Intravenous chemotherapy for resected gastric cancer:meta-analysis of randomized controlled trials

AIM: To assess the safety and efficacy of different intravenous chemotherapeutic regimens in patiedts with gastric acrcinomas who had undergone gastrectomy.

Comparative evaluation of immune response after laparoscopical and open total mesorectal excisions with anal sphincter preservation in patients with rectal cancer

AIM: The study of immune response of open versus laparoscopical total mesorectal excision with anal sphincter preservation in patients with rectal cancer has not been reported yet. The dissected retroperitoneal area that contacts directly with carbon dioxide is extensive in laparoscopic total mesorectal excision with anal sphincter preservation surgery. Tt is important to clarify whether the immune response of laparoscopic total mesorectal excision with anal sphincter preservation (LTME with ASP) in patients with rectal cancer is suppressed more severely than that of open surgery (OTME with ASP). This study was designed to compare the immune functions after laparoscopic and open total mesorectal excision with anal sphincter preservation for rectal cancer.METHODS: This study involved 45 patients undergoing laparoscopic (n=20) and open (n=25) total mesorectal excisions with anal sphincter preservation for rectal cancer.Serum interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor α (TNFα) were assayed preoperatively and on days 1 and 5 postoperatively. CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ natural killer cell (NK)count and immunoglobulin (IgG/IgM/IgA) were assayed preoperatively and on day 5 postoperatively. The numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells were counted using flow cytometry. An enzyme-linked immunosorbent assay (ELISA) was used for IL-2, TL-6 and TNFα determination. And IgG, IgM, and IgA were assayed using immunonephelometry.RESULTS: The demographic data of the two groups had no difference. The preoperative levels of CD3+ and CD56+ T lymphocyte count, CD3- and CD56+ NK count, serum IgG,IgM, IgA, IL-2, IL-6 and TNFα also had no significant difference in the two groups (P＞0.05). The CD3+ and CD56+ T lymphocyte counts had no obvious changes after surgery in laparoscopic (d=-0.79±3.83 %) and open (d=0.42±2.09 %)groups. The CD3- and CD56+ NK counts were decreased postoperatively in both laparoscopic (d=-7.23±11.33 %) and open (d=-9.21±13.93 %) groups. The differences of the determined values of serum IgG, IgM and IgA on the fifth day after operation subtracted those before operation were -2.56±2.14 g/L, -252.35±392.94 mg/L, -506.15±912.24 mg/L in laparoscopic group, and -1.81±2.10 g/L, -282.72±356.75mg/L, -252.20±396.28 mg/L in open group, respectively. The levels of IL-2 were decreased after operation in both groups.However, the levels of IL-6 were decreased after laparoscopic surgery (d1=-23.14±263.97 ng/L and d5=-40.08±272.03 ng/L),and increased after open surgery (d1=27.38±129.14 ng/L and d5=21.67±234.31 ng/L). The TNFα levels were not elevated after surgery in both groups. There were no significant differences in the numbers of CD3+ and CD56+ T lymphocytes and CD3- and CD56+ NK cells, the levels of IgG, IgM, IgA,IL-2, IL-6 and TNFα between the two groups (P＞0.05).CONCLUSION: There are no differences in immune responses between the patients having laparoscopic total mesorectal excision with anal sphincter preservation and those undergone open surgery for rectal cancer.

Tumor micrometastases in mesorectal lymph nodes and their clinical significance in patients with rectal caner

AIM: To investigate the number, size, and status of lymph nodes within the mesorectum and to explore the prognostic significance of lymph node micrometastases in patients with rectal cancer. METHODS: Thirty-one patients with rectal cancer undergone total mesorectal excision between October 2001 and October 2002 were included. Mesorectal nodes retrieved from the resected specimens were detected with a combination of haematoxylin and eosin (HE) staining and immunohistochemistry (IHC). The relations between lymph node metastases, micrometastases and postoperative recurrence were analyzed. RESULTS: A total of 548 lymph nodes were harvested, with 17.7±8.2 nodes per case. The average number of metastatic nodes in HE-positive patients and micrometastatic nodes in IHC-positive patients was 5.2±5.1 per case and 2.2±1.3 per case, respectively. The mean size of all nodes and metastatic nodes was 4.1±1.8mm and 5.2±1.7mm in diameter, respectively. The mean size of micrometastatic nodes was 3.9±1.4mm in diameter. The size of the majority of mesorectal nodes (66.8%), metastatic nodes (52.6%), and micrometastatic nodes (79.5%) was less than 5mm in diameter. During a median follow-up period of 24.6±4.7mo, 5 patients (16.7%) had recurrence, of them 2 died and 3 survived. Another case died of tumor unrelated cause and was excluded. All 5 recurrent cases had 3 or more nodes involved, and one of them developed only lymph node micrometastases. The mean number of both metastatic and micrometastatic nodes per case differed significantly between the recurrent and non-recurrent groups (P<0.01 and P=0.01, respectively). CONCLUSION: The majority of lymph nodes, metastatic, and micrometastatic lymph nodes within the mesorectum are smaller than 5mm in diameter. The nodal status and the number of lymph nodes involved with tumor metastases and micrometastases are related to the rapid postoperative recurrence.

Role of COX-2 in microcirculatory disturbance in experimenta pancreatitis

AIM: To elucidate the role of COX-2 in the development of capillary leakage in rats with acute interstitial pancreatitis. METHODS: Rats with acute interstitial pancreatitis were induced by caerulein subcutaneous injection. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the gene expression of COX-2 in pancreatic tissues, spectrophotometry was used to assay the parameters of acute pancreatitis such as the serum amylase and plasma myeloperoxidase, and determination of capillary permeability in the pancreas by quantifying the permeability index (PI)assisted response of pancreatic microvascular via intravital fluorescence microscope video image analysis system.RESULTS: A significant increase of COX-2 expression,elevation of serum amylase, and plasma myeloperoxidase were detected in rats with acute edematous pancreatitis compared with control rats. The changes of pancreatic microvascular after caerulein injection were as following: (a)the decrease of pancreatic capillary blood flow (4th h,0.56±0.09 nL/min, P＜0.05; 8 th h, 0.34±0.10 nL/min, P＜0.001);(b) reduction of functional capillary density (4 bh h, 381±9 cm^-1,P＞0.05; 8th h, 277±13 cm^-1, P＜0.001); (c) irregular and intermittent capillary perfusion was observed at the 8th h and these vessels were also prone to permeation.CONCLUSION: COX-2 plays an important role in mediating capillary permeability in pancreatitis, thereby contributing to capillary leakage.

Microscopic spread of low rectal cancer in regions of mesorectum:Pathologic assessment with whole-mount sections

AIM: To assess the microscopic spread of low rectal cancer in mesorectum regions to provide pathological evidence for the necessity of total mesorectal excision (TME). METHODS: A total of 62 patients with low rectal cancer underwent low anterior resection and TME, surgical specimens were sliced transversely on the serial embedded blocks at 2.5 mm interval, and stained with hematoxylin and eosin (HE). The mesorectum on whole-mount sections was divided into three regions: outer region of mesorectum (ORM), middle region of mesorectum (MRM) and inner region of mesorectum (IRM). Microscopic metastatic foci were investigated microscopically on the sections for the metastatic mesorectal regions, frequency, types, involvement of lymphatic vessels and correlation with the original rectal cancer. RESULTS: Microscopic spread of the tumor in mesorectum and ORM was observed in 38.7% (24/62) and 25.8% (16/62) of the patients, respectively. Circumferential resection margin (CRM) with involvement of microscopic metastaticfoci occurred in 6.5% (4/62) of the patients, and distal mesorectum (DMR) involved was 6.5% (4/62) with the spread extent within 3 cm of low board of the main lesions. Most (20/24) of the patients with microscopic metastasis in mesorectum were in Dukes C stage. CONCLUSION: Results of the present study support that complete excision of the mesorectum without destruction of the ORM is essential for surgical management of low rectal cancer, an optimal DMR clearance resection margin should be no less than 4 cm, further pathologic assessment of the regions in extramesorectum in the pelvis is needed.

Pathological study of distal mesorectal cancer spread to determine a proper distal resection margin

AIM: Local recurrence after curative surgical resection for rectal cancer remains a major problem. Several studies have shown that incomplete removal of cancer deposits in the distal mesorectum contributes a great share to this dismal result. Clinicopathologic examination of distal mesorectum in lower rectal cancer was performed in the present study to assess the incidence and extent of distal mesorectal spread and to determine an optimal distal resection margin in sphincter-saving procedure.METHODS: We prospectively examined sepecimens from 45 patients with lower rectal cancer who underwent curative surgery. Large-mount sections were performed to microscopically observe the distal mesorectal spread and to measure the extent of distal spread. Tissue shrinkage ratio was also considered. Patients with involvement in the distal mesorectum were compared with those without involvement with regard to clinicopathologic features.RESULTS: Mesorectal cancer spread was observed in 21patients (46.7%), 8 of them (17.8%) had distal mesorectal spread. Overall, distal intramural and/or mesorectal spreads were observed in 10 patients (22.2%) and the maximum extent of distal spread in situ was 12 mm and 36 mm respectively. Eight patients with distal mesorectal spread showed a significantly higher rate of lymph node metastasis compared with the other 37 patients without distal mesorectal spread (P = 0.043).CONCLUSION: Distal mesorectal spread invariably occurs in advanced rectal cancer and has a significant relationship with lymph node metastasis. Distal resection margin of 1.5 cm for the rectal wall and 4 cm for the distal mesorectum is proper to those patients who are arranged to receive operation with a curative sphincter-saving procedure for lower rectal cancer.

Changes of cytosolic [Ca^(2+)]i in neutrophils in pancreatic microcirculation of rats with caerulein-induced acute pancreatitis under fluid shear stress

AIM: To investigate the fluid shear stress induced changes of [Ca^2+]i in neutrophils in pancreatic microcirculation of experimental acute pancreatitis (AP).METHODS: Wistar rats (n = 36) were randomized into three groups. A model of AP was established by subcutaneous injection of caerulein. Low-shear 30 viscometer was used to provide steady fluid shear stress on separated neutrophils. The mean fluorescent intensity tested by flow cytometry was used as the indication of [Ca2+]i quantity.RESULTS: Under steady shear, cytosolic [Ca^2+]i showed biphasic changes. The shear rate changed from low to high, [Ca^2+]i in different groups decreased slightly and then increased gradually to a high level (P<0.05). A close correlation was observed between the cytosolic [Ca^2+]i level and the alteration of fluid shear stress in regional microcirculation of AP. CONCLUSION: The increase of [Ca^2+]i is highly related to the activation of neutrophils, which contributes to neutrophil adhesion to endothelium in the early phase of AP. The effect of fluid shear stress on [Ca^2+]i may play a crucial role in pancreatic microcirculatory failure of AP.

Differences in platelet endothelial cell adhesion molecule-1 expression between peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis

AIM: To investigate the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1) expression on polymorphonuclear leukocytes (PMNs) in peripheral circulation and pancreatic microcirculation in cerulein-induced acute edematous pancreatitis (AEP).METHODS: Fifty Wistar rats were randomly divided into control group (n=10) and AEP group (n=40). A model of AEP was established by subcutaneous injection of cerulein 5.5 and 7.5 μg/kg at 0 and 1 h after the beginning of experiment respectively. PECAM-1 expression on PMNs from splenic vein and inferior vena cava was determined by RT-PCR at mRNA level and determined by flow cytometry at protein level.RESULTS: In experimental rats, an increased PECAM-1mRNA expression was seen from 4 to 8 h of AEP in peripheral circulation (0.77±0.25%, 0.76±0.28%, 0.89±0.30%,1.00±0.21% ), while in pancreatic microcirculation,expression decreased from 2 h and reached the lowest level at 6 h of AEP (0.78±0.29%, 0.75±0.26%, 0.62±0.28%,0.66±0.20%). There were significant differences at 8-h time point of AEP between peripheral circulation and pancreatic microcirculation (1.00±0.21% vs0.66±0.20%, P＜0.05).Meanwhile,the difference at protein level was also found.CONCLUSION: A reverse expression of PECAM-1 on PMNs was found between peripheral circulation and pancreatic microcirculation, suggesting that inhibition of PECAM-1expression may improve the pathological change of AEP.

Nodal spread and micrometastasis within mesorectum

AIM: To study the distribution of positive lymph nodes within mesorectum and to investigate the possible micrometastasis in negative lymph nodes. METHODS: Large slice technique combined with tissue microarray was used in the pathologic study of 31 specimens.RESULTS: A total of 992 lymph nodes were harvested and cancer metastasis was found in 148 lymph nodes. Some positive lymph nodes were located in the outer layer of mesorectum and more at the same site of mesorectum as the primary tumor. Circumferential margin lymph node metastasis was observed in nine cases. No significant difference in occurrence of micrometastasis was observed in different stage tumors. CONCLUSION: Positive lymph nodes are distributed in mesorectum and micrometastasis can be found in negative lymph nodes.