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Introduction: It is unclear whether the histological glandular differentiation (HGD) score that evaluates the tumor grade of two dominant components is prognostic for survival in patients with intrahepatic cholangiocarcinoma (ICC)., Method: We retrospectively analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at 5 university hospitals in the Kansai region of Japan., Results: Survival was statistically significantly stratified by trinal HGD grade (p < 0.05). Median disease-free survival (DFS) of patients with high HGD grade was significantly shorter compared with moderate HGD grade (13.0 vs 31.2 months, respectively; p = 0.004). By Cox proportional hazards regression analysis, HGD grade had the fifth-highest hazard ratio (HR = 1.77, p = 0.002) for DFS after vascular and/or biliary invasion, extrahepatic invasion, lymph node metastasis and multiple tumors. Multivariate logistic regression analysis revealed four predictors of early recurrence after hepatectomy (lymph node metastasis: odds ratio [OR] = 3.74, p = 0.001; tumor size > 50 mm: OR = 2.80, p = 0.002; HGD grade, high: OR = 2.11, p = 0.012; and vascular or biliary tract invasion: OR = 2.11, p = 0.048)., Conclusion: Trinal HGD grade had a significant prognostic impact on the survival of patients with ICC after radical hepatectomy., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background/purpose of the Study: Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients., Methods: Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array., Results: The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence., Conclusion: CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation., (© 2021. The Author(s).)

Background: This study aimed to assess the safety and efficacy of carbon-ion radiotherapy (CIRT) for salvage of previously X-ray-irradiated (XRT) locally recurrent rectal cancer (LRRC)., Methods: Between September 2005 and December 2017, 77 patients with LRRC were treated with CIRT re-irradiation. All the patients had received prior XRT with a median dose of 50.0 Gy (range 20-74 Gy), principally for neoadjuvant or adjuvant recurrence prophylaxis in 34 patients and for recurrence in 43 patients. The total CIRT dose of 70.4 Gy (RBE) (gray relative biologic effectiveness) was administered in 16 fixed fractions during 4 weeks (4.4 Gy [RBE] per fraction)., Results: All the patients completed the scheduled treatment course. None of the patients received resection after CIRT. Acute grade 3 toxicities occurred for eight patients (10 %), including five grade 3 pelvic infections (2 involving pain and 1 involving neuropathy). Late grade 3 toxicities occurred for 16 patients (21 %): 13 with late grade 3 pelvic infections, 9 with gastrointestinal toxicity, 1 with skin toxicity, 2 with pain, and 4 with neuropathy. No grade 4+ toxicity was noted. The overall local control rates (infield + out-of-field recurrence) were 69 % at 3 years and 62 % at 5 years. In the planning target volume (PTV), the infield recurrence rates were 90 % and 87 % respectively. The control rates for regional recurrence were 85 % at 3 years and 81 % at 5 years. The median overall survival time was 47 months. The survival rates were 61 % at 3 years and 38 % at 5 years., Conclusion: Carbon-ion re-irradiation of previously X-ray-irradiated locally recurrent rectal cancer appears to be safe and effective, providing good local control and survival advantage without unacceptable morbidity., (© 2021. The Author(s).)

Background: The laparoscopic magnified visual effects and evolution of the laparoscopic camera system have recently enabled us to observe details in the deep pelvic floor. Indications of laparoscopic surgery for colorectal cancer have been expanded, and laparoscopic (Lap) lateral pelvic node dissection (LLND) has been introduced in some institutions. We investigated the feasibility of Lap LLND in patients with locally advanced rectal cancer (LARC)., Methods: Lap LLND was performed in 38 patients diagnosed with cT3-4 or cN1-2 cancer during 2014-2018. We retrospectively analyzed their surgical and short-term outcomes., Results: Laparoscopic surgery was performed in all patients. cStages II/III/IV were found in 6/31/1 patients, respectively. Among them, 25 patients underwent neoadjuvant chemotherapy without radiotherapy. Lap unilateral LLND was performed in 6 patients and Lap bilateral LLND was performed 32 patients. The number of harvested lymph nodes (LNs) were 4 in the unilateral group and 15 in the bilateral group. Operation time was 531 min, and blood loss was 105 ml. Oral intake has started on postoperative day (POD) 3, and pelvic drain was removed on POD 7. Hospital stay was 18.5 days. Seven patients developed a neurogenic bladder (all Clavien-Dindo grade (CD) II and all occured in the bilateral LLND group), one patient developed abdominal bleeding (CD IIIb) and one patient developed anastomotic leakage (CD IIIb). Pathological results revealed 2/5/16/14/1 patients with pStages 0/I/II/III/IV, respectively. Four patients had histopathologically verified lateral pelvic lymph node metastases. There were no local recurrences after curative surgery (median follow-up 24.2 months)., Conclusion: Although the median follow-up period is relatively short and further follow-up is necessary, oncologically, especially in the point of local control rate, Lap LLND appears to have acceptable in the treatment of LARC without radiotherapy in experienced centers. Further investigations focusing on indications and the Lap LLND procedural technique are required.

Purpose: It is important to accurately estimate accurate vancomycin (VCM) clearance (CLvcm) for appropriate VCM dosing in the treatment of patients with sepsis. However, the pathophysiology of sepsis can make CLvcm prediction less accurate. Clearance of hydrophilic antibiotics is disturbed by organ dysfunction, and hemoglobin levels are negatively correlated with sequential organ function assessment scores. We investigated whether hemoglobin levels are associated with CLvcm in sepsis patients., Methods: We performed a retrospective cohort study of patients treated with VCM in the Emergency and Critical Care Center of Nihon University Itabashi Hospital between 2005 and 2015. We enrolled 72 patients after exclusion of patients who received renal replacement therapy or surgery, had a change in hemoglobin levels more than 2 g/dL or received an erythrocyte infusion during the interval between initial VCM administration and measurement of initial trough levels, had a serum baseline creatinine level of ≥ 2 mg/dL, or were under 18 years old., Results: Enrolled patients consisted of 13 non-sepsis patients and 59 sepsis patients. In sepsis patients, although CLvcm was correlated with CrCl in HGB ≥ 9 group as well as in non-sepsis patients, its correlation was not observed in HGB < 9 group. Hemoglobin levels were correlated with CLvcm in sepsis patients but not in non-sepsis patient. Multiple linear regression analysis also indicated that lower CLvcm was associated with lower hemoglobin and CrCl., Conclusion: Lower hemoglobin levels influence a relationship between CLvcm and CrCl in sepsis patients. We propose that VCM dosing should be adjusted for hemoglobin levels in sepsis patients.

Background: Nutritional status is one of the most important clinical determinants of outcome after surgery. The aim of this study was to compare changes in the body composition of patients undergoing pancreaticoduodenectomy (PD), distal gastrectomy (DG), or total gastrectomy (TG)., Methods: The parameters of body composition were measured using multifrequency bioelectrical impedance analysis with an inBody 720 (Biospace Inc. Tokyo. Japan) in 60 patients who had undergone PD (n = 18), DG (n = 30), or TG (n = 12). None of the patients had recurrence or were treated with chemotherapy. Changes between the preoperative data and results and those obtained 12 months after surgery were evaluated., Results: Twelve months after surgery, the body weight change in the PD group was significantly lower than in the TG and DG groups (-1.2 ± 3.8 vs -7.4 ± 4.4 and -4.0 ± 3.2 kg, respectively; p < 0.01 vs TG, p < 0.05 vs DG). The body weight change correlated with the fat mass change in all groups., Conclusions: The type and extent of surgery has a different effect on long-term body weight and body composition. Bioelectric impedance analysis can be used to assess body composition and may be useful for nutritional assessment in patients who have undergone these surgeries.

Purpose: The main feature of locally recurrent rectal cancer (LRRC) is infiltrating growth; thus, preoperative chemoradiation therapy (preCRT) is recommended to improve patient outcomes. However, no studies have reported the potential impact of preCRT on oncological and surgical outcomes in posterior invasive LRRC (piLRRC) that requires sacrectomy., Methods: Forty-one patients with piLRRC were treated with (n = 25) or without (n = 16) preCRT. Oncological outcomes regarding local re-recurrence-free survival, distant metastasis-free survival, and overall survival (OS) were analyzed. Surgical complications were assessed using the Clavien-Dindo scale., Results: The preCRT group had higher 5-year local re-recurrence-free survival (24.4 vs. 0 %) and OS (46.6 vs. 29.3 %) than the non-preCRT group. Univariate analysis demonstrated that preCRT (p = 0.03) and microlymphatic involvement (p = 0.01) were significantly related to local re-recurrence. Microlymphatic involvement occurred less frequently in the preCRT group than in the non-preCRT group (23.8 vs. 71.4 %; p = 0.01) despite the similarity in primary cancers between groups. Major infectious complications occurred with similar frequency in the preCRT and non-preCRT groups (24 vs. 18.8 %, p = 1)., Conclusions: PreCRT significantly benefited oncological outcome without compromising surgical results for piLRRC.

Background: Malnutrition is an independent risk factor for postoperative mortality and morbidity in major gastrointestinal surgery. The aim of this study was to investigate the prevalence of malnutrition and identify the optimal preoperative nutritional support for preventing postoperative surgical site infections (SSIs) in malnourished gastric cancer patients undergoing gastrectomy., Methods: We analyzed 800 patients with gastric cancer who underwent gastrectomy. Nutritional risk factors included weight loss >10 % within 6 months, body mass index <18.5 kg/m(2), Subjective Global Assessment Grade C, and serum albumin <3.0 g/dl. Adequate energy intake was defined as receiving ≥25 kcal/kg ideal body weight per day. Optimal nutritional support was examined in terms of both duration and calorie intake., Results: Overall, 152 patients (19.0 %) were classified as malnourished. The incidence of SSIs was significantly higher in malnourished patients than in well-nourished patients (35.5 vs. 14.0 %; p < 0.0001). The incidence of SSIs in malnourished patients was significantly lower in the well-supported group receiving adequate energy support for at least 10 days than in the poorly-supported group, which received inadequate or no energy support or adequate energy support for <10 days (17.0 vs. 45.4 %; p = 0.0006). In multivariate analysis, well-managed nutritional support was identified as an independent factor associated with fewer SSIs (odds ratio 0.14; 95 % confidence interval 0.05-0.37; p = 0.0002)., Conclusions: Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.

Purpose: Single-port laparoscopic surgery is more difficult for sigmoid colon and rectal cancers than for right-sided colon cancer. We sought to analyze the feasibility of this procedure for sigmoid colon and rectal cancers and to estimate its difficulty., Methods: We analyzed prospectively collected data from 63 consecutive patients with sigmoid colon or rectal cancers who underwent single-port laparoscopic surgery at our institution from June 2009 to December 2011. Patient and tumor characteristics, including patients' pelvic anatomy which was assessed on CT scan imaging, were evaluated to elucidate what factors would affect the difficulty of the procedure and the necessity of using an additional trocar., Results: Overall, the median operative duration was 190 min and blood loss was 20 ml, with no postoperative complications. The median number of lymph nodes harvested was 17 and the distal margin was 58 mm. The tumor was located significantly closer to the anus in cases in which an additional trocar was required in the right lower quadrant (9.5 vs 18 cm, p < 0.0001). Procedural difficulty was significantly increased in cases in which the sacral promontory protruded ventrally (odds ratio 0.779 [95% confidence interval 0.613 to 0.945], p = 0.0236)., Conclusions: Depending on tumor location and sacral promontory shape, the introduction of an additional trocar might render single-port laparoscopic surgery feasible for sigmoid colon and rectal cancer resection.

Background: Single-site laparoscopic colectomy (SLC) is an emerging concept that, compared with conventional multiport laparoscopic colectomy (MLC), yields reduced postoperative pain and improved cosmesis. Complete mesocolic excision (CME) is a novel concept for colon cancer surgery that provides improved oncologic outcomes; however, there are no reports of SLC with CME. We conducted a prospective case-control study to evaluate the feasibility and safety of SLC with CME for colon cancer., Methods: Prospectively collected data of patients with stage I-III colon cancer who underwent SLC (n = 150) or MLC (n = 150) between June 2008 and March 2012 were analyzed. Patients who underwent SLC were, in terms of clinical characteristics and tumor location, matched as closely as possible with those undergoing MLC. Within each group, patients were classified as having right-sided (n = 69 in each group) or left-sided (n = 81 in each group) colon cancer, and short-term outcomes were compared between the two procedures overall and per side., Results: Overall perioperative outcomes, including operation time, blood loss, number of lymph nodes harvested, length of the resected specimen, and complications, were similar between the two procedures, whereas postoperative pain was significantly lower with SLC. Operation time for right-sided SLC was significantly shortened. SLC with CME was completed successfully in 94 % (65/69) of right-sided cases and in 88 % (71/81) of left-sided cases. Conversion rates were 1.4 % (1/69) and 1.1 % (1/81), respectively. The umbilical scars were nearly invisible 3 months after the procedure, and most patients reported being quite satisfied with the cosmetic outcomes., Conclusions: SLC with CME for colon cancer is feasible when performed by experienced surgeons in selected patients. Excellent cosmesis and reduced postoperative pain as well as oncologic clearance can be expected. A large-scale, prospective, randomized, controlled trial should be conducted to confirm the superiority of this procedure over MLC with CME.

Background: Recently, it has been reported that a small population of cancer stem cells (CSCs) play a role in resistance to chemotherapy and radiation therapy. We reported that CD13(+) liver CSCs survive in hypoxic lesions after chemotherapy, presumably through increased expression of CD13/Aminopeptidase N, which is a scavenger enzyme in the reactive oxygen species (ROS) metabolic pathway. On the other hand, the concept of epithelial-mesenchymal transition (EMT) was indicated by a recent study showing an increased plasticity linked to the cellular "stemness" of CSCs., Methods: To study the relationship between CSCs and EMT, we examined biological characteristics of liver cancer cell lines with EMT by exposing transforming growth factor-β (TGF-β)., Results: We showed that a TGF-β-induced EMT-like phenomenon is associated with increased CD13 expression in liver cancer cells. This phenomenon prevents further increases in the ROS level as well as the induction of apoptosis, promoting the survival of CD13(+) CSCs, whereas inhibition of CD13 stimulates apoptosis. Immunohistochemical analysis also indicated that after chemotherapy, CD13 was coexpressed with N-cadherin in surviving cancer cells within fibrous capsules. We have demonstrated that CD13 expression plays a role in supporting the survival of CSCs and that there is an EMT-associated reduction in ROS elevation., Conclusions: This novel and consistent linkage between functional CSC markers and the EMT phenomenon suggests a bona fide candidate for targeted therapy for EMT-mediated invasion and metastasis of liver cancer.

PURPOSE : Single-incision laparoscopic surgery (SILS) brings cosmetic benefits for patients, but this procedure is more difficult than laparoscopic surgery. In order to reduce surgeons' burden, we have developed a master-slave robot system which can provide robot-assisted SILS as if it were performing conventional laparoscopic surgery and confirmed the feasibility of our proposed system. METHODS : The proposed system is composed of an input device (master side), a surgical robot system (slave side), and a control PC. To perform SILS in the same style as regular laparoscopic surgery, input instruments are inserted into multiple incisions, and the tip position and pose of the left-sided (right-sided) robotic instrument on the slave side follow those of the right-sided (left-sided) input instruments on the master side by means of a control command from the PC. To validate the proposed system, we defined four operating conditions and conducted simulation experiments and physical experiments with surgeons under these conditions, then compared the results. RESULTS : In the simulation experiments, we found learning effects between trials (P = 0.00013 < 0.05). Our proposed system had no significant difference from a condition simulating classical laparoscopic surgery (P = 0.23 > 0.1), and the task time of our system was significantly shorter than the simulated SILS (P = 0.011 < 0.05). In the physical experiments, our system performed SILS more easily, efficiently, and intuitively than the other operating conditions. CONCLUSION : Our proposed system enabled the surgeons to perform SILS as if they were operating conventionally with laparoscopic techniques.

Background: To minimize bleeding and biliary leakage after open hepatectomy, fibrin sealing is undertaken at the transaction plane of the liver. Recently, clinicians have begun using polyglycolic acid PGA felt as an absorbable cross-linker. However, this method has not been well studied for laparoscopic hepatectomy because available laparoscopic devices are quite limited. This study aimed to investigate the feasibility and efficacy of using fibrin sealant with PGA felt in laparoscopic hepatectomy., Methods: A retrospective analysis of prospectively collected data from 1997 for laparoscopic hepatectomy was performed. Application of fibrin sealant with PGA felt in laparoscopic hepatectomy was begun in February 2009, and the data collected until November 2009 were used. The differences in the perioperative factors were compared including hematocrit and bilirubin concentration changes in the drainage fluid between the surgical procedures conducted with and without the use of fibrin sealant and PGA felt., Results: Fibrin sealant with PGA felt was used in 18 patients who underwent laparoscopic hepatectomy after February 2009. The data for these patients were compared with those for 22 patients who underwent laparoscopic hepatectomy before the start of fibrin sealant use. The operative procedure and devices differed according to the period. No significant differences in preoperative factors were observed between the groups. The use of fibrin sealant had no influence on the operation time or changes in the leukocyte count or serum C-reactive protein. No cases of postoperative bleeding or biliary leakage occurred in either group, and the time course of the perioperative hematocrit and drain bilirubin concentrations did not differ between the two groups., Conclusion: Use of fibrin sealant with PGA felt in laparoscopic hepatectomy appears to be feasible, and the outcomes are not inferior to those in the control group.

Purpose: The paired-like homeodomain transcription factor 2 (PITX2) gene encodes a transcription factor controlled by the WNT/Dvl/CTNNB1 and Hedgehog/TGFB pathways in the pathogenesis of colorectal cancer (CRC). Although PITX2 is reportedly involved in various functions, including tissue development by controlling cell growth, its significance in CRC remains unclear. We report our findings regarding abnormal PITX2 expression in human CRC., Methods: PITX2 expression was evaluated in 5 human CRC cell lines and 92 primary CRC samples. Cell growth was evaluated after inhibition of PITX2 expression or after exogenous introduction of PITX2., Results: PITX2 expression was seen in all the five CRC cell lines. The study of tissue samples indicated that PITX2 expression was significantly higher in cancerous tissue than in paired control tissue (P = 0.0471). Patients with lower PITX2 expression showed a poorer overall survival rate than those with higher PITX2 expression (P = 0.0481). Multivariate analysis demonstrated that PITX2 expression was an independent prognostic factor. Experimental knockdown and introduction of PITX2 also demonstrated that the level of PITX2 expression is inversely associated with cell growth and invasion in vitro., Conclusions: PITX2 expression is significantly related to the biological behavior of CRC cells and appears to be correlated with clinical survival. Thus, this study revealed a previously uncharacterized unique role and significance of PITX2 expression in CRC.

Background: Lymph node (LN) metastasis in colorectal cancer (CRC) is a critical factor in making accurate prognoses and therapeutic decisions. This study evaluated the clinical performance of the one-step nucleic acid amplification (OSNA) assay in accurately diagnosing LN metastases in CRC patients through the specific detection of cytokeratin 19 mRNA levels in LNs., Methods: The OSNA assay was performed on 121 LNs dissected from early-stage CRC patients (pStage 0 or I) or from patients with benign colorectal disease (study 1). Separately, 385 LNs were dissected from 85 CRC patients (any stage); the OSNA assay was performed on half of each LN, and the results were compared with histopathological examination in 2-mm intervals of the other LN half (study 2)., Results: In study 1, all 121 histopathologically negative LNs were also negative by the OSNA assay (concordance rate for metastasis negative: 1.0, 95% confidence interval [95% CI]: 0.976-1.0). In study 2, the concordance rate between the OSNA assay and the 2-mm-interval histopathological examination was 0.971 (95% CI: 0.950-0.984), with a sensitivity of 0.952 (95% CI: 0.881-0.987) and a specificity of 0.977 (95% CI: 0.953-0.991)., Conclusions: The OSNA assay provided a judgment performance equivalent to a 2-mm-interval histopathological examination, a more detailed assay than the common pathological examination. Therefore, the OSNA assay is considered a new molecular examination method for the diagnosis of LN metastases in CRC patients in clinical settings.

Background: Local re-recurrence after R0 resection of local recurrence of rectal cancer (LRRC) is not rare. The purpose of this study was to examine the pathological features of LRRC and determine the prognostic factors., Methods: Twenty-one patients underwent R0 resection of LRRC without preoperative therapy from 2000 to 2008. Tumor progression patterns were classified into three types: A, expanding type; B, infiltrating type; and C, intermediate type. Distant isolated cancer cells (DICCs) were defined as cancer cells present in isolation and at a distance (>1 mm) from the tumor edge., Results: Venous invasion was identified in all but one patient (95%). DICCs were observed in 11 of 21 cases. Type A patients had a significantly lower local re-recurrence rate (0/5) compared with type B and/or C patients (11/16, P = 0.012) and a significantly lower incidence of distant metastasis compared with type B and C patients (0/5 vs. 13/16, respectively; P = 0.0028). Multivariate regression analysis identified venous invasion of the primary lesion (P = 0.027) and tumor progression patterns (P = 0.039) as independent predictors of local re-recurrence., Conclusions: The main features of LRRC were infiltrating growth, venous invasion, and DICCs. Tumor progression patterns correlated with local re-recurrence and distant metastasis. Preoperative adjuvant therapy to terminate peri-tumor cancer cells may be required for better tumor control.

Purpose: Although recent studies show that leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)(+ve) cells targeted by Wnt drive self-renewal in the skin and gastrointestinal organs, the clinicopathological significance of Lgr5(+ve) cancer stem cells (CSCs) of the colon remains to be elucidated., Experimental Design: We studied the Wnt-targeted Lgr5 pathway in colorectal cancer (CRC). The expression of LGR5, c-MYC, p21CIP1/WAF1/CDKN1A, glutaminase (GLS), and miRs-23a and -23b (that target LGR5 and GLS) was evaluated by quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR). The Lgr5 protein was evaluated by immunohistochemistry. The clinical relevance of gene expression in terms of patient survival was also evaluated., Results: Overexpression of LGR5 was significantly associated with expression of c-MYC, p21CIP1/WAF1/CDKN1A, and GLS (p < 0.0001), and inversely associated with miR-23a/b (p < 0.05). Immunohistochemical analysis indicated that Lgr5 may be embedded in benign adenomas, localized at the tumor-host interface, and detectable over a broad area in established tumors. High level of LGR5 expression was associated with poor prognosis for CRC cancer patients (disease-free survival; p < 0.05)., Conclusions: This study supports a significant role for LGR5 in the CSC hypothesis in CRC: (1) Lgr5(+ve) CSCs, presumably derived from normal stem cells in colonic crypts, proliferate, and the gene is overexpressed during CRC development; (2) LGR5 expression is associated with activation of Wnt pathway, including oncogenic c-MYC and high energy production via glutaminolysis; (3) LGR5 expression may be a poor prognostic factor for CRC patients. Further study of LGR5 should contribute to the development of CSC-based cancer therapeutics.

Aim: Curative resection of sigmoid and rectal cancer includes "high tie" of the inferior mesenteric artery (IMA). However, IMA ligation compromises blood flow to the anastomosis, which may increase the leakage rate. Accordingly, some surgeons employ a technique of lymph node (LN) dissection around the IMA, preserving the IMA and left colic artery (LCA). The same technique was reported to need longer time in laparoscopic surgery due to technical difficulties. We present herein a simple and secure method of laparoscopic LN dissection around the IMA that allows preservation of the IMA and LCA, and report the operative results., Methods: Our method involves peeling off the vascular sheath from the IMA and dissection of the LN around the IMA together with the sheath. The feasibility of the technique was evaluated in 72 consecutive cases of laparoscopic resection of sigmoid and rectal cancer., Results: The IMA was ligated at its root in 27 cases (high tie, group A). Lymph nodes around the IMA were dissected with preservation of the IMA and LCA in 21 cases (group B). The root of the superior rectal artery was ligated in 24 cases of Tis and T1N0 ("low tie," group C). Mean operative time was 207.6, 221.2, and 198.5 min for group A, B, and C, respectively. Respective blood loss was 47.8, 44.0, and 58.5 g, and mean numbers of harvested LN were 17.3, 16.3, and 10.7. None of the operative results of groups A and B were different statistically. LN dissection was not associated with any morbidity., Conclusion: Our method allows equivalent laparoscopic lymph node dissection to the high tie technique without excessive operative time or bleeding.

Background: Prefoldin 4 (PFDN4) is a transcriptional factor that regulates the cell cycle. PFDN4 is upregulated in breast tumor and breast cancer cell lines, but its significance in colorectal cancer (CRC) is not fully understood., Methods: The present study assessed 129 patients who underwent surgery for CRC and assessed three cell lines derived from human CRC. The correlation of gene expression with clinical parameters in patients was assessed by knockdown experiments with these cell lines., Results: Patients with high PFDN4 expression had a statistically relatively better prognosis, and those with low PFDN4 expression showed poorer overall survival than those with high expression. The assessment of PFDN4 knockdown in the three cell lines demonstrated that the siRNA inhibition resulted in a statistically significant increase in cell growth and invasiveness., Conclusions: The data strongly suggest that PFDN4 expression is a prognostic factor in CRC.

Background: Double stapling technique (DST) is a physiological end-to-end anastomosis that is currently used widely in rectal surgery and also in sigmoidectomy. In laparoscopy-assisted sigmoidectomy, we occasionally encounter obstruction during insertion of the circular stapler device from the anus. In such cases, we used to cut the residual rectosigmoid colon additionally and to allow DST anastomosis. Here, we propose an alternative way to overcome this difficulty, that is to perform an anastomosis to the anterior wall of the rectosigmoid colon., Methods: Between 2001 and 2007, we experienced the cases of 10 sigmoid colon cancer patients who underwent laparoscopic surgeries with a conversion from DST to end to side (anterior wall) anastomosis., Results: None of the patients suffered from anastomosis leakage, and none had complained of their stool habits. Colonoscopy showed that anastomosis window is kept wide and that stool is not pooled in the blind pocket of the rectosigmoid colon, suggesting the passage is well preserved., Conclusion: Our experience indicates that though several technical points should be noted, an end to anterior wall anastomosis procedure is easy and safe. This method is a useful alternative way when end-to-end DST anastomosis is not performed smoothly in laparoscopic surgery.

Background: Transumbilical single-incision laparoscopic surgery is an emerging concept that could offer excellent cosmetic results [1]. The authors describe an index case of curatively intended resection of early-stage sigmoid colon cancer using this technique [2, 3]., Methods: A 75-year-old woman with a body mass index of 24 underwent surgery by two colorectal surgeons who had hundreds of experiences with laparoscopic colorectal surgery. Three 5-mm ports were placed linearly in the vertical 2-cm skin incision in the umbilicus. Almost all the procedures were performed with usual laparoscopic instruments such as a 5-mm flexible laparoscope and the Harmonic ACE (Ethicon Endo-Surgery, Cincinnati, OH, USA). Also, the operative procedures were much the same as in usual laparoscopic surgery. The sigmoid colon was mobilized using a medial approach. Then the root of the superior rectal artery and inferior mesenteric vein were divided using the EnSeal tissue sealing and hemostasis system (SurgRx, Inc. Redwood City, CA, USA). Low-profile trocars were mandatory to minimize interferences among instruments. The rectum was divided 5 cm distal to the lesion with one firing of an endoscopic stapler. The specimen was extracted through a 2-cm transumbilical laparotomy. End-to-side anastomosis using a circular stapler was performed intraabdominally, and air tightness was confirmed by the anastomotic leak test., Results: The operative time was 192 min. There was no intra- or postoperative morbidity. Altogether, 20 cm of sigmoid was resected with negative tumor margins, and 14 lymph nodes were harvested. The patient started receiving meals and was discharged on postoperative days 2 and 7, respectively. The final pathology showed Tis, N0, M0, stage 0. The scar was invisible at 1 month., Conclusion: Single-incision laparoscopic colectomy is feasible and safe for selected patients and gives a favorable cosmetic result. By well-trained surgeons, this technique could be a realistic option for colorectal cancer surgery.

Aims: The aim of this retrospective study is to examine risk factors for postoperative delirium in elderly patients with colorectal cancer., Methods: The study subjects were patients aged 71 years and older who underwent open surgery (OS) or laparoscopically assisted surgery (LAS) for colorectal cancer from January 2004 to December 2007. Preoperative evaluation, operative factors, morbidity, and mortality were analyzed using the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) and Prognostic Nutritional Index (PNI). Delirium was diagnosed by the Confusion Assessment Method (CAM)., Results: Postoperative delirium was diagnosed in 10.9% of elderly patients with colorectal cancer. Age, American Society of Anesthesiologists (ASA) score, and PNI were significantly higher in patients with delirium than those without (P < 0.05, each). Postoperative delirium occurred more frequently in patients with encephalopathy than in those without (P = 0.003). Logistic regression analysis identified PNI and encephalopathy as two independent risk factors for postoperative delirium., Conclusions: Preoperative evaluation of nutritional status is important in elderly patients with colorectal cancer in order to prevent postoperative delirium.

Background: Transglutaminase 2 (TGM2) plays a role in cell growth and survival through the antiapoptosis signaling pathway., Methods: We analyzed TGM2 gene expression in 91 paired cases of colorectal cancer (CRC) and noncancerous regions and seven CRC cell lines to demonstrate the importance of TGM2 expression for the prediction of prognosis of CRC. TGM2 expression was higher in CRC tissue than in corresponding normal tissue by real-time reverse transcriptase-polymerase chain reaction (P = .015)., Results: Patients in the high TGM2 expression group showed a poorer overall survival rate than those in the low expression group (P = .001), indicating that the increase in TGM2 expression was an independent prognostic factor. TGM2 was also expressed in the seven CRC cell lines. The in vitro proliferation assay showed that TGM2 expression is involved with tumor growth., Conclusions: The present study suggests that TGM2 is useful as a predictive marker for patient prognosis and may be a novel therapeutic target for CRC.

Background: The RGS family, comprising 22 homologues of proteins, plays a role in cellular proliferation, differentiation, membrane trafficking, and embryonic development through the involvement of the mitogen-activated protein kinase signaling pathway., Methods: In order to demonstrate the importance of RGS16 expression for the prediction of prognosis of colorectal cancer (CRC), we analyzed RGS16 gene expression in 22 human gastrointestinal cell lines and 124 paired cases of CRC and noncancerous regions., Results: RGS16 was expressed in 17 human gastrointestinal cancer cell lines examined in this study. RGS16 expression was higher in colorectal cancer tissue than in corresponding normal tissue (P < 0.001) in messenger RNA (mRNA) and protein levels. Patients in the RGS16 high-expression group showed a poorer overall survival rate than those in the low-expression group (P < 0.001), indicating that high RGS16 expression was an independent prognostic factor., Conclusion: The present study suggests that RGS16 is useful as a predictive marker for patient prognosis of CRC.

Background: Laparoscope manipulating robots are useful for maintaining a stable view during a laparoscopic operation and as a substitute for the surgeon who controls the laparoscope. However, there are several problems to be solved. A large apparatus sometimes interferes with the surgeon. The setting and repositioning is awkward. Furthermore, the initial and maintenance costs are expensive. This study was designed to develop a new laparoscope manipulating robot to overcome those problems., Methods: We developed a compact robot applicable for various types of laparoscopic surgery with less expensive materials. The robot was evaluated by performing an in vitro laparoscopic cholecystectomy using extracted swine organs. Then, the availability of the robot to various operations was validated by performing a laparoscopic cholecystectomy, anterior resection of the rectum, and distal gastrectomy using a living swine. The reliability of the system was tested by long-time continuous running., Results: A compact and lightweight laparoscope manipulating robot by the name of P-arm was developed. The surgical time of an in vitro laparoscopic cholecystectomy with and without the P-arm was not different. The three types of operations were accomplished successfully. During the entire procedure, the P-arm worked without trouble and did not interfere with the surgeons. Continuous 8-h operating tests were performed three times and neither discontinuance nor trouble occurred with the system., Conclusions: The P-arm worked steadily for various swine operations, without interfering with surgeon's work.

Background: For treatment of locally recurrent rectal cancer (LRRC), extended radical surgery is sometimes required to obtain a negative margin. Such surgery is often associated with severe postoperative pelvic abscess (PA) formation. The aim of this study was to determine the effects of reconstructive surgery using a large rectus abdominis myocutaneous (RAM) flap and anal preservation surgery on the incidence of severe PA., Method: Between February 1998 and June 2008, 44 patients underwent extended surgery for LRRC. Patients were divided into the pre-2004 group (n = 15) and the post-2004 group (n = 29). To reduce the risk of infections, we modified the surgical approach after 2004 to include a larger volume of RAM flap (modified RAM flap) and implemented anal preservation surgery., Results: The overall incidence of severe PA was significantly lower in the post-2004 group [6 of 29 (21%)] than the pre-2004 group [9 of 15 (60%), P = 0.017]. The incidence of severe PA was lower in the anal preservation group [1 of 12 (8.3%)] compared with those who did not undergo such surgery [14 of 32 (44%), P = 0.035]. Modified RAM flap reduced the incidence of severe PA, albeit insignificantly (pre-2004 group: 57%, post-2004 group: 23%). All three patients who underwent anal preservation and modified RAM flap reconstruction did not develop severe PA. Multiple logistic analysis identified no anal preservation (Odds ratio [OR] = 10.6) and performing of sacrectomy (OR = 20.0) as risk factors for severe PA., Conclusion: Anal preservation surgery is an effective measure against the development of severe PA after radical resection of LRRC.

An important factor for defining a good image during laparoscopic surgery is the zooming ratio, which corresponds to the depth of insertion of the laparoscope along its longitudinal axis. However, it is not clear how surgeons (camera assistants) decide the zooming ratio of laparoscopic images during surgery. Conventional automatic camera positioning systems define the zooming ratio "uniformly" based on simple heuristics. However, because the most adequate zooming ratio varies widely during surgery, these conventional systems may not offer the specific view that the surgeon wants. Therefore, we first investigated how the camera assistant decides the zooming ratio of laparoscopic images by fully analyzing the positional relationship between the laparoscope and the surgical instrument during laparoscopic surgery. Then, we extracted the zooming behavior and implemented it in the robotic laparoscope positioner that we previously developed. As a result, the zooming behavior of our robotic system became very similar to that of the human camera assistant. It was found that the proposed zooming motion of our robotic system may be suitable for fast and compact operations during surgery.

Background: In general, visceral fat and adhesion greatly influence the technical difficulty in performing abdominal surgery. Body mass index (BMI) has been widely used to express the degree of obesity, but it does not always properly reflect the degree of visceral fat. This retrospective study investigated the impact of visceral fat on the operation time to examine whether a quantified visceral fat area (VFA) could be used as a sensitive predictor of technical difficulty in performing a laparoscopic resection of rectosigmoid carcinoma., Methods: Between February 1999 and April 2004, 58 consecutive patients underwent a laparoscopically assisted sigmoidectomy or anterior resection. After a review of the medical charts, the relationship between the operation time and the following variables was analyzed: sex, depth of invasion, approach (medial-to-lateral, lateral-to-medial), subjectively graded degree of visceral fat and adhesion, history of previous abdominal surgery, and BMI. The correlations between VFA, VFA/body surface area (BSA) measured by the "FatScan," software package for quantifying the VFA from the preoperative CT images, and operation time were investigated. Next, the impact of the VFA amount on the early surgical outcome was examined., Results: According to the intraoperative findings, two patients with a severe adhesion required a significantly longer operation time. A history of previous abdominal surgery was not a significant factor in the operation time. Instead, the VFA/BSA had a stronger correlation with the operation time than the BMI. A significantly longer operation time (209 +/- 42 vs 179 +/- 37 min; p = 0.031) was observed for the patients in the high VFA/BSA group (> or =85 cm(2)/m(2)) group than in the normal VFA/BSA group (<85 cm(2)/m(2))., Conclusion: For predicting the technical difficulty of performing a laparoscopic resection of rectosigmoid carcinoma, VFA/BSA may be a more useful index than BMI.

Objective: To assess the prevalence of medical student abuse during clinical clerkships in Japan., Design: A cross-sectional questionnaire survey., Setting: Six medical schools in Japan., Participants: Final year (sixth-year) and fifth-year medical students in the period from September 2003 to January 2004. From a total of 559 students solicited, 304 (54.4%) returned the questionnaire, and 276 (49.4%: 178 male and 98 female) completed it., Measurements: Prevalence of medical student abuse in 5 categories: verbal abuse, physical abuse, academic abuse, sexual harassment, and gender discrimination; differences in abusive experience between male and female students; types of alleged abusers; reporting abusive experiences to authorities; and emotional effects of abusive experiences., Results: Medical student abuse was reported by 68.5% of the respondents. Verbal abuse was the most frequently experienced abuse (male students 52.8%, female students 63.3%). Sexual harassment was experienced significantly more often (P<.001) by female students (54.1%) than by male students (14.6%). Faculty members were most often reported as abusers (45.2% of cases). Abuse occurred most frequently during surgical rotations (42.0% of cases), followed by internal medicine (25.1%) and anesthesia rotations (21.8%). Very few abused students reported their abusive experiences to authorities (8.5%). The most frequent emotional response to abuse was anger (27.1% of cases)., Conclusions: Although experience of abuse during clinical clerkships is common among medical students in Japan, the concept of "medical student abuse" is not yet familiar to Japanese. To improve the learning environment, medical educators need to take action to resolve this serious issue.

Background: We devised a new method incorporating cyber visual training whereby novices in endoscopic surgery are instructed via repetition of a video-recorded procedure. We then conducted a study designed to investigate the impact of this cyber visual training on the mastery of intracorporeal knot-tying as an endoscopic technique., Methods: For the cyber visual training a 10-min video of the same procedure was replayed at normal, slow, and rapid speeds or presented in a series of still images. The training was undertaken by 36 medical students and 1st year trainee doctors who had had no experience of endoscopic surgery. They were divided into three groups, each of all received the same introductory lecture. Group A was only given training with the instructor for 15 min. Group B trained with the instructor for 15 min and was allowed self-training for 10 min. Group C viewed the cyber video beforehand and then underwent training with the instructor for 15 min. For all participants, the time required to complete a knot-tying task was measured and the level of endoscopic skill before and after the training was assessed using a virtual reality system the minimally Invasive Surgical Trainer-Virtual Reality (MIST-VR), in terms of the following three parameters: time, errors, and efficiency of hand movements. The Steel-Dwass test was used to evaluate the differences among the three groups in task performance., Results: Group C completed the knot-tying task faster than group A (p = 0.0375), but there were significant differences between groups A and B and groups B and C. There were no significant differences in the parameters assessed using the MIST-VR., Conclusions: Our new concept of cyber visual training is effective for mastering the knot-tying technique. This type of training should be widely applicable to other procedures, such as dissection, clipping, and hemostasis.

Background: The aim of this study was to evaluate the clinical and therapeutic value of digital fusion image (FI) of positron emission tomography (PET) using (18)F-fluorodeoxy glucose and computed tomography (CT) in patients who were suspected of having a local recurrence of rectal cancer., Methods: Forty-two patients (32 men and 10 women; mean age, 61.4 years, range, 40-79 years) with a suspicion of local recurrence after curative resection of rectal cancer were prospectively recruited and underwent (18)F-fluorodeoxy glucose-PET and CT. The FI was reconstructed with a commercially available digital software program, T-B Fusion. Wilcoxon signed rank test was used to compare FI with CT alone or PET alone., Results: FI yielded a correct diagnosis in 39 (93%) of 42 patients, whereas CT alone and PET alone did so in 33 (79%) and 37 (88%) patients, respectively. FI had better diagnostic accuracy than CT alone (P = .0138) and PET alone (P = .0156). Overall, FI altered patient management in 11 (26.2%) patients on the basis of additional information, including differentiation of the tumor from the postoperative scar in 6 patients, exact anatomical location in 3 patients, and both in 2 patients., Conclusions: FI has a potential clinical value in the treatment of suspected local recurrence of rectal cancer.

Background: Laparoscopic extended lymph node dissection for gastric cancer is difficult to perform because it requires dissection with preservation of vessels. Therefore, an intraoperative navigation system for the angioarchitecture would be helpful. Recent enhanced volume-rendering computed tomography (CT) can produce clear intraluminal three-dimensional (3D) images. This advanced radiological technology can provide 3D angiographic images reconstructed in the same view as would be observed from a laparoscope inserted into the abdominal cavity. We report our experience with laparoscopic gastrectomy with radical lymph node dissection using this advanced radiological technology., Methods: 3D CT angiographic images from the celiac axis to the proper hepatic artery were reconstructed in two ways preoperatively. The first was only 3D angiographic images that were reconstructed as the laparoscopic view (LapView 3D CT angiography). The second was LapView 3D CT angiography with images of the body of the pancreas, which was more useful for intraoperative navigation in comprehensing anatomy. Two monitors were placed over the shoulder of the patient during surgery. One monitor, which was controlled by the image mixer, projected the laparoscopic images with picture in picture of 3D CT angiographic images. The surgeon performed the surgery with reference to this monitor during lymph node dissection., Results: 3D angiographic CT clearly showed all vessels of interest in laparoscopic lymph node dissection for gastric cancer in 10 cases. The anatomy of vessels appeared as if looking beyond visible surface. LapView 3D CT angiography was useful for laparoscopic navigation surgery.

As a result of the recent improvement of the prognosis of esophageal cancer, the reporting frequency of gastric tube cancer following esophageal cancer has increased. Gastric tube total resection following median sternotomy, a highly invasive surgical procedure, is applied to the cases of advanced gastric tube cancer, whereas endoscopic mucosal resection is selected for the cases of early gastric tube cancer. If endoscopic mucosal resection is not applicable for some reason, partial or total resection of the gastric tube following median sternotomy has been selected. We applied laparoscopic intragastric surgery to such a case: The patient, a 59-year-old man with esophageal cancer, had undergone subtotal esophagectomy followed by gastric tube reconstruction through the retrosternal route 6 years before. Since endoscopy revealed early gastric cancer in the body of the stomach, we tried to perform mucosal resection but failed because of anastomotic stenosis. However, we successfully performed intragastric surgery, in which a camera and forceps were inserted directly into the gastric tube. Thus, laparoscopic intragastric surgery is a useful technique in cases to which endoscopic mucosal resection is not applicable.

Background: CO2 pneumoperitoneum provides a new surgical environment to treat malignant disease. The purpose of this study was to investigate the influence of CO2 pneumoperitoneum during laparoscopic surgery on cancer cell growth., Methods: WiDr human colon cancer cells were incubated for 3 h under the following two conditions: 100% CO2 at 10 mmHg, and 95% air/5% CO2 (control). Cell proliferation was assessed by the WST-1 assay and BrdU assay. Tumor growth was assessed by subcutaneous injection into 20 nude mice. Cellular damage was measured by lactate dehydrogenase (LDH) assay., Results: The number of WiDr cells under pneumoperitoneal conditions decreased in the first 24 h. However, no significant difference was observed in the proliferation rate and tumor growth of the viable cells. LDH release of the CO2 pneumoperitoneal group was higher than that of the controls., Conclusions: Our data indicate that CO2 pneumoperitoneum does not promote cancer cell proliferation but instead has a toxic effect on cancer cells.

Several reports have been published which describe the technique of using an Endo GIA to resect submucosal tumors on the anterior wall of the stomach. Lesions on the posterior wall, however, especially near the esophagocardiac junction (ECJ), are difficult to resect using these reported techniques. This is because the surgeon must divide the omentum and enter the omental bursa in order to use a similar extraluminal technique. Furthermore, special care must be taken to ensure that resections do not involve the ECJ and narrow the esophagus. In order to overcome these difficulties, we have proposed a new technique for the laparoscopic excision of a submucosal tumor located on the posterior wall of the gastric fundus. The principle of this procedure involves the intraluminal resection of the submucosal tumor, including the surrounding stomach wall, using the Endo GIA. This technique is safe, simple, and effective. We believe that we are the first to address the excision of a submucosal lesion by resecting the full thickness of the posterior gastric wall lesion intraluminally.

Background: Bile duct injuries during laparoscopic cholecystectomy (LC) are thought to occur because surgeons tend to confuse the common bile duct (CBD) with the cystic duct. Among reasons for this misidentification, the difference in the way the operating field is exposed in LC compared to open cholecystectomy should be noticed. Using Dr. Reddick's technique, which is commonly practiced, the upward and the lateral traction of the gallbladder results in a narrower Calot's triangle and angulation of the CBD. These anatomical distortions are thought to contribute to ductal injuries during LC., Methods: We propose a new method to expose Calot's triangle during LC. The principle of this technique is to expose the hepatic hilus by retracting the caudal surfaces of the quadrate and lateral lobes of the liver using an atraumatic curved instrument., Results: The advantages of this technique are that one gains wide exposure of the hepatic hilus, leaves Calot's triangle undistorted, and avoids tenting the CBD., Conclusions: This new technique may make LC safer and decrease the number of bile duct injuries associated with the misidentification of the anatomy.