Olivier Facy

C-reactive protein and procalcitonin for the early detection of anastomotic leakage after elective colorectal surgery: pilot study in 100 patients.

INTRODUCTION Anastomotic leakage is the most important complication after colorectal surgery. Its prognosis depends on its early diagnosis. C-reactive protein (CRP) has already shown its usefulness for the early detection of anastomotic leaks. Procalcitonin (PCT) is widely used in intensive care units and is more expensive, but its usefulness in the postoperative period of digestive surgery is not well established. PATIENTS AND METHODS Between May 2010 and June 2011, 100 patients undergoing elective colorectal surgery were prospectively included in a database. CRP and PCT were measured before surgery and daily until postoperative day 4. All intraabdominal infections were considered as anastomotic leaks, regardless of their clinical impact and their management. The kinetics of PCT and CRP were recorded, as well as their accuracy for the detection of anastomotic fistula. RESULTS The incidence of fistula was 13% and the overall mortality rate was 2%. Both CRP and PCT were significantly higher in patients with leakage. Areas under the receiver-operating characteristics (ROC) for CRP were higher than those for PCT each day. The best accuracy was obtained for CRP on postoperative day 4 (areas under the ROC curve were 0.869 for CRP and 0.750 for PCT). CONCLUSION Procalcitonin is neither earlier nor more accurate than CRP for the detection of anastomotic leakage after elective colorectal surgery.

Diagnostic Accuracy of Inflammatory Markers As Early Predictors of Infection After Elective Colorectal Surgery: Results From the IMACORS Study.

Background:Intra-abdominal infections are frequent and life-threatening complications after colorectal surgery. An early detection could diminish their clinical impact and permit safe early discharge. Objective:This study aimed to find the most accurate marker for the detection of postoperative intra-abdominal infection and the appropriate moment to measure it. Methods:A prospective, observational study was conducted in 3 centers. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. C-reactive protein and procalcitonin were measured daily until the fourth postoperative day. Postoperative infections were recorded according to the definitions of the Centres for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the diagnostic accuracy of each marker. Results: :Five-hundred and one patients were analyzed. The incidence of intra-abdominal infection was 11.8%, with 24.6% of patients presenting at least one infectious complication. Overall mortality was 1.2%. At the fourth postoperative day, C-reactive protein was more discriminating than procalcitonin for the detection of intra-abdominal infection (areas under the ROC curve: 0.775 vs 0.689, respectively, P = 0.03). Procalcitonin levels showed wide dispersion. For the detection of all infectious complications, C-reactive protein was also significantly more accurate than procalcitonin on the fourth postoperative day (areas under the ROC curve: 0.783 vs 0.671, P = 0.0002). Conclusions:C-reactive protein is more accurate than procalcitonin for the detection of infectious complications and should be systematically measured at the fourth postoperative day. It is a useful tool to ensure a safe early discharge after elective colorectal surgery.

High pressure enhances the effect of hyperthermia in intraperitoneal chemotherapy with oxaliplatin: an experimental study.

Background:Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) achieve good results in selected patients with peritoneal carcinomatosis. High intra-abdominal pressure could enhance the penetration of chemotherapy drugs. The aim of this study was to compare the effects of high pressure and hyperthermia when used separately and when combined in terms of blood and tissue absorption of oxaliplatin in a swine model of intraperitoneal chemotherapy. Methods:Four groups of 5 pigs each underwent laparotomy and open intraperitoneal chemotherapy with oxaliplatin at a constant concentration (150 mg/L) for 30 minutes in normothermia and atmospheric pressure (group 1), or hyperthermia (42°C) and atmospheric pressure (group 2), or normothermia and high pressure (25 cm H2O) (group 3), or hyperthermia and high pressure (group 4). High pressure was achieved thorough a water column over the abdomen. Systemic absorption and abdominal tissue mapping of the penetration of oxaliplatin in each group were studied. Results:Blood concentrations of oxaliplatin were similar in the different groups. Hyperthermia achieved higher concentrations in visceral surfaces (P = 0.0014), but not in parietal surfaces. High pressure enhanced diffusion of the drug in both the visceral and parietal peritoneum (P = 0.0058 and P = 0.0044, respectively). The combination of hyperthermia and high pressure significantly increased the penetration of oxaliplatin and achieved the highest tissue concentrations (10.39 mg/kg vs 5.48 mg/kg; P = 0.00001 in the visceral peritoneum, and 66.16 mg/kg vs 35.62 mg/kg; P = 0.0003 in the parietal peritoneum). Conclusions:Open high-pressure HIPEC with oxaliplatin is feasible in the pig. Hyperthermia enhances diffusion in the visceral peritoneum, whereas high pressure is effective in the visceral and parietal peritoneum. The combination of the two achieves the highest tissue concentrations of oxaliplatin.

Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX- nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8(+) T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.

Epidemiology, Management, and Survival of Peritoneal Carcinomatosis from Colorectal Cancer: A Population-Based Study.

BACKGROUND: Modern chemotherapy aims to improve long-term survival for selected patients with peritoneal carcinomatosis. Publications suggest promising results, but the spread of these new aggressive treatment strategies in the general population is not well known. OBJECTIVE: The aim of this study was to draw a picture of epidemiology, management, and survival in synchronous and metachronous peritoneal carcinomatosis from colorectal cancer. DESIGN: The cumulative risk of metachronous peritoneal carcinomatosis was estimated in patients resected for cure. Net survival rates were calculated for synchronous and metachronous peritoneal carcinomatosis. SETTINGS: The study was conducted with the use of the Burgundy Digestive Cancer Registry. PATIENTS: Overall, 9174 primary colorectal cancers registered between 1976 and 2011 by the population-based digestive cancer registry were considered. RESULTS: In total, 7% of patients were diagnosed with synchronous peritoneal carcinomatosis. The 5-year cumulative risk of metachronous peritoneal carcinomatosis was 6%, and the stage of the colorectal cancer at diagnosis was the major risk factor. Other independent risk factors were mucinous adenocarcinoma, ulceroinfiltrating tumors, and diagnosis after obstruction or perforation. The proportion of patients resected for cure was 11% and 9% for synchronous and metachronous peritoneal carcinomatosis, and 3-year overall net survival was 8% and 5%. The corresponding rates after resection for cure were 21% and 17%. There was a dramatic increase in the proportion of patients receiving systemic chemotherapy: from 11% before 1997 to 48% in 2011 for synchronous peritoneal carcinomatosis and from 3% to 38% for metachronous peritoneal carcinomatosis. LIMITATIONS: This is a retrospective observational population-based study. CONCLUSION: Peritoneal carcinomatosis complicating colorectal cancer is a major reason for treatment failure. This study identified patients at a high risk of developing peritoneal carcinomatosis who may benefit from specific surveillance. New therapeutic modalities are also needed to improve the prognosis.

Incidence and survival in late liver metastases of colorectal cancer

Data concerning the risk of long‐term liver metastasis following surgery of colorectal cancer in the general population are scarce. The 10‐year incidence and prognosis of metachronous liver metastases remain unknown.

Using a heating cable within the abdomen to make hyperthermic intraperitoneal chemotherapy easier: Feasibility and safety study in a pig model

BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex, expensive and time-consuming procedure. Despite its good results in the treatment of peritoneal carcinomatosis, these factors have precluded the wider use of this procedure around the world. We hypothesized that HIPEC could be performed by heating the liquid within the abdomen and thus avoiding the need for an external heating circuit and a pump. The aim of this study was to assess the feasibility and safety of an internal heating device for hyperthermic intraperitoneal chemotherapy in an experimental model. METHODS Four large-white pigs underwent one-hour open intraperitoneal hyperthermia with closed abdomen using this new device. Constant stirring of the liquid around the viscera was performed in the first three animals, but not in the fourth one. At the end of the procedure, all of the viscera were carefully examined to look for thermal injury. Any lesion or doubtful area was removed and sent to pathologic examination. RESULTS No adverse events occurred during surgery in any of the animals. A temperature of 42 degrees C was reached in an average time of 14 min and maintained homogeneously between 42 degrees C and 43 degrees C for one hour. No visceral injury was detected in the first three animals. Three foci of thermal injury to the mucosa were detected in the absence of stirring (fourth animal). CONCLUSION Heating the solution within the abdomen during hyperthermic intraperitoneal chemotherapy is feasible, safe and achieves perfect thermal homogeneity. This device provides a time-saving inexpensive way to perform intraperitoneal hyperthermic chemotherapy.

Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

BackgroundThe best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.MethodsFour groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).ResultsIn vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.ConclusionAdrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

C-reactive protein and procalcitonin as predictors of anastomotic leak.

To the Editor—thank you for the opportunity to answer the comments made by Dr ortega-Deballon and his colleagues and for the interest shown to our study. in our article, in order to homogenize the results in tables 4 and 5, we decided to describe all the variables using the mean and standard deviation. as a matter of fact, when describing procalcitonin, the dispersion of the values was important, and, for this variable, the median would have better described its distribution and relation with the cutoff proposed. in fact, median and interquartile ranges for procalcitonin at postoperative day 5 in patients without major anastomotic leak were 0.17 ng/ml and 0.09–0.35 ng/ml, situating the anastomotic leak cutoff (0.31 ng/ml) at the 72nd percentile. these data coincide with the results described in table 6 (specificity 0.72 for procalcitonin at postoperative day 5 in detecting major anastomotic leak). in regard of the second comment, we concluded our article by stating that both procalcitonin and C-reactive protein are reliable indicators to rule out the presence of major anastomotic leak. in our opinion, they are complementary, and they both must be taken under consideration before discharging the patient. We do not think that our results are challenged by the 2 articles cited in Dr ortega-Deballons letter. lagoutte et al in their article included 100 patients who underwent elective colorectal surgery and defined as anastomotic leak all intraabdominal infections regardless of their clinical impact and their management; they concluded that the area under the reC-Reactive Protein and Procalcitonin as Predictors of Anastomotic Leak

Minimally invasive surgery for gastric cancer: A comparison between robotic, laparoscopic and open surgery

AIM To investigate the role of minimally invasive surgery for gastric cancer and determine surgical, clinical, and oncological outcomes. METHODS This is a propensity score-matched case-control study, comparing three treatment arms: robotic gastrectomy (RG), laparoscopic gastrectomy (LG), open gastrectomy (OG). Data collection started after sharing a specific study protocol. Data were recorded through a tailored and protected web-based system. Primary outcomes: harvested lymph nodes, estimated blood loss, hospital stay, complications rate. Among the secondary outcomes, there are: operative time, R0 resections, POD of mobilization, POD of starting liquid diet and soft solid diet. The analysis includes the evaluation of type and grade of postoperative complications. Detailed information of anastomotic leakages is also provided. RESULTS The present analysis was carried out of 1026 gastrectomies. To guarantee homogenous distribution of cases, patients in the RG, LG and OG groups were 1:1:2 matched using a propensity score analysis with a caliper = 0.2. The successful matching resulted in a total sample of 604 patients (RG = 151; LG = 151; OG = 302). The three groups showed no differences in all baseline patients characteristics, type of surgery (P = 0.42) and stage of the disease (P = 0.16). Intraoperative blood loss was significantly lower in the LG (95.93 ± 119.22) and RG (117.91 ± 68.11) groups compared to the OG (127.26 ± 79.50, P = 0.002). The mean number of retrieved lymph nodes was similar between the RG (27.78 ± 11.45), LG (24.58 ± 13.56) and OG (25.82 ± 12.07) approach. A benefit in favor of the minimally invasive approaches was found in the length of hospital stay (P < 0.0001). A similar complications rate was found (P = 0.13). The leakage rate was not different (P = 0.78) between groups. CONCLUSION Laparoscopic and robotic surgery can be safely performed and proposed as possible alternative to open surgery. The main highlighted benefit is a faster postoperative functional recovery.