Surgery for gastric cancer patients of age 85 and older: Multicenter survey

To investigate the surgical therapies for gastric cancer (GC) patients of age 85 or older in a multicenter survey.METHODSTherapeutic opportunities for elderly GC patients have expanded in conjunction with extended life expectancy. However, the number of cases encountered in a single institution is usually very small and surgical therapies for elderly GC patients have not yet been standardized completely. In the present study, a total of 134 GC patients of age 85 or older who underwent surgery in 9 related facilities were retrospectively investigated. The relationships between surgical therapies and clinicopathological or prognostic features were analyzed.RESULTSEighty-nine of the patients (66%) presented with a comorbidity, and 26 (19% overall) presented with more than two comorbidities. Radical lymphadenectomy was performed in 59 patients (44%), and no patient received pre- or post-operative chemotherapy. Forty of the patients (30%) experienced perioperative complications, but no surgical or perioperative mortality occurred. Laparoscopic surgery was performed in only 12 of the patients (9.0%). Univariate and multivariate analyses of the 113 patients who underwent R0 or R1 resection identified the factors of pT3/4 and limited lymphadenectomy as predictive of worse prognosis (HR = 4.68, P = 0.02 and HR =2.19, P = 0.05, respectively). Non-cancer-specific death was more common in cStage I patients than in cStage II or III patients. Limited lymphadenectomy correlated with worse cancer-specific survival (P = 0.01), particularly in cStage II patients (P < 0.01). There were no relationships between limited lymphadenectomy and any comorbidities, except for cerebrovascular disease (P = 0.07).CONCLUSIONNon-cancer-specific death was not negligible, particularly in cStage I, and gastrectomy with radical lymphadenectomy appears to be an effective treatment for cStage II elderly GC patients.

Role of near-infrared fluorescence in colorectal surgery

Near-infrared fluorescence(NIRF)is a technique of augmented reality that,when applied in the operating theatre,allows the colorectal surgeon to visualize and assess bowel vascularization,to identify lymph nodes draining a cancer site and to identify ureters.Herein,we review the literature regarding NIRF in colorectal surgery.

Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy

AIM： TO re-evaluate the recent clinicopathological fea- tures of remnant gastric cancer （RGC） and to develop desirable surveillance programs.METHODS： Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural Uni- versity of Medicine, Japan. Of these, 33 patients un- derwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gas- tric cancer. The hospital records of these patients were reviewed retrospectively. RESULTS： Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter in- terval [P 〈 0.05; gastric cancer vs benign disease： 12 （2-22） vs 30 （4-51） years] and were more frequently reconstructed by Billroth- I procedure than those fol- lowing benign lesions （P 〈 0.001）. Regarding recon- struction, RGC following Billroth-]_l reconstruction showed a longer interval between surgical procedures [P 〈 0.001; Billroth-11 vs Billroth- I ： 32 （5-51） vs 12 （2-36） years] and tumors were more frequently associated with benign disease （P 〈 0.001） than those following Billroth- I reconstruction. In tumor location of RGC, after Billroth- I reconstruction, RGC occurred more fre- quently near the suture line and remnant gastric wall. After Billroth- 1I reconstruction, RGC occurred more fre- quently at the anastomotic site. The duration of follow- up was significantly associated with the stage of RGC （P 〈 0.05）. Patients diagnosed with early stage RGC such as stage Ⅰ-Ⅱ tended to have been followed up almost every second year. CONCLUSION： Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.

Optimal duration of the early and late recurrence of hepatocellular carcinoma after hepatectomy

AIM: To determine the best cut-off value between the early and late recurrence periods after the initial recurrence of hepatocellular carcinoma(HCC).METHODS: The clinical records of 404 patients who underwent macroscopic curative hepatectomy for HCC between 1980 and 2010 were retrospectively examined. We divided the 252 patients experienced a recurrence of HCC into two groups, the early and late recurrence groups using the "minimum P-value" approach. Factors for early recurrence were investigated using all 404 patients, and factors related to late recurrence were investigated in the patients who were confirmed to be recurrence free at the end of the early recurrence period.RESULTS: For the 252 patients who experienced a recurrence, the optimal cut-off value for differentiating early and late recurrence based on the overall survival after initial recurrence was 17 mo(5-year overall survival after initial recurrence: 15.4% vs 36.3%, P = 0.000018). Cox proportional hazard analysis identified early recurrence(P = 0.003) as one of the independent prognostic factors associated with overall survival after initial recurrence. A logistic regression model showed that an alpha-fetoprotein level > 100 ng/m L(P < 0.001), multiple HCC(P < 0.001), serosal invasion(P = 0.031), and microvascular invasion(P = 0.012) were independent factors associated with early recurrence, whereas the only independent factor related to late recurrence was liver cirrhosis(P = 0.002).CONCLUSION: Seventeen months after hepatectomy is a useful cut-off value between early and late recurrence of HCC based on the prognosis and different etiologies.

Liquid biopsy of gastric cancer patients:Circulating tumor cells and cell-free nucleic acids

To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called &#x0201c;liquid biopsy&#x0201d;, would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of &#x0201c;tailor-made&#x0201d; cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.

Reducing anastomotic leak in colorectal surgery: The old dogmas and the new challenges

Anastomotic leak(AL)constitutes a significant issue in colorectal surgery,and its incidence has remained stable over the last years.The use of intra-abdominal drain or the use of mechanical bowel preparation alone have been proven to be useless in preventing AL and should be abandoned.The role or oral antibiotics preparation regimens should be clarified and compared to other routes of administration,such as the intravenous route or enema.In parallel,preoperative antibiotherapy should aim at targeting collagenase-inducing pathogens,as identified by the microbiome analysis.AL can be further reduced by fluorescence angiography,which leads to significant intraoperative changes in surgical strategies.Implementation of fluorescence angiography should be encouraged.Progress made in AL comprehension and prevention might probably allow reducing the rate of diverting stoma and conduct to a revision of its indications.

Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt

We report a case of hepatocellular carcinoma (HCC) that caused a severe arterioportal shunt (APS). A 49-year-old man was admitted to hospital due to esophagogastric variceal hemorrhage and HCC, and underwent endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). He was then referred to our hospital. Abdominal computed tomography revealed a lowdensity lesion in the posterior segment of the liver and an intratumoral APS, which caused portal hypertension. Although the patient underwent EVL, EIS, Hassab’s operation, and transcatheter arterial embolization for APS, he vomited blood due to rupture of esophagogastric varices. Right hepatectomy was performed for the treatment of HCC and APS, although the indocyanine green retention value at 15 min after intravenous injection was poor (30%). The patient’s postoperative course was uneventful. Eventually, APS disappeared and the esophagogastric varices improved.

Recent advances in photodynamic diagnosis of gastriccancer using 5-aminolevulinic acid

Photodynamic diagnosis based on 5-aminolevulinic acidinduced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative realtime fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients

AIM： To clarify the expression change of Wnt-induced secreted protein-1 （WISP-l） in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer.METHODS： Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining.RESULTS： WISP-1 gene overexpression was found in 65% （56/86） primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues （P = 0.001）. The mRNA expression level was correlated with Duke＇s staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group （1.40±0.35） was different from that in control group （1.04± 0.08, P 〈 0.001）. Moreover, in cancer group the positive staining degree in high-level mRNA cancers （1.46 ±0.37, n = 56） was higher than that in low-level mRNA （1.28 ± 0.28, n = 30, P = 0.018）.CONCLUSION： Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer.

Clinicopathological characteristics of clinical early gastric cancer in the upper-third stomach

AIM: To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions.METHODS: A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach(U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography(CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach(ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth.RESULTS: Patients in the U group were older(P = 0.029), had a higher ratio of males to females(P = 0.015), and had more histologically differentiated tumors(P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients(8.3%), and was more frequent in the U group than in the ML group(16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group(P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors(P = 0.094) and in those larger than 4 cm(P = 0.024). The medianfollow-up period after surgery was 56 mo(range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group(P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study.CONCLUSION: Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors.

Detection of fusion gene in cell-free DNA of a gastric synovial sarcoma

Synovial sarcoma(SS) is genetically characterized by chromosomal translocation, which generates SYT-SSX fusion transcripts. Although SS can occur in any body part, primary gastric SS is substantially rare. Here we describe a detection of the fusion gene sequence of gastric SS in plasma cell-free DNA(cf DNA). A gastric submucosal tumor was detected in the stomach of a 27-year-old woman and diagnosed as SS. Candidate intronic primers were designed to detect the intronic fusion breakpoint and this fusion sequence was confirmed in intron 10 of SYT and intron 5 of SSX2 by genomic polymerase chain reaction(PCR) and direct sequencing. A locked nucleic acid(LNA) probe specificto the fusion sequence was designed for detecting the fusion sequence in plasma and the fusion sequence was detected in preoperative plasma cfD NA, while not detected in postoperative plasma cfD NA. This technique will be useful for monitoring translocation-derived diseases such as SS.

Clinical characteristics of hepatoduodenal lymph node metastasis in gastric cancer

AIM: To assess the clinical features of hepatoduodenal lymph node(HDLN) metastasis and to clarify the optimal indication of HDLN dissection.METHODS: We investigated a total of 276 patients who underwent gastrectomy with extended lymphadenectomy,including HDLN dissection,for gastric cancer between 1999 and 2012. Of these,26 patients(9.4%) had HDLN metastasis. First,we investigated the clinicopathological characteristics,their perioperative clinical outcomes,such as postoperative complications,and prognostic outcomes between patients with and without HDLN metastasis. Second,we detected the prognostic factors,particularly in patients with HDLN metastasis. Third,we assessed the therapeutic value of HDLN dissection to determine its optimal indication.RESULTS: The five-year overall survival rate of the patients with HDLN metastasis was 29%. Univariate and multivariate logistic regression analyses revealed that the tumour location(the middle or lower stomach [P = 0.005,OR = 5.88(95%CI: 1.61-38.1)] and p T category [T3 or T4,P = 0.017,OR = 4.45(95%CI: 1.28-21.3)] were independent risk factors for HDLNmetastasis. Cox proportional hazard analysis identified p N3 as an independent poor prognostic factor in the patients with HDLN metastasis [P = 0.021,HR = 5.17(95%CI: 1.8-292)]. For patients who underwent radical HDLN dissection,HDLN metastasis was a prognostic indicator in p N3 gastric cancer(P < 0.0001),but not p N1-2(P = 0.602). Furthermore,the index of therapeutic value of HDLN dissection for gastric cancer in the middle or lower stomach and the upper stomach was 3.4 and 0.0,respectively.CONCLUSION: We suggest that HDLN dissection should be indicated for p N1 or p N2 gastric cancers located at the middle or lower stomach.

Histological evaluation for chemotherapeutic responses of metastatic lymph nodes in gastric cancer

AIM: To investigate the effect of preoperative chemotherapy(pre-CTx) for metastatic lymph nodes(MLNs) of gastric cancer(GC). METHODS: A retrospective cohort of patients with advanced GC, who underwent pre-CTx followed by gastrectomy, was reviewed. The histological tumor regression grade(TRG), which considered the percentage of residual cancer in the visible tumor bed, was applied to primary tumors and individual MLNs: G1a(complete response), G1b(< 10%), G2(10%-50%) and G3(> 50%). The clinical response to pre-CTx was retrospectively evaluated using only MLNs information, and we compared the histological and clinical evaluations of MLNs.RESULTS: Twenty-eight patients were enrolled. A total of 438 MLNs were retrieved, and 22(5%), 48(11%), 63(14%) and 305(70%) LNs were assigned as G1 a, G1 b, G2 and G3, respectively. Stratification of the residual MLNs based on the TRGs was as follows: 28 G1 b MLNs(9%), 48 G2 MLNs(15%), and 253 G3 MLNs(76%) in the D1 region; 20(23%), 15(17%), and 52(60%) in the D2 region, respectively. However, no significant correlation was found between TRGs in MLNs and clinical response in the subgroup for which evaluation of clinical response was available.CONCLUSION: Pre-CTx does not provide any outstanding histological benefit for MLNs, and an appropriate D2 lymphadenectomy should routinely be performed to offer the chance of curative resection.

Laparoscopic and endoscopic co-operative surgery for nonampullary duodenal tumors

AIM To assess the safety and feasibility of laparoscopic and endoscopic co-operative surgery(LECS) for early nonampullary duodenal tumors.METHODS Twelve patients with a non-ampullary duodenal tumor underwent LECS at our hospital. One patient had two mucosal lesions in the duodenum. The indication for this procedure was the presence of duodenal tumors with a low risk for lymph node metastasis. In particular, the tumors included small(less than 10 mm) submucosal tumors(SMT) and epithelial mucosal tumors, such as mucosal cancers or large mucosal adenomas with malignant suspicion. The LECS procedures, such as full-thickness dissection for SMT and laparoscopic reinforcement after endoscopic submucosal dissection(ESD) for epithelial tumors, were performed for the 13 early duodenal lesions in 12 patients. Here we present the short-term outcomes and evaluate the safety and feasibility of this new technique.RESULTS Two SMT-like lesions and eleven superficial epithelial tumor-like lesions were observed. Seven and Six lesions were located in the second and third parts of the duodenum, respectively. All lesions were successfully resected en bloc. The defect in the duodenal wall was manually sutured after resection of the duodenal SMT. For epithelial duodenal tumors, the ulcer bed was laparoscopically reinforced via manual suturing after ESD. Intraoperative perforation occurred in two out of eleven epithelial tumor-like lesions during ESD; however, they were successfully laparoscopically repaired. The median operative time and intraoperative estimated blood loss were 322 min and 0 mL, respectively. Histological examination of the tumors revealed one adenoma with moderate atypia, ten adenocarcinomas, and two neuroendocrine tumors. No severe postoperative complications(Clavien-Dindo classification grade Ⅲ or higher) were reported in this series, but minor leakage secondary to pancreatic fistula occurred in one patient.CONCLUSION LECS can be a safe and minimally invasive treatment option for non-ampullary early duodenal tumors.

Conservative management of cholestasis with and without fever in acute biliary pancreatitis

The presence of cholestasis in both mild and severe forms of acute biliary pancreatitis(ABP)does not justify,of itself,early endoscopic retrograde cholangiography(ERC)or endoscopic sphincterotomy(ES).Clinical support treatment of acute pancreatitis for one to two weeks is usually accompanied by regression of pancreatic edema,of cholestasis and by stone migration to the duodenum in 60%-88%of cases.On the other hand,in cases with both cholestasis and fever,a condition usually characterized as ABP associated with cholangitis,early ES is normally indicated.However,in daily clinical practice,it is practically impossible to guarantee the coexistence of cholangitis and mild or severe acute pancreatitis.Pain,fever and cholestasis,as well as mental confusion and hypotension,may be attributed to inflammatory and necrotic events related to ABP. Under these circumstances,evaluation of the bile duct by endo-ultrasonography(EUS)or magnetic resonance cholangiography(MRC)before performing ERC and ES seems reasonable.Thus,it is necessary to assess the effects of the association between early and opportune access to the treatment of local and systemic inflammatory/infectious effects of ABP with cholestasis and fever, and to characterize the possible scenarios and the subsequent approaches to the common bile duct,directed by less invasive examinations such as MRC or EUS.

Cellular physiological approach for treatment of gastric cancer

Recent studies show that ion channels/transporters play important roles in fundamental cellular functions that would be involved in the cancer process. We review the evidence for their expression and functioning in human gastric cancer (GC), and evaluate the potential of cellular physiological approach in clinical management. Various types of ion channels, such as voltage-gated K+ channels, intracellular Cl- channels and transient receptor potential channels have been found to express in GC cells and tissues, and to control cell cycles. With regard to water channels, aquaporin 3 and 5 play an important role in the progression of GC. Regulators of intracellular pH, such as anion exchanger, sodium-hydrogen exchanger, vacuolar H+-ATPases and carbonic anhydrases are also involved in tumorigenesis of GC. Their pharmacological manipulation and gene silencing affect cellular behaviours, suggesting their potential as therapeutic targets for GC. Our studies indicate the intracellular Cl- concentration could act as a mediator of cellular signaling and control cell cycle progression in GC cells. Further, we demonstrate the cytocidal effects of hypotonic shock on GC cells, and indicate that the blockade of Cl- channels/transporters enhances these effects by inhibiting regulatory volume decrease. A deeper understanding of molecular mechanisms may lead to the discovery of these cellular physiological approaches as a novel therapeutic strategy for GC.

Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett's esophagus

Barrett's esophagus(BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE(LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach(LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of thearch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 m L of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis.

Role of the Na^+/K^+/2Cl^- cotransporter NKCC1 in cell cycle progression in human esophageal squamous cell carcinoma

AIM: To investigate the role of Na+/K+/2Cl- cotransporter 1 (NKCC1) in the regulation of genes involved in cell cycle progression and the clinicopathological significance of its expression in esophageal squamous cell carcinoma (ESCC).

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland(HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery(LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor(SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm intothe submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG.

Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability

AIM： To establish the role of human T Cell Factor-4 （hTCF-4） gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability （MSI）. METHODS： Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI （MSI-H）. Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls （5 microsatellite stability （MSS） cases and 5 cases with normal mucosa）. The sequencing and MSI identification were used. RESULTS： Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I （391insA, 392 G 〉 A, 393 A 〉 G and 395delC） and another nucleotide deletion （395delC） is present in MSI-H cases （5/10 and 4/10, respectively） but completely absent in the controls.CONCLUSION： Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H.