Treatment of Complicated Hepatic Cystic Hydatidosis with Intrabiliary Rupture by Pericystectomy in Combination with Roux-en-Y Hepaticojejunostomy

This study retrospectively reviewed 9 cases of complicated hepatic cystic hydatidosis with intrabiliary rupture who were surgically treated with pericystectomy in combination with Roux-en-Y hepaticojejunostomy in our hospital from 2004 to 2010. The clinical features, results of laboratory tests, B-mode ultrasonography and CT, post-operative recovery, days of hospital stay after the operation and post-operative complications were statistically analyzed and the patients were followed up. The subjects in our series included 7 males and 2 females, whose average age was 50.78±7.58 years. Before operation, 9 patients suffered from pain of the right upper quadrant and jaundice, which, in 4 cases (44.45%), were accompanied with fever and chills. Preoperative B-mode ul-trosonography and CT showed that all the 9 patients had single hydatid cyst, with their diameter being 9.33±1.58 cm on average. The lesions involved segments Ⅴ, Ⅵ in 6 cases, and segment Ⅳ in 3 cases. By WHO classification, 7 cases were classified as CE3 and 2 cases as CE4. They all had choledochectasia. The subjects underwent the surgery uneventfully. Intraoperatively, 2–4 biliary fistula orifices were found, with the average of the orifice being (0.79±0.20) cm. After the operation, one patient developed incision infection, one had pulmonary infection and one suffered from reflux cholangitis. No anastomotic leaks or peri-operative deaths took place and follow-up revealed no recurrence and implantative metastasis. We are led to conclude that pericystectomy in combination with Roux-en-Y hepaticojejunostomy can achieve satisfactory results for the treatment of complicated hepatic cystic hydatidosis with intrabiliary rupture.

Food insecurity increases the risk of overweight and chronic diseases in adolescents: a systematic review and meta-analysis

To investigate the relationship between food insecurity(FI)and overweight/obesity(OW/OB)or corresponding chronic diseases in adolescents,33 studies with 181135 individuals were included in this meta-analysis.Six studies and 10 studies,reported a higher risk of overweight and obesity in adolescents experiencing FI,respectively(OR 1.38,95%CI 1.20‒1.58,P<0.0001;OR 1.11,95%CI 1.01‒1.22,P=0.035,respectively).Based on the pooled results,adolescents with severe FI had the highest risk of OW/OB(OR 1.45,95%CI 1.20‒1.75,P<0.0001).The pooled OR indicated no signifi cant association between FI and OW/OB,when the adolescents were stratifi ed into those under 6 years old and those between 6 and 18 years old.Eleven studies assessed the relationship between FI and the risk of chronic diseases.The anemia subgroup was significantly associated with FI(OR 1.67,95%CI 1.30‒2.13,P<0.0001).Severe FI was reported to increase the risk of hypertension(OR 1.59,95%CI 1.28‒1.98,P<0.0001).Furthermore,a pooled analysis revealed a signifi cant association between FI and the risk of chronic diseases in both 6 and 6-18-year-old subgroups.

Frequent Down-regulation and Deletion of KLF6 in Primary Hepatocellular Carcinoma

Kruppel-like factor 6 (KLF6) was reported as tumor suppressor in multiple cancers. However, loss of chromosomal locus spanning KLF6 is relatively infrequent in previous published studies. To explore the role of KLF6 in hepatocellular carcinoma (HCC), we examined the gene for expression change, loss of heterozygosity (LOH) and mutation in 26 HCC samples. The expression levels of KLF6 were significantly down-regulated in HCCs, as detected by qRT-PCR. LOH occurred in 11 (52%) of 21 tumors, and all the samples with LOH showed KLF6 down-regulation. The mutational frequency was 24%, and sequence changes located in activation domain of KLF6. Furthermore, MTT assay showed a significant antiproliferative effect of the wt KLF6 transfected in HepG2 hepatoblastoma cells. Fluorescence-activated cell sorting analysis revealed that KLF6 could induce apoptosis. These findings indicate that deregulation of KLF6, together with genetic abnormalities of allelic imbalance and mutations, may play a role in HCC pathogenesis.

Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

Objective: To investigate the expression of fragile histidine triad (FHIT) protein in normal colorectal tissue, colorectal adenoma and colorectal cancer (CRC), and to study the relationships between the expression of FHIT protein and the clinical pathology, the apoptosis-associated protein (Bcl-2, Bax, Survivin), apoptosis in colorectal cancer. Methods: Tissue microarray (TMA) and immunohistochemistry SP were used to detect the expression of FHIT gene, Bcl-2, Bax and Survivin in 16 cases of the normal colorectal tissue, 16 cases of colorectal adenoma and 80 cases of the colorectal cancer. TUNEL was used to detect the apoptosis index (AI) in 80 cases of the colorectal cancer. Results: (1) The positive rates of FHIT gene expression in normal colorectal tissue, colorectal adenoma and adenocancer were 93.75%, 68.75% and 46.25% respectively. There were no significant differences in the relationships between the FHIT gene expression and histological types, the gender as well as the age (P>0.05). There were significant relationships between FHIT gene expression and lymph node metastasis, histological grades, Duke’s system as well as the 5-year survival rate after operation. (2) The positive rates of Bax, Bcl-2 and Survivin in colorectal adenocancer were 72.50%, 51.25%, 77.50% respectively. The expression of FHIT gene was positively correlated with that of Bcl-2, Bax and Survivin. (3) The mean AI in FHIT negative tumors was significantly lower than that in FHIT positive tumors (P<0.01). Conclusion: FHIT gene may play a role in the oncogenesis and progression of colorectal cancer. The abnormal regulation of apoptosis may play an important role in the pathogenesis of colorectal cancer.

Decreased fragile histidine triad expression in colorectal cancer and its association with apoptosis inhibition

AIM: To detect the expression of fragile histidine triad (FHIT) in normal colorectal tissue, colorectal adenoma and colorectal cancer (CRC) tissue, and to analyze its relationship with the clinicopathological features of CRC, and apoptosis-associated proteins (Bcl-2, Bax, survivin) and apoptosis in colorectal cancer. METHODS: FHIT mRNA analysis was performed by nested reverse transcription-polymerase chain reaction (RT-PCR) assay. Tissue microarray (TMA) was established to detect the expression of FHIT, Bcl-2, Bax and survivin genes in 80 CRC tissue specimens, 16 colorectal adenoma tissue specimens and 16 hemorrhoid (PPH) tissue specimens during the same period of time as the control. Citrate-microwave-SP was used as immunohistochemical method. The relationship between clinicopathological factors, such as differentiation grades and 5-year survival rate was observed. TUNEL assay was used to detect the apoptosis index in 80 CRC tissue specimens. RESULTS: Ten out of 26 (38.5%) CRC tissue specimens expressed aberrant FHIT transcripts, none of the aberrant FHIT transcripts was observed in the matchednormal tissue and colorectal adenoma tissue by nested RT-PCR assay. The positive rate of FHIT gene expression in normal colorectal tissue, colorectal adenoma and carcinoma tissue was 93.75%, 68.75% and 46.25%, respectively. Clinicopathological analysis of patients showed that the decreased FHIT gene expression was not associated with age, sex, serum CEA levels, tumor site and size, histological classification. However, the expression of FHIT was correlated with differentiation grades, pathological stages, lymph node metastases and 5-year survival rate after operation. The positive rate of apoptosis-associated proteins (Bax, Bcl-2 and survivin) in CRC tissue was 72.50%, 51.25% and 77.50%, respectively. The expression of these apoptosis- associated proteins in CRC tissue was correlated with the expression of FHIT. The mean apoptosis index in FHIT negative tumors was significantly lower than that in FHIT positive tumors (5.41 ± 0.23 vs 0.56 ± 0.10, P < 0.01). CONCLUSION: The FHIT gene plays an important role in the regulation of apoptosis and decreased FHIT expression plays a key role in the initiation and progression of colorectal carcinoma.

Surgical treatment of hepato-pancreato-biliary disease in China:the Tongji experience

Hepato-pancreato-biliary(HPB) tumors are common in China. However, these tumors are often diagnosed at intermediate/advanced stages because of the lack of a systemic surveillance program in China. This situation creates many technical challenges for surgeons and increases the incidence of postoperative complications. Therefore, Dr. Xiao-Ping Chen has made many important technical improvements, such as Chen's hepatic portal occlusion method, the anterior approach for liver resection of large HCC tumors, the modified technique of Belghiti's liver-hanging maneuver, inserting biliary-enteric anastomosis technique, and invaginated pancreaticojujunostomy with transpancreatic U-sutures. These techniques are simple, practical, and easy to learn. Owing to these advantages, complicated surgical procedures can be simplified, and the curative effects are greatly improved. These improved techniques have been widely applied in China and will benefit many additional patients. In this review, we introduce our experience of surgically treating intermediate/advanced hepatocellular carcinoma(HCC), hilar cholangiocarcinoma(HC), and pancreatic carcinoma, mainly focusing on technical innovations established by Dr. Chen in HPB surgery.

Bone metastasis of hepatocellular carcinoma:facts and hopes from clinical and translational perspectives

Patients with hepatocellular carcinoma(HCC)and bone metastasis(BM)suffer from greatly reduced life quality and a dismal prognosis.However,BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades.To date,no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM.Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention.The risk factors,diagnosis,prognosis,and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists.We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions.We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities.Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms,as well as the development of novel effective therapies for HCC patients with BM.

Absence of FHIT expression is associated with apoptosis inhibition in colorectal cancer

The fragile histidine triad(FHIT)gene,a candidate tumor suppressor gene located at 3p14.2,has been shown to be involved in the carcinogenesis of many human tissues,including digestive tract tissues.However,the expression and the role of the FHIT in the initiation and the development of the colorectal cancer(CRC)are poorly understood.We have shown that the FHIT gene exhibits significantly decreased expression in human CRC compared to colorectal adenoma and normal colorectal tissue by tissue microarray(TMA).The positive rate of FHIT gene expression in normal colorectal tissue,adenoma and adenocarcinoma were 93.75%,68.75%and 46.25%,respectively.We show this decreased expression to be significantly correlated with the progression of colorectal carcinoma(P<0.05)as well as with differentiation and lymph node metastasis(P<0.05).We detected two somatic alterations in the FHIT gene in human CRC.The presence of this mutation correlated significantly with decreased FHIT expression in the human CRC.In our present study we tested the hypothesis that the decreased FHIT expression resulted in apoptosis inhibition associated with abnormal expression of apoptosis related proteins.To test this hypothesis we did a series of experiments.In the first test,we assessed apoptosis status using a standard TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling)assay by comparing FHIT-positive CRC vs.FHIT-negative CRC.In the second experiment,the protein expression of the FHIT and other apoptosis related proteins(Bax,Bcl-2 and Survivin)were measured in human CRC by TMA.Our combined results demonstrate the mutation in the FHIT gene significantly reduced FHIT expression in human CRC.Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and the up-regulation of Survivin and Bcl-2.Collectively,these studies identify the mechanism by which an important tumor suppressor gene,FHIT is inactivated specifically in human CRC contributing to our understanding of the mechanism of colorectal carcinogenesis.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

Resident to exhausted CD4+T cell ratio is associated with the prognosis of gastric cancer

Gastric cancer(GC)ranks fifth for cancer incidence and fourth for mortality globally.1 Clinical outcomes have varied among patients receiving similar treatments at the same stage,suggesting the current prognostic tools remain somewhat flawed.2,3 single-cell analysis of GC data allowed us to dissect transcriptional programs underlying lymphocyte residency and exhaustion.