Prognostic value of preoperative protein-induced vitamin K absence or antagonist II after liver resection for hepatitis B-related hepatocellular carcinoma: a nationwide multicenter study.

Purpose: Although protein-induced vitamin K absence or antagonist II (PIVKA-II) has been used as a diagnostic tool for hepatocellular carcinoma (HCC), its prognostic value remains unclear. Methods: This was a nationwide multicenter study using the database of the Korean Liver Cancer Association. Patients with hepatitis B-related HCC who underwent liver resection as the first treatment after initial diagnosis (2008-2014) were selected randomly. Propensity score matching (1:1) was performed for comparative analysis between those with low and high preoperative PIVKA-II. Univariable and multivariable Cox proportional-hazards regression were used to identify prognostic factors for HCC-specific survival. Results: Among 6,770 patients, 956 patients were included in this study. After propensity score matching, the 2 groups (n = 245, each) were well balanced. The HCC-specific 5-year survival rate was 80.9% in the low PIVKA-II group and 78.7% in the high PIVKA-II group (P = 0.605). In univariable analysis, high PIVKA-II (>106.0 mAU/mL) was not a significant predictor for worse HCC-specific survival (hazard ratio [HR], 1.183; 95% confidence interval [CI], 0.76-1.85; P = 0.461). In multivariable analysis, hyponatremia of <135 mEq/L (HR, 4.855; 95% CI, 1.67-14.12; P = 0.004), preoperative ascites (HR, 4.072; 95% CI, 1.59-10.43; P = 0.003), microvascular invasion (HR, 3.112; 95% CI, 1.69-5.74; P < 0.001), and largest tumor size of ≥5.0 cm (HR, 2.665; 95% CI, 1.65-4.31; P < 0.001), but not preoperative high PIVKA-II, were independent predictors for worse HCC-specific survival. Conclusion: Preoperative PIVKA-II is not an independent prognostic factor for HCC-specific survival after liver resection for hepatitis B-related HCC.

Is Laparoscopic Complete Mesocolic Excision and Central Vascular Ligation Really Necessary for All Patients With Right-Sided Colon Cancer?

Colon cancer treatment is on the way to evolution over several decades. The minimally invasive surgery has improved postoperative short-term outcomes. Adjuvant chemotherapy has prolonged the survival of advanced colon cancer patients. Hohenberger proposed the noble concept of complete mesocolic excision (CME) which consists of 3 components: plane surgery, sufficient longitudinal bowel resection, and central vascular ligation (CVL). Mesocolic plane surgery shares the same surgical principle of total mesorectal excision, which is maintaining the intact mesothelial envelope. However, there remain debates about the extent of bowel resection and the level of CVL for maximizing lymph node dissection. There is no solid clinical evidence for the oncological necessity and benefit of extended radical dissection in right hemicolectomy. CME with CVL based on open surgery has been adopted in laparoscopic surgery. So, it is also necessary to look at how the CME could be transformed and successfully implanted in the laparoscopic era. Recent rapid advances in surgical technology and cancer biology are preparing for fundamental changes in cancer surgery. In this study, we reviewed the history, oncological necessity, and compatibility of CME for the right hemicolectomy in the laparoscopic era and outline the new perspectives on the evolution of cancer surgery.

Robotic Total Mesorectal Excision for Rectal Cancer: Current Evidences and Future Perspectives.

Despite the technical limitations of minimally invasive surgery, laparoscopic total mesorectal excision (LTME) for rectal cancer has short-term advantages over open surgery, but the pathological outcomes reported in randomized clinical trials are still in controversy. Minimally invasive robotic total mesorectal excision (RTME) has recently been gaining popularity as robotic surgical systems potentially provide greater benefits than LTME. Compared to LTME, RTME is associated with lower conversion rates and similar or better genitourinary functions, but its long-term oncological outcomes have not been established. Although the operating time of RTME is longer than that of LTME, RTME has a shorter learning curve, is more convenient for surgeons, and is better for sphincter-preserving operations than LTME. The robotic surgical system is a good technical tool for minimally invasive surgery for rectal cancer, especially in male patients with narrow deep pelvises. Robotic systems and robotic surgical techniques are still improving, and the contribution of RTME to the treatment of rectal cancer will continue to increase in the future.

Optimal Treatment Strategy and Natural History of Isolated Superior Mesenteric Artery Dissection Based on Long-Term Follow-up CT Findings.

BACKGROUND: Isolated superior mesenteric artery dissection (ISMAD) was previously considered a rare disorder; however, this condition has been increasingly diagnosed as time progressed. Although treatment regimen and treatment outcomes have become clearer, the optimal treatment strategy has not yet been well established. MATERIALS AND METHODS: This study included 54 patients diagnosed with ISMAD by computed tomography (CT) between November 2004 and December 2017. Thirteen patients were excluded from the analysis of natural course as 6 were lost to follow-up, and 7 underwent endovascular therapy. RESULTS: Of the 54 patients included in the study, 50 were male, and 4 were female. The mean age of the patients was 52.3 years (range 40-74). The mean follow-up duration was 18.5 months (range 1.0-131.0). Thirty-eight patients were symptomatic, and 16 were asymptomatic. All aneurysmal changes observed on follow-up CT scans were initially classified as type III or IV. Of these patients, 7 underwent endovascular therapy. The failure rate of conservative treatment was 13%. CONCLUSIONS: Conservative treatment is safe and effective if bowel necrosis or arterial rupture is not present. Symptomatic patients classified as type III or IV on the initial CT scan should be followed up. If there is recurrent pain or aneurysmal progression, endovascular therapy should be performed.

Squalene Epoxidase Correlates E-Cadherin Expression and Overall Survival in Colorectal Cancer Patients: The Impact on Prognosis and Correlation to Clinicopathologic Features

Squalene epoxidase (SE), coded by SQLE, is an important rate-limiting enzyme in the cholesterol biosynthetic pathway. Recently, the aberrant expression of SQLE, which is responsible for epithelial to mesenchymal transition (EMT), has been reported in various types of cancer. This study was undertaken to clarify the clinicopathologic implications of SE in patients with stage I to IV colorectal cancer (CRC). We also analyzed the expression patterns of SE in association with E-cadherin in a series of CRCs. We detected the cytoplasmic expression of SE in 59.4% of carcinoma samples by immunohistochemistry (IHC). There was a significant correlation between a high level of SE expression and lymphovascular (LV) invasion (p < 0.001), tumor budding (p < 0.001), invasion depth (p = 0.002), regional lymph node metastasis (p < 0.001), and pathologic TNM stage (p < 0.001). SE is more abundantly expressed at the invasive front, and reversely correlated with E-cadherin expression. Patients with SE-positive CRC had shorter recurrence-free survival (RFS) and poor overall survival (OS) than those with SE-negative CRC in multivariate analysis (p < 0.001 and p < 0.001, respectively). These data suggest that SE can serve as a valuable biomarker for unfavorable prognosis, and as a possible therapeutic target in CRCs.

TPL2 expression is correlated with distant metastasis and poor prognosis in colorectal cancer.

Tumor progression locus 2 (TPL2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K). The present study aimed to elucidate the clinicopathological significance and prognostic role of TPL2 expression in colorectal cancer (CRC) through immunohistochemistry. In the present study, the correlations between TPL2 expression and clinicopathological parameters, including survival rate, were investigated using 262 archival paraffin-embedded CRC tissue samples. In addition, the correlation between TPL2 expression and tumor-infiltrating lymphocytes was evaluated using immunoscore. High TPL2 expression was found in 40.1% of the 262 CRCs analyzed. Patients with high TPL2 expression had frequent distant metastasis compared to patients with low TPL2 expression. However, there was no significant correlation between high TPL2 expression and other clinicopathological parameters. High TPL2 expression was significantly correlated with low immunoscore. In subgroup analysis based on distant metastasis, there was a significant correlation between high TPL2 expression and low immunoscore in only CRCs without distant metastasis. High TPL2 expression significantly correlated with poor overall survival. In both CRCs with and without distant metastasis, CRCs with high TPL2 expression showed worse prognosis compared to CRCs with low TPL2 expression (P = .034 and P = .010, respectively). Taken together, our results showed that high TPL2 expression was significantly correlated with distant metastasis and low immunoscore. In addition, TPL2 expression can be useful for predicting the prognosis of patients with CRC.

Increased Expression of Thymosin ß4 Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer.

BACKGROUND: Thymosin ß4 is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin ß4 expression in human colorectal cancers (CRCs). METHODS: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin ß4 expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series. RESULTS: High expression of thymosin ß4 was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin ß4 showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin ß4 and HIF-1α were overexpressed and that thymosin ß4 expression increased in parallel with HIF-1α expression in CRC. CONCLUSIONS: A high expression level of thymosin ß4 indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin ß4 is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

Clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer: initial results in a center for minimally invasive surgery.

PURPOSE: A robotic system was mainly designed to allow precise dissection in deep and narrow spaces. We report the clinical and oncologic outcomes of totally robotic total mesorectal excision for rectal cancer. METHODS: Between July 2009 and January 2012, 60 consecutive patients undergoing robotic surgery for rectal cancer at the Eulji University Hospital were included. RESULTS: The mean total operation time, docking time, and surgeon console time were 466.8 ± 115.6, 7.5 ± 6.7, and 261 ± 87.5 min, respectively. Oral intake of diet was started at 3.3 ± 0.9 days and the mean hospital stay was 8.6 ± 2.4 days. All 60 procedures were technically successful without the need for conversion to open or laparoscopic surgery. Complications included anastomotic leakage, anastomotic stricture, postoperative bleeding, ileus, and perineal wound infection in 3 (5 %), 1 (1.7 %), 2 (3.3 %), 2 (3.3 %), and 1 (1.7 %) patient, respectively. The mean distal resection margin and total number of lymph nodes harvested was 3.1 ± 1.7 cm and 20.1 ± 11.5, respectively. During the mean follow-up period of 48.5 months (range, 7-75), the 4-year overall and disease-free survival rates were 87.7 and 72.8 %, respectively. CONCLUSIONS: A totally robotic approach for rectal cancer operations was a time-consuming procedure, although we already had a lot experience in laparoscopic colorectal surgery. However, the dexterity of the robotic surgery could enable the surgeon to expand the choice of surgical methods according to the condition of the rectal cancer without the need for conversion.

Predictive Factors to Distinguish Between Patients With Noncomplicated Appendicitis and Those With Complicated Appendicitis.

PURPOSE: Recently, randomized controlled trials have reported that conservative therapy can be a treatment option in patients with noncomplicated appendicitis. However, preoperative diagnosis of noncomplicated appendicitis is difficult. In this study, we determined predictive factors to distinguish patients with noncomplicated appendicitis from those with complicated appendicitis. METHODS: A total of 351 patients who underwent surgical treatment for acute appendicitis from January 2011 to December 2012 were included in this study. We classified patients into noncomplicated or complicated appendicitis groups based on the findings of abdominal computed tomography and pathology. We performed a retrospective analysis to find factors that could be used to discriminate between noncomplicated and complicated appendicitis. RESULTS: The mean age of the patients in the complicated appendicitis group (54.5 years) was higher than that of the patients in the noncomplicated appendicitis group (40.2 years) (P < 0.001), but the male-to-female ratios were similar. In the univariate analysis, the appendicocecal junction's diameter, appendiceal maximal diameter, appendiceal wall enhancement, periappendiceal fat infiltration, ascites, abscesses, neutrophil proportion, C-reactive protein (CRP), aspartate aminotransferase, and total bilirubin were statistically significant factors. However, in the multivariate analysis, the appendiceal maximal diameter (P = 0.018; odds ratio [OR], 1.129), periappendiceal fat infiltration (P = 0.025; OR, 5.778), ascites (P = 0.038; OR, 2.902), and CRP (P < 0.001; OR, 1.368) were statistically significant. CONCLUSION: Several factors can be used to distinguish between noncomplicated and complicated appendicitis. Using these factors, we could more accurately distinguish patients with noncomplicated appendicitis from those with complicated appendicitis.

Upregulation of stromal cell-derived factor 1α expression is associated with the resistance to neoadjuvant chemoradiotherapy of locally advanced rectal cancer: angiogenic markers of neoadjuvant chemoradiation.

The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor 1α (HIF­1α), vascular endothelial growth factor (VEGF), stromal cell­derived factor 1α (SDF-1α) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1α protein was downregulated after NCRT in the rectal cancer tissues (P<0.001, P=0.001 and P=0.044, respectively). However, SDF-1α was upregulated after NCRT (P<0.001). Moreover, upregulated expression of SDF-1α (P=0.016) and positive PlGF staining (P=0.001) after NCRT were significantly associated with resistance to NCRT. On multivariate analysis, positive PlGF staining after NCRT was found to be independently associated with resistance to NCRT (P=0.013). Our data suggest that SDF-1α and PlGF should be evaluated as new targets for NCRT in LARC.

Multicenter nonrandomized trial of ramosetron versus palonosetron in controlling chemotherapy-induced nausea and vomiting for colorectal cancer.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) have a negative impact on patients' quality of life and frequently pointed to as a major factor for treatment abandonment. Serotonin (5-HT3) receptor antagonist is considered as key treatment for CINV. Ramosetron and palonosetron are recently developed 5-HT3 receptor antagonists and known as more superior than other first-generation 5-HT3 receptor antagonists. The purpose of this study was to compare the efficacy of ramosetron and palonosetron and determine which drug is more effective for prevention of CINV. METHODS: Colorectal cancer patients treated with chemotherapy were enrolled consecutively. Patients were assigned to receive intravenous injection of ramosetron 0.3 mg or palonosetron 0.25 mg at 30 minutes before initiation of moderately emetogenic chemotherapy. Ramosetron group added oral administration of 0.1 mg ramosetron on the second and third days of chemotherapy. Efficacy parameter consisted of nausea and vomiting. RESULTS: Ninety-one patients received ramosetron and 89 patients received palonosetron. Presentation of vomiting and nausea symptoms was not significantly different between the two groups during acute (0-24 hours) and delayed period (after 24 hours). CONCLUSION: The incidence of CINV between the ramosetron and the palonosetron group has not shown any difference during acute, delayed, and overall period.

Treatment results for spontaneous isolated superior mesenteric artery dissection according to our previous guidelines and collective literature review.

BACKGROUND: Isolated superior mesenteric artery dissection (ISMAD) is not a rare disease. However, its optimal treatment strategy has not yet been established. METHODS: This study included 13 consecutive patients with ISMAD who were treated between April 2010 and July 2013 according to published treatment guidelines. Through a literature search, 10 studies on treatments and outcomes for ISMAD that were published from 2007 to the present were analyzed. RESULTS: In the present study, 11 patients had acute onset abdominal pain and 2 patients were asymptomatic. Twelve patients were treated with conservative treatment, whereas 1 patient underwent coil embolization. In the literature review, initial conservative treatment, endovascular procedure, and surgical repair were done in 172, 25, and 14 patients, respectively. Bowel resection was done in 8 patients (3.7%) due to bowel necrosis. Conservative treatment failed in 15 patients (6.8%) during follow-up. CONCLUSIONS: If bowel necrosis or arterial rupture was not present, conservative treatment of ISMAD was a safe and effective treatment. Aneurysmal type IV patients on computed tomography scan should be carefully followed up, and if there is a recurrence of pain or aneurysmal progression, an endovascular procedure could be safely performed.