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.

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.

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.

Heme oxygenase-1 attenuates epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells has been regarded as an early mechanism of peritoneal fibrosis. A substantial and rapidly growing literature indicates that HO-1 provides the provenance for pathways that can interrupt virtually all major mechanisms of tissue injury. The effects of HO-1 expression on EMT, which plays a critical role in the development of peritoneal membrane (PM) fibrosis, are unknown and its roles in peritoneal fibrosis has not been studied, yet. METHODS: A piece of human omentum obtained from consenting patients undergoing elective abdominal surgery was used for study. We treated the human peritoneal mesothelial cells (HPMCs) with high glucose solution and HO-1 inducer (hemin, 10 µmol/L). To further investigate the pure effect of HO-1 on EMT of mesothelium, gene transfer of recombinant Adenovirus-harboring human HO-1 (Adv-HO-1 gene) to HPMCs was done. RESULTS: Exposure of HPMCs to HG solution resulted in an increase of the expression of mesenchymal markers such as α-smooth muscle actin (α-SMA) and was associated with a decrease in the expression of epithelial markers, E-cadherin. HO-1 protein expression was decreased in the same situation. Treatment of HPMCs with HO-1 inducer, hemin showed a dosage-dependent amelioration of HG induced changes in markers of EMT with increase of expression of HO-1. Human HO-1 gene transfection resulted in a significant increase in HO-1 expression and ameliorated HG-induced changes in expression of E-cadherin and α-SMA. CONCLUSION: Taken together, our results suggest that HO-1 has a critical role in the modulation of peritoneal fibrosis, and, more important, the suppression of EMT. This study is the first to show the beneficial effect of HO-1 on reversing EMT in MC.

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.

Enhanced S100A4 protein expression is clinicopathologically significant to metastatic potential and p53 dysfunction in colorectal cancer.

To investigate the expression levels of S100A4 in human colorectal carcinoma (CC) and its relationship with clinicopathological parameters and metastatic potential, 73 pathological specimens from patients with CC were examined for S100A4 expression by RT-PCR and immunohistochemistry. An increase of S100A4 mRNA was observed in 19/23 (82.6%) CC specimens, and S100A4 was up-regulated in 40/73 (54.7%) CC cases compared with non-neoplastic mucosal tissues. Upregulation of S100A4 was significantly related to invasion, nodal status, distant metastasis and p53 expression. Next, we investigated whether S100A4 could affect p53 transactivation and stability. Interestingly, it was revealed that treatment with exogenous S100A4 protein reduced transcriptional activity of p53 and abrogated the modification of calcium binding affinity of S100A4 protein. These findings suggested that S100A4 might be involved in the progression and metastasis of human CC, presumably via modulation of the wild-type p53 protein.

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.

[A case of subphrenic abscess with ileal fistula caused by metastatic adenocarcinoma of unknown origin].

Usual sources of subphrenic abscess with intestinal fistula are previous abdominal operation, inflammatory bowel disease and malignancy. Reported cases of intestinal fistula caused by adenocarcinoma were complicated by direct invasion. In this report, a 70-year-old male had a subphrenic abscess with intestinal fistula and the cause was a metastatic adenocarcinoma of unknown origin. As far as we know, this has not been reported previously in the literatures. The abscess went on chronic course for six months because intermittent administration of antibiotics modified its clinical presentation. The fistulous tract between the abscess and ileum was demonstrated by tubogram via the drainage catheter in abscess. The patient underwent surgical treatment because the cause of fistula was obscure. Invasion of the ileum by metastatic adenocarcinoma was diagnosed by the histologic examination of surgical specimen. Therefore, when a fistula develops without any apparent cause, there is a possibility of malignancy, and surgical approach must be considered. An early surgical approach will prevent the delay in treatment and reduce the mortality.

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.

The Bmi-1 oncoprotein is overexpressed in human colorectal cancer and correlates with the reduced p16INK4a/p14ARF proteins.

To clarify the roles of Bmi-1 in colorectal carcinoma, we examined the expression of Bmi-1 in 41 samples out of 46 colorectal carcinomas by reverse transcription-PCR, whereas all 46 were analyzed by immunostaining. In addition, we analyzed the expression patterns of Bmi-1 in association with p16INK4a and p14ARF (in mouse p19ARF) in a series of colorectal carcinomas. The level of Bmi-1 mRNA in the carcinoma tissues was significantly higher than those of the adjacent non-neoplastic colonic mucosal tissues. Immunohistochemistry for Bmi-1 showed moderate or strong expression levels in 65% (30/46) of colorectal carcinomas. Colorectal carcinomas with moderate or strong Bmi-1 expression were more likely to have low levels of the INK4 locus proteins (p16INK4a/p14ARF) (P<0.07). These results suggested that modulation of Bmi-1 protein might be involved in human colorectal carcinogenesis by repressing the INK4a/ARF proteins.

The role of hand-assisted laparoscopic surgery in a right hemicolectomy for right-sided colon cancer.

PURPOSE: The purpose of this study is to evaluate the perioperative and long-term oncologic outcomes of hand-assisted laparoscopic surgery (HALS) and standard laparoscopic surgery (SLS) and assess the role of HALS in the management of right-sided colon cancer. METHODS: The study group included 53 patients who underwent HALS and 45 patients who underwent SLS for right-sided colon cancer between April 2002 and December 2008. RESULTS: The patients in each group were similar in age, American Society of Anesthesiologist (ASA) score, body mass index, and history of previous abdominal surgeries. Eight patients in the HALS group and no patient in the SLS group exhibited signs of tumor invasion into adjacent structures. No differences were noted in the time to return of normal bowel function, time to toleration of diet, lengths of hospital stay and narcotic usage, and rate of postoperative complications. The median incision length was longer in the HALS group (HALS: 7.0 cm vs. SLS: 4.8 cm, P < 0.001). The HALS group had a significantly higher pathologic TNM stage and significantly larger tumor size (HALS: 6.0 cm vs. SLS: 3.3 cm, P < 0.001). The 5-year overall, disease-free, and cancer-specific survival rates of the HALS and the SLS groups were 87.3%, 75.2%, and 93.9% and 86.4%, 78.0%, and 90.7%, respectively (P = 0.826, P = 0.574, and P = 0.826). CONCLUSION: Although patients in the HALS group had more advanced disease and underwent more complex procedures than those in the SLS group, the short-term benefits and the oncologic outcomes between the two groups were comparable. HALS can, therefore, be considered an alternative to SLS for bulky and fixed right-sided colon cancer.

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.

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.