Single-Port Laparoscopic and Robotic Cholecystectomy in Obesity (>25 kg/m2).

BACKGROUND AND OBJECTIVES: Single-port cholecystectomy has emerged as an alternative technique to reduce the number of ports and improve cosmesis. Few previous studies have assessed obesity-related surgical outcomes following single-port cholecystectomy. In this study, technical feasibility and surgical outcomes of single-port laparoscopic cholecystectomy (SPLC) and robotic single-site cholecystectomy (RSSC) in obese patients were investigated. METHODS: We conducted a two-center collaborative study and retrospectively reviewed initial experiences of RSSC and SPLC in patients whose body mass index was over 25 kg/m2. Medical records of patients were reviewed. Clinical characteristics and short-term oncologic outcomes were considered and compared between SPLC and RSSC groups. RESULTS: RSSC and SPLC were performed in 39 and 78 patients, respectively. In comparative analysis, the total operative time was longer in the RSSC group (109.92 minutes vs. 60.99 minutes; P < .001).However, requiring additional port for completion of surgical procedure was less frequent in the RSSC group (0% vs. 12.8%; P = .029). Immediate postoperative pain score was not significantly different between the two groups (4.95 vs. 5.00; P = .882). However, pain score was significantly lower in the RSSC group at the time of discharge (1.79 vs. 2.38; P = .010). Conversion to conventional multiport cholecystectomy, intraoperative bile spillage, or complication rate was not significantly different between the two groups (P > .05). CONCLUSIONS: SPLC and RSSC could be safely performed in selected patients with high body mass index, showing no significant clinical differences.

Abdominal actinomycosis misconceived as intestinal lymphoma: Report of a case.

INTRODUCTION: Abdominal actinomycosis is a rare clinical entity and it is difficult to make the correct preoperative diagnosis because of its nonspecific clinical symptoms and varied radiological findings. The diagnosis is usually made after the patient undergoes an operation and tissue is available for pathological evaluation. When the diagnosis is made, the patient should be treated with the appropriate long-term antibiotics. PRESENTATION OF CASE: A 69-year-old male patient was transferred to our hospital complaining of a palpable mass, painful abdominal discomfort, weight loss, and night sweating. After colonoscopy and radiologic studies, our presumptive diagnosis was intestinal lymphoma combined with ileocecal intussusception. He was found to have abdominal actinomycosis after surgery and successfully treated with ampicillin for six months. DISCUSSION: Pre-operative radiological imaging in abdominal actinomycosis is unlikely to allow a definitive diagnosis, but CT scanning is the single most useful imaging modality. Although we performed preoperative radiological studies, including CT, none led to a diagnosis of abdominal actinomycosis, we mistakenly considered the case as intestinal lymphoma combined with ileocecal intussusception. CONCLUSION: Physicians should include abdominal actinomycosis in the differential diagnosis when an abdominal mass presents an irregular, infiltrative growth pattern, even though ileocecal intussusception is an extremely rare presentation in abdominal actinomycosis.

Impact of Adjuvant Therapy Type on Survival in Stage II/III Rectal Cancer Without Preoperative Chemoradiation: A Korean Multicenter Retrospective Study.

PURPOSE: This study compared the oncologic impact of postoperative chemotherapy and chemoradiotherapy on patients with rectal cancer without preoperative chemoradiation. METHODS: This retrospective study analyzed 713 patients with a mean follow-up of 58 months who had undergone radical resection for stage II/III rectal cancer without preoperative treatment in nine hospitals from January 2004 to December 2009. The study population was categorized a chemotherapy group (CG, n = 460) and a chemoradiotherapy group (CRG, n = 253). Five-year overall survival (OS) and disease-free survival (DFS) were analyzed, and independent factors predicting survival were identified. RESULTS: The patients in the CRG were significantly younger (P < 0.001) and had greater incidences of low rectal cancer (P < 0.001) and stage III disease (P < 0.001). Five-year OS (P = 0.024) and DFS (P = 0.012) were significantly higher in the CG for stage II disease; however, they were not significantly different for stage III disease. In the multivariate analysis, independent predictive factors were male sex, low rectal cancer and stage III disease for OS and male sex, abdominoperineal resection, stage III disease and tumor-positive circumferential margin for DFS. However, adjuvant therapy type did not independently affect OS (hazard ratio [HR], 1.243; 95% confidence interval [CI], 0.794-1.945; P = 0.341) and DFS (HR, 1.091; 95% CI, 0.810-1.470; P = 0.566). CONCLUSION: Adjuvant therapy type did not affect survival of stage II/III rectal cancer patients without neoadjuvant chemoradiotherapy. These results suggest that adjuvant therapy can be chosen based on the patient's condition and the policies of the surgeons and hospital facilities.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer.

PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Laparoscopic approach to mucocele of appendiceal mucinous cystadenoma: feasibility and short-term outcomes in 24 consecutive cases.

BACKGROUND: Mucocele of the appendix is an uncommon condition where luminal distention by mucin is usually attributable to a mucinous cystadenoma. From a surgical standpoint, it is critical that the mucin-filled tumor remains intact during resection. Spillage of mucin into peritoneal cavity may otherwise lead to pseudomyxoma peritonei. Although acute appendicitis is managed successfully by laparoscopic appendectomy, the potential for rupture has fueled concerns over laparoscopic resection of appendiceal mucoceles. Our aim was to evaluate feasibility, safety, and short-term outcomes of laparoscopic resection in patients with a mucocele of appendix secondary to mucinous cystadenoma. METHODS: Data collected prospectively at the Department of Surgery from October 2005 to December 2013 were reviewed, selecting all instances of preoperatively identified appendiceal mucoceles, which was confirmed as mucinous cystadenomas by histology after elective laparoscopic surgery. Patient demographics, surgical data (operative procedures and times, intraoperative complications), and short-term postoperative outcomes were analyzed retrospectively. RESULTS: Twenty-four consecutive patients (female 14) were studied. Mean age was 60.0 years (range 42-81 years). Surgical procedures included simple appendectomy (1/24, 4.2 %), partial cecectomy (15/24, 62.5 %), and ileocecal resection (8/24, 33.3 %). Mean operative time was 108.5 min (range 40-205 min). No intraoperative spillage of mucin occurred due to inadvertent rupture of tumor. Resection margins uniformly were negative for tumor. Mean maximal length and diameter of tumors were 7.9 cm (range 3.0-20.0 cm) and 3.2 cm (range 1.0-7.5 cm), respectively. One patient (4.2 %) suffered postoperative morbidity (wound infection). CONCLUSIONS: A laparoscopic approach proved feasible and safe for surgical management of appendiceal mucocele due to mucinous cystadenoma. However, long-term follow-up is warranted for more conclusive support.

Integration of open and laparoscopic approaches for rectal cancer resection: oncologic and short-term outcomes.

BACKGROUND: Laparoscopy is increasingly used for rectal cancer surgery. Laparoscopic surgery is not attempted for some suitable patients because of concerns for conversion or technical difficulty. This study aimed to evaluate oncologic and short-term outcomes for patients undergoing curative resection for rectal cancer via laparoscopic and open approaches. METHODS: A prospective database was reviewed to identify rectal cancer resections from 2005 to 2011. Patients who had primary rectal cancer within 15 cm of the anal verge were included in the study. Those with recurrent or metastatic disease were excluded. Patients were assigned to laparoscopic or open approaches preoperatively based on clinical criteria and imaging. All patients underwent a standard total mesorectal excision and followed a standardized enhanced recovery pathway. The oncologic and clinical outcomes were evaluated by approach. RESULTS: The analysis included 81 patients. The preoperative assignments consisted of 62 laparoscopic (77%) and 19 open (23%) procedures. Nine laparoscopic procedures (14.5%) were converted to open procedures. After a median follow-up period of 25 months, all oncologic outcomes were comparable. Three patients (two laparoscopic, one open) had a positive circumferential margin (≤1 mm). The laparoscopic and open groups were similar in terms of their 3-year disease-free periods (93.6 vs. 88.2%; P = 0.450) and overall survival periods (93.5 vs. 90.9%; P = 0.766). The local recurrence rate was 2.5%. CONCLUSIONS: Laparoscopic resection for rectal cancer can be attempted for most patients. Conversion to open procedure does not compromise clinical or oncologic outcomes. In practice, combining laparoscopic and open surgery optimizes resource use and results in at least equivalent outcomes.

Intestinal Anastomosis by Use of a Memory-shaped Compression Anastomosis Clip (Hand CAC 30): Early Clinical Experience.

PURPOSE: The safety and the efficacy of the compression anastomosis clip (Hand CAC 30) have been demonstrated by animal studies. This study was designed to evaluate the clinical validity of the Hand CAC 30 in enterocolic side-to-side anastomosis after colonic or enteric resections. METHODS: A non-randomized prospective data collection was performed for patients undergoing a side-to-side anastomosis using the Hand CAC 30. Eligibility criteria for the use of the Hand CAC 30 were for anastomoses between the colon and the ileum or between two small bowels. The primary short-term endpoint was the rate of anastomotic leakage. Other clinical outcomes, including intra- and postoperative complications, length of operation time and hospital stay, and the clip elimination time were recorded. RESULTS: A total of 63 patients (male, 36) underwent an enteric or right-sided colonic resection followed by a side-to-side anastomosis using the Hand CAC 30. Laparoscopic surgery was performed in 36 patients, in whom one patient who underwent a laparoscopic right hemicolectomy was converted to an open procedure (1/32, 3.1%). One patient with ascending colon cancer showed postoperative anastomotic leakage and died of co-morbid ischemic heart disease. There were no other surgical mortalities. The exact date of expulsion of the clip could not be recorded because most patients were not aware of clip elimination. No patients manifested clinical symptoms of anastomotic stricture. CONCLUSION: Short-term evaluation of the Hand CAC 30 anastomosis in patients undergoing enterocolic surgery proved it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.

Laparoscopic complete mesocolic excision for right colon cancer.

Laparoscopic colectomy for colon cancer has become a standard of care, with a number of publications highlighting its safety, improved postoperative recovery, and excellent oncologic outcomes. Complete mesocolic excision, recently reemphasized, is associated with superior oncologic outcomes, although this has not been discussed for laparoscopic surgery. A laparoscopic approach was performed for right colon cancer using a four-trocar technique. The key steps demonstrated are identification and high division of the ileocolic pedicle, medial-to-lateral mobilization of the ascending colon preserving the posterior mesocolic fascia, identification and high division of the right branch of the middle colic artery, mobilization of the greater omentum and hepatic flexure, completion of lateral mobilization of the ascending colon from the retroperitoneum, and mobilization of the small bowel mesentery up to the duodenum. A prospective series of 52 consecutive patients with right colon cancer underwent laparoscopic complete mesocolic excision with high-vessel ligation. Four of the patients required laparoscopic en bloc extended resections for local invasion. The median operative time was 136 min (interquartile range [IQR], 105-167 min), and the median blood loss was 20 ml (IQR, 10-45 ml). The median hospital stay was 3 days (IQR, 3-5 days). All the patients had an R0 oncologic resection with median margins of 12 cm, and a median of 22 lymph nodes (IQR, 18-29 lymph nodes) was retrieved. The median follow-up period was 38 months (IQR, 23-54 months). Of 14 patients with tumor-positive lymph nodes, 2 experienced distant recurrence. There were no local recurrences, but four patients experienced metastatic disease at a median of 37 months (IQR, 22-46 months). The median overall survival time was 38 months (IQR, 23-54 months). The embedded didactic video demonstrates a straight laparoscopic complete mesocolic excision with high-vessel ligation for a patient who had a right colon cancer. Laparoscopic right complete mesocolic excision is a safe and effective procedure associated with excellent 3-year oncologic outcomes and accelerated postoperative recovery.

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer.

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p < 0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p=0.002 and p=0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102-3.335; p=0.021).

Anastomosis by use of compression anastomosis ring (CAR™ 27) in laparoscopic surgery for left-sided colonic tumor.

PURPOSE: The safety and efficacy of the compression anastomosis ring (CAR™ 27) had been demonstrated by animal studies. This study was designed to evaluate clinical validity of the CAR™ 27 anastomosis in laparoscopic surgery for patients with left-sided colonic neoplasm. METHODS: Intracorporeal anastomosis using the CAR™ 27 (CAR group) was performed in 66 patients (male 35; median age, 64.5 years), and short-term results were compared with consecutive 116 patients (male 70; median age, 64 years) where the anastomosis was constructed by double stapling technique using a circular stapler for the same indications (stapled group). RESULTS: There were no statistically significant differences between the two groups in terms of gender, age, and distribution of pathologic lesion. The laparoscopic procedures, pathologic diagnosis/stage, and length of operation time and postoperative hospital stay were comparable between the two groups. Conversion rate in the CAR and stapled group was 3% and 6%, respectively. There was no surgical mortality in either group. No intraoperative complications associated with the CAR™ 27 anastomosis were encountered. One patient in the CAR group was complicated by anastomotic leakage and none in the stapled group (p = 0.36). There was intestinal obstruction in two patients, in whom one required re-operation for entrapped small bowel adhesions within pelvis. No patient in either group showed symptomatic anastomotic stricture. CONCLUSIONS: The anastomosis using the CAR™ 27 is an innovative technique. The CAR™ 27 anastomosis in patients undergoing laparoscopic colectomy for left-sided colonic tumor proved to be a safe and efficacious alternative to the standard double stapling technique.

Early experience of the compression anastomosis ring (CAR™ 27) in left-sided colon resection.

AIM: To evaluate clinical validity of the compression anastomosis ring (CAR™ 27) anastomosis in left-sided colonic resection. METHODS: A non-randomized prospective data collection was performed for patients undergoing an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27 between November 2009 and January 2011. Eligibility criteria of the use of the CAR™ 27 were anastomoses between the colon and at or above the intraperitoneal rectum. The primary short-term clinical endpoint, rate of anastomotic leakage, and other clinical outcomes, including intra- and postoperative complications, length of operation time and hospital stay, and the ring elimination time were evaluated. RESULTS: A total of 79 patients (male, 43; median age, 64 years) underwent an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27. Colectomy was performed laparoscopically in 70 patients, in whom two patients converted to open procedure (2.9%). There was no surgical mortality. As an intraoperative complication, total disruption of the anastomosis occurred by premature enforced tension on the proximal segment of the anastomosis in one patient. The ring was removed and another new CAR™ 27 anastomosis was constructed. One patient with sigmoid colon cancer showed postoperative anastomotic leakage after 6 d postoperatively and temporary diverting ileostomy was performed. Exact date of expulsion of the ring could not be recorded because most patients were not aware that the ring had been expelled. No patients manifested clinical symptoms of anastomotic stricture. CONCLUSION: Short-term evaluation of the CAR™ 27 anastomosis in elective left colectomy suggested it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.

Laparoscopic rectosigmoid flap vaginoplasty.

Various methods have been developed for vaginoplasty, of which the rectosigmoid flap has its own advantages including sufficient increase in the vaginal length and lower incidence of complications such as contracture or strain after vaginoplasty. Laparoscopic operation can greatly minimise the abdominal scar associated with laparotomy and allow cosmetically superior outcomes. Its minimally invasive procedure can also achieve rapid recovery and shorten the duration of hospital stay. Twelve patients (age range 18-40 years) had vaginoplasty using the rectosigmoid colon. We evaluated the ecological changes of the neovagina from the change of pH in the neovagina, culture of the normal flora, and vaginal wall biopsy taken 6 to 12 months postoperatively. Details of sexual activity were also examined. No patient from interviews developed vaginal narrowing as a result of the contracture that caused painful intercourse, or had smelly discharge or spontaneous bleeding from the vagina. Laparoscopic procedures may need only five-openings of 1-1.5 cm in diameter. Mean operating time was 130 minutes (IQR, 113-140) and duration of hospital stay 8.5 days (IQR, 7-11). Twelve months postoperatively the intravaginal pH was about 6. In one case, the histological test showed that the original columnar cell of the intestinal mucosa had been transformed to stratified squamous cell tissue. The key to the vaginoplasty is that it should give functional satisfaction and a minimal rate of complications. The laparoscopic rectosigmoid flap technique of vaginoplasty allowed less morbidity and excellent aesthetic and functional postoperative outcomes.

Prognostic implication of metastatic lymph node ratio in node-positive rectal cancer.

PURPOSE: The aim of this study was to evaluate the prognostic significance of the ratio between metastatic and examined lymph nodes (LNs) in patients with stage III rectal cancer. METHODS: A review was made of 175 (male, 98) patients with stage III rectal cancer of R0 resection. LN disease was stratified both by the American Joint Committee on Cancer/International Union Against Cancer nodal classification (pN) and by quartiles of the lymph node ratio (LNR). Disease-free survivals (DFS) were made using Kaplan-Meier curves and assessed by the log rank test and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Patients ranged in age from 29 to 83 (median, 60) years with median follow-up of 47 months (range, 13 to 181 months). months. There was a significant correlation between the number of metastatic LNs and the LNR (r = 0.8681, P < 0.0001). Cut-off points of LNR quartiles best to separate patients with regard to 5-year DFS were between quartile 2 and 3, and between 3 and 4 (LNR1, 2, and 3); the 5-year DFS according to such stratification was 89.6%, 55.8%, and 18.2% in LNR1, 2, and 3, respectively (P < 0.0001). Cox model identified the LNR as the most significant independent prognostic covariate; LNR2 showed 3.6 times (95% confidence interval [CI], 1.682 to 7.584; P = 0.0009) and LNR3, 18.7 times (95% CI, 6.872 to 50.664; P < 0.0001) more risky than LNR1. CONCLUSION: This study suggests that ratio-based LN staging, which reflects the number of LNs examined and the quality of LN dissection, is a simple and reliable system for prognostic LN stratification in patients with stage III rectal cancer.

Isolated primary schwannoma arising on the colon: report of two cases and review of the literature.

Primary schwannoma of the large intestine is an extremely rare neoplasm. Here, we report two cases of colonic schwannoma confirmed pathologically after laparoscopic resection. A 52-year-old female and a 59-year-old female were referred by their general practitioners to our coloproctologic clinic for further evaluation and management of colonic submucosal masses. Colonoscopies performed in our institution revealed round submucosal tumors with a smooth and intact mucosa in the mid-ascending and descending colon, respectively. Computed tomography (CT) scans showed an enhancing soft tissue mass measuring 2 × 2 cm in the right colon and well-defined soft tissue nodule measuring 1.5 × 1.7 cm in the proximal descending colon, respectively. We performed laparoscopic right hemicolectomy and segmental left colectomy under the preoperative impression of gastrointestinal stromal tumors. Two cases were both diagnosed to be benign schwannoma of the colon after immunohistochemical stains (S-100 (+), smooth muscle actin (-), CD117 (-), and CD34 (-)).

Adjuvant Chemotherapy Using the FOLFOX Regimen in Colon Cancer.

PURPOSE: Great progress has been made in the adjuvant treatment of colon cancer. The aim of this study was to evaluate the efficacy of postoperative adjuvant chemotherapy using the FOLFOX regimen in patients with stage III and high-risk stage II colon cancer. METHODS: Eighty-two patients who underwent a potentially curative resection for stage III or high-risk stage II colon cancer were enrolled in this retrospective study. They received FOLFOX4 or modified FOLFOX6. The primary endpoint was disease-free survival. RESULTS: During the median follow-up of 37 months (range, 21 to 61 months), 14 patients experienced disease relapse. The disease-free survival rate at 3 years was 82.9%: 84.6% for stage II and 82.6% for stage III. At the time of the analysis, 8 patients were dead from recurrence. The probability of overall survival at 5 years was 74.5%: 90% for stage II and 74.6% for stage III. Grade 3 or 4 hematologic adverse events included neutropenia (40.2%), anemia (2.4%), and thrombocytopenia (1.2%). Gastrointestinal toxicities included grade 3 or 4 nausea (4.9%) and stomatitis (2.4%). Peripheral sensory neuropathy was observed in 81.7% of the patients during treatment. Of the 11 patients (13.4%) who had grade 3 peripheral sensory neuropathy during treatment, grade 3 symptoms were persistent in 3 patients with gait disturbance at the time of analysis. No treatment-related deaths were recorded. CONCLUSION: Postoperative chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with stage III and high-risk stage II colon cancer.

Clinicopathological significance of p53, hypoxia-inducible factor 1alpha, and vascular endothelial growth factor expression in colorectal cancer.

BACKGROUND: The principal objective of this study was to evaluate the prognostic significances of p53, hypoxia inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) expression in colorectal cancer. MATERIALS AND METHODS: The tumor tissues of 311 patients with colorectal carcinoma that had undergone potentially curative resections were immunohistochemically assessed using monoclonal antibodies against p53, HIF-1α, and VEGF. RESULTS: Positivity rates of p53, HIF-1α, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1α expression in tumor tissues was determined to be correlated significantly with the expression of VEGF (p=0.040), and depth of invasion (p=0.019). Multivariate analysis demonstrated that HIF-1α was independently associated with poor overall survival (p=0.002). CONCLUSION: HIF-1α expression is associated with VEGF expression and angiogenesis in colorectal carcinoma. Additionally, the expression of HIF-1α in tumor tissue is associated with angiogenesis and poor overall survival in patients with colorectal cancer.

Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer.

BACKGROUND: Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis. METHODS: A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry. RESULTS: Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (p = 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (p = 0.531, p = 0.701, respectively) and overall survival (p = 0.563, p = 0.572, respectively). Multivariate analysis showed that VEGF (p = 0.032), CEA (p = 0.012), lymph node metastasis (p = 0.002), and TNM stage (p = 0.025) were independently associated with overall survival. CONCLUSIONS: Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.

Clinicopathological significance of nuclear factor-kappa B, HIF-1 alpha, and vascular endothelial growth factor expression in stage III colorectal cancer.

Nuclear factor-kappaB (NF-kappaB), hypoxia-inducible factor 1alpha (HIF-1alpha), and vascular endothelial growth factor (VEGF) are involved in cell proliferation, invasion, angiogenesis, and metastases. The principal objective of this study was to assess the prognostic significance of NF-kappaB, HIF-1alpha, and VEGF expression in stage III colorectal cancer. Tumor tissues from 148 patients with stage III colorectal carcinoma, all of whom underwent potentially curative resection, were immunohistochemically evaluated using monoclonal antibodies against NF-kappaB, HIF-1alpha, and VEGF. Positivity rates of NF-kappaB, HIF-1alpha, and VEGF were 47.3%, 42.6%, and 61.5%, respectively. NF-kappaB expression in tumor tissues was correlated significantly with HIF-1alpha expression (P < 0.001), VEGF expression (P = 0.044), and the presence of vascular invasion (P = 0.013). Univariate analysis demonstrated that NF-kappaB expression was associated with poor 5-year overall survival (55.8 months vs 76.9 months, P = 0.012). Multivariate analysis verified that NF-kappaB was independently associated with adverse outcomes (relative risk: 1.92, P = 0.049). However, HIF-1alpha and VEGF did not appear to be related to clinical outcomes. NF-kappaB expression in tumor tissue is associated with angiogenesis and poor 5-year overall survival in stage III colorectal cancer patients.

A case of pathologic splenic rupture as the initial manifestation of acute myeloid leukemia M2.

A pathologic splenic rupture refers to a rupture without trauma. A splenic rupture as the initial manifestation of acute myeloid leukemia is extremely rare. In this study, we described a rare case of acute myeloid leukemia presenting principally as an acute abdomen due to a pathologic splenic rupture in a 35-year old male patient. We can assert that a pathologic splenic rupture in hematologic diseases is a potentially life-threatening complication, which necessitates immediate operative intervention. Any such patient complaining about left upper abdominal tenderness should be closely observed, and further diagnostic investigations (ultrasonograph of the abdomen, abdominal CT scan) should be initiated in order to rule out a splenic rupture. The oncologist should be aware of this rare initial presentation of acute myeloid leukemia (AML) M2, as the condition generally necessitates a prompt splenectomy.

Efficacy on anaplastic thyroid carcinoma of valproic acid alone or in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative, or lactacystin.

The present study investigated the mechanism underlying the antitumor activity of the histone deacetylases inhibitor valproic acid (VPA), alone and in combination with doxorubicin, a synthetic chenodeoxycholic acid derivative (HS-1200), or the proteasome inhibitor lactacystin on cultured anaplastic thyroid carcinoma KAT-18 cells. Cell viability was evaluated by trypan-blue exclusion. Western blotting determined caspase and histone deacetylase activities and expression of poly(ADP)-ribose polymerase. Induction of apoptosis was identified by Hoechst staining, DNA electrophoresis, DNA hypoploidy and cell cycle phase analysis, and measurement of mitochondrial membrane potential. Subcellular translocation of apoptosis inducing factor and caspase-activated DNase after treatment was determined by confocal microscopy following immunofluorescent staining. VPA treatment increased apoptotic death of KAT-18 cells. VPA treatment was also associated with degradation of procaspase-3, procaspase-7, and poly(ADP)-ribose polymerase; induction of histone hyperacetylation; condensation of peripheral chromatin; decreased mitochondrial membrane potential and DNA content; and decreased translocation of apoptosis inducing factor and caspase-activated DNase. VPA in combination with doxorubicin, HS-1200, or lactacystin, applied at the highest concentrations that did not induce KAT-18 cell death, efficiently induced apoptosis in KAT-18 cells. The results suggest VPA combination therapy may represent an alternative therapeutic strategy for anaplastic thyroid carcinoma.