The role of liver transplantation or resection for patients with early hepatocellular carcinoma.

Liver resection (LR) and liver transplantation (LT) are curative treatments for early hepatocellular carcinoma (HCC), although their performance remains debated. We compared the survival of patients with HCC conforming to the Milan criteria (MC) after LT and LR and analyzed factors affecting clinical outcomes. Between January 2006 and January 2013, 65 and 184 patients received LT and LR for HCCs fulfilling the MC, respectively. Overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. To investigate effects of liver function and living donor liver transplantation (LDLT) on survival, two subgroup analyses were performed and associations with OS and DFS were examined. We found that OS rates were higher after LT than after LR since 3 years postoperatively. DFS rates were significantly better after LT than after LR. Performance of LR, vascular invasion, and tumor multiplicity were associated with poor DFS, and factors affecting OS included the presence of vascular invasions, liver cirrhosis, and tumor multiplicity. In conclusion, despite of the effects of tumor characteristics on clinical outcomes, LT, including LDLT, should be considered the treatment of choice for patients with HCCs who met the MC. The role of LR is to identify poor prognostic factors through pathological examination.

CDH1 polymorphisms and haplotypes in sporadic diffuse and intestinal gastric cancer: a case-control study based on direct sequencing analysis.

BACKGROUND: Findings related to the influence of the -160C → A promoter polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case-control study to investigate the association of the CDH1 - 160C → A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis. METHODS: We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis. Genotype frequencies were compared. The CDH1 - 160C → A promoter polymorphism and four polymorphisms (48 + 6 T → C, 2076C → T, 2253C → T and 1937-13 T → C) were included in the haplotype analyses, which were estimated using the expectation-maximization algorithm. RESULTS: Compared to controls, the frequency of the -160A allele was significantly higher in diffuse gastric cancer cases (P = 0.005), but it was not significantly different in intestinal gastric cancer cases (P = 0.119). Two sets of three-marker haplotypes (-160C → A, 48 + 6 T → C, 2076C → T and -160C → A, 1937-13 T → C, 2253C → T) were associated with the risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively). CONCLUSION: Based on direct sequencing analysis, our findings suggest that the CDH1 - 160C → A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.

The Risk of Breast Cancer between Western and Mediterranean Dietary Patterns.

Breast cancer is a significant public health problem globally and prevention strategies have become of great interest as its incidence rises. Exploring the connection between dietary patterns and the reduction of breast cancer risk is considered a promising approach. High levels of fiber, phytochemicals, a good antioxidant profile, and a composition of advantageous fatty acids are characteristics of healthy dietary programs such as the Mediterranean diet. This review summarized and discussed the active compounds that are considered important in preventing breast cancer, including dietary components from recent related reports. These include polyunsaturated fatty acids, fiber, phytochemicals, and alcohol. Although the exact mechanism for preventing breast cancer using these dietary factors is not well understood, the combination of all the elements in a healthy diet plays a role in reducing breast cancer risk. Considering the elevated probability of breast cancer relapse and mortality, it is crucial to investigate the correlation between a nutritious dietary pattern and breast cancer, while identifying bioactive components that have the potential to mitigate the risk of breast cancer incidence.

Management of spontaneously ruptured hepatocellular carcinoma and hemoperitoneum manifested as acute abdomen in the emergency room.

BACKGROUND: Spontaneously ruptured hepatocellular carcinoma (HCC) with hemoperitoneum has a poor prognosis, especially in cases of cirrhosis. Patients usually present to emergency rooms (ERs) with acute abdomen. The aim of the present study was to determine the factors affecting mortality and to compare the prognosis of conservative treatment, transcatheter arterial embolization (TAE), or hepatectomy in these situations. METHODS: Fifty-four patients with spontaneously ruptured HCC diagnosed between January 2004 and August 2010 were enrolled in this retrospective review of clinical data. Grouping by survival or mortality, univariate and multivariate analyses of factors affecting 30-day mortality, and long-term survival were conducted. The outcomes of the various treatments were analyzed. RESULTS: After primary fluid resuscitation in the ER, 6 of 54 patients underwent conservative treatment. Emergency hepatectomy was performed on 19 patients; TAE was used for 29 patients, 18 of whom received staged hepatectomy thereafter. Poor liver function, prolonged international normalized ratio (INR), and conservative treatment were associated with increased 30-day mortality. Logistic regression analysis of cumulative survival revealed that INR ≥ 1.4, multiple intrahepatic HCC, and conservative treatment were related to poorer long-term survival. The patients who received hepatectomy, either immediate or staged after TAE, had higher survival rates of 85.2 % at 30 days and 62.2 % at 1 year. CONCLUSIONS: The treatment of ruptured HCC should be tailored to the individual case. Prolonged survival is possible in patients with preserved liver function through curative liver resection. Emergency physicians, radiologists, and surgeons play essential roles in managing these patients.

Transcutaneous electrical nerve stimulation on ST36 and SP6 acupoints prevents hyperglycaemic response during anaesthesia: a randomised controlled trial.

BACKGROUND AND OBJECTIVE: Hyperglycaemia is a common result of stress signals caused by pain and surgical procedure. Volatile anaesthetics also directly manipulate glucose homeostasis by affecting pancreatic insulin release and induce hyperglycaemia without surgical stress. We determined the preoperative application of transcutaneous electrical nerve stimulation (TENS) to the Chinese acupoints ST36 (Zusanli) and SP6 (Sanyinjiao) as a complementary therapy for controlling plasma glucose and improving insulin resistance during anaesthesia. METHODS: We designed a single-blind, randomised controlled clinical study of female patients, scheduled for elective hysterectomy. The 52 patients consented to enrolment and were assigned to receive either TENS (n = 26) on bilateral ST36 and SP6 acupoints with continuous mode at a frequency of 15 Hz and the intensity of 10 mA synchronously for 30 min or non-stimulation (placebo group, n = 26) preoperatively. Haemodynamics, blood glucose and plasma insulin were measured during general anaesthesia. RESULTS: At baseline, there was no significant difference between the TENS group and the placebo group in plasma glucose and insulin levels as well as homeostasis model assessment (HOMA) index. In the placebo group, plasma glucose, insulin and HOMA index increased during induction of general anaesthesia, surgical incision, and throughout the operation. Plasma glucose and insulin levels as well as HOMA index were significantly lower in the TENS group as compared to the placebo group at different time points after discontinuation of TENS application. These results indicate the positive effect of prevention of hyperglycaemia and the increased sensitivity of plasma insulin in the TENS group. CONCLUSION: We found TENS at bilateral ST36 and SP6 acupoints to be an alternative means of managing the plasma glucose level and improving insulin resistance perioperatively.

MicroRNA-21 Plays Multiple Oncometabolic Roles in Colitis-Associated Carcinoma and Colorectal Cancer via the PI3K/AKT, STAT3, and PDCD4/TNF-α Signaling Pathways in Zebrafish.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Patients with inflammatory bowel disease (IBD) have a high risk of developing CRC. Inflammatory cytokines are regulated by complex gene networks and regulatory RNAs, especially microRNAs. MicroRNA-21 (miR-21) is amongst the most frequently upregulated microRNAs in inflammatory responses and cancer development. miR-21 has become a target for genetic and pharmacological regulation in various diseases. However, the association between inflammation and tumorigenesis in the gut is largely unknown. Hence, in this study, we generated a zebrafish model (ImiR-21) with inducible overexpression of miR-21 in the intestine. The results demonstrate that miR-21 can induce CRC or colitis-associated cancer (CAC) in ImiR-21 through the PI3K/AKT, PDCD4/TNF-α, and IL-6/STAT3 signaling network. miR-21 activated the PI3K/AKT and NF-κB signaling pathways, leading to initial inflammation; thereafter, miR-21 and TNF-α repressed PDCD4 and its tumor suppression activity. Eventually, active STAT3 stimulated a strong inflammatory response and activated the invasion/metastasis process of tumor cells. Hence, our findings indicate that miR-21 is critical for the development of CRC/CAC via the PI3K/AKT, STAT3, and PDCD4/TNF-α signaling networks.

Transection of the esophagus is optional in the Modified Sugiura procedure.

BACKGROUND/AIMS: Esophageal transection in the Modified Sugiura procedure is advocated by some authors, but considered unnecessary by others. We compared the effectiveness of the Modified Sugiura procedure to our simplified Sugiura procedure that omits esophageal transection for the emergency treatment of bleeding esophagogastric varices. METHODOLOGY: From January 1999 to September 2004 we treated 51 patients with cirrhosis of the liver and bleeding esophagogastric varices. All patients had failed management with emergency endoscopy treatment or balloon tamponade with vasopressin infusion. The patients were randomly divided into two groups and underwent the Modified Sugiura procedure with or without esophageal transections. RESULTS: There were no significant differences in age, gender, cause of cirrhosis, or Child-Pugh classification between the two groups. The preoperative hemoglobin levels, preoperative and intraoperative transfusion volume, mortality, morbidity, and days of hospitalization showed no significant differences between the groups. The operative time was shorter with the simplified Sugiura procedure. The 1-3 year survival rates and the rebleeding rates did not differ significantly between the two groups. CONCLUSION: Both treatments are effective emergency procedures for bleeding esophagogastric varices. Our simplified Sugiura procedure is an effective treatment for bleeding esophagogastric varices and requires a shorter operating time than the Modified Sugiura procedure.

Management and patient survival in hepatocellular carcinoma: does the physician's level of experience matter?

INTRODUCTION: The prognostic determinants of hepatocellular carcinoma (HCC) depend on tumor stage, liver function reserve, and treatments offered. The clinical impact of the physician's experience on HCC management and the survival outcome is unknown. METHODS: A total of 103 patients were managed by one high-volume physician and 249 patients by seven low-volume physicians. The experience of high-volume physician in HCC management was five times more than that of low-volume physicians. Patient survival was the single end point for this study. RESULTS: Compared to the low-volume physician group, more of the patients allocated to the high-volume physician had early stage HCC on the date of diagnosis (66/103, 64.1%; vs 119/249, 47.8%; P = 0.008), and they received curative therapies including radiofrequency ablation or liver resection (66/103, 64.1% vs 54/249, 21.7%, P < 0.001), and had significantly better survival outcome (median survival of 34 months, 95% confidence interval [CI], 17.6-50.4; vs 6 months, 95% CI, 4.3-7.7; P < 0.001) with a multivariable-adjusted hazard ratio (HR) for survival of 1.94 (95%, CI, 1.31-2.87, P < 0.001). A multivariate analysis of the pretreatment prognostic factors for these two groups identified alpha-fetoprotein (AFP) level (HR, 1.42; 95% CI, 1.01-1.99; P = 0.042), ascites (HR, 1.68; 95% CI, 1.15-2.46; P = 0.007), maximum tumor diameter (HR, 1.78; 95% CI, 1.16-2.74; P = 0.009), and portal vein thrombosis (PVT) (HR, 2.17; 95% CI, 1.49-3.17; P < 0.001) as independent factors for the low-volume physician group. However, only maximum tumor diameter (HR, 4.54; 95% CI, 1.77-11.67; P < 0.001) and PVT (HR, 5.73; 95% CI, 2.30-14.22; P = 0.002) were independent factors for the high-volume physician group. CONCLUSION: The survival of HCC patients was dependent on the level of experience of the physicians who oversaw these patients.

Leptin promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-27b in human chondrosarcoma cells.

Chondrosarcoma is the second most frequently occurring type of bone malignancy that is characterized by the distant metastasis propensity. Vascular endothelial growth factor-C (VEGF-C) is the chief lymphangiogenic mediator, and makes crucial contributions to tumor lymphangiogenesis. Leptin is an adipocytokine and has been indicated to facilitate tumorigenesis, angiogenesis and metastasis. However, the effect of leptin on VEGF-C regulation and lymphangiogenesis in human chondrosarcoma has hugely remained a mystery. Our results showed a clinical correlation between leptin and VEGF-C as well as tumor stage in human chondrosarcoma tissues. We further demonstrated that leptin promoted VEGF-C production and secretion in human chondrosarcoma cells. The conditioned medium from leptin-treated chondrosarcoma cells induced lymphangiogenesis of human lymphatic endothelial cells. We also found that leptin-induced VEGF-C is mediated by the FAK, PI3K and Akt signaling pathway. Furthermore, the expression of microRNA-27b was negatively regulated by leptin via the FAK, PI3K and Akt cascade. Our study is the first to describe the mechanism of leptin-promoted lymphangiogenesis by upregulating VEGF-C expression in chondrosarcomas. Thus, leptin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.

CCL3 promotes angiogenesis by dysregulation of miR-374b/ VEGF-A axis in human osteosarcoma cells.

Osteosarcoma is the most frequent bone tumor, characterized by a high metastatic potential. However, the crosstalk between chemokine (C-C motif) ligand 3 (CCL3), which facilitates tumor progression and metastasis. Vascular endothelial growth factor-A (VEGF-A), an angiogenesis inducer and a highly specific mitogen for endothelial cells, has not been well explored in human osteosarcoma. Here we demonstrate the correlation of CCL3 and VEGF-A expressions, quantified by immunohistochemistry, with the tumor stage of human osteosarcoma tissues. Furthermore, CCL3 promotes VEGF-A expression in human osteosarcoma cells that subsequently induces human endothelial progenitor cell (EPC) migration and tube formation. Phosphorylation of JNK, ERK, and p38 was found after CCL3 stimulation. In addition, JNK, ERK, and p38 inhibitors also abolished CCL3-induced VEGF-A expression and angiogenesis. We noted that CCL3 reduces the expression of miR-374b and miR-374b mimic by reversing CCL3-promoted VEGF-A expression and angiogenesis in vitro and in vivo. This study shows that CCL3 promotes VEGF-A expression and angiogenesis in human osteosarcoma cells by down-regulating miR-374b expression via JNK, ERK, and p38 signaling pathways. Thus, CCL3 may be a new molecular therapeutic target in osteosarcoma angiogenesis and metastasis.

Giant malignant gastrointestinal stromal tumors: recurrence and effects of treatment with STI-571.

AIM: Malignant gastrointestinal stromal tumors (GISTs) are rare. Tumors larger than 10 cm tend to recur earlier: the larger the volume of the tumor, the worse the prognosis. We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kit tyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection. METHODS: We performed a retrospective analysis of the effects of resection on patients with giant GISTs (>10 cm in diameter) to determine the overall survival and recurrence rates. Twenty-three patients diagnosed with giant GISTs were included from June 1996 to December 2003. STI-571 was not available until January 2000. After that time, 9 patients received this drug. The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed. We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor. RESULTS: The positive surgical margin group had a significantly higher recurrence rate than the negative margin group (P = 0.012). A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test, P<0.05). Age, sex and tumor location were not significant prognostic variables. The 5-year survival rate of the surgical margin free patients was 80% and the 2-year survival rate of the surgical margin positive patients was 28%. The 5-year survival rate was 80% for the patients given STI-571 and 30% for the patients not given STI-571. The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection. CONCLUSION: A negative surgical margin and the use of STI-571 after surgical resection were good prognostic indicators. Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors. If STI-571 is used immediately when the surgical margin is positive and the tumor recurs after resection, then the prognosis of patients with giant GISTs can be improved.

Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy.

AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy (IPC). METHODS: Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation (group A), and 16 did not (group B). Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group (group C). All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization. RESULTS: Gender, the type of resection, operating time, blood loss, tumor status and amount of narcotics were comparable in the three groups. However, the group C patients were older than those in groups A and B (67.5+/-17.7 vs 56.8+/-13.2, 57.5+/-11.7 years, P = 0.048). First bowel flatus occurred after 4.35+/-0.93 d in group A, 4.94+/-1.37 d in group B, and 4.71+/-1.22 d in group C (P>0.05). Oral feeding of a soft diet was tolerated 7.21+/-1.92 d after operation in group A, 10.15+/-2.17 d in group B, and 7.53+/-1.35 d in group C (groups A and C vs group B, P<0.05). There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients. Levels of C-reactive protein (CRP) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met. CONCLUSION: The results suggest that a combination of intravenous Met and epidural pain control may be required to achieve a considerable decrease in time to resumption of oral soft diet in advanced gastric cancer patients who underwent gastrectomy and IPC. Furthermore, the administration of Met did not increase anastomotic leakage. Met has a role in the prevention of prolonged post-operative ileus.

The preoperative evaluation prevent the postoperative complications of thyroidectomy.

OBJECTIVE: Thyroid surgery is generally a safe surgery but its complications are still common. We wish to identify preoperative factors that predict postoperative complications. METHODS: A nationwide survey was conducted by senior surgeons from 16 medical centers and 5 regional hospitals in Taiwan to thyroid operations performed over 3 years. 3846 cases were retrospectively examined to identify factors influencing complications: indication for surgery, preoperative evaluation, such as ultrasonography, chest X-ray, computed tomography and magnetic resonance imaging, isotope scanning, fine-needle aspiration cytology (FNAC) and thyroid function test, and patient characteristics. RESULTS: Eighty-four percent of patients were female. Seven percent of the patients had immediate postoperative hypocalcemia (mild and severe) and 2.3%, hoarseness (recurrent laryngeal nerve (RLN) injury, temporary/permanent). Logistic regression analysis identified an association between hypocalcemia and RLN injury with age, hospital category, surgical procedure types (total thyroidectomy, unilateral, bilateral subtotal or total resection). A lower incidence of hypocalcemia was related to preoperative neck ultrasound and FNAC analysis (the odds ratio (OR) = 0.5 and 0.65, [95% confidence interval (CI) 0.331-0.768 and 0.459-0.911], P = 0.0014 and 0.0127, respectively), while RLN injury was not associated with any preoperative evaluation. The ORs of hypocalcemia and RLN injury for patients older than 50 years were 0.55 and 2.15, [0.393-0.763 and 1.356-3.4], P < 0.001 and 0.0012, respectively. CONCLUSIONS: The success of thyroid surgery depends on careful preoperative planning, including a preoperative neck ultrasound to determine the proximity of the nodule to the recurrent laryngeal nerve course, and the consideration of the type of anesthesia, adjuvant devices for intra-op monitoring of the RLN, and surgical modalities. Our results suggest that preoperative evaluation implementations are positively associated with strategy of surgery and postoperative hypocalcemia prevention.

Gallbladder contractility and volume characteristics in gallstone dyspepsia.

AIM: It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility. METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500 mL) and fatty meal in 10 normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group II). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups. RESULTS: In group I, there were significant decreases in gallbladder volumes 5-25 min after gastric distension, compared to fasting volumes. Compared to normal volunteers and group II, group I had significantly decreased gallbladder volumes 10-20 min after drinking 500 mL of normal saline and 10 to 50 min after eating fatty meal. CONCLUSION: Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.

Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients.

AIM: To investigate whether the non-invasive real-time Indocyanine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r(2)=0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients.

Comparison of transcatheter arterial chemoembolization, laparoscopic radiofrequency ablation, and conservative treatment for decompensated cirrhotic patients with hepatocellular carcinoma.

AIM: To compare the therapeutic effect of transcatheter arterial chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patients with hepatocellular carcinomas (HCC). METHODS: Between October 2000 and July 2003, one hundred patients with histologically proven primary HCC and clinical decompensated liver cirrhosis (Child classification B or C) were included in this study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE group), and forty received conservative treatment (control group). We compared the survival, recurrence, and complication rates in these three groups, making adjustment using the tumor metastatic node staging system. RESULTS: The major complication rate in the TACE group (9/20) was significantly higher than that in the LRFA group (7/40). For patients with TMN stage II HCC, the survival rate of the LRFA group was better than that of the TACE and control groups (P=0.003) but the recurrence rates between the LRFA and TACE groups did not differ. CONCLUSION: The LRFA group of patients had better clinical outcomes in terms of survival and complication rates in comparison with the TACE group or conservative treatment in patients with decompensated liver cirrhosis, especially in TMN patients with stage II HCC. LRFA is thus an appropriate alternative treatment for poor liver function among patients with HCC.

Severity of illness influences the efficacy of enteral feeding route on clinical outcomes in patients with critical illness.

BACKGROUND: Few trials have studied the influence of illness severity on clinical outcomes of different tube-feeding routes. Whether gastric or postpyloric feeding route is more beneficial to patients receiving enteral nutrition remains controversial. OBJECTIVE: To test whether illness severity influences the efficacy of enteral feeding route on clinical outcomes in patients with critical illness. DESIGN: A 2-year prospective, randomized, clinical study was conducted to assess the differences between the nasogastric (NG) and nasoduodenal (ND) tube feedings on clinical outcomes. PARTICIPANTS/SETTING: One hundred one medical adult intensive care unit (ICU) patients requiring enteral nutrition were enrolled in this study. INTERVENTION: Patients were randomly assigned to the NG (n=51) or ND (n=50) feeding route during a 21-day study period. Illness severity was dichotomized as "less severe" and "more severe," with the cutoff set at Acute Physiology and Chronic Health Evaluation II score of 20. MAIN OUTCOME MEASURES: Daily energy and protein intake, feeding complications (eg, gastric retention/vomiting/diarrhea/gastrointestinal bleeding), length of ICU stay, hospital mortality, nitrogen balance, albumin, and prealbumin. STATISTICAL ANALYSES PERFORMED: Two-tailed Student t tests and Mann-Whitney U tests were used to analyze significant differences between variables in the study groups. Multiple regression was used to assess the effects of illness severity and enteral feeding routes on clinical outcomes. RESULTS: Among less severely ill patients, no differences existed between the NG and ND groups in daily energy and protein intake, feeding complications, length of ICU stay, and nitrogen balance. Among more severely ill patients, the NG group experienced lower energy and protein intake, more tube feeding complications, longer ICU stay, and poorer nitrogen balance than the ND group. CONCLUSIONS: To optimize nutritional support and taking medical resources into account, the gastric feeding route is recommended for less severely ill patients and the postpyloric feeding route for more severely ill patients.

Early enteral 5% glucose infusion maintains the epidermal growth factor levels in the jejunal flap used for pharyngo-oesophageal reconstruction.

BACKGROUND: Free jejunal flap reconstruction is the main treatment for patients after pharyngo-oesophagectomy. Flaps are unavoidably subjected to ischaemia and reperfusion (I/R) during preparation. Enteral nutrition has been shown to improve the recovery of injured intestine, although the precise underlying mechanism remains unclear. This study was aimed to determine whether early enteral 5% glucose infusion is beneficial for the recovery of flap. Further, the possibility that enteral glucose infusion induces altered mucosal responses was evaluated. PATIENTS AND METHODS: Patients, who underwent free jejunal flap reconstructions after pharyngo-oesophagectomy, were enrolled. An externalised monitor loop was made to observe the viability of flap and to collect intestinal fluid. Control patients (n = 11) received peripheral parenteral nutrition for seven post-operation days. For early enteral-fed patients (n = 12), in addition to fluid infusion, administration of 5% glucose (25 ml h(-1)) via a jejunostomy tube was initiated 6h after surgery. Blood, flap fluid and mucosal specimens were harvested. Plasma and flap luminal levels of interleukin (IL)-6, IL-10, epidermal growth factor (EGF) and secretory immunoglobulin A (sIgA) were measured. Further, mucosal morphology was examined. RESULTS: There were no significant differences in either plasma or luminal concentrations of IL-6, IL-10 and sIgA at different time points between groups. The luminal EGF level in the control group reduced markedly from the 3rd postoperative day, contrasting with a well-maintained level in the early enteral-fed group. No significant difference in mucosal histology between groups was observed. CONCLUSION: Early enteral glucose infusion does not significantly benefit the ischaemia-reperfusion-injured flap; however, it does preserve EGF levels in the flap lumen.

Effect of weight loss on proinflammatory state of mononuclear cells in obese women.

In order to investigate whether weight loss can lead to improvement of the mononuclear cell (MNC) proinflammatory state, 21 nondiabetic obese women with mean age 34+/-2 years (mean+/-s.e.m.) and BMI 32.5+/-1.2 kg/m2 were enrolled in a 12-week caloric restriction and light exercise-based weight loss program. Ten lean women served as controls. Reverse transcription-PCR of proinflammatory cytokines and adipocytokines as well as homeostasis model assessment of insulin resistance (HOMA-IR) were determined before and after weight reduction. Nuclear factor kappaB (NF-kappaB) binding to DNA and inhibitors of NF-kappaB (IkappaB-alpha and IkappaB-beta) obtained from peripheral MNCs were measured. Overall, subjects lost a mean of 4.0+/-0.4 kg (5.0+/-0.3% of their initial body weight) (P<0.01). In addition to significant reductions in BMI, fasting glucose and insulin concentrations, mean serum high-sensitivity C-reactive protein (hs-CRP), migration inhibitor factor (MIF), leptin and visfatin levels decreased by 49.0, 66.6, 17.2, and 50.2%, respectively (all P<0.05), while adiponectin concentrations rose by 33.9% (P<0.05). The DNA binding of the transcriptionally active NF-kappaB from (p65/p50) decreased by 38.1% (P<0.05). Elevated levels of mRNA of NF-kappaB related proinflammatory genes, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), MIF, and matrix metalloproteinase-9 (MMP-9), decreased significantly after weight loss. Although mRNA expression of Rel-A, p105, IkappaB-alpha, IkappaB-beta decreased significantly, their protein levels did not change after weight loss. As a group, NF-kappaB binding activity correlated with HOMA-IR (r=0.332, P=0.049) and marginally with values of BMI (r=0.308, P=0.059). In conclusion, weight loss by 5% of initial weight in nondiabetic obese women led to significant improvement in activated intranuclear NF-kappaB binding as well as several transcriptions of proinflammatory genes regulated by NF-kappaB.

Periodic alterations of jejunal mucosa morphology following free microvascular transfer for pharyngoesophageal reconstruction.

BACKGROUND: Free jejunal flap reconstruction is the treatment of choice for patients after pharyngoesophagectomy. It remains unclear as to how the transplanted jejunal mucosal damage proceeds after the warm ischaemia. The current study aims to assess the relationship between the duration of ischaemia and the damage of jejunal mucosa. PATIENTS AND METHODS: From May 2002 to February 2003, 15 free jejunal flaps in 15 patients were transplanted to the cervical area for the reconstruction after pharyngoesophagectomy. Biopsy specimens were taken from the monitor loop at the time of pedicle ligation, 10 min after reperfusion, every day for 10 days, 14th day, 28th day, and 40th day after operation. Mucosal injury was assessed based on an accepted three-point scale which evaluates oedema, inflammation, mucosal necrosis or exfoliation, shortening of villi, and increase of goblet cells. FINDINGS: All 15 jejunal flaps survived. The mean ischaemia time was 68.7+/-5.2 min (range: 37-116). Serious injury to the mucosa was observed at 10 min after reperfusion, and gradually recovered until the 8th day, when it became normal in all flaps. The degree of damage was not found to be correlated with the length of ischaemia (less than 116 min). Severe ischaemia/reperfusion-induced mucosal damage occurs immediately following reperfusion and gradually recovers with time. The severity of the damage is not related linearly to the ischaemia time within 2h. The mucosa recovers gradually from the 8th day and returns to normal at the 28th day.