Management of patients with high C-reactive protein levels after elective colorectal surgery: Pilot study on a proactive diagnostic and therapeutic approach (GESPACE).

STUDY OBJECTIVE: To evaluate the feasibility and benefit of a diagnostic and therapeutic algorithm for management of patients presenting with a high C-reactive protein (CRP) level after colorectal surgery. PATIENTS AND METHODS: Prospective study including patients with CRP>125mg/L at the 4th postoperative day following elective colorectal surgery. The protocol involved CT-scan of which the results were to orient subsequent management: antibiotics, radiological drainage, endoscopy or surgical redo. Success (primary endpoint) consisted in the proportion of patients with total duration of hospitalization fewer than 15d. Secondary endpoints were: applicability of the protocol in real-life conditions, number of stomas created, duration of hospitalization in an intensive care unit. RESULTS: One hundred and six (106) patients were included: 51 patients (48%) presented with postoperative complications, of which 21 (41%) were severe. No death occurred. Among the included patients, 68% had a hospital stay<15d. Major deviations from the management algorithm occurred in 38% of cases. No patients had an early endoscopy. There was no significant difference with regard to the secondary endpoints according to whether or not the protocol was strictly observed. CONCLUSION: It is necessary to define a protocol for management of patients presenting with high CRP levels after colorectal surgery, the objective being to reduce the impact of complications and to avoid excessive lengthening of hospital stay. The protocol begins with CT-scan, which is to orient subsequent management.

Predictive Factors of Local Recurrence after Colorectal Cancer Liver Metastases Thermal Ablation.

BACKGROUND: Identify risk factors for local recurrence (LR) after radiofrequency (RFA) and microwave (MWA) thermoablations (TA) of colorectal cancer liver metastases (CCLM). METHODS: Uni- (Pearson's Chi2 test, Fisher's exact test, Wilcoxon test) and multivariate analyses (LASSO logistic regressions) of every patient treated with MWA or RFA (percutaneously and surgically) from January 2015 to April 2021 in Centre Georges François Leclerc in Dijon, France. RESULTS: Fifty-four patients were treated with TA for 177 CCLM (159 surgically, 18 percutaneously). LR rate was 17.5% of treated lesions. Univariate analyses by lesion showed factors associated with LR: sizes of the lesion (OR = 1.14), size of nearby vessel (OR = 1.27), treatment of a previous TA site LR (OR = 5.03), and non-ovoid TA site shape (OR = 4.25). Multivariate analyses showed that the size of the nearby vessel (OR = 1.17) and the lesion (OR = 1.09) remained significant risk factors of LR. CONCLUSIONS: The size of lesions to treat and vessel proximity are LR risk factors that need to be considered when making the decision of thermoablative treatments. TA of an LR on a previous TA site should be reserved to specific situations, as there is an important risk of another LR. An additional TA procedure can be discussed when TA site shape is non-ovoid on control imaging, given the risk of LR.

Benefit of a flash dose of corticosteroids in digestive surgical oncology: a multicenter, randomized, double blind, placebo-controlled trial (CORTIFRENCH).

BACKGROUND: The modulation of perioperative inflammation seems crucial to improve postoperative morbidity and cancer-related outcomes in patients undergoing oncological surgery. Data from the literature suggest that perioperative corticosteroids decrease inflammatory markers and might be associated with fewer complications in esophageal, liver, pancreatic and colorectal surgery. Their benefit on cancer-related outcomes has not been assessed. METHODS: The CORTIFRENCH trial is a phase III multicenter randomized double-blind placebo-controlled trial to assess the impact of a flash dose of preoperative corticosteroids versus placebo on postoperative morbidity and cancer-related outcomes after elective curative-intent surgery for digestive cancer. The primary endpoint is the frequency of patients with postoperative major complications occurring within 30 days after surgery (defined as all complications with Clavien-Dindo grade > 2). The secondary endpoints are the overall survival at 3 years, the disease-free survival at 3 years, the frequency of patients with intraabdominal infections and postoperative infections within 30 days after surgery and the hospital length of stay. We hypothesize a reduced risk of major complications and a better disease-survival at 3 years in the experimental group. Allowing for 5% of drop-out, 1 200 patients (600 per arm) should be included. DISCUSSION: This will be the first trial focusing on the impact of perioperative corticosteroids on cancer related outcomes. If significant, it might be a strong improvement on oncological outcomes for patients undergoing surgery for digestive cancers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03875690, Registered on March 15, 2019, URL: https://clinicaltrials.gov/ct2/show/NCT03875690 .

Safety and efficacy of a docetaxel-5FU-oxaliplatin regimen with or without trastuzumab in neoadjuvant treatment of localized gastric or gastroesophageal junction cancer: A retrospective study.

BACKGROUND: Triplet chemotherapy, with docetaxel-5FU-oxaliplatin FLOT regimen recently became the standard perioperative treatment for localized gastric cancer (GC). An adapted regimen called TeFOX was recently tested in metastatic setting and gave promising results. AIM: To determine safety and efficacy of TeFOX perioperative regimen. METHODS: This monocentric retrospective study aims to test efficacy and safety of the perioperative TeFOX regimen given alone or in combination with trastuzumab in patients with localized GC. TeFOX consist in docetaxel (50 mg/m²) with oxaliplatin 85 mg/m² and and leucovorin (400 mg/m2) 5 FU bolus (400 mg/m2) on day 1, followed by continuous infusion of 5FU for 46 h (2400 mg/m2) every 2 wk. RESULTS: Thirty-three consecutive patients were included in this retrospective study. Eighteen patients have a gastroesophageal junction cancer and 11 have a GC. Median follow-up of surviving patients was 32 mo. R0 resection was obtained in 30 (91) patients. Twelve patients (36) had a pathological complete response and 8 (24) patients a nearly complete pathological response. Median OS and PFS were not reached at data base lock. We have observed 6 metastatic relapses and 1 localized relapse. No relapse was observed in patients with pathological complete responses. The most common grade 3-4 adverse events were peripheral neuropathy (21) and asthenia (20). CONCLUSION: TeFOX regimen could be safely administrated in perioperative treatment of localized GC. TeFOX and the FLOT regimen have comparable efficacy and safety profiles.

Inflammatory markers as early predictors of infection after colorectal surgery: the same cut-off values in laparoscopy and laparotomy?

PURPOSE: C-reactive protein and procalcitonin are reliable early predictors of infection after colorectal surgery. However, the inflammatory response is lower after laparoscopy as compared to open surgery. This study analyzed whether a different cutoff value of inflammatory markers should be chosen according to the surgical approach. METHODS: A prospective, observational study included consecutive patients undergoing elective colorectal surgery in three academic centers. All infections until postoperative day (POD) 30 were recorded. The inflammatory markers were analyzed daily until POD 4. Areas under the ROC curve and diagnostic values were calculated in order to assess their accuracy as a predictor of intra-abdominal infection. RESULTS: Five-hundred-one patients were included. The incidence of intra-abdominal infection was 11.8%. The median levels of C-reactive protein (CRP) and procalcitonin (PCT) were lower in the laparoscopy group at each postoperative day (p < 0.0001). In patients without intra-abdominal infection, they were also lower in the laparoscopy group (p = 0.0036) but were not different in patients presenting with intra-abdominal infections (p = 0.3243). In the laparoscopy group, CRP at POD 4 was the most accurate predictor of overall and intra-abdominal infection (AUC = 0.775). With a cutoff of 100 mg/L, it yielded 95.7% negative predictive value, 75% sensitivity, and 70.3% specificity for the detection of intra-abdominal infection. CONCLUSION: The impact of infection on inflammatory markers is more important than that of the surgical approach. Defining a specific cutoff value for early discharge according to the surgical approach is not justified. A patient with CRP values lower than 100 mg/L on POD 4 can be safely discharged.

Preoperative inflammation increases the risk of infection after elective colorectal surgery: results from a prospective cohort.

BACKGROUND: Septic complications after colorectal surgery are frequent and sometimes life threatening. It is well known that inflammation impairs the healing process. It has been suggested that preoperative ongoing inflammation could increase the risk of postoperative infections. This study aimed to elucidate the role of preoperative inflammation on postoperative infectious complications and to understand if, through biological markers, it is possible to identify preoperatively patients at higher risk of infection. METHODS: A prospective, observational study was conducted in three centers from November 2011 to April 2014. Consecutive patients undergoing elective colorectal surgery with anastomosis were included. Any ongoing infection was an exclusion criterion. C-reactive protein, albumin, prealbumin, and procalcitonin plasma levels were measured preoperatively. Postoperative infections were recorded according to the definitions of the Centers for Diseases Control. The areas under the receiver operating characteristic curve were analyzed and compared to assess the accuracy of each preoperative marker. RESULTS: Four-hundred and seventy two patients were analyzed. Infectious complications occurred in 118 patients (25 %) and mortality in 6 patients (1.3 %). In the univariate analysis, preoperative C-reactive protein and albuminemia were found significantly associated with postoperative infectious complications (P = 0.008 and P = 0.0002, respectively). Areas under the ROC curve for preoperative C-reactive protein and albuminemia were 0.57and 0.62, respectively. CONCLUSIONS: This study confirms the association between preoperative inflammatory activity, hypoalbuminemia, and the onset of infections after surgery. Trials aiming to decrease the inflammatory activity before surgery in order to prevent postoperative complications are warranted.

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients.

Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17+, CD8+, Foxp3+, Tbet+ T cells and CD20+ B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8+ and IL17+ T-cell densities were not significantly associated with gastric cancer prognosis. In contrast, high infiltration of Tbet+ T cells, high numbers of CD20+ B-cell follicles, and low infiltration of Foxp3+ T cells, were associated with better relapse-free survival. Interestingly, treatment with neoadjuvant chemotherapy or histological tumor type (diffuse versus intestinal) did not influence type and density of immune infiltrates or their prognostic value. Immunohistochemical analysis of the gastric cancer stromal microenvironment revealed organized T and B cell aggregates, with strong structural analogies to normal secondary lymphoid organs and which could be considered as tertiary lymphoid structures. Using transcriptomic data from an independent cohort of 365 localized gastric cancer, we confirmed that a coordinated Th1, and B cell stromal gene signature is associated with better outcome. Altogether, these data suggest that tumor infiltration by B and Th1 T cells could affect gastric cancer prognosis and may be used to better define the outcome of patients with localized gastric cancer.

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.

[An IgG4-related pancreatitis mimicking an adenocarcinoma: A case report]. / Une pancréatite auto-immune à IgG4 simulant un adénocarcinome : à propos d'un cas.

Type 1 auto-immune pancreatitis (type 1 AIP) is the pancreatic manifestation of IgG4-related systemic disease (IgG4-RD). This disease has recently been individualized and is characterized by elevated serum IgG4 levels and extrapancreatic lesions with common histologic characteristic: dense infiltration of lymphocytes, IgG4-positive plasma cells and storiforme fibrosis. Obliterative phlebitis is frequently detected. The pancreas is frequently involved in this disease. As approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological and histopathological features. In pseudotumoral cases, AIP can be misdiagnosed as pancreatic cancer. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection. We report here a case of a patient who underwent surgery for presumed pancreatic cancer. The final diagnosis was type 1 AIP.

Are Adiponectin and Leptin Good Predictors of Surgical Infection after Colorectal Surgery? A Prospective Study.

BACKGROUND: Infections are the most frequent complication after colorectal surgery. It has been suggested that adipose tissue metabolism could be related to the risk of post-operative infection, but this could be partially related to the body-mass index. The aim of this study was to look for a relation between adipocytokine levels and the risk of post-operative infection and its type. METHODS: This prospective cohort study was conducted between March 2013 and March 2014 in two French teaching hospitals. Pre-operative plasma levels of adiponectin and leptin were measured in consecutive patients undergoing elective colorectal surgery. All infections in the 30 d following surgery were recorded. RESULTS: Among the 142 patients included, 29 (20.4%) presented a post-operative infection: 26 surgical site infections and three extra-abdominal infections. Adiponectin and leptin levels correlated weakly but substantially with the body mass index (rspearman=-0.26 and +0.31, respectively). While there was no substantial difference between patients with and those without post-operative infection for adiponectin, median pre-operative leptin was substantially greater in patients with post-operative infection (8.67 vs. 4.37 ng/mL, p=0.003). A substantial interaction was found between leptin and cancer. In patients operated on for cancer, the area under the receiver-operating characteristic (ROC) curve was lower than in patients with benign diseases (0.597 vs. 0.858, p=0.011). Similar results were observed for intra-abdominal infection and surgical site infection. CONCLUSION: Patients with greater levels of leptin before colorectal surgery have an increased risk of post-operative surgical infection. This effect is stronger in patients without cancer. Adiponectin levels are not related to the risk of infection in Western patients.

Resection of pancreatic ductal adenocarcinoma with synchronous distant metastasis: is it worthwhile?

BACKGROUND: The purpose of this study is to report prolonged survival in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) managed by chemotherapy and surgery. METHODS: Between January 2009 and August 2013, 284 patients with metastatic PDAC were managed in our oncologic department. Among them, three (1%) with a single metastasis (liver in two cases and interaorticaval in one case) underwent one- or two-stage surgical resection of the metastasis and the main tumor. Perioperative data were recorded retrospectively, including disease-free and overall survival. RESULTS: The three patients had chemotherapy (FOLFOX or FOLFIRINOX regimen) with objective response or stable disease prior to surgery. Median time between chemotherapy and surgery was 9 (8 to 15) months. Resection consisted in pancreaticoduodenectomy in the three cases. None of the patients had grade III/IV postoperative complications, and median hospital stay was 12 (12 to 22) days. All the patients had postoperative chemotherapy. Only one patient experienced recurrence 11 months after surgery and died after 32.5 months. The two other patients were alive with no recurrence 26.3 and 24.7 months after initial treatment. CONCLUSION: Radical resection of PDAC with single distant metastases can offer prolonged survival with low morbidity after accurate selection by neoadjuvant chemotherapy.

Bevacizumab efficacy in metastatic colorectal cancer is dependent on primary tumor resection.

PURPOSE: Bevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis. METHODS: We performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients. RESULTS: In the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60-1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55-0.92, P = 0.009). Similar results were observed in the validation cohort. CONCLUSIONS: Addition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.

Parathyroid hormone decline 4 hours after total thyroidectomy accurately predicts hypocalcemia.

BACKGROUND: The level of parathyroid hormone (iPTH) serum has been controversial in the prediction of postthyroidectomy hypocalcemia. Analysis of the decrease between preoperative and postoperative iPTH levels should be more accurate. Therefore, the aim of our study was to prospectively establish the reliability of the iPTH decrease for early diagnosis of postoperative hypocalcemia and to identify the patients who are not at risk for hypocalcemia. METHODS: A prospective study of 137 consecutive patients who underwent total thyroidectomy was performed. Serum iPTH level was measured preoperatively and 4 hours postoperatively (iPTH(H4)). The sensitivity, specificity, and positive and negative predictive values for the iPTH(H4) and for the iPTH decline were estimated by confidence interval from thresholds determined by ROC curve analysis. RESULTS: Thirty-nine patients developed hypocalcemia (28.5%). Patients who developed hypocalcemia had a significantly lower iPTH(H4) and a significantly greater iPTH decrease (P < .001). The thresholds enabling prediction of hypocalcemia were 19.4 ng/L for iPTH(H4) and 68.5% for iPTH decline. Sensitivity, specificity, and positive and negative predictive values for iPTH(H4) were 84.6%, 92.9%, 82.5%, and 93.8% (overall accuracy, 90.5%). iPTH decline was more accurate to predict hypocalcemia (sensitivity, 97.4%; specificity, 95.9%; positive predictive values 90.5%; negative predictive values, 98.6%; and overall accuracy, 96.4%). CONCLUSION: The decrease in iPTH is more precise than the iPTH(H4) alone and can accurately predict hypocalcemia after total thyroidectomy. Patients with a decrease in iPTH less than 68.5% can be discharged at postoperative day one without any supplementation. Patients with iPTH decline more than 68.5% should be administered calcium and vitamin D supplementation before symptoms appear.

Resectable pancreatic metastasis of left thighbone leiomyosarcoma: case report and literature review.

INTRODUCTION: Metastases to the pancreas gland are uncommon, especially from leiomyosarcoma. We report a case of asymptomatic pancreatic metastasis resection of leiomyosarcoma. CASE REPORT: A 59-year-old patient was treated for thighbone leiomyosarcoma, with surgical resection and adjuvant radiotherapy. After 4 years of follow-up, although that patient was asymptomatic, a pancreatic metastasis was identified by CT and fine needle aspiration. Open left pancreatectomy was performed. DISCUSSION: We discuss diagnosis findings and interest in the surgical resection. Furthermore, we reviewed previously reported cases.