A multicenter phase II trial of preoperative chemoradiotherapy with S-1 plus oxaliplatin and bevacizumab for locally advanced rectal cancer.

BACKGROUND: We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 + oxaliplatin + bevacizumab). METHODS: This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m2/day on days 1-5, 8-12, 15-19, and 22-26) and infusions of oxaliplatin (50 mg/m2 on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. RESULTS: All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. CONCLUSIONS: Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 + oxaliplatin + bevacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

Lymphocyte to C-reactive protein ratio predicts long-term outcomes for patients with lower rectal cancer.

BACKGROUNDS: The lymphocyte to C-reactive protein (CRP) ratio (LCR) is an indicator of systemic inflammation and host-tumor cell interactions. The aim of this study was to investigate the prognostic significance of LCR in lower rectal cancer patients who received preoperative chemo-radiotherapy (CRT). METHODS: Forty-eight patients with lower rectal cancer who underwent CRT followed by curative surgery were enrolled in this study. Routine blood examinations were performed before and after CRT were used to calculate pre-CRT LCR and post-CRT LCR. The median LCR was used to stratify patients into low and high LCR groups for analysis. The correlation between pre- and post-CRT LCR and clinical outcomes was retrospectively investigated. RESULTS: The pre-CRT LCR was significantly higher than the post-CRT LCR (11,765 and 6780, respectively, P < 0.05). The 5-year overall survival rate was significantly higher for patients with high post-CRT LCR compared with low post-CRT LCR (90.6% and 65.5%, respectively, P < 0.05). In univariate analysis, post-CRT LCR, post-CRT neutrophil to lymphocyte ratio, and fStage were significant prognostic factors for overall survival. In multivariate analysis, post-CRT LCR, but not other clinicopathological factors or prognostic indexes, was a significant prognostic factor for overall survival (P < 0.05). CONCLUSIONS: Post-CRT LCR could be a prognostic biomarker for patients with lower rectal cancer.

Clinical analysis of postoperative venous thromboembolism in Japanese patients after colorectal cancer surgery.

PURPOSE: Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). METHODS: The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. RESULTS: Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 µg/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days-3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). CONCLUSION: The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE.

Usefulness of virtual three-dimensional image analysis in inguinal hernia as an educational tool.

INTRODUCTION: The pre-operative three-dimensional (3D) imaging technique has resulted in a better surgical outcome for patients and has been used as an education and diagnostic tool. However, there are no reports concerning the usefulness of the 3D imaging technique in laparoscopic transabdominal pre-peritoneal repair (TAPP) so the aim of this study was to investigate the usefulness of the 3D imaging technique in laparoscopic TAPP as an educational tool for medical students. PATIENTS AND METHODS: Six (6) patients who underwent laparoscopic TAPP for inguinal hernia were enrolled in this study. 3D reconstruction was performed from pre-operative computed tomography (CT) and the usefulness of pre-operative 3D simulation compared with intra-operative laparoscopic imaging was validated. Moreover, thirty (30) medical students at the university completed a multiple-choice questionnaire (MCQ) to determine the level of their satisfaction and understanding of anatomy resulting from the study. RESULT: The local anatomy of the patients was identified as the same during the operation as the pre-operative 3D simulation. The results of the MCQ showed that most of the medical students were extremely (23%) or very (67%) satisfied with the effect of pre-operative 3D simulation on the quality of the surgery. Moreover, most students could understand the surgery anatomy by the 3D simulation extremely well (40%) or very well (47%) and agreed on the usefulness of this procedure for learning anatomy. CONCLUSIONS: Pre-operative 3D simulation increases the understanding of detailed anatomy and virtual three-dimensional image analysis in laparoscopic TAPP is useful as an educational tool for medical students.

Downregulation of microRNA-100/microRNA-125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion.

A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples. The transfection of a miR-100 or miR-125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR-100 or miR-125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR-100-silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real-time PCR identified mammalian target of rapamycin (mTOR) and insulin-like growth factor 1 receptor (IGF1R) as direct, and Fas and X-linked inhibitor-of-apoptosis protein (XIAP) as indirect candidate targets for miR-100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR-100 and miR-125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR-100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR-100 and miR-125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.

Duodenal-jejunal bypass changes the composition of the gut microbiota.

This study investigated the composition of the gut microbiota in rats after duodenal-jejunal bypass (DJB) in comparison to that in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Six male 16-week-old OLETF rats were divided into three groups: a DJB group, a sham operation group, and a daily injection with a GLP-1 receptor agonist (liraglutide) group. The gut microbiota of the three groups was analyzed at postoperative week 8 using the PCR-clone library method targeting the 16S ribosomal RNA gene. The DJB group showed a decrease in Bacteroidia in comparison to the other two groups (DJB, 3.9 %/2.8 %; sham, 10.8 %/11.6 %; liraglutide, 33.2 %/14.1 %). In addition, DJB markedly increased the ratio of Gammaproteobacteria (DJB, 10.8 %/13.7 %; sham, 0.2 %/1.2 %; liraglutide, 0 %/0.1 %). DJB changes the composition of gut microbiota; these changes might be the factors that contribute to the effects of DJB.

Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection.

BACKGROUND: Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. METHODS: A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. RESULTS: PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. CONCLUSIONS: PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer.

Propensity score-matched study of laparoscopic and open surgery for colorectal cancer in rural hospitals.

BACKGROUND AND AIM: Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. METHODS: This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. RESULTS: In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. CONCLUSIONS: Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.

Duodenal-jejunal bypass improves diabetes and liver steatosis via enhanced glucagon-like peptide-1 elicited by bile acids.

BACKGROUND AND AIM: Bariatric surgery not only elicits weight loss but also rapidly resolves diabetes. However, the mechanisms remain unclear. The present study investigates how diabetes and liver steatosis are improved after duodenal-jejunal bypass (DJB) compared with a glucagon-like peptide-1 (GLP-1) analog and correlations between bile acids and GLP-1 secretion. METHODS: We initially determined the effects of bile acids on GLP-1 in vitro and then assigned 12 male 16-week-old Otsuka Long-Evans Tokushima Fatty rats to groups that underwent DJB, a sham operation, or were treated with the GLP-1 receptor agonist, liraglutide (n = 4 each). Blood glucose, insulin, GLP-1, serum bile acids, liver steatosis, and the number of GLP-1 positive cells (L cells) in the small intestine and colon were investigated in the three groups at eight weeks postoperatively. RESULTS: Levels of GLP-1mRNA were upregulated and GLP-1 secretion increased in cells incubated with bile acids in vitro. Weight gain was suppressed more in the DJB than in the sham group in vivo. Diabetes was more improved and GLP-1 levels were significantly higher in the DJB than in the sham group. Serum bile acids were significantly increased, the number of L cells in the ileum was upregulated compared with the sham group, and liver steatosis was significantly improved in the DJB compared with the other two groups. CONCLUSIONS: Duodenal-jejunal bypass might improve diabetes and liver steatosis by enhancing GLP-1 secretion through increasing serum bile acids and the proliferation of L cells in the ileum, compared with liraglutide.

Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study.

BACKGROUND: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG's potential for reducing peripheral neuropathy in patients with colorectal cancer. METHODS: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). FINDINGS: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). CONCLUSION: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

Characteristics of internal hernia after gastrectomy with Roux-en-Y reconstruction for gastric cancer.

BACKGROUND: Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. METHODS: Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. RESULTS: The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. CONCLUSIONS: The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects.

CD133 expression is correlated with poor prognosis in colorectal cancer.

BACKGROUND/AIMS: Cancer stem cells (CSC) was reported to play an important role in various kinds of cancer. CD133 is one of the cancer stem cell markers in solid cancers. However, the correlation between CD133 expression and the clinicopathological factors in colorectal cancer (CRC) remains unclear. METHODOLOGY: Forty patients with CRC who underwent operations were enrolled. Expression of CD133 was investigated by immunohistochemistry (IHC). The staining was observed in the cytoplasm of cancer cells and the patients who have the staining were defined as CD133-positive cases. The patients were divided into two groups: the CD133-positive group (n = 22) and negative group (n = 18). Clinicopathological factors were compared between the two groups. The prognostic factors were investigated by multivariate analysis. RESULTS: In the CD133-positive group, the incidence of lymph node and liver metastasis, lymphatic and venous invasion, as well as the progression of stage of cancer were higher than that in the CD133-negative group. The 5-year survival rate and the disease-free survival rate in the CD133-positive group were lower than that in the CD133-negative group. The multivariate analysis revealed that CD133 expression tended to be an independent prognostic factor. CONCLUSIONS: CD133 expression is correlated with poor prognosis in CRC.

Usefulness of Diagnostic Staging Laparoscopy for Advanced Gastric Cancer.

BACKGROUND: For advanced gastric cancer (AGC), peritoneal metastasis is the most common determinant of unresectability, but accurate preoperative diagnosis for peritoneal metastasis is challenging. Staging laparoscopy (SL) can detect unsuspected peritoneal metastasis. This study retrospectively evaluated the utility of SL and its indication in patients with AGC. METHODS: In this study, we enrolled 114 patients with pathologically diagnosed gastric adenocarcinoma who underwent SL. RESULTS: Of the 114 patients, 43 (37.7%) had peritoneal metastasis (P1 or CY1). Higher age, larger tumor size, type 4 GC, deeper tumor depth, elevated CA125, and ascites findings in preoperative CT were found to be significant predictors of peritoneal metastasis. In multivariate analysis, peritoneal metastasis was associated with type 4 GC (odds ratio [OR]: 6.11; 95% confidence interval [CI]: 1.87-19.8; P < .01) and ascites in CT (OR: 4.25; 95% CI: 1.48-12.1; P < .01). CONCLUSIONS: Staging laparoscopy is an effective tool to detect peritoneal metastasis from AGC. It can increase the curative resection rate and decrease unnecessary laparotomies.

Intestinal hypomotility due to longitudinal enterotomy can be alleviated by transverse closure.

BACKGROUND: Heineke-Mikulicz (HM) strictureplasty is commonly used to treat short stenoses in Crohn's disease. However, the degree to which intestinal motility is maintained remains unclear. We compared the peristalsis and transport capacity of the sutured intestines with HM configuration and transverse (TS) and longitudinal (LS) incisions. METHODS: The intestinal diameter, intraluminal pressure, and bead transit time of each sutured group were compared with that of the non-treatment (NT) group in the isolated proximal colon of rats. Propulsive contractions were induced using hydroxy-?-sanshool (HAS), a constituent of Japanese pepper. RESULTS: There was no change in the intestinal diameter between HM, TS, and NT groups ; however, it was significantly narrowed at the suture site and its distal side in the LS group. After HAS administration, the intestinal diameter at the suture site in the HM group was higher than that in the LS group. The intraluminal pressure was higher and the transit time was shorter in the HM group compared to those in the LS group. CONCLUSIONS: The HM configuration, which widens the incision site and distal diameter and shortens the cut surface of the circular muscle in the longitudinal direction, may help maintain basal and HAS-induced intestinal peristalsis and motility. J. Med. Invest. 70 : 180-188, February, 2023.

Thymidylate synthase (TS) protein expression as a prognostic factor in advanced colorectal cancer: a comparison with TS mRNA expression.

BACKGROUND/AIMS: The role of intratumoral thymidylate synthase (TS) mRNA or protein expression is still controversial and little has been reported regarding relation of them in colorectal cancer. METHODOLOGY: Forty-six patients with advanced colorectal cancer who underwent surgical resection were included. TS mRNA expression was determined by the Danenberg tumor profile method based on laser-captured micro-dissection of the tumor cells. TS protein expression was evaluated using immunohistochemical staining. RESULTS: TS mRNA expression tended to relate TS protein expression. Statistical significance was not found in overall survival between the TS mRNA high group and low group regardless of performing adjuvant chemotherapy. The overall survival in the TS protein negative group was significantly higher than that in positive group in all and the patients without adjuvant chemotherapy. Multivariate analysis showed TS protein expression was as an independent prognostic factor. CONCLUSIONS: TS protein expression tends to be related TS mRNA expression and is an independent prognostic factor in advanced colorectal cancer.

Clinicopathological analysis of distal margin for rectal cancer after preoperative chemoradiation therapy.

BACKGROUND/AIMS: Preoperative chemoradiation therapy (CRT) for advanced rectal cancer allows anal sphincter preservation in some patients who would require an abdominoperineal resection. But adequate distal margin in patients with locally advanced rectal cancer requiring preoperative CRT is unclear. The objective was to evaluate necessary distal margin from reduced tumor by preoperative CRT for anal sphincter preservation. METHODOLOGY: This study included 11 consecutive patients who performed low anterior resection and abdominoperineal resection for rectal cancer after preoperative CRT. Distal margin length from reduced tumor by preoperative CRT to residual viable cancer, tumor grade, lymph-node-metastasis stage and pathological changes of tumors were examined. RESULTS: Length from anal side edge of reduced tumor by preoperative CRT to pathological residual tumor ranged from +6 mm to -9 mm. Tumor stages were as follows: T0-2, N0, M0=3, T3, N0, M0=5, T4, N0, M0=1 and T3, N0, M+1=2. Median follow-up was 19 months. Recurrence occurred in one patient and was distant and not local. Pathological examinations showed that no patient had lymph-node-metastasis and residual tumors by preoperative CRT. CONCLUSIONS: This study suggests that for patients with locally advanced rectal cancer undergoing resection and preoperative CRT, distal margins ≥1 cm from reduced tumor by preoperative CRT seem to compromise pathological outcome.

Evaluation of relation of RAD51 and the effect of chemo-radiation therapy for advanced rectal cancer.

BACKGROUND/AIMS: Chemo-radiation therapy (CRT) has been used to improve local control and survival in patients with advanced rectal carcinoma. However, a significant proportion of patients shows poor response to adjuvant CRT. We thus investigated the usefulness of RAD51 expressions as a predictive maker of the CRT response. METHODOLOGY: Forty two patients who suffered from lower rectal cancer were investigated. All patients received preoperative CRT consisting of TS-1, concurrent with 40Gy of pelvic irradiation before having curative radical resection. The relationship between pathological responses of the tumors after therapy and expression of RAD51 was evaluated by immunostaining of resected specimen. RESULTS: Positive expression of RAD51 was observed in 24 of 42 patients (57.1%). RAD51 positively expressed in 68.2% (15 of 22 cases) of SD and 42.2% (9 of 20 cases) of PR and CR. There is a tendency of reverse correlation between clinical response and expression of RAD51. Regarding the correlation between pathological response and RAD51 expression, positive expression of RAD51 was recognized in 75.0% (15 of 20 cases) of Grade 1, 47.1% (8 of 17 cases) of Grade 2 and 20.0% (1 of 5 cases) of Grade 3. A significant reverse correlation was recognized between RAD51 expression and pathological responses. CONCLUSIONS: RAD51 expression could be one of the most important predictive factors of preoperative CRT for advanced lower rectal cancer.

Impact of education with authorized technical experts on colorectal laparoscopic skills.

BACKGROUND/AIMS: Laparoscopic skills training is becoming the standard for educating surgical residents. Because of the specific procedure which differs from that of open surgery, it is imperative to establish a unique training system to promote efficiency of learning laparoscopic skills. The aim of this study was to evaluate the efficiency of learning laparoscopic skills with or without authorized experts of JSES. METHODOLOGY: Among 71 patients who underwent laparoscopic colectomy from 2004 to 2009, 30 patients who underwent operation in introduction era without a technical expert (2004-2006), 17 patients who underwent operation in late period of introduction era without a technical expert (2006-2008), 12 patients who underwent operation by resident with technical expert (2008-2009) and 12 patients who underwent operation by technical expert, were investigated. Operative time, amount of blood loss, intra- and post-operative complications and conversion to open surgery were investigated. RESULTS: Operative time: 477:333:262:220 minutes (early period:late period:resident:expert), amount of blood loss: 494:73:21:20mL and complications: ileus: 0:1:0:0, leakage: 1:1:3:0, neurological disturbance: 2:1:0:0. CONCLUSIONS: Instruction by authorized technical experts of JSES is helpful to avoid pitfalls which are not seen in open surgery without an expert.

Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

PURPOSE: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. METHODS: Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. RESULTS: Interleukin (IL)-1ß, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1ß and IFN-γ expression was improved significantly by DKT (P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT (P < 0.05). CONCLUSIONS: DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

Strategy for laparoscopic repair of inguinal hernia after robot-assisted radical prostatectomy.

INTRODUCTION: Robot-assisted radical prostatectomy (RARP) is nowadays being performed worldwide, and inguinal hernia (IH) continues to be a common complication of radical prostatectomy. Laparoscopic repair of IH is often difficult via internal dissection because of adhesion of the preperitoneal cavity. This study aimed to categorize the intraoperative condition of, and devise a strategy for, IH after RARP. METHODS: Of 577 patients who underwent RARP, 18 developed IH. These 18 patients then underwent laparoscopic IH repair using the transabdominal preperitoneal approach (TAPP) or modified intraperitoneal onlay mesh repair (mIPOM). Internal dissection was categorized into two groups according to the appearance of Cooper's ligament (exposed or not exposed). RESULTS: After RARP, four patients had exposure of Cooper's ligament while 14 patients showed no exposure. Both patients in the exposed group underwent TAPP and all patients in the not-exposed group underwent mIPOM. There was no significant difference between normal TAPP and RARP regarding operative factors, and IH recurrence was not observed. CONCLUSION: Laparoscopic repair of IH after RARP is rendered safe and efficient by using our categorization based on the exposure of Cooper's ligament and extension of preperitoneal space.