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Objective To examine risk factors for and causes of severe postoperative pancreatic fistula (sPOPF) after laparoscopic gastrectomy (LG). Summary of Background Data There are few reports on POPF after LG. Methods Between February 2012 and March 2014, we examined 86 patients who underwent LG, comparing them with 33 patients who underwent open gastrectomy (OG) for gastric cancer. Risk factors for severe POPF (sPOPF) of Clavien–Dindo grade IIIa or higher were examined. To investigate causes of sPOPF, we reviewed unedited video recordings of laparoscopic surgical procedures. Results sPOPF occurred in 3 patients (3.5%) after LG and 1 patient (3.0%) after OG, indicating no significant difference (P = 0.901). Univariate analysis showed no significant risk factors for sPOPF after LG. By reviewing video recordings, all 3 patients with sPOPF after LG had direct pancreatic injury by ultrasonically activated device (USAD) during peripancreatic lymphadenectomy. In 2 patients, pancreas was injured while the contour of pancreas was obscured by bleeding. Durations of drain placement and postoperative hospitalization were longer for patients with sPOPF than for those without POPF or grades I and II POPF (P = 0.003, 0.018; respectively). Conclusions No risk factors for sPOPF after LG could be identified. USAD-induced direct pancreatic injury resulted in sPOPF, which significantly complicated the postoperative clinical course. Direct pancreatic injury can occur whether patient has previously reported risk factors (i.e., male, high body mass index, distal pancreatectomy) or not. To prevent pancreatic injury, surgeons should manage hemostasis and keep good surgical field to recognize the contour of pancreas accurately.

Purpose To determine the feasibility of diffusion-tensor imaging (DTI) and tractography as means of evaluating the depth of mural invasion by gastric carcinomas. Materials and methods This study was approved by our institutional review board, and written informed consent was obtained from each patient. Twenty gastric specimens containing a carcinoma were studied with a 7.0-T MR imaging system equipped with a four-channel phased-array surface coil. DTI was performed by using a field of view of 50–60 mm × 25–30 mm, matrix of 256 × 128, section thickness of 1 mm, b value of 1000 s/mm2, and motion-probing gradients in seven noncollinear directions. The MR images were compared with the histopathologic findings as the reference standard. Results In all 20 carcinomas (100%) the diffusion-weighted images, apparent diffusion coefficient (ADC) maps, fractional anisotropy (FA) maps, λ1 maps, and direction-encoded color FA maps made it possible to identify the same depth of tumor invasion of the gastric wall as observed during histopathologic examination. The λ1 maps provided the best contrast between the carcinomas and the layers of the gastric wall. The carcinomas also had lower ADC values and lower FA values than the normal gastric wall; thus, the carcinomas were clearly demarcated from the normal gastric wall. Tractography images were also useful for determining the depth of tumor invasion of the gastric wall. Conclusions DTI and tractography are feasible means of evaluating gastric specimens and provide excellent diagnostic accuracy for evaluating mural invasion by gastric carcinomas.

Purpose The purpose of this study was to establish the feasibility of q-space imaging (QSI) as a method of assessing the depth of mural invasion, histologic grade, and the presence of lymph node metastasis in gastric carcinomas. Methods A 7.0 Tesla MR imaging system was used to investigate 20 gastric specimens containing a carcinoma. QSI was performed by using the following parameters: 50–60 mm × 25–30 mm field of view, 2-mm section thickness, 256 × 128 matrix, 10 b values in the 0–7163 s/mm2 range, which corresponded to q values of 0–1026/cm, and motion-probing gradients perpendicular to the gastric wall. The MR images and the histopathologic findings were then compared. Results The depth of tumor invasion of the gastric wall in all 20 carcinomas (100%) was established by using mean displacement, zero-displacement probability, and kurtosis maps. The QSI parameters were significantly correlated with the histologic grades of the gastric carcinomas (all P

Background Laparoscopic gastrectomy (LG) has been established as a procedure for the treatment of gastric cancer. However, there have been few reports on the long-term outcomes of LG for gastric cancer. The aim of this study is to investigate the long-term outcomes of LG for gastric cancer. Methods A total of 278 consecutive patients who underwent LG in our unit between January 1999 and December 2006 were included in this study. Survival, recurrence, and late gastrointestinal complications were analyzed. Results The median follow-up period was 73.7 mo (6–165 mo). Distal gastrectomy was performed in 229 patients, total gastrectomy in 23 patients, proximal gastrectomy in 15 patients, and pylorus-preserving gastrectomy in 11 patients. Five-year overall and disease-specific survival rates were 91% and 99% for stage IA, 75% and 91% for stage IB, 72% and 88% for stage II, and 40% and 50% for stage III, respectively. Recurrences were detected in 15 (5.4%) patients, including 5 distant lymph node, 5 peritoneal, 4 hematogenous, and 1 locoregional recurrences. Bowel obstruction occurred in 4 (1.4%) patients, and gallstones developed in 37 (15%) patients. Conclusions This follow-up investigation suggested that LG for gastric cancer is a feasible procedure from the standpoint of long-term oncological outcome and postoperative complications.

Background To clarify the patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy. Methods From January 1999 to March 2012, 577 patients underwent laparoscopic or laparoscopy-assisted gastrectomy for curative resection of gastric cancer. Recurrence patterns were classified as locoregional, hematogenous, peritoneal, distant lymph node and mixed. Recurrence patterns and time to recurrence were retrospectively examined and risk factors for recurrence were analyzed. Results Recurrence occurred in 28 (4.9%) cases with patterns as follows: locoregional in 2 patients (7.1%), hematogenous in seven (25.0%), peritoneal in nine (32.1%), distant lymph node in four (14.3%), and mixed in 6 (21.4%). There was no recurrence pattern peculiar to laparoscopic surgery. Recurrence occurred at one site in 21 patients (78.6%), two in 4 patients (14.3%), and three in 2 patients (7.1%). The median time to recurrence was 384 days (range 83–1497 days). Recurrence was detected within a year in 13 cases (46.4%), within two years in 21 (75%), and within three years in 25 (89.3%). Univariate analysis revealed tumor location, tumor size, type of operation, tumor depth, and lymph node classification as risk factors for recurrence. Multivariate analysis indicated tumor depth and lymph node classification as risk factors of recurrence. Conclusions Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy are similar to those after open gastrectomy, with no peculiarities specific to laparoscopic gastrectomy. Thus, as long as laparoscopic gastrectomy is performed according to the present inclusion criteria, follow-up can be similarly performed as for open gastrectomy.

To decrease the incidence of internal hernia after laparoscopic Roux-en-Y gastric bypass, recent recommendations indicated closure of mesenteric defects and Petersen's defect. Laparoscopic distal gastrectomy for gastric cancer is used increasingly, so the incidence of Petersen's hernia can also increase, but the trend has not been studied.This study retrospectively reviewed 358 consecutive patients who underwent laparoscopic distal gastrectomy for gastric cancer at one institution, with antecolic Roux-en-Y (RY) reconstruction.Petersen's hernia occurred in 6 (2.2 %) of 268 patients whose Petersen's defect was not closed by a mean of 351 days after surgery. All the patients underwent reoperation with reduction and repair of the hernia except the first case. In 90 subsequent cases, with closure of the Petersen's defect, internal hernias did not occur (0/90 cases; p = 0.06). Focusing on the totally laparoscopic procedure, Petersen's hernia occurred in 2 (5.1 %) of 39 patients, whereas in 81 subsequent cases, with closure of Petersen's defect, internal hernias did not occur (0/81 cases; p = 0.03).Based on the recent recommendations for bariatric surgery, closure of this potential hernia defect is necessary after laparoscopic distal gastrectomy with R-Y reconstruction for gastric cancer.

Laparoscopy-assisted gastrectomy (LG) is an established treatment for early gastric cancer. However, CO2 pneumo- peritoneum during laparoscopic surgery can adversely affect car- diac function in the presence of heart disease (HD). We performed LG in 546 patients and conventional open gastrectomy (OG) in 448 patients. Patients with preoperatively diagnosed and treated HD were identified. The clinical outcomes of patients with HD who underwent LG (HD-LG) were compared with those of patients with HD who underwent OG (HD-OG), as well as those of patients with no operative risk who underwent LG (NR-LG). Variables of cardiac function were similar in the HD-LG and HD-OG groups. Postoperative cardiac complications did not differ between the groups (8.3% vs. 13.6%, P = 0.51). The HD-LG group had sig- nificantly more cardiac and abdominal complications than the NR-LG group (P = 0.0011 and 0.0070, respectively). LG was tol- erated in patients with gastric cancer and mild or moderate HD, similar to OG.

Laparoscopy-assisted gastrectomy (LG) is an established treatment for early gastric cancer. However, carbon dioxide pneumoperitoneum during laparoscopic surgery can adversely affect the pulmonary function of patients with chronic obstructive pulmonary disease (COPD). This retrospective cohort study was performed to assess the feasibility of LG for patients with COPD.Among 1,053 patients who underwent radical gastrectomy with lymph node dissection between 1999 and 2011 at the authors' hospital, 220 patients with COPD were studied retrospectively. The clinical outcomes for the patients with COPD who underwent LG (LG group) were compared with those of COPD patients who underwent open gastrectomy (OG group), as well as those of patients with no operative risk and normal pulmonary function who underwent LG (NOR group). Postoperative pulmonary complications (PPCs) were defined as pneumonia, atelectasis, pneumothorax, prolonged mechanical ventilation (24 h), and adult respiratory distress syndrome within 30 days after operation.Pulmonary function variables were similar in the LG and OG groups. The findings showed PPCs to be slightly but not significantly less frequent in the LG group (1.7 %) than in the OG group (6.3 %) (p = 0.09). No difference in PPCs was found between the LG group and the NOR group (p0.99). For patients with COPD, advanced stage (stage 2 or 3 vs stage 1) was significantly associated with PPCs (p = 0.03), but was not an independent risk factor for PPCs (p = 0.12).The LG procedure is tolerated in patients with gastric cancer who have mild or moderate COPD, similar to OG.

Introduction The purpose of this study was to identify the frequency, severity, and risk factors of complications after open gastrectomy using the Clavien- Dindo classification because institution-specific criteria were mostly used in the previous articles. Materials and Methods All complication data were obtained from our prospectively collected database of open gastrectomy from January 1999 to December 2012 (n=539). Complications were classified into either major surgical complications such as pancreatic fistula, abdominal abscess, and anastomotic leakage, or others. Frequency and severity were graded retrospectively according to the Clavien- Dindo classification for subsequent analysis of risk factors. Results There were 222 events occurred in 156 patients (28.9%). Complications of grade IIIa or greater were 8.3% for major surgical complications and 10.6% for all complications. The mortality rate was 1.1%. Blood loss was the only independent risk factor for major surgical complications of grade IIIa or greater (odds ratio 1.923, 95% Confidence Interval 0.320-0.786, p=0.003). Total gastrectomy was the only independent risk factor for all complications of grade IIIa or greater (Odds ratio 2.075, 95% Confidence Interval 0.260-0.896, p=0.021). Disscussion The present study provided the objective overview regarding complications after open gastrectomy. Blood loss and total gastrectomy were revealed as the significant risk factors for complications.

A 55-year-old woman was referred to our hospital with dysuria. We were unable to catheterize her using a nelaton catheter because of a urethral stricture, resulting in a large residual urine volume on ultrasonography. The circumference of the periurethral tissue was also thickened and the entire length of the urethra was stenotic, without apparent cause, on magnetic resonance imaging. Biopsy did not reveal malignancy. The pathological diagnosis of the periurethral tissue was simply fibrosis, and there was no definitive diagnosis. We decided to place a guidewire to attempt transurethral dilation, but it was unsuccessful because of the urethral stricture. The patient then underwent Mitrofanoff appendicovesicostomy. Three years later, there was no difficulty with catheterization through the appendix, despite her suffering from a bladder stone during the interim. We consider the Mitrofanoff appendicovesicostomy a good substitute technique for catheterization in patients with very severe urethral stricture.

The use of laparoscopy-assisted distal gastrectomy (LADG) in advanced gastric cancer (AGC) remains a controversial topic, mainly because of doubts about its oncologic validity. To date, literature on the prognosis for AGC after LADG is scarce. This study evaluated the procedure’s long-term benefits compared with those of the conventional, open distal gastrectomy (ODG). This study involved 201 patients, 66 of whom underwent LADG, with a mean follow-up period of 49.2 months, from January 1999 to March 2010. A clear set of criteria was used to select patients (including no evidence of lymph node metastasis) and surgeons (subject to their experience). Survival outcomes were assessed by Kaplan–Meier analysis and log-rank testing. The postoperative recovery and complications of the patients also were monitored. No significant difference was observed between LADG and ODG in terms of overall survival or disease-specific survival. The corresponding 5-year survival rates for individual tumor node metastasis stages also were comparable in each group. The number of lymph nodes harvested was similar in the two groups, although the operation time was significantly shorter for ODG. The postoperative hospital stay was shorter for LADG patients (average stay of 8.4 vs. 18.1 days in the ODG group; p

Laparoscopic distal gastrectomy (LDG) is an established procedure for the treatment of early gastric cancer. Roux-en-Y (R-Y) or Billroth-I (B-I) reconstruction is generally performed after LDG in Japan. The aim of this retrospective cohort study was to compare the effectiveness of R-Y and B-I reconstructions and thereby determine which has better clinical outcomes.We analyzed data from 172 patients with gastric cancer who underwent LDG. Reconstruction was done by R-Y in 83 patients and B-I in 89. All patients were followed up for 5 years. Evaluated variables included symptoms, nutritional status, endoscopic findings, gallstone formation, and later gastrointestinal complications.Scores for the amount of residue in the gastric stump, remnant gastritis, and bile reflux, calculated according to the "residue, gastritis, bile" scoring system, were significantly lower in the R-Y group (score 0 vs. 1 and more; p = 0.027,0.001, and0.001, respectively). The proportion of patients with reflux esophagitis was significantly lower in the R-Y group (p 0.001). Relative values (postoperative 5 years/preoperative) for body weight, serum albumin level, and total cholesterol level were similar in the two groups (p = 0.59, 0.56, and 0.34, respectively). Gallstone formation did not differ between the groups (p = 0.57). As for later complications, the incidence of gastrointestinal ulcer was 4.5 % in the B-I group, and that of ileus was 3.6 % in the R-Y group, but differences between the groups were not significant (p = 0.12, 0.11, respectively).As compared with B-I, R-Y was associated with lower long-term incidences of both bile reflux into the gastric remnant and reflux esophagitis.

Objective: To evaluate the clinical usefulness of effective renal plasma flow (ERPF) measured using preoperative mercaptoacetyltriglycine-3 (MAG3) renogram for the prediction of chronic renal insufficiency after nephrectomy. Methods: A total of 47 patients underwent preoperative MAG3 renal scintigraphy and subsequent unilateral nephrectomy. Correlations between the 5-year postoperative estimated glomerular filtration rate (eGFR) and the preoperative ERPF of the contralateral kidney (cERPF), ERPF of the diseased kidney (dERPF), total ERPF (tERPF), cERPF to dERPF ratio, serum creatinine (sCr) level, eGFR, as well as the influence of preoperative comorbidities (diabetes, hypertension) on the postoperative eGFR, were evaluated with both univariate and multivariate analyses. Results: Multiple linear regression analysis showed that preoperative cERPF significantly correlated with postoperative eGFR. However, a much stronger correlation was observed between the preoperative and postoperative eGFR. Multiple logistic regression analysis showed that only preoperative eGFR was a significant predicator of the development of advanced-stage chronic kidney disease (CKD). Conclusions: Preoperative MAG3 renogram is not superior to eGFR measurement as a prognostic indicator of long-term renal function after unilateral nephrectomy.

Background Practical questionnaires for evaluating duodenogastric reflux following gastrectomy are currently unavailable. The present study evaluated the usefulness of the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) questionnaire in the diagnosis of duodenogastric reflux after laparoscopy-assisted distal gastrectomy (LADG), which minimizes the risk of adhesions affecting the gastrointestinal tract. Methods Subjects in this study comprised 163 patients who had undergone LADG (Billroth-I (B-I), n = 57, Roux-en-Y (R-Y), n = 106). All subjects underwent endoscopy at least 6 mo postoperatively. The FSSG questionnaire was administered a few weeks after endoscopy, and FSSG scores were compared with endoscopic findings. Results In the R-Y group, FSSG scores were significantly higher in subjects with remnant gastritis than in those without ( P = 0.002), and a significant correlation was seen between FSSG scores and bile reflux ( P = 0.046). In the B-I group, FSSG scores were significantly higher in subjects with reflux esophagitis than in those without ( P = 0.01), but degree of remnant gastritis and residual food did not correlate significantly with FSSG scores. With a cut-off FSSG score of six points, sensitivity and specificity for predicting remnant gastritis in R-Y reconstruction were 71% and 76%, respectively. Conclusion The FSSG questionnaire is a viable and less invasive alternative to other modalities for evaluating duodenogastric reflux in R-Y reconstruction, but is unsuitable for B-I reconstruction after LADG.

Hepatic resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) at the bifurcation of the portal has the potential to cure the disease. Herein, we report 2 cases of HCC with Vp3 treated with a multidisciplinary approach that might include preoperative transcatheter arterial chemoembolization (TACE) or postoperative hepatic arterial infusion chemotherapy (HAIC). Case 1: A 73-year-old man was diagnosed with HCC with Vp3 located in segment 1 during follow up that was treated by performing a left hepatectomy with removal of the tumor thrombus. After surgery, the patient underwent HAIC, and he was alive without disease recurrence 2 years and 2 months after surgery. Case 2: A 77-year-old man with cirrhotic nonalcoholic steatohepatitis underwent liver resection followed by TACE. However, recurrent HCC with Vp3 was detected in segments 2 and 5, so we performed a repeat liver resection. The patient was alive without disease recurrence 1 year and 8 months after surgery without having received postoperative adjuvant chemotherapy. In select patients diagnosed with HCC with PVTT (Vp3/4), long-term survival can be obtained with multidisciplinary treatment such as surgery and preoperative TACE or postoperative HAIC.

A-71-year-old man underwent right hemicolectomy combined with partial resection of the small intestine and duodenum for an ascending colon carcinoma in July 2009. He presented with a liver metastasis adjacent to the inferior vena cava in November 2009. He received 6 courses of FOLFOX4, but the therapeutic effect was SD, so he underwent an extended posterior sectionectomy combined with partial S8 resection, inferior vena cava resection, and cholecystectomy. He developed remnant liver recurrence in February 2011 and another partial S8 resection was performed. He presented with remnant liver recurrence in October 2011, and radiofrequency ablation and systemic chemotherapy were performed, but were not effective. In June 2013, we performed an extended S8 segmentectomy combined with median hepatic vein and diaphragm resection. He is alive 2 years after the third hepatectomy without any recurrence. Although non-anatomical resection is often performed in repeat liver resections for colorectal liver metastases, sometimes detection of recurrent lesions in the same segment indicates Glisson invasion; therefore, anatomic resection may prolong long-term survival.

We compared the perioperative and oncological outcomes of laparoscopic radical cystectomy (LRC) between elderly patients over 75 years old and younger patients. Fifty-three patients underwent LRC between 2003 and 2014 at Tenriyorozu Hospital. Eighteen patients were classified as elderly (over 75) and the other 35 patients were considered young. The median operating time (434 vs 465 min, p＝0.35), estimated bloodloss (534 vs 525 g, p＝0.74), time to recommencing foodintake (7 vs 6 days, p＝1.00), and hospital stay (35 vs 32 days, p＝0.81) were not significantly different between the groups. Perioperative pyelonephritis was significantly more frequent in the elderly group (50% vs 20%, p＝0.02), while other complications were not significantly different between the two groups. The perioperative mortality rate was 0% in both groups. There were no significant differences between the elderly and young groups with respect to 2-year overall survival (74. 4% vs 91. 6%), cancer-specific survival (74. 4% vs 91. 6%), and recurrence-free survival (70.2% vs 81. 8%). LRC is a safe andefficient procedure for selected elderly patients.

The management of vulvar cancer has changed in the past two decades. Modern treatment of vulvar cancer must be individualized, and less radical surgery is now being performed if possible, in consideration of the quality of life (QOL) of patients. Even though the treatment now tends to be conservative, lymph nodes in all patients should be appropriately treated, with the only exception being microinvasive cancer with less than 1-mm stromal invasion. Here we review the up-to-date management of lymph nodes in patients with vulvar cancer.

Background It has been proposed that the human endometrium may contain a population of adult stem cells that are responsible for its remarkable regenerative capability. Recently, a subset of stem cells or progenitor cells in adult tissue has been identified as side-population cells (SP cells) displaying low staining with Hoechst 33342 by fluorescence-activated cell sorter (FACS) analysis. In this study, we isolated SP cells from the human endometrium and analysed their properties. Method Endometrial cells were obtained using enzymatic digestion from uterine hysterectomy for the treatment of uterine myoma and stained with Hoechst 33342 dye either alone or in combination with verapamil. The cells were then analysed using FACS. Results SP cells were present among normal human endometrial cells. Most SP cells were enriched in the CD9(-)CD13(-) fraction. These SP cells showed long-term repopulating properties and produced gland (CD9(+))- and stroma (CD13(+))-like cells. CD9(-)CD13(-) cells isolated from the endometrium also generated gland- or stroma-like cells. Conclusions SP cells in the human endometrium can function as progenitor cells. This is the first report of the phenotype of SP cells from normal human endometrial cells.

Gastric cancer is the second most common cause of cancer deaths worldwide. The identification of molecular genetic parameters that are associated with response to chemotherapy and prognosis is of utmost interest. We examined methylation of the apoptosis-related genes, TMS1 and DAPK, in 81 primary gastric cancers using methylation-specific PCR and compared their methylation status with clinicopathological findings. Aberrant methylation of TMS1 and DAPK genes was detected in 26 (32.1%) tumors and in 18 (22.2%) tumors, respectively. The overall survival of patients with both methylated genes was significantly shorter compared with those with only one methylated gene or no methylated genes (p = 0.0003). Neither gene methylation had any relation to other clinicopathological findings. Next, we examined 43 patients treated by 5-fluorouracil-based chemotherapy, who had distant metastasis or recurrence after radical resection, to determine the relation between chemosensitivity and methylation. The response rate was lower in patients with either methylation than without (TMS1: 22.2% vs. 48.0%; DAPK: 21.4% vs. 44.8%). Overall survival tended to be shorter in the patients with both methylations compared with either or no methylations (p = 0.0806). The time to progression of patients with methylation of TMS1 or DAPK was significantly shorter than patients without methylation (TMS1: p = 0.0123; DAPK: p = 0.0464). Furthermore, the time to progression of patients with both methylated genes was significantly shorter than patients with one methylation or no methylation (p = 0.0082). In conclusion, TMS1 and DAPK methylation might predict the prognosis and response to chemotherapy in gastric cancer.

Background: Some recent reports have noted that copper deficiency can occur in obese patients who have undergone bariatric surgery, such as Roux-en-Y (RY) gastric bypass or biliopancreatic diversion, or in patients who receive enteral nutrition through a jejunostomy. No reports appear to have assessed the serum copper state of patients following gastrectomy with RY reconstruction for gastric cancer. Methods: A cross-sectional study was conducted from June 2013 to December 2014. Serum copper levels (SCLs) in 242 out-clinic patients who underwent curative gastrectomy were obtained. Patients were classified into an RY group (n = 208) and a non-RY group (n = 34). Results: Hypocupremia was identified in 3 patients in the RY group (1.4%), and 2 patients in the non-RY group (5.9%; p = 0.146), but none experienced any symptoms caused by hypocupremia. No significant difference in the mean SCL was seen between the RY group (105.8 ± 21.2 µg/dl) and non-RY group (107.9 ± 22.7 µg/dl; p = 0.499). In the RY group, the mean SCL was significantly lower in younger patients, patients with follow-up period Conclusion: Some patients developed hypocupremia after gastrectomy with RY reconstruction, but the number is acceptably low, and physical symptoms were unusual.

Aberrant promoter hypermethylation is an epigenetic change that silences the expression of crucial genes, resulting in inactivation of the apoptotic pathway in various cancers. This hypermethylation can be restored by the demethylating agent 5-aza-2'-deoxycytidine (DAC). DAC might increase the tumor sensitivity to chemotherapy through demethylation and restoration of gene expression. We investigated the effect of combined therapy with DAC and irinotecan (CPT-11) on the human colon cancer cell line HCT-15.Human colon cancer cell line HCT-15 was treated with DAC and/or CPT-11 both in vitro and in vivo. The changes in mRNA expression of several apoptosis-related genes were investigated by reverse transcriptase-polymerase chain reaction (PCR). Promoter methylation was detected by methylation-specific PCR and combined bisulfite restriction analysis. Suppression of tumor growth was observed during the treatment with DAC and/or CPT-11 and apoptosis in the tumors was investigated by TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay.Promoter methylation of p14ARF, p16 INK4a, BNIP3, and XAF1 was confirmed, and DAC restored mRNA expression of these genes. Demethylation and restoration of gene expression was observed with low-dose DAC, and demethylation status was sustained for several weeks. Combined therapy with DAC and CPT-11 produced marked suppression in tumor growth compared with DAC or CPT-11 alone, both in vitro and in vivo.Pretreatment with low-dose DAC may have the potential to be used as a "biosensitizer" of DNA-damaging agents such as CPT-11 when the apoptotic pathway is inactivated as a result of aberrant promoter methylation in the cancer.