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mRNA expression varies in human cancers. Such altered mRNA expression is negatively regulated by the expression of microRNAs (miRNAs), which play an important role in human tumorigenesis. According to this theory, inverse mRNA/miRNA expression may be a direct driver of cancer development, and certain genetic events may occur prior to the development of any discernible histological abnormalities. We examined the inverse expression between mRNAs and their corresponding miRNAs in colorectal cancer (CRC) and adjacent normal mucosa and performed pathway analysis to identify mRNA/miRNA networks. The cancer samples were divided into first (20 cases) and second (24 cases) cohorts, and 48 samples were obtained from two sections of the normal mucosa adjacent to the tumors from the second cohort. We investigated mRNAs with commonly altered expression in CRC and adjacent normal mucosa using isolated cancer glands and normal crypts from the first cohort, compared with that of distal normal crypts, using an array-based method. As a result, significant inverse correlations between CEACAM1 and miRNA-7114-5p and between AK1 and miRNA-6780-5p were found in CRC and adjacent normal mucosa. We validated these correlations in the second cohort using RT-PCR. To confirm these findings, transfection and immunohistochemical assays were also performed, which verified the inverse correlation between CEACAM1 and miRNA-7114-5p. Our findings suggest that the inverse correlations between the CEACAM1/miRNA-7114-5p and possibly AK1/miRNA-6780-5p pairs play an important role in early CRC development, and may help identify potential molecular targets for early detection of CRC.

MicroRNA (miRNA) expression is dysregulated in human tumors, thereby contributing to tumorigenesis through altered expression of mRNA. Thus, identification of the relationships between miRNAs and mRNAs is important for evaluating the molecular mechanisms of tumors. Additionally, elucidation of the molecular features of serrated lesions is essential in colorectal tumorigenesis. Here, we examined the relationships of miRNA and mRNA expressed in serrated lesions, including 26 sessile serrated lesions (SSLs), 12 traditional serrated adenomas (TSAs), and 11 colorectal cancers (CRCs) with a microsatellite instability (MSI) phenotype using crypt isolation. We divided the samples into the first and second cohorts for validation. Array-based expression analyses were used to evaluate miRNAs and mRNAs with opposite expression patterns in isolated tumor glands. In addition, we validated the relationships of miRNA/mRNA pairs in the second cohort using real-time polymerase chain reaction. We found that the expression of miRNA-5787 was correlated with reciprocal expression of 2 mRNAs, i.e., SRRM2 and POLR2J3, in SSL samples. In TSA samples, 2 pairs of miRNAs/mRNAs showing opposite expression patterns, i.e., miRNA-182-5p/ETF1 and miRNA-200b-3p/MYB, were identified. Ultimately, three pairs of miRNAs/mRNAs with opposite expression patterns, including miRNA-222-3p/SLC26A3, miRNA-6753-3p/FABP1, and miRNA-222-3p/OLFM4, were retained in CRC with an MSI phenotype. Finally, we performed transfection with an miR-222-3p mimic to confirm the expression of SLC26A3 and OLFM4; the results showed that ectopic expression of miR-222-3p moderately suppressed OLFM4 and downregulated SLC26A3 to some extent. Overall, our results provided basic insights into the evaluation of colorectal tumorigenesis of serrated lesions and CRC with an MSI phenotype. This article is protected by copyright. All rights reserved.

Aim Recent reports have described the use and efficacy of several types of transanal tube (TAT) for preventing anastomotic leakage by reducing intraluminal pressure. The aim of this study was to evaluate the safety and efficacy of a newly developed TAT for the prevention of anastomotic leakage after low anterior resection (LAR) for rectal cancer. Method A multicentre confirmatory single-arm trial was designed to evaluate the safety and efficacy of a new TAT after LAR for rectal cancer. A total of 115 patients were registered in the trial at several cancer centres and other hospitals. All patients initially received reconstruction with a stapled anastomosis, but 18 then underwent creation of a diverting stoma. Of the remaining 97 patients, the first 96 were included in the protocol-defined primary analysis set. The primary outcome was the incidence of symptomatic leakage and the secondary endpoint was the incidence of complications associated with use of the TAT. The TAT was placed during LAR without creating a covering stoma and the drain was removed 4 or 5 days postoperatively. Results The rate of symptomatic leakage was 5.2% (95% confidence interval 1.7-11.7), which was significantly lower than the predetermined threshold value of 15.8% (one-sided p-value 0.0013). Only one patient had Grade 3 rectal bleeding that might have been related to use of the TAT. Conclusion This nonrandomized study shows that the TAT appears to be safe and results in lower rates of anastomotic leakage in LAR compared with previous studies.

Background Circulating tumour DNA (ctDNA) is known as a tumour-specific personalised biomarker, but the mutation-selection criteria from heterogeneous tumours remain a challenge. Methods We conducted multiregional sequencing of 42 specimens from 14 colorectal tumours of 12 patients, including two double-cancer cases, to identify mutational heterogeneity to develop personalised ctDNA assays using 175 plasma samples. Results “Founder” mutations, defined as a mutation that is present in all regions of the tumour in a binary manner (i.e., present or absent), were identified in 12/14 tumours. In contrast, “truncal” mutations, which are the first mutation that occurs prior to the divergence of branches in the phylogenetic tree using variant allele frequency (VAF) as continuous variables, were identified in 12/14 tumours. Two tumours without founder and truncal mutations were hypermutators. Most founder and truncal mutations exhibited higher VAFs than “non-founder” and “branch” mutations, resulting in a high chance to be detected in ctDNA. In post-operative long-term observation for 10/12 patients, early relapse prediction, treatment efficacy and non-relapse corroboration were achievable from frequent ctDNA monitoring. Conclusions A single biopsy is sufficient to develop custom dPCR probes for monitoring tumour burden in most CRC patients. However, it may not be effective for those with hypermutated tumours.

The role of somatic copy number alterations (SCNAs) that occur in colorectal tumors is poorly understood. SCNAs are correlated with corresponding gene expression changes that may contribute to neoplastic progression. Thus, we examined SCNAs and the expression of messenger RNAs (mRNAs) located at corresponding loci in colorectal neoplasia, a progression model of human neoplasm. We used 42 colorectal neoplastic samples, including adenomas, intramucosal cancers (IMC) and invasive colorectal cancers (CRC) that were microsatellite stable (MSS) using a genome‐wide SNP array and gene expression array (first cohort). In addition, validation analyses were examined (37 colorectal neoplasias). None of the mRNAs with a corresponding SCNA was found in the adenomas. However, three mRNAs, including ARFGEF2 at 20q13.13, N4BP2L2 at 13q13.1 and OLFM4 at 13q14.3 with a copy number (CN) gain at the corresponding locus were upregulated in IMCs of the first cohort. Moreover, upregulated expression of ARFGEF2 and OLFM4 was upregulated in the validation analysis. Finally, 28 mRNAs with gains of corresponding loci were pooled in invasive CRC of the first cohort. The mRNAs, including ACSS2 (20q11.22), DDX27 (20q13.13), MAPRE1 (20q11.21), OSBPL2 (20q11.22) and PHF20 (20q11.22‐q11.23) with CN gains of the corresponding loci were identified in 28 mRNAs. Four of these mRNAs (DDX27, MAPRE1, OSBPL2 and PHF20) were upregulated in the invasive CRC in the validation analysis. We conclude that specific 13q and 22q CN gains with gene expression changes in the corresponding loci may play an important role in IMC cells' progression into invasive CRC.

Background Pylorus-preserving gastrectomy (PPG) has been accepted as a function-preserving surgery for the treatment of early gastric cancer in East Asian countries. Therefore, this study aimed to evaluate the feasibility and safety of totally laparoscopic PPG (TLPPG) with intracorporeal anastomosis. Methods A total of 43 patients with early gastric cancer underwent laparoscopy-assisted PPG (LAPPG) with extracorporeal anastomosis between May 2006 and November 2012. The operative outcomes of 22 patients who underwent TLPPG between November 2012 and February 2019 were evaluated, and data were compared with that of the LAPPG group. Results No significant difference in the operative time was observed between the two groups. Blood loss was lower in the TLPPG group (18.5 mL) than in the LAPPG group (30.7 mL, p = 0.008), and the length of abdominal incision was shorter in the TLPPG group (3.8 cm) than in the LAPPG group (4.7 cm, p < 0.001). No significant difference in the complication rate was observed between the two groups (13.6% in the TLPPG vs. 9.3% in the LAPPG group, p = 0.594). No anastomosis-related complications occurred in either group. No significant between-group difference was observed in the delayed gastric emptying (TLPPG, 9.1 vs. LAPPG, 7%, p = 0.762). The initiation of postoperative fluid (TLPPG, 1.0 day vs. LAPPG, 3.0 days, p < 0.001) and meal (TLPPG, 3.0 days vs. LAPPG, 4.0 days, p < 0.001) intake was earlier in the TLPPG group than in the LAPPG group. No significant between-group difference was observed in the postoperative hospital stay. Conclusions The findings of this study suggest that TLPPG with intracorporeal reconstruction not only is as feasible and safe as LAPPG for the treatment of patients with early gastric cancer but also provides certain advantages such as reduced blood loss and wound size.

Introduction Recent studies have reported that induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (DCF) is an effective treatment for unresectable, locally advanced esophageal cancer. The aim of this study was to investigate the safety and feasibility of thoracoscopic esophagectomy (TE) after DCF for initially unresectable esophageal squamous cell carcinoma (ESCC). Methods Twenty-three patients with initially unresectable T4 thoracic ESCC underwent TE after induction DCF. Results The neighboring organs with tumors were the tracheobronchus in nine patients, thoracic aorta in 13, and pericardium and diaphragm in three each (concurrent overlapping invasion occurred in five patients). The mean total operation time was 556.3 ± 107.2 minutes, and the mean time of the thoracic procedure was 258.9 ± 83.9 minutes. The mean total blood loss was 166.2 ± 117.8 mL, and the loss during the thoracic procedure was 33.5 ± 24.6 mL. All patients achieved complete R0 resection under TE. No conversions to open thoracotomy were performed. The postoperative morbidity rate was 34.8%. The postoperative hospital stay was 24.3 (range, 13-38) days. Five patients had recurrence: four had distant metastasis (lung, two; liver, three; and one with overlap), and one had mediastinal lymph node recurrence. No local recurrence was noted at the site of the primary T4 tumor. Conclusions TE was safely performed in 23 patients after DCF therapy for locally advanced unresectable ESCC. Induction DCF, followed by TE, could be an alternative treatment for unresectable T4 ESCC.

Colorectal adenocarcinoma (CRA) is characterized by marked heterogeneity and may be composed of an admixture of various histologic patterns, including well-formed gland and cribriform types. Although tumors displaying a prominent or predominant cribriform feature are frequently found in CRA, this type may contain specific histologic variants with a characteristic molecular alteration. We investigated the molecular features of 51 primary CRAs with a predominant cribriform histology using array-based analyses [somatic copy number alterations (SCNAs); mRNA expression]. Mutations (TP53, KRAS, PIK3CA and BRAF) and DNA methylation status were also analyzed. The crypt isolation method was used to obtain isolated tumor glands of each type separately. All patients were classified by their CRA histologic subtype into two groups: well-formed gland and cribriform. Next, we performed cluster analysis to stratify SCNA and mRNA expression patterns between the two subtypes. Two distinctive subgroups were stratified based on patterns of SCNA and mRNA expression and were correlated with each histologic subtype. The cribriform type was characterized by a high frequency of SCNA compared with that of the well-formed gland type and was closely associated with the expression of specific mRNAs. In addition, the frequency of KRAS mutation was significantly higher in the cribriform type than in the well-formed gland type. Finally, there was no difference in DNA methylation status between the two subtypes. Overall, these data suggest that the cribriform type provides important insights into colorectal carcinogenesis, suggesting specific potential histologic implications based on the molecular profile.

Although microRNAs (miRNAs) play an important role in invasive tumor lesions, which involve cancer tissues mixed with stromal tissues, the differences in miRNA expression between cancer and stromal cells remain unclear. We selected 13 miRNAs and examined their differential expression patterns in cancer gland cells and surrounding stromal cells isolated from 24 colorectal cancer (CRC) specimens using a crypt isolation method. Although six miRNAs were upregulated in gland cells, only three were upregulated in the corresponding stromal cells, in the cancer compared with non-cancer specimens. Next, we examined the differences in miRNA expression between isolated cancer gland and stromal cells. Five miRNAs showed statistical differences in their cancer-related differential expression patterns between isolated cancer gland and stromal cells. We then compared these miRNA expression patterns in isolated cancer gland and stromal cells with those in fresh intact tumor tissues, consisting of cancer nests and stromal tissue, obtained from the 24 CRCs. The expression patterns of three miRNAs in the intact cancer tissue samples did not correspond with those in the isolated components. Identification of the expression patterns of miRNAs in both the cancer gland and stromal cell components of the tumor microenvironment greatly contributes to evaluating epigenetic regulation in CRC.

Recent study has shown that there is a close association of desmoplastic reactions (DRs) with the survival of patient with colorectal cancer (CRC). Here, we examined the correlation of DR classification with disease-free survival and overall survival of CRC. Moreover, we also investigated the association of the histological transition of the DR with the expression of cancer-associated fibroblast (CAF)- and epithelial-mesenchymal transition (EMT)-related proteins in CRC in stages II and III. We examined 157 cases of stage II CRC and 163 cases in stage III. We classified DRs into mature, intermediate, and immature types and examined the correlation of the DR patterns with patient survival. Next, the expression of CAF- and EMT-related markers was examined in CRC samples using immunohistochemistry. In stage II CRC, we found a significant correlation of disease-free survival with DR subtype (immature vs mature) in univariate and multivariate analyses. In stage III CRC, however, such association was not identified. Finally, the DR was closely associated with two EMT-related markers in stages II and III CRC. Our findings suggest that classification of the DR may help to predict patient prognosis in CRC. Furthermore, classification of the DR is correlated with the expression of EMT-related proteins.

MicroRNAs (miRNAs) are potential biomarkers of neoplastic lesions, but additional information on dysregulated miRNA expression during progression of the adenoma-adenocarcinoma sequence may be helpful to identify the role of miRNAs in this sequence. We examined the expression levels of 13 miRNAs (hsa-miRNA-19a-3p, hsa-miRNA-21-5p, hsa-miRNA-27a-3p, hsa-miRNA-27b-3p, hsa-miRNA-31-5p, hsa-miRNA-34b-3p, hsa-miRNA-125b-5p, hsa-miRNA-143-3p, miRNA-191-5p, hsa-miRNA-193b-3p, hsa-miRNA-195-5p, hsa-miRNA-206 and hsa-let-7a-5p) that are closely associated with colorectal carcinogenesis in 40 conventional adenomas (tubular and tubulovillous adenomas), 20 intramucosal carcinomas (IMCs) and 60 invasive colorectal cancers (iCRCs) using reverse-transcription polymerase chain reaction. These 120 tumors were divided into two cohorts, that is, cohort 1 (60 cases) and cohort 2 (for validation; 60 cases). We analyzed the expression levels of these miRNAs in the first step (adenoma→IMC) and second step IMC→iCRC) of the adenoma-carcinoma sequence in both cohorts. Although no significant differences in the expression of any of the 13 miRNAs were found between adenomas and IMCs consistently in both cohorts, the expression levels of hsa-miRNA-125b-5p, hsa-miRNA-143-3p, and hsa-miRNA-206 were significantly upregulated in iCRC in both cohorts compared with those in IMC. The current results suggest that certain miRNAs, including hsa-miRNA-125b-5p, hsa-miRNA-143-3p and hsa-miRNA-206, are candidate markers that play critical roles in the progression of IMC to iCRC.

Background Indications for laparoscopic liver resection (LLR) are continuously expanding. The Japanese Society of Hepato-Biliary-Pancreatic Surgery defines highly difficult hepatectomy as a procedure involving one or more sections (except for left lateral sectionectomy) or anatomical segmentectomy. This study aimed to assess the outcomes of complex LLR procedures and compare their technical difficulties, about which only a little is known to date. Methods We performed a retrospective review of the operative outcomes of 118 consecutive patients who underwent pure laparoscopic complex hepatectomy. The surgical outcomes, including operative times, blood loss amounts, and postoperative morbidity rates, were compared among complex LLR procedures. Results The overall median operative time was 280 minutes, and the median intraoperative blood loss was 86 mL. Two patients required conversion to open laparotomy (1.7%). The postoperative major morbidity rate was 11.0% Posterosuperior segmentectomy, right hemihepatectomy, and anterior sectionectomy required the longest operative times. Anterior and posterior sectionectomy resulted in the highest blood loss, and right hemihepatectomy and anterior sectionectomy resulted in the most complications. Conclusions The surgical difficulties associated with complex LLR procedures vary. It is critical to recognize the specific risks and cautionary points to ensure patient safety and provide proper systemic training to surgeons.

Background Reduced port laparoscopic surgery (RPLS) is comparable to conventional multiport laparoscopic surgery and has the potential to provide improved cosmesis and decreased pain; as such, it satisfies a growing demand for less invasive surgical procedures. Moreover, a zigzag incision of the umbilicus results in a less visible scar in plastic surgery. Here we report a series of two cases with bilateral organ tumors treated by single-stage RPLS using a combination of a transumbilical approach and a zigzag incision. Case presentation Case 1: A 63-year-old man was diagnosed with right renal cell carcinoma (RCC) (clear cell carcinoma, pT1a, venous invasion (−)) and a splenic tumor (cavernous hemangioma). Case 2: An 84-year-old woman was diagnosed with concurrent left RCC (clear cell carcinoma, pT1b, 65 × 65 mm, venous invasion (+)) and ascending colon cancer (adenocarcinoma pT3 with no nodal involvement (0/48)). The perioperative course was uneventful in both cases. However, an additional incision was required in Case 2 for specimen excision. Therefore, the scars were more obvious in Case 2 than in Case 1. Conclusions Although more cases are required to evaluate the superiority of this technique, this novel procedure could be considered for patients with bilateral lesions.

Preoperative chemotherapy with cisplatin and 5-fluorouracil (CF) has become the standard treatment for resectable stage II/III thoracic esophageal carcinoma in Japan. Recently, preoperative triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) has been reported to be effective for locally advanced esophageal cancer. Thoracoscopic esophagectomy (TE) has been increasingly accepted worldwide for the treatment of esophageal cancer. We conducted a retrospective study to evaluate the safety and outcomes of TE after DCF therapy for patients with advanced esophageal cancer. The medical records of 63 consecutive patients with esophageal squamous cell carcinoma who underwent thoracoscopic surgery after chemotherapy were reviewed. Thirty-four patients received neoadjuvant chemotherapy with CF, and 29 received DCF as first-line chemotherapy. The clinical T stage was significantly higher in the DCF group than in the CF group (p

We aimed to evaluate the effectiveness of intervention by a perioperative multidisciplinary support team for radical esophagectomy for esophageal cancer. We retrospectively reviewed 85 consecutive patients with esophageal cancer who underwent radical esophagectomy via right thoracotomy or thoracoscopic surgery with gastric tube reconstruction. Twenty-one patients were enrolled in the non-intervention group (group N) from May 2011 to September 2012, 31 patients in the perioperative rehabilitation group (group R) from October 2012 to April 2014, and 33 patients in the multidisciplinary support team group (group S) from May 2014 to September 2015. Morbidity rates were 38, 45.2, and 42.4% for groups N, R, and S, respectively. Although there were no significant differences in the incidence of pneumonia among the groups, the durations of fever and C-reactive protein positivity were shorter in group S. Moreover, postoperative oral intake commenced earlier [5.9 (5–8) days] and postoperative hospital stay was shorter [19.6 (13–29) days] for group S. The intervention by a perioperative multidisciplinary support team for radical esophagectomy was effective in preventing the progression and prolongation of pneumonia as well as earlier ambulation, oral feeding, and shortening of postoperative hospitalization.

Several studies have demonstrated that prehabilitation helps reduce the incidence of postoperative complications. In this study, we investigated the safety and efficacy of enhanced prehabilitation (EP) in the hospital for patients with esophageal cancer. We retrospectively reviewed the data of 48 consecutive patients who underwent radical esophagectomy with gastric tube reconstruction between September 2015 and June 2019. EP program had been introduced in August 2017. In the EP group, patients received the EP program during hospitalization 7 days before surgery in addition to conventional perioperative rehabilitation. The EP program consisted of aerobic exercise and muscle strength training in the morning and afternoon. Operative outcomes were compared between patients who received EP (EP group; 23 patients) and patients who did not receive EP (control group; 25 patients). The preoperative (EP group vs. control group, 492.9 ± 79.7 vs. 418.9 ± 71.8 m, p

Besides antibiotic prophylaxis, antiseptic skin preparation is an important measure to prevent surgical site infection (SSI). No reports have detailed the relationship between SSI and umbilical microflora following laparoscopic colorectal cancer with a transumbilical longitudinal incision. Risk factors and the rate of SSI were investigated in 453 patients who underwent laparoscopic colorectal resection over a 3-year period. Microbiological samples were collected from the umbilicus and SSI areas. After laparoscopic procedure, we observed SSIs in approximately 5% of cases, with superficial SSI in 15 (3.3%) patients and organ/space SSIs 7 (1.5%). In univariate analysis, preoperative albumin (Alb) value and anastomosis of enterocolostomy were significantly associated with superficial SSI development. Also, age, blood loss, stoma, tumor site (rectum), and Hartmann/abdominal perineal resection (APR) were significant risk factors for organ/space SSI. In multivariate analysis, the preoperative Alb value was the most significant factor associated with a predisposition to superficial SSI. The bacteria detected in SSI were mostly different from those at wound closure. Antibiotic-resistant bacteria were included in organ/space SSI all cases. SSI development with laparoscopic surgery reportedly occurs in about 3–15% cases. The SSI rate in this study and other reports was comparable. Using small transumbilical longitudinal incision in laparoscopic colorectal surgery is less likely to cause SSI when sufficient control measures are enacted, even though the umbilicus contains resident bacteria in abundance.

The aim of this study was to compare the postoperative short- and long-term outcomes after laparoscopic colorectal surgery (LCS) between octogenarians and healthy middle-aged patients. Between January 1997 and July 2009, 655 consecutive laparoscopic surgeries for colorectal cancer patients were operated by 1 colorectal surgeon. Ninety-three patients were octogenarians (≥80 years), and 133 patients were case-matched middle-aged (60–69 years) patients. We analyzed the mean operative time, blood loss, type of surgery for rectal cancer, length of hospital stay, mortality, and morbidity. The overall survival curve was constructed using the Kaplan–Meier method. The American Society of Anesthesiologists classification was significantly higher in the octogenarians than in the middle-aged controls. However, there were no significant differences between the two groups in terms of the incidence of morbidities (11.7 vs. 9.2 %) and length of hospital stay (12.1 vs. 10.9 days). The number of lymph nodes harvested was significantly fewer (p

Background Anastomotic leakage during laparoscopic low anterior resection (Lap-LAR) for rectal cancer remains challenging for colorectal surgeons. Firing linear staplers multiple times has been reported as a risk factor for iatrogenic anastomotic leakage. Our institute usually performs rectal transection using 2 planned stapler fires followed by anastomosis with the double-stapling technique. Methods Between November 2009 and September 2016, a total of 272 consecutive patients underwent Lap-LAR with double-stapling anastomosis for rectal cancer. We inserted a linear 45-mm stapler cartridge from a port in the lower right quadrant of the abdomen. The first transection was made up to three-quarters of the rectal wall, and the remaining rectum was completely resected using a second stapler. During this procedure, the intersection of the 2 staple lines, which might otherwise cause anastomotic leakage, was located in the center of the stump of the distal rectum, so the intersection at the rectal stump was able to be easily removed using a circular stapler. Results None of our patients were converted to open surgery. Among the 272 Lap-LAR procedures for which use of 2 stapler fires was planned, 3 fires occurred in error only once (0.4%). Rectovaginal fistula and anastomotic leakage occurred in 1 patient (0.4%) and 9 patients (3.3%), respectively, and 49 (18.0%) patients required protective diverting stoma. Conclusion Rectal transection with 2 planned stapler fires appears safe, practical, and straightforward to standardize, and reduces the need for multiple linear fires and the incidence of anastomotic leakage.

We investigated the operative outcomes of thoracoscopic esophagectomy (TE) in the prone position, using the concept of total meso-esophageal excision for esophageal cancer. The medical records of 140 consecutive patients with esophageal cancer who underwent radical esophagectomy by TE were reviewed retrospectively, and operative outcomes were compared between patients treated before (non-meso-esophagus; non-ME group) and after (ME group) the introduction of total meso-esophageal excision (ME). There were no significant differences between the groups in postoperative morbidity (non-ME group vs. ME group, 28.3% vs. 41.4%, p = 0.119), 30-day mortality (non-ME group vs. ME group, 0% vs. 1.1%; p = 0.433), and in-hospital mortality (non-ME group vs. ME group, 1.9% vs. 0%, p = 0.199). Although overall survival and relapse-free survival did not differ significantly between the groups, the overall recurrence rate was significantly lower in the ME group than the non-ME group (non-ME group vs. ME group, 43.4% vs. 23%, p = 0.011). In particular, the rate of regional lymph node recurrence in the mediastinum was lower in the ME group (non-ME group vs. ME group, 11.3% vs. 2.3%; p = 0.026). Our results suggest that the ME procedure might be one of the procedures that reduce regional lymph node recurrence in the mediastinum without any deterioration in short-term outcomes.

Background Docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy can cause severe adverse events, including neutropenia and febrile neutropenia. The feasibility of DCF therapy is a concern, particularly for elderly patients, patients with moderate organ disorders, and patients suffering from malnutrition caused by dysphagia or insufficient oral intake. We introduced a biweekly DCF therapy (bDCF) for the purpose of reducing severe adverse events for these fragile patients. This study investigated the feasibility and outcome of an esophagectomy after bDCF therapy for patients with advanced esophageal squamous cell carcinoma. Methods Fifty-nine patients with esophageal carcinoma underwent an esophagectomy after DCF or bDCF therapy as primary chemotherapy. DCF was administered to 37 patients in the DCF group, whereas bDCF was administered to 22 patients in the bDCF group. Results Patients in the bDCF group were significantly older than those in the DCF group (p = 0.016). Heart and pulmonary comorbidities were significantly more common in the bDCF than in the DCF group (p

Radiological evaluation of the efficacy of preoperative chemotherapy for colorectal liver metastasis (CRLM) is the most important tool for determining treatment strategies. The aim of this study was to identify a correlation between morphologic appearance on computed tomography (CT) and histologic findings of CRLM after preoperative chemotherapy. We examined 47 patients who had undergone a first hepatic resection for CRLM after preoperative chemotherapy and had received contrast-enhanced CT scans. We assessed the morphologic appearance of the overall attenuation based on metastases changing from heterogeneous to mixed and homogenous lesions, the tumor–liver interface, and the peripheral rim enhancement on CT. Histologic parameters included usual necrosis (UN), infarct-like necrosis (ILN), three-zonal change, dangerous halo, mucous lake, shape of ILN, dominant type of necrosis, and presence of viable tumor cells. The relationship between morphologic appearance and histologic findings was evaluated. CT overall attenuation revealed that UN predominance was more common in the heterogeneous group than in the mixed and homogeneous groups (P = 0.011). The frequency of ILN increased sequentially from ill-defined to variable and sharp at the tumor–liver interface (P = 0.038), and the frequency of UN decreased sequentially from present to partially resolved and completely resolved in the peripheral rim enhancement (P = 0.023). The histologic presence of viable tumor cells was closely associated with the tumor–liver interface (P = 0.0003) and the peripheral rim enhancement (P = 0.004). CT morphologic appearance of CRLM after preoperative chemotherapy is correlated with histologic findings regarding necrosis.

Laparoscopy-assisted pylorus-preserving gastrectomy has been increasingly reported as a treatment for early gastric cancer located in the middle third of the stomach because of its low invasiveness and preservation of pyloric function. Advantages of a totally laparoscopic approach to distal gastrectomy, including small wound size, minimal invasiveness, and safe anastomosis, have been recently reported. Here, we introduce a new procedure for intracorporeal gastro-gastrostomy combined with totally laparoscopic pylorus-preserving gastrectomy (TLPPG). The stomach is transected after sufficient lymphadenectomy with preservation of infrapyloric vessels and vagal nerves. The proximal stomach is first transected near the Demel line, and the distal side is transected 4 to 5 cm from the pyloric ring. To create end-to-end gastro-gastrostomy, the posterior wall of the anastomosis is stapled with a linear stapler and the anterior wall is made by manual suturing intracorporeally. We retrospectively assessed the postoperative surgical outcomes via medical records. The primary endpoint in the present study is safety. Sixteen patients underwent TLPPG with intracorporeal reconstruction. All procedures were successfully performed without any intraoperative complications. The mean operative time was 275 min, with mean blood loss of 21 g. With the exception of one patient who had gastric stasis, 15 patients were discharged uneventfully between postoperative days 8 and 11. Our novel hybrid technique for totally intracorporeal end-to-end anastomosis was performed safely without mini-laparotomy. This technique requires prospective validation.

Background Laparoscopic liver resection for liver metastases from colorectal cancer (CRLM) is performed in a relatively small number of institutions. Its operative results have been reported to be comparable with that of open laparotomy; however, information on its oncologic outcomes is scarce. This study aimed to compare the long-term outcomes of laparoscopic hepatectomy (LH) and open hepatectomy (OH) to treat CRLM at a single institution. Methods We retrospectively reviewed data from 168 consecutive patients who underwent LH (n = 100) or OH (n = 68) for CRLM. The tumor characteristics, operative results, overall survival (OS) rate, recurrence-free survival (RFS) rate, and recurrence patterns were analyzed and compared. A previously published survival-predicting nomogram was applied to compare OS and RFS between the 2 patient groups. Results The largest tumor diameter and the number of tumors were significantly larger in the OH group than in the LH group; however, no differences in other tumor factors were observed between the 2 groups. When matched by the nomogram, OS and RFS remained comparable between the 2 groups in every examined stratum, not only for low-risk patients but also for those with high risk. The recurrence patterns also were similar (liver: 30.2% vs 26.8%, P = .72; lung: 22.6% vs 34.1%, P = .22; peritoneum: 7.6% vs 4.9%, P = .45). Conclusion The long-term outcomes of laparoscopic liver resection for CRLM were comparable with those of the open procedure in not only low-risk but also high-risk patients.

This study aimed to clarify the histological characteristics related to preoperative chemotherapy for colorectal liver metastases (CRLM). Sixty-three patients with CRLM were divided into two groups: CRLM with chemotherapy (41 cases, group A) and CRLM without chemotherapy (22 cases; surgical treatment alone, group S) to identify the histological differences associated with chemotherapy. In addition, we investigated the effects of combination chemotherapy on the histology of metastatic lesions. Infarct-like necrosis (ILN), three-zonal changes, and cholesterol clefts were more frequent in group A than in group S (P < 0.05). ILN and three-zonal changes were more common in the 5-FU with leucovorin and oxaliplatin (FOLFOX), or 5-FU with leucovorin and irinotecan (FOLFIRI) with or without additional bevacizumab groups than in group S (P < 0.05). Cholesterol clefts in the FOLFOX or FOLFIRI with bevacizumab group and foamy macrophages in the FOLFOX or FOLFIRI group were more common than in group S (P < 0.05). Cases with more than three of the four histological findings—i.e. ILN, three-zonal changes, cholesterol clefts, and foamy macrophages—were more frequent in the FOLFOX or FOLFIRI with or without additional bevacizumab groups than in group S (P < 0.05). We showed histological findings for every representative chemotherapy regimen for CRLM to clarify the effects of preoperative chemotherapy.

The patient was a 56-year-old man who presented with perianal pain and a perianal abscess. After admission, he underwent debridement and colostomy due to poor control of the perianal abscess. Following a biopsy of the resected specimens, he was diagnosed with adenocarcinoma in the anorectal fistula. CT and MRI revealed that the tumor had invaded into the internal obturator muscle. Therefore, preoperative chemoradiotherapy and chemotherapy were given for locally advanced cancer. Subsequent to tumor shrinkage, we performed an abdominoperineal resection. Histopathologically, no cancer cells were detected on the surgical margin, and the effect of the preoperative therapy was judged to be Grade 1b. There has been no indication of recurrence of cancer after 5 years.

A 66-year-old man diagnosed with rectal cancer underwent high anterior resection and received adjuvant chemotherapy (UFT plus UZEL). One year after the surgery, lung and para-aortic lymph node(PLN)metastases were identified. We chose mFOLFOX6 for first-line chemotherapy. After 7 courses, we changed the regimen to sLV5FU2 because of Grade 3 neuropathy. After 5 courses, to treat progressive disease(PD), we changed the regimen to FOLFIRI. Then, the patient had stable disease (SD), and surgical excision was performed for both lung and lymph node recurrence without adjuvant chemotherapy. Six years after the excision, a CT scan revealed PLNagain. We chose FOLFIRI plus cetuximab. After 9 courses, the lymph nodes decreased in size and there was no other recurrence; thus we performed resection. However, a third PLNrecurrence was identified 20 months after the resection. Chemotherapy has continued for 47 courses, and he has maintained SD for more than 2 years.

Purpose The role of laparoscopic total proctocolectomy (TPC) and ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP) has been controversial, given its technical difficulty of selecting the appropriate distal transection line and achieving safe anastomosis. We herein describe our initial experience with the prolapsing technique for laparoscopic-assisted TPC and IPAA (J-pouch) in the treatment of FAP. Methods A consecutive series of patients with FAP undergoing laparoscopic-assisted TPC with IPAA were identified from a prospectively collected database between June 2004 and February 2012. Medical records were reviewed for patient demographics, operative outcomes, and follow-up. Results The surgery was successfully completed in all 6 patients without any conversion to open surgery. The median operating time was 279 minutes (range, 240 to 386 min) and the median blood loss was 17.5 mL (range, 5 to 161 mL). No patient required blood transfusion. The median length of diet resumption and postoperative hospital stay were 7 days (range, 6 to 10 d) and 15 days (range, 13 to 21 d), respectively. A postoperative complication, wound infection, occurred in 1 patient. No anastomotic leakages or small bowel obstructions occurred. At a median follow-up of 59 months (range, 14.2 to 107.5 mo), no carcinoma had developed at the pouch or at the anastomotic site. Sexual function and fertility were unchanged as compared with preoperatively in 2 male patients. None of the patients experienced night-time incontinence or had to use a pad. Conclusions Our limited experience suggests that this prolapsing technique helps prevent problems with laparoscopic-assisted TPC and IPAA for FAP patients.

Postoperative hyperglycemia is associated with infectious complications after various types of surgery. Our objective was to determine whether postoperative blood glucose levels up to 1 week after highly invasive esophageal cancer surgery are associated with the incidence of postoperative infections (POIs). We conducted a retrospective chart review of 109 consecutive thoracic esophageal squamous cell cancer patients who underwent invasive esophagectomy with thoracotomy and laparotomy. The incidence of postoperative POIs and risk factors for POIs, including postoperative blood glucose levels, were evaluated. Of the 109 patients, 37 (34.0 %) developed POIs. Clinically, 73.0 % of the POIs became evident on or after postoperative day 4 (median, 5.25 days; interquartile range, 3.00–9.25 days). On and after postoperative day 3, chronological changes in blood glucose levels were significantly different between two groups of patients with or without POIs, as indicated by repeated measures ANOVA (P = 0.006). Multivariate logistic regression analysis results showed that an increased blood glucose concentration on postoperative day 3 was a significant risk factor for POIs. Our findings suggested that postoperative hyperglycemia on postoperative day 3 was a predictive factor of POIs after highly invasive esophageal cancer surgery.

We herein report a case of single-port laparoscopic and endoscopic cooperative surgery (LECS) for a gastric gastrointestinal stromal tumor (GIST). A 75-year-old female with an endoluminal GIST located near the esophagogastric junction underwent LECS. Both the mucosal and submucosal layers around the tumor were circumferentially dissected using endoscopic submucosal dissection via intraluminal endoscopy. The endoluminal GIST was exteriorized to the abdominal cavity. The tumor and the edge of the incision line were closed using an endoscopic linear stapler. The LECS was successfully accomplished without the need for any skin incisions or additional ports. The length of the operation was 120 min and blood loss was 5 ml. Oral intake was resumed on the second day and the length of hospital stay was 5 days. No complications were noted and the patient had an excellent cosmetic result. In our experience, single-port LECS is feasible and safe for gastric GIST when performed by a surgeon experienced in laparoscopic and gastric surgery.

Background In a statement from the second International Consensus Conference for Laparoscopic Liver Resection, adult-to-adult laparoscopic donor surgery was the earliest phase of development. It was recommended that the procedure be performed under institutional ethical approval and a reporting registry. Method At our institute, we started laparoscopy-assisted donor hepatectomy (LADH) in 2007 and changed to pure laparoscopic donor hepatectomy (PLDH) in 2012. This study included 40 living donors who underwent LADH and 14 live donors who underwent PLDH. We describe the technical aspects and outcomes of our donor hepatectomy from assist to pure and examine the liver allograft outcomes of the recipients after LADH and PLDH. Results There was significantly less blood loss in the PLDH group (81.07 ± 52.78 g) than that in the LADH group (238.50 ± 177.05 g), although the operative time was significantly longer in the PLDH group (454.93 ± 85.60 minutes) than in the LADH group (380.40 ± 44.08 minutes). And there were no significant differences in postoperative complication rate in the 2 groups. The liver allograft outcomes were acceptable and comparable with open living donor hepatectomy. Conclusions By changing our routine approach from assist to pure, PLDH can be performed safely, with better exposure due to magnification, and with less blood loss under pneumoperitoneal pressure. PLDH, which has become our promising donor procedure, results in less blood loss, better cosmesis, and the donor's complete rehabilitation without deterioration in donor safety.

Previous randomized controlled trials demonstrated similar oncological outcomes between laparoscopic and open colectomies, except for cases involving transverse colon and splenic flexure colon cancer. The objective of this study was to confirm the oncological safety and advantages of the short-term results of laparoscopic surgery for transverse and descending colon cancer in comparison with open surgery.The study data were retrospectively collected from the databases of 45 hospitals. Patients with transverse or descending colon cancer who underwent laparoscopic or open R0 resection were registered. The primary end-points were the 3-year overall survival and relapse-free survival rates according to pathological stage. The secondary end-points were the short-term results, including blood loss, operative time, diet intake, hospital stay, and postoperative complications.Of the 1830 eligible patients, 872 underwent open colectomy and 958 underwent laparoscopic colectomy. The median follow-up period was 38.4 months. The conversion rate to open resection was 4.5%. The 3-year overall survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients (96.2% vs 99.2%; P = 0.04); it was also higher for stage II (94.0% vs 95.5%) and stage III (87.4% vs 90.2%) patients, but there were no significant differences. The 3-year relapse-free survival rate of the laparoscopic group was significantly higher than that of the open group for stage I patients; there were no differences between the open and laparoscopic groups among the stage II and III patients. In the multivariate analyses, laparoscopic resection was a significant factor in relapse-free survival. Laparoscopic patients had significantly lower blood loss and a significantly longer operative time than the open groups. Also, postoperative hospital stay was significantly shorter and postoperative morbidity was significantly lower in the laparoscopic group.Although this retrospective study has limitations, we can conclude that laparoscopic surgery for transverse and descending colon cancer is oncologically safe and yields better short-term results than open surgery.

Tylosis is an inherited disorder characterized by abnormal palmoplantar skin thickening and a highly elevated risk of esophageal squamous cell carcinoma (ESCC). Analyses of tylosis in families have localized the responsible gene locus to a region of chromosome 17q25.1. Frequent loss of heterozygosity (LOH) in 17q25.1 was also observed in the sporadic form of ESCC. A putative tumor suppressor gene for ESCC may exist at this locus. We investigated the expression patterns of genes on 17q25.1 in tumor and corresponding normal tissues from patients with sporadic ESCC using RNA sequence analysis. For candidate genes, quantitative real-time reverse transcription-PCR (qRT-PCR), direct sequence, LOH and methylation analyses were performed using 93 clinical ESCC samples and 10 cell lines. A significant downregulation of ST6GALNAC1 was demonstrated in ESCC tissues compared to its expression in normal tissues by qRT-PCR (n=93, p

For patients with colorectal cancer, lymph node metastasis is a very important factor for prognostic and treatment determinations. Fluorine-18 fludeoxyglucose positron emission tomography/CT ((18)F-FDG-PET/CT) is among the useful tools for detecting lymph node metastasis. Recently, a new (18)F-FDG-PET/CT reconstruction technique for improving spatial resolution and signal-to-noise ratios, point spread function (PSF), has become available. We assessed the effect of PSF reconstruction on standardized uptake values and its diagnostic accuracy for lymph node staging in patients with colorectal cancer.We retrospectively analysed records from patients with colorectal cancer who underwent (18)F-FDG-PET/CT for pre-operative staging. All positron emission tomography CT (PET/CT) examinations were reconstructed using ordered subset expectation maximization (OSEM) and OSEM + PSF. We compared sensitivities, specificities, positive-predictive values (PPVs), negative-predictive values (NPVs) and accuracies of conventional PET/CT (reconstructed with OSEM) and PSF-PET/CT (reconstructed with OSEM + PSF) for identifying lymph node metastases. We also analysed the diagnostic confidence level on a 5-point scale.With conventional PET/CT, the sensitivity, specificity, PPV, NPV and accuracy were 53.1%, 99.1%, 94.4%, 88.3% and 89.1%, respectively. With PSF PET/CT, the corresponding values were 65.6%, 99.1%, 95.4%, 91.2% and 91.8%, respectively. Conventional PET/CT and PSF PET/CT did not differ significantly in terms of N-stage definition (p = 0.125). However, the diagnostic confidence level of PSF PET/CT was significantly higher than that of conventional PET/CT (p 0.01).PSF reconstruction might slightly increase sensitivity without impairing specificity. Moreover, this technique is expected to facilitate more confident radiological decisions when compared with conventional PET/CT. Advance in knowledge: This study demonstrates the clinical effectiveness of PSF PET/CT for lymph node staging in colorectal cancer.

We herein report a case of single-incision laparoscopic access (SILA) splenectomy for idiopathic thrombocytopenic purpura (ITP). A 24-year-old female patient with a diagnosis of ITP received corticosteroid therapy. However, as the side effects became serious, a splenectomy option was chosen. The SILA splenectomy using a transumbilical approach is cosmetically more attractive than a conventional laparoscopic approach, but it has an increased risk of major bleeding due to technical considerations. Therefore, we prioritized the patient's safety during the SILA splenectomy by choosing a left lower abdominal approach. The operating time was 123 min and blood loss was 1 ml. This was comparable to a conventional laparoscopic splenectomy. The present case appears to be the first SILA splenectomy reported in Japan. In our experience, a SILA splenectomy is feasible and safe, with favorable perioperative and shortterm patient outcomes. Further studies are necessary before the universal adoption of this new technique.

The aim of this study was to evaluate the feasibility and outcomes of endoscopic subtotal thyroidectomy for Graves’ disease. From August 1998 to April 2008, a total of 100 patients with benign thyroid diseases underwent endoscopic thyroidectomy via the breast approach. Among these patients, 42 underwent subtotal thyroidectomy for Graves’ disease. The resection was successfully completed endoscopically in 41 patients (98%). Overall, the mean operating time, mean blood loss, and mean resected thyroid weight were 277 minutes, 76 ml, and 49.9 g, respectively. As the resected thyroid weight increased, the operating time was significantly prolonged and the blood loss significantly increased. Morbidities included one permanent and one temporary case of recurrent laryngeal nerve palsy with hypocalcemia. A hypertrophic scar was seen in the right breast medial margin in three men. Thyroid function was classified as euthyroidism, hypothyroidism, and recurrent hyperthyroidism in 5, 34, and 3 patients, respectively. At 92 months of median follow-up, two patients had modest operation-associated symptoms: one with swallowing discomfort and another with paresthesia in the anterior chest wall at the time of discharge. However, both patients’ symptoms disappeared within 36 months after surgery. Young women were highly satisfied, with an overall mean satisfaction rating of 9.3 points. Although the endoscopic approach may be relatively contraindicated for large thyroid glands, endoscopic subtotal thyroidectomy via the breast approach is a safe, feasible procedure with excellent cosmetic benefits, and it may be the procedure of choice in carefully selected patients with Graves’ disease.

Objective: No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC. Methods: Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR). Results: In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progression-free survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥3, 17%). Conclusions: The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS.

The recommended intake of clear liquids until 2 hours before surgery is reportedly safe and effective. We investigated whether oral rehydration therapy before surgery had improved satisfaction, stress response, and hemodynamics in patients during perioperative period.Patients scheduled to undergo laparoscopic colectomy were enrolled and randomly divided into 2 groups. The oral rehydration therapy (ORT) group (29 cases) was allowed to drink clear liquids until 2 hours before anesthesia induction and the control group (29 cases) fasted from 21 : 00 the night before surgery. All patients entered the operating room at 8: 40. Patient satisfaction was examined after admission to the operating room. The volume and pH of gastric fluid were measured after anesthetic induction. The serum concentrations of cortisol and catecholamine were measured as stress response indicators after anesthetic induction and at the completion of surgery. Intraoperative hemodynamics was also recorded.There were no differences in patient satisfaction, stress response, and hemodynamics between the 2 groups. Intraoperative urine volume was significantly larger in the ORT group. Vomiting and aspiration were not observed in any patientOral rehydration therapy until 2 hours before surgery seemed safe but did not improve satisfaction, stress response, and hemodynamics in perioperative patients.

The aim of the study is to assess the relationship between the introduction of biologic and immunosuppressant therapy and the number of patients undergoing surgery for ulcerative colitis (UC). A questionnaire survey about patients undergoing surgery for UC was sent to 26 teaching hospitals throughout Japan. The questionnaire period spanned from 2008 to 2013, to account for the introduction of tacrolimus (2009) and infliximab (2010). The total number of patients who underwent surgery was 297, 291, 273, 255, 300, and 305 in 2008, 2009, 2010, 2011 2012, and 2013, respectively. The emergency surgery rate remained stable at 32–34 % each year. The proportion of patients who underwent surgery for cancer increased from 13.8 % in 2008 to 20 % in 2013. In 2013, 41, 38, and 6 % of patients who underwent surgery had received treatment with a biologic, tacrolimus, and cyclosporine, respectively. No institution reported an increase in postoperative complications among patients treated with immunosuppressive drugs. The number of patients undergoing surgery decreased temporarily soon after infliximab and tacrolimus first became widely available, but subsequently increased again. The emergency surgery rate remained unchanged throughout the study period. These data show that immunosuppressive drugs have had little effect on the risk of postoperative complications.

Situs inversus totalis (SIT) is a rare congenital condition in which the abdominal and thoracic organs are on the opposite sides to their normal anatomic positions. Reports of laparoscopic surgery for colorectal cancer with SIT are very few. Due to the mirror-image transposition of organs and vascular abnormalities, laparoscopic surgery for patients with SIT is technically complicated. Therefore, it has been reported as easier for left-handed surgeons. This report presents that operative procedures can be conducted as usual by changing the positions of the operator and assistants, even if the operator is right-handed. A 71-year-old woman visited our hospital with a 2-month history of hematochezia. Colonoscopy revealed an ulcerative tumor in the sigmoid colon and biopsy confirmed well-differentiated adenocarcinoma. Laparoscopic sigmoidectomy radical lymphadenectomy was performed. The operating time was 189 minutes and blood loss was 13 mL. The patient was discharged on postoperative day 7, without any complications. We report that complicated surgical procedures for patients with SIT can be simplified by changing viewpoints. Due to the altered anatomy in SIT, the positions of the operator and assistants are very important. Location of the pelvis is almost the same as in orthotopic patients, by moving the operator from the left side to the right side of the patient. Changing the position of the operator to the right side seems to be effective for patients with SIT during pelvic procedures.

We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.

Panitumumab was approved in June 2010 for use in the treatment of unresectable advanced/recurrent colorectal cancer. Here, we report outcomes and adverse events of panitumumab combination therapy or single-agent chemotherapy for K-ras wild-type unresectable or recurrent colorectal cancers. Our study focused on first-line treatments. The study involved 18 patients who started receiving panitumumab in October 2010. Nine patients received panitumumab as a first-line treatment; 4, as a second-line treatment; and 5, as a third-line or subsequent treatment. The overall response rate was 27.8%. Among the patients who received panitumumab as a first-line treatment, the response rate was 55.6%. Grade 1 and 2 skin disorders were common adverse events. Grade 2 interstitial pneumonia was observed in 1 patient(5.6%). Grade 3 or higher events comprised peripheral neuropathy in 1 patient(5.6%)and neutropenia in another patient(5.6%). The treatment was beneficial, and metastatic foci were resected in 3 patients. In this study, the only adverse events of Grade 3 or higher were 1 case each of peripheral neuropathy and neutropenia. Accordingly, adequate control seemed possible. The specific line of treatment that panitumumab should belong to remains controversial. However, active initiation as first-line treatment should be considered for cases in which resection of metastatic foci can be expected from tumor reductions due to panitumumab.

Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs.Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P0.05). There were no significant intergroup differences in secondary endpoints and adverse events.DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.

We describe 6 cases of laparoscopic splenectomy for multiple, fusiform splenic artery aneurysm (SAA) in patients difficult to treat with interventional radiology procedure and present a literature review.Between November 1999 and May 2008, 6 patients with SAA underwent laparoscopic surgery. Among these patients, 4 had splenectomy alone and 2 had splenectomy with distal pancreatectomy. The mean size of the aneurysm was 3.1 cm (range: 2 to 4 cm).Laparoscopic surgeries for SAA were completed successfully in all the 6 patients. The mean operative time and the blood loss were 186.7 minutes (range: 115 to 300 min) and 187.8 mL (range: 3 to 850 mL). The length of the hospital stay was 8.5 days (range: 3 to 15 d). In only 1 case, portal system thrombosis was observed, and the other serious morbidities such as hemorrhage or pancreatic leakage were not observed. No recurrence was observed during a mean follow-up period of 116 months (range: 14 to 260 mo).Laparoscopic surgery should be considered to be a safe therapeutic option for SAA patients with the risk of rupture who are difficult to treat with interventional radiology therapy.

Frequent frameshift mutations of simple nucleotide repeats in the protein-encoding regions, as well as replication errors (RERs) at microsatellite loci, have recently been demonstrated in gastrointestinal tumors. These genetic instabilities have been considered indicative of an increased risk of accumulating mutations in cancer-associated genes and of developing multiple cancers. We studied frameshift (or insertion/deletion) mutations of simple nucleotide repeats in five genes (TGFbeta type II receptor [TGFbetaRII], E2F4, MSH2, MSH3, and MSH6) in 23 tumors from 12 patients who had synchronous cancers of the esophagus and other organs. Genetic instability at four microsatellite loci, as well as mutations in the TP53, APC, and KRAS2 genes, were also studied. No frameshift mutations were observed in the TGFbetaRII, MSH3, and MSH6 genes. RER and a deletion mutation of BAT26 in MSH2 were present in one (1/23; 4%) gastric cancer. This tumor also carried a deletion mutation in the serine (AGC) repeat of the E2F4 gene. Mutation screening of the TP53, APC, and KRAS2 genes revealed that the synchronous cancers did not carry the same mutations. Our results suggested that genetic instability, such as insertion/deletion mutations in simple nucleotide repeats, is not significantly associated with the development of multiple primary cancers of the esophagus and other organs, and that these synchronous cancers developed independently according to their different environmental factors.

Our patient was a 58-year-old woman with internal bleeding hemorrhoids who was undergoing FOLFOX6 treatment for unresectable multiple hepatic metastases of colorectal cancer. Response evaluation after 6 courses showed stable disease (SD), but side effects necessitated a change in regimen. Hemorrhoidal bleeding had also increased, and hemorrhoid-sclerosing therapy with ALTA(ZION)injections was administered. Because no bleeding was evident after treatment and the clinical course was uneventful, chemotherapy with bevacizumab was restarted. No hemorrhoidal bleeding occurred after bevacizumab administration, and the patient is currently continuing chemotherapy. In patients with advanced cancer who have bleeding internal hemorrhoids that cannot be controlled with conservative treatment, hemorrhoid-sclerosing therapy using ALTA appears to offer an effective treatment variation that enables the use of bevacizumab in cases with limited available therapeutic regimen options.

Purpose The aim of this study was to compare the outcomes of single-port laparoscopic gastric resection (SPLGR) with multiport laparoscopic gastric resection (MPLGR) for gastric gastrointestinal stromal tumors (GISTs). Methods Between April 2009 and December 2012, 16 consecutive patients with gastric GISTs underwent SPLGR. The patients undergoing the SPLGR were casematched for age, sex, body mass index and tumor location with those undergoing MPLGR. The demographic and surgical outcomes were analyzed and compared from the review of a prospectively collected database of 16 patients who underwent MPLGR. Results All 16 patients underwent complete SPLGR without any intraoperative complications. No significant differences were observed in the mean length of the operation (91.4 vs. 94.1 min), blood loss (6.3 vs. 10.1 ml) and length of postoperative hospital stay (4.7 vs. 5.4 days) between the SPLGR and MPLGR groups. The tumor size was similar (37.8 vs. 32.1 mm) and negative surgical margins were achieved in all patients. At a mean follow-up of 27 months, all 16 SPLGR patients were disease-free. Conclusions Our initial comparison demonstrated that SPLGR, when performed by experienced surgeons, is a safe and feasible procedure for patients with gastric GISTs, resulting in good surgical and oncological outcomes.

We evaluated the outcome of esophageal stenting for esophagorespiratory fistula in patients with advanced esophageal cancer. Six patients with such fistula underwent esophageal stenting at our department from January 2000 to May 2012. Intraoral ingestion improved in all patients. Cough decreased immediately after stenting in 3 patients, and pneumonia detected by chest radiography improved within 1 week in 2 patients. Ventilation was weaned 2 days after stenting in 1 patient. The median survival duration after stenting was 31 days, and the cause of death was cancer in all patients. The following background factors were identified at the time of death: bleeding(n=3), mediastinitis(n=1), and pneumonia(n=1). Esophageal stenting, which should always be performed with the informed consent of the patient, improves respiratory symptoms, intraoral ingestion, and quality of life. Therefore, it is one of the best palliative therapies for patients with esophagorespiratory fistula associated with advanced esophageal cancer.

Purpose Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colorectal cancer. However, conventional palpation of the liver and adequate observation of the abdominal cavity are not achievable during LAC. The aim of this study was to assess the clinical value of using Sonazoid (contrast enhanced)-intraoperative laparoscopic ultrasonography (S-IOLUS) in patients with primary colorectal cancer. Methods From May 2005 to August 2008, 454 patients underwent 339 LACs and 115 open colectomies for colorectal cancer. One hundred forty-eight patients with clinical stage II or III colorectal cancer, as determined by preoperative imaging, who were undergoing LACs were prospectively enrolled. Results Although IOLUS did not detect any lesions, small hypoechoic lesions were detected by the S-IOLUS (n = 71) in the Kupffer-phase view of two patients (2.8 %). None of the 71 patients who underwent S-IOLUS showed liver metastases within 6 months after LAC. In the conventional IOLUS group (n = 77), metastatic lesions were identified in two patients (2.6 %). The new liver metastases in these two patients were detected within 6 months after LAC. Conclusions S-IOLUS of the liver during colorectal cancer surgery is useful for staging and as a diagnostic modality. It can identify lesions that are undetectable by preoperative imaging, and may be considered for routine use during LAC.

Background Pregnane X receptor (PXR) is a key transcription factor that regulates drug metabolizing enzymes such as cytochrome P450 (CYP) 3A4, and plays important roles in intestinal first-pass metabolism. Although there is a large inter-individual heterogeneity with intestinal CYP3A4 expression and activity, the mechanism driving these differences is not sufficiently explained by genetic variability of PXR or CYP3A4. We examined whether epigenetic mechanisms are involved in the regulation of PXR/CYP3A4 pathways in colon cancer cells. Methods mRNA levels of PXR, CYP3A4 and vitamin D receptor (VDR) were evaluated by quantitative real-time PCR on 6 colon cancer cell lines (Caco-2, HT29, HCT116, SW48, LS180, and LoVo). DNA methylation status was also examined by bisulfite sequencing of the 6 cell lines and 18 colorectal cancer tissue samples. DNA methylation was reversed by the treatment of these cell lines with 5-aza-2'-deoxycytidine (5-aza-dC). Results The 6 colon cancer cell lines were classified into two groups (high or low expression cells) based on the basal level of PXR/CYP3A4 mRNA. DNA methylation of the CpG-rich sequence of the PXR promoter was more densely detected in the low expression cells (Caco-2, HT29, HCT116, and SW48) than in the high expression cells (LS180 and LoVo). This methylation was reversed by treatment with 5-aza-dC, in association with re-expression of PXR and CYP3A4 mRNA, but not VDR mRNA. Therefore, PXR transcription was silenced by promoter methylation in the low expression cells, which most likely led to downregulation of CYP3A4 transactivation. Moreover, a lower level of PXR promoter methylation was observed in colorectal cancer tissues compared with adjacent normal mucosa, suggesting upregulation of the PXR/CYP3A4 mRNAs during carcinogenesis. Conclusions PXR promoter methylation is involved in the regulation of intestinal PXR and CYP3A4 mRNA expression and might be associated with the inter-individual variability of the drug responses of colon cancer cells.