Surgical management of gallbladder sarcomatoid carcinoma

AIM:To study the behavior as well as optimal treatment of gallbladder sarcomatoid carcinoma, we reviewed the results of treatment of gallbladder sarcomatoid carcinoma from Chang Gung Memorial Hospital. METHODS:From 1987 to 2005,six patients were diagnosed with gallbladder sarcomatoid carcinoma and treated at our institution.Tumor staging was based on 2002 revised tumor-node-metastasis(TNM)staging for gall bladder cancer from the American Joint Committee on Cancer.The clinical presentation,laboratory data and preoperative workup were reviewed retrospectively. RESULTS:Five patients were female and one was male.The age ranged from 51 to 66 years(median, 58 years).Surgical procedures included three curative resections,two palliative resections and one biopsy. There were two surgical complications(33.3%)and one case of surgical mortality(16.7%).The followup time ranged from 30 d to 5 mo.The median survival was 2.5 mo.The prognosis was extremely poor,even after curative resection and postoperative chemotherapy. CONCLUSION:The prognosis of gallbladder sarcomatoid carcinoma was not dependent on TNM stage and was always dismal.The clinicopathological features were different from those of gall bladder cancer.

Predictive factors for lymph node metastasis in early gastric cancer

AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumorswith LNM. Univariate analysis found that female gen-der, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. CONCLUSION: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.

Prognosis and feasibility of en-bloc vascular resection in stage Ⅱ pancreatic adenocarcinoma

AIM:To establish the prognosis and feasibility of en-bloc vascular resection of stage pancreatic adenocarcinoma of the head and uncinate process.METHODS:We retrospectively analyzed 87 patients with stage pancreatic adenocarcinoma,who were subjected to pancreaticoduodenectomy (PD) and pylo-rus-preserving PD (PPPD) between 1996 and 2006 in Chang Gung Memorial Hospital,Taiwan. Twelve and 75 patients underwent PD/PPPD with and without resection of portal vein/superior mesenteric vein (PV/SMV),respectively.RESULTS:The overall 1-and 3-year survival rates of patients undergoing PD/PPPD with and without vas-cular resection were 50.0% and 16.7%,and 44.4% and 12.2%,respectively. Morbidity and mortality rates in the PV/SMV resection vs non-resection group were 50.0% and 0.0%,and 40.0% and 2.7%,respectively. In multivariate analysis,serum bilirubin,histological differentiation and adjuvant chemotherapy were independent prognostic factors that influenced survival.CONCLUSION:In stage adenocarcinoma of the pancreatic head and uncinate process,serum bilirubin,histological differentiation and adjuvant chemotherapy were independent prognostic factors,and en-bloc vascular resection is a feasible option in carefully selected patients.

Quercetin exerts anti-inflammatory effects via inhibiting tumor necrosis factor-α-induced matrix metalloproteinase-9 expression in normal human gastric epithelial cells

BACKGROUND Gastric injury is the most common digestive system disease worldwide and involves inflammation,which can lead to gastric ulcer or gastric cancer(GC).Matrix metallopeptidase-9[MMP-9(gelatinase-B)]plays an important role in inflammation and GC progression.Quercetin and quercetin-rich diets represent potential food supplements and a source of medications for treating gastric injury given their anti-inflammatory activities.However,the effects and mechanisms of action of quercetin on human chronic gastritis and whether quercetin can relieve symptoms remain unclear.AIM To assess whether tumor necrosis factor-α(TNF-α)-induced MMP-9 expression mediates the anti-inflammatory effects of quercetin in normal human gastric mucosal epithelial cells.METHODS The normal human gastric mucosa epithelial cell line GES-1 was used to establish a normal human gastric epithelial cell model of TNF-α-induced MMP-9 protein overexpression to evaluate the antiinflammatory effects of quercetin.The cell counting Kit-8 assay was used to evaluate the effects of varying quercetin doses on cell viability in the normal GES-1 cell line.Cell migration was measured using Transwell assay.The expression of proto-oncogene tyrosine-protein kinase Src(cSrc),phospho(p)-c-Src,extracellular-signal-regulated kinase 2(ERK2),p-ERK1/2,c-Fos,p-c-Fos,nuclear factor kappa B(NF-κB/p65),and p-p65 and the effects of their inhibitors were examined using Western blot analysis and measurement of luciferase activity.p65 expression was detected by immunofluorescence.MMP-9 m RNA and protein levels were measured by quantitative reverse transcription polymerase chain reaction(q RT–PCR)and gelatin zymography,respectively.RESULTS q RT-PCR and gelatin zymography showed that TNF-αinduced MMP-9 m RNA and protein expression in a dose-and time-dependent manner.These effects were reduced by the pretreatment of GES-1 cells with quercetin or a TNF-αantagonist(TNFR inhibitor)in a dose-and timedependent manner.Quercetin and TNF-αantagonists decreased the TNF-α-induced phosphorylation of c-Src,ERK1/2,c-Fos,and p65 in a dose-and time-dependent manner.Quercetin,TNF-αantagonist,PP1,U0126,and tanshinone IIA(TSIIA)reduced TNF-α-induced c-Fos phosphorylation and AP-1–Luciferase(Luc)activity in a dose-and time-dependent manner.Pretreatment with quercetin,TNF-αantagonist,PP1,U0126,or Bay 11-7082 reduced TNF-α-induced p65 phosphorylation and translocation and p65–Luc activity in a dose-and timedependent manner.TNF-αsignificantly increased GES-1 cell migration,and these results were reduced by pretreatment with quercetin or a TNF-αantagonist.CONCLUSION Quercetin significantly downregulates TNF-α-induced MMP-9 expression in GES-1 cells via the TNFR-c-Src–ERK1/2 and c-Fos or NF-κB pathways.

Metabolomic alterations and chromosomal instability status in gastric cancer

AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS Nineteen GC patients were classified as CIN and nonCIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatographymass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.RESULTS In total,twelve men and seven women were enrolled, with a median age of 66 years(range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC(32-218 vs 2-17; P < 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-Nacetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels(all P < 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors(all P < 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.CONCLUSION Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.

Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy

AIM:To investigate the effect of pain relief after infu-sion of ropivacaine at port sites at the end of surgery.METHODS:From October 2006 to September 2007,72 patients undergoing laparoscopic cholecystectomy(LC) were randomized into two groups of 36 patients.One group received ropivacaine infusion at the port sites at the end of LC and the other received normal saline.A visual analog scale was used to assess postoperative pain when the patient awakened in the operating room,6 and 24 h after surgery,and before discharge.The amount of analgesics use was also recorded.The demographics,laboratory data,hospital stay,and perioperative complications were compared between the two groups.RESULTS:There was no difference between the two groups preoperatively in terms of demographic and lab-oratory data.After surgery,similar operation time,blood loss,and no postoperative morbidity and mortality were observed in the two groups.However,a significantly lower pain score was observed in the patients undergo-ing LC with local anesthesia infusion at 1 h after LC and at discharge.Regarding analgesic use,the amount of meperidine used 1 h after LC and the total used during admission were lower in patients undergoing LC with local anesthesia infusion.This group also had a shorter hospital stay.CONCLUSION:Local anesthesia with ropivacaine at the port site in LC patients signif icantly decreased post-operative pain immediately.This explains the lower meperidine use and earlier discharge for these patients.

Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: Two decades of experience at Chang Gung Memorial Hospital

AIM: To analyze the prognostic factors influencing the overall survival of peripheral cholangiocarcinoma (PCC) patients undergoing surgical treatment during 25 years at a single institution. METHODS: This study retrospectively reviewed prospectively collecting data about 373 patients with historically proven PCC who underwent surgical treatment between 1977 and 2001. RESULTS: Three hundred and seventy-three PCC patients (159 men and 214 women) underwent surgical treatment from 1977 to 2001. Among them, 187 PCC patients underwent hepatectomy and 135 had curative resection (curative resectability rate: 36.2%). The follow-up duration ranged from 1.05 to 167.6 mo (mean/median = 14.1/7.2 mo). Overall cumulative survival rates at 1, 3, and 5 years were 32.5%, 9.2%, and 4.1%, respectively. Univariate log-rank analysis identified the following as adverse influences on overall survival: presence of symptoms, absence of mucobilia, elevated CEA and CA 19-9 levels, non-papillary tumor type, receiving non-hepatectomy, advanced tumor staging, lack of post-operative chemotherapy, and radiotherapy. Meanwhile, multivariate Cox's proportional hazard analysis demonstrated that absence of mucobilia, non-papillary tumor type, advanced tumor staging, non-hepatectomy, and lack of post-operative chemotherapy were the five independent prognostic factors that adversely affected overall survival. CONCLUSION: Favorable overall survival of PCC patients undergoing surgical treatment depends on early tumor stage, presence of mucobilia, papillary tumor type, hepatic resection, and post-operative chemotherapy.

Molecular mechanism of therapeutic approaches for human gastric cancer stem cells

Gastric cancer(GC)is a primary cause of cancer-related mortality worldwide,and even after therapeutic gastrectomy,survival rates remain poor.The presence of gastric cancer stem cells(GCSCs)is thought to be the major reason for resistance to anticancer treatment(chemotherapy or radiotherapy),and for the development of tumor recurrence,epithelial–mesenchymal transition,and metastases.Additionally,GCSCs have the capacity for self-renewal,differentiation,and tumor initiation.They also synthesize antiapoptotic factors,demonstrate higher performance of drug efflux pumps,and display cell plasticity abilities.Moreover,the tumor microenvironment(TME;tumor niche)that surrounds GCSCs contains secreted growth factors and supports angiogenesis and is thus responsible for the maintenance of the growing tumor.However,the genesis of GCSCs is unclear and exploration of the source of GCSCs is essential.In this review,we provide up-todate information about GCSC-surface/intracellular markers and GCSC-mediated pathways and their role in tumor development.This information will support improved diagnosis,novel therapeutic approaches,and better prognosis using GCSC-targeting agents as a potentially effective treatment choice following surgical resection or in combination with chemotherapy and radiotherapy.To date,most anti-GCSC blockers when used alone have been reported as unsatisfactory anticancer agents.However,when used in combination with adjuvant therapy,treatment can improve.By providing insights into the molecular mechanisms of GCSCs associated with tumors in GC,the aim is to optimize anti-GCSCs molecular approaches for GC therapy in combination with chemotherapy,radiotherapy,or other adjuvant treatment.

Enterovesical fistula caused by a bladder squamous cell carcinoma

Enterovesical fistulas are not uncommon in patients with inflammatory or malignant colonic disease, however, fistulas secondary to primary bladder carcinomas are extremely rare. We herein reported a patient presenting with intractable urinary tract infection due to enterovesical fistula formation caused by a squamous cell carcinoma of the urinary bladder. This patient underwent en bloc resection of the bladder dome and involved ileum, and recovered uneventfully without urinary complaint. To the best of our knowledge, this is the first case reported in the literature.

Glycerophospholipids pathways and chromosomal instability in gastric cancer: Global lipidomics analysis

BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer(GC) into four subtypes, characterized by the chromosomal instability(CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection.AIM To explore the associations of CIN with downstream lipidomics profiles.METHODS We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P <0.05.RESULTS Twelve men and six women participated in this study; the participants had a median age of 67.5 years(range, 52–87 years) and were divided into CIN(n = 9)and non-CIN(n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine,phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels(phosphocholine, phosphatidylethanolamine, and phosphatidylinositol)were 1.4-to 2.3-times higher in the CIN group compared with the non-CIN group(P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN.CONCLUSION The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.