pancreatitis

ObjectiveA randomized, controlled, multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality. Summary Background DataSecondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis. Controlled clinical trials to study the effect of selective decontamination in such patients are not available. MethodsBetween April 22, 1990 and April 19, 1993, 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals. Patients were entered into the study if severe acute pancreatitis was indicated, on admission, by multiple laboratory criteria (Imrie score ≥ 3) and/or computed tomography criteria (Balthazar grade D or E). Patents were randomly assigned to receive standard treatment (control group) or standard treatment plus selective decontamination (norfloxacin, colistin, amphotericin; selective decontamination group). All patients received full supportive treatment, and surveillance cultures were taken in both groups. ResultsFifty patients were assigned to the selective decontamination group and 52 were assigned to the control group. There were 18 deaths in the control group (35%), compared with 11 deaths (22%) in the selective decontamination group. (adjusted for Imrie score and Balthazar grade: p = 0.048). This difference was mainly caused by a reduction of late mortality (> 2 weeks) due to significant reduction of gram-negative pancreatic infection (p = 0.003). The average number of laparotomies per patient was reduced in patients treated with selective decontamination (p < 0.05). Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients (6%) and transient gram-negative pancreatic infection was seen in one (2%). In both groups of patients, all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria.

Survival and Prognostic Indicators in Hepatitis B Surface Antigen-Positive Cirrhosis of the Liver

To evaluate indications for new therapies such as liver transplantation and antiviral therapy, survival of histologically proven hepatitis B surface antigen (HBsAg)-positive cirrhosis of the liver was assessed in a cohort of 98 patients followed up for a mean of 4.3 years. The overall survival probability was 92% at 1 year, 79% at 3 years, and 71% at 5 years. Variables significantly associated with the duration of survival were age, serum aspartate aminotransferase levels, presence of esophageal varices, and all five components of the Child-Pugh index (bilirubin, albumin, coagulation factors, ascites, encephalopathy). Multivariate analysis showed that only age, bilirubin, and ascites were independently related to survival. Survival of patients with decompensated cirrhosis (determined by the presence of ascites, jaundice, encephalopathy, and/or a history of variceal bleeding) and those with compensated cirrhosis at 5 years was 14% and 84%, respectively. For patients with compensated liver cirrhosis, hepatitis B e antigen (HBeAg) positivity was also a prognostic factor with a 5-year survival of 72% for HBeAg-positive cirrhosis and 97% for HBeAg-negative cirrhosis; the risk of death was decreased by a factor of 2.2 when HBeAg seroconversion occurred during follow-up. It is concluded that liver transplantation should be considered for patients with decompensated HBsAg-positive liver cirrhosis and antiviral therapy for patients with HBeAg-positive compensated cirrhosis.

Hybrid genotypes in the pathogenic yeast Cryptococcus neoformans

Amplified fragment length polymorphism (AFLP) genotyping of isolates of the pathogenic fungus Cryptococcus neoformans suggested a considerable genetic divergence between the varieties C. neoformans var. neoformans and C. neoformans var. grubii on the one hand versus C. neoformans var. gattii on the other. This divergence is supported by additional phenotypic, biochemical, clinical and molecular differences. Therefore, the authors propose the existence of two species, C. neoformans (Sanfelice) Vuillemin and C. bacillisporus Kwon-Chung, which differ in geographical distribution, serotypes and ecological origin. Within each species three AFLP genotypes occur, which differ in geographical distribution and serotypes. Differences in ecological origin (AIDS patients, non-AIDS patients, animals or the environment) were found to be statistically not significant. In C. neoformans as well as in C. bacillisporus one of the genotypes represented a hybrid. The occurrence of hybridization has consequences for the reproductive biology of the species, as new genotypes with altered virulence or susceptibility to antifungal drugs may arise through the exchange of genetic material.

Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure : a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors

Objective:A prospective randomized multicenter study was performed to assess whether the results of pylorus-preserving pancreaticoduodenectomy (PPPD) equal those of the standard Whipple (SW) operation, especially with respect to duration of surgery, blood loss, hospital stay, delayed gastric emptying (DGE), and survival. Summary Background Data:PPPD has been associated with a higher incidence of delayed gastric emptying, resulting in a prolonged period of postoperative nasogastric suctioning. Another criticism of the pylorus-preserving pancreaticoduodenectomy for patients with a malignancy is the radicalness of the resection. On the other hand, PPPD might be associated with a shorter operation time and less blood loss. Methods:A prospective randomized multicenter study was performed in a nonselected series of 170 consecutive patients. All patients with suspicion of pancreatic or periampullary tumor were included and randomized for a SW or a PPPD resection. Data concerning patients’ demographics, intraoperative and histologic findings, as well as postoperative mortality, morbidity, and follow-up up to 115 months after discharge, were analyzed. Results:There were no significant differences noted in age, sex distribution, tumor localization, and staging. There were no differences in median blood loss and duration of operation between the 2 techniques. DGE was observed equally in the 2 groups. There was only a marginal difference in postoperative weight loss in favor of the standard Whipple procedure. Overall operative mortality was 5.3%. Tumor positive resection margins were found for 12 patients of the SW group and 19 patients of the PPPD group (P < 0.23). Long-term follow-up showed no significant statistical differences in survival between the 2 groups (P < 0.90). Conclusions:The SW and PPPD operations were associated with comparable operation time, blood loss, hospital stay, mortality, morbidity, and incidence of DGE. The overall long-term and disease-free survival was comparable in both groups. Both surgical procedures are equally effective for the treatment of pancreatic and periampullary carcinoma.