Yakup Kulu

Hepatic platelet and leukocyte adherence during endotoxemia

IntroductionLiver microcirculation disturbances are a cause of hepatic failure in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. The time course and reciprocal influences of ongoing microcirculatory events during endotoxemia have not been clarified.MethodsMale Wistar rats (232 ± 17 g) underwent cecal ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3, 5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet rolling in postsinusoidal venules and sticking of leukocytes and platelets in postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR), mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured. Blood count and investigation of hepatic enzyme release was performed after each IVM time point.ResultsHepatic platelet-endothelial adherence in liver sinusoids and postsinusoidal venules occurred one hour after the induction of endotoxemia. Leukocyte-endothelial interaction started three to five hours after CLP. A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was reduced one hour after CLP. HR remained stable and MAP decreased ten hours after CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP.ConclusionHepatic platelet-endothelial interaction is an early event during endotoxemia. Leukocyte adherence occurs later, which underlines the probable involvement of platelets in leukocyte recruitment. Although PBF is reduced immediately after CLP, the later onset of hepatic microperfusion decrease makes the existence of autoregulatory liver mechanisms likely.

Validation of the International Study Group of Rectal Cancer definition and severity grading of anastomotic leakage.

BACKGROUND The International Study Group of Rectal Cancer (ISREC) has proposed a generally applicable definition and severity grading of (AL) after sphincter-preserving resection of the rectum. This work has been carried out to test for validity. METHODS A total of 746 patients who were identified from a prospective rectal cancer database underwent sphincter-preserving anterior resection of the rectum between October 2001 and January 2011. The incidence and severity of AL was determined using the criteria established by the ISREC. Patients with AL were categorized according to the ISREC scheme. The clinical outcomes were analyzed and compared between the groups. RESULTS The overall AL rate was 7.5% (56/746). The 56 patients with AL were distributed among the different groups as follows: Grade A, 16%; grade B, 23%; and grade C, 61%. Compared with the grade A patients, grades B and C patients had significantly elevated serum C-reactive protein levels (P < .01). None of the grade A patients were transferred to the intensive care unit (ICU). Their further hospital stay was uneventful. The length of stay in the ICU was significantly longer for grade C patients compared with grade B patients (P < .001). The median hospital stay of grade C patients was significantly longer than that of grades A and B patients (P < .001). CONCLUSION The definition and severity grading of AL after anterior resection of the rectum proposed by the ISREC provides a simple, easily applicable, and valid classification. Using this classification system may facilitate comparison of results from different studies on AL after sphincter-preserving rectal surgery.

Total pancreatectomy for pancreatic cancer: indications and operative technique.

Total pancreatectomy (TP) was abandoned by many surgeons because of its lack of benefits and other major drawbacks. The potential benefits of TP, including its oncological as well as its technical advantages, did not prove to be valid. Problems associated with insulin-deprived diabetes mellitus and high perioperative morbidity and mortality rates were not easily manageable. However, in the new era of pancreatic surgery, new indications for TP have been defined. These have been paralleled by improvements in surgical technique, multidisciplinary management and postoperative intensive care. These factors have transformed TP into a safe and reasonable surgical procedure with excellent perioperative morbidity and mortality, as well as good longterm outcome. We review the indications for TP and describe our operative technique in detail.

Resectable Rectal Cancer: Which Patient Does Not Need Preoperative Radiotherapy?

It is well known that some patients with resectable rectal cancer benefit from preoperative radiotherapy in combination with or without chemotherapy. In order to reduce local recurrence and improve long-term survival, current guidelines advocate such neoadjuvant treatment in UICC (Union for International Cancer Control) stage II and III patients. However, the vast majority of patients may be adequately treated by rectal resection with total mesorectal excision (TME) alone. Recent evidence suggests an overtreatment of patients leading to unnecessary exposure to acute and long-term toxicity of radiation therapy. The question which consequently arises is which patient does not need preoperative radiotherapy. Improvements in MRI combined with better understanding of prognostic indicators suggest that patients with UICC stage I tumors, with tumors more than 12 cm proximal the anal verge can and patients with a circumferential resection margin ≥2 mm as assessed by preoperative MRI might be managed by radical surgery with adequate TME alone.

Impact of Anatomic Location on Locally Recurrent Rectal Cancer: Superior Outcome for Intraluminal Tumour Recurrence

BackgroundLocal recurrence of rectal cancer after curative surgery predicts patients’ prognosis. The correlation between the exact anatomic location of tumour recurrence and patients’ survival is still under debate. Thus, this study aimed to investigate the impact of the exact location of recurrent rectal cancer on post-operative morbidity and survival.MethodsThis is a retrospective study including 90 patients with locally recurrent rectal cancer. The location of tumour recurrence was classified into intraluminal and extraluminal recurrence. Univariate and multivariable Cox regression analyses were used to determine the impact on post-operative morbidity and survival.ResultsPatients’ survival with intraluminal recurrence was significantly longer compared to patients with extraluminal recurrence (p = 0.027). Curative resection was associated with prolonged survival in univariate and multivariable analyses (p = 0.0001) and was more often achieved in patients with intraluminal recurrence (p = 0.024). Survival of curative resected patients with intraluminal recurrence was significantly longer compared to curatively resected patients with extraluminal recurrence (p = 0.0001). The rate of post-operative morbidity between intraluminal and extraluminal recurrence was not statistically different (p = 0.59).ConclusionBased on the present investigation, intraluminal recurrence is associated with superior outcome. Post-operative morbidity did not differ significantly between both groups.

Sphincter-Preserving Surgery for Low Rectal Cancer: Do We Overshoot the Mark?

PurposeIntersphincteric resection (ISR) is an alternative to abdominoperineal resection (APR) for a selected subset of patients with low rectal cancer, combining equivalent oncological outcome and sphincter preservation. However, functional results are heterogeneous and often imperfect. The aim of the present investigation was to determine the long-term functional results and quality of life after ISR.MethodsOne hundred forty-three consecutive patients who underwent surgery for low rectal cancer were analysed. Sixty patients received ISR and 83 patients APR, respectively. Kaplan-Meier estimate was used to analyse patients’ survival. The EORTC QLQ-C30, -C29 and the Wexner score were used to determine functional outcome and quality of life.ResultsISR and APR were both associated with comparable morbidity and no mortality. Patients’ disease- and recurrence-free survival after ISR and APR were similar (p = 0.2872 and p = 0.4635). Closure of ileostomy was performed in 73% of all patients after ISR. Long-term outcome showed a rate of incontinence (Wexner score ≥10) in 66% of the patients. Despite this, patients’ quality of life was significantly better after ISR compared to APR in terms of abdominal complaints and psycho-emotional functioning.ConclusionsISR is technically feasible with acceptable postoperative morbidity rates. Functional results following ISR are compromised by incontinence as the most important complication. However, long-term quality of life is superior to APR, which should be considered when selecting patients for ISR.

Surgical treatment of peritoneal carcinomatosis: current treatment modalities

BackgroundSelected patients with peritoneal surface malignancies (PSM) have been treated effectively by the combination of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).PurposeThe purpose of this study is to summarize the treatment outcomes and general considerations regarding definitions and staging systems of current CRS and HIPEC modalities in malignant peritoneal mesothelioma and in secondary peritoneal malignancies such as peritoneal metastasis from appendiceal, colorectal, gastric, and epithelial ovarian cancers.ConclusionDisease progression within the peritoneal cavity has in the past been regarded as a terminal event. Accumulating evidence underlines the therapeutic potential and the acceptable morbidity and mortality rates of CRS and HIPEC in selected patients.

Postoperative course and prognostic value of circulating angiogenic cytokines after pancreatic cancer resection

Background Circulating angiogenic cytokines (CACs) have been confirmed as prognostic biomarkers and therapeutic targets in several solid tumors. However, their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma (PDAC) is unknown. Results The expression of CACs in patients with PDAC differs from those with CP both pre- and postoperatively. Correlation analyses show significant correlations between circulating levels of CACs: VEGF was correlated with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF-1α (r = 0.784) before the surgery. The circulating levels of TNF-α correlated with the serum concentration of IL-4 before (r= 0.656) and after the resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any correlation with serum levels of CAC, except for significantly higher levels of EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65 vs. > 65 years), T, N, or UICC stage did not have an association with the cytokine levels. The multivariate model including the entire angiogenic panel revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P = 0.024), TNF-α (P = 0.001) and IL-8 (P = 0.049) were associated with a favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with a poor cancer-specific survival. Materials and Methods Preoperative and postoperative blood samples were collected in patients undergoing surgery for PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-α, VEGF, HGF, SDF-1α, IL-8, EGF, Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic factors were identified by a Cox proportional hazards model. Conclusions Postoperative changes of serum levels of certain angiogenic cytokines correlate with patients’ prognosis after resection for pancreatic cancer. CACs should thus be considered as biomarkers in patients with resected pancreatic cancer.