Efficacy and safety of mesh non-fixation in patients undergoing laparo-endoscopic repair of groin hernia: a systematic review and meta-analysis.

PURPOSE: To examine updated evidence on the efficacy and safety of mesh non-fixation in patients undergoing laparo-endoscopic repair of groin hernias. METHODS: We searched MEDLINE, Cochrane Central Library, Embase, ClinicalTrials. gov, and ICTRP databases to identify randomized controlled trials. The primary outcomes were recurrence, chronic pain, and return to daily life. The certainty of evidence (CoE) was assessed by grading recommendations, assessments, developments, and evaluations. We performed a subgroup analysis based on the surgical type. This study was registered with PROSPERO (CRD 42022368929). RESULTS: We included 25 trials with 3,668 patients (4,038 hernias) were included. Mesh non-fixation resulted in little to no difference in hernia recurrence (relative risk [RR]:1.40, 95% confidence interval [CI]:0.59-3.31; I2 = 0%; moderate CoE) and chronic pain (RR:0.48, 95% CI:0.13-1.78; I2 = 77%; moderate CoE), but reduced return to daily life (mean difference [MD]: - 1.79 days, 95% CI: - 2.79 to -0.80; I2 = 96%; low CoE). In subgroup analyses, the transabdominal preperitoneal approach (TAPP) (MD: - 2.97 days, 95% CI: - 4.87 to - 1.08; I2 = 97%) reduced return to daily life than total extraperitoneal inguinal approach (MD: - 0.24 days, 95% CI - 0.71 to 0.24; I2 = 61%) (p = 0.006). CONCLUSIONS: Mesh nonfixation improves the return to daily life without increasing the risk of hernia recurrence or chronic pain. Surgeons and patients may discuss mesh nonfixation options to accommodate a patient's desired return to daily life. Further trials focusing on TAPP are required to confirm these findings.

Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study.

BACKGROUND: We previously reported that indocyanine green fluorescence imaging (ICG-FI)-guided laparoscopic lateral pelvic lymph node dissection (LPLND) was able to increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. However, the long-term outcomes of ICG-FI-guided laparoscopic LPLND have not been evaluated. The aim of the present study was to compare the long-term outcomes of ICG-FI-guided laparoscopic LPLND to conventional laparoscopic LPLND without ICG-FI. METHODS: This was a retrospective, multi-institutional study with propensity score matching. The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic LPLND between January 2013 and February 2018. The main evaluation items in this study were the 3-year overall survival, relapse-free survival (RFS), local recurrence rate, and lateral local recurrence (LLR) rate. RESULTS: A total of 172 patients with middle-lower rectal cancer who had undergone laparoscopic LPLND were included in this study. After propensity score matching, 58 patients were matched in each of the ICG-FI and non-ICG-FI groups. There were no substantial differences in the baseline characteristics between the two groups. The ICG-FI group and non-ICG-FI group included 40 and 38 women and had a median age of 65 (IQR 60-72) and 66 (IQR 60-73) years, respectively. The median follow-up for all patients was 63.7 (IQR 51.3-76.8) months. The estimated respective 3-year overall survival, RFS, and local recurrence rates were 93.1%, 70.7%, and 5.2% in the ICG-FI group and 85.9%, 71.7%, and 12.8% in the non-ICG-FI group (p = 0.201, 0.653, 0.391). The 3-year cumulative LLR rate was 0% in the ICG-FI group and 9.3% in the non-ICG-FI group (p = 0.048). CONCLUSIONS: This study revealed that laparoscopic LPLND combined with ICG-FI was able to decrease the LLR rate. It appears that ICG-FI could contribute to improving the quality of laparoscopic LPLND and strengthening local control of the lateral pelvis. TRIALS REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 ( http://www.umin.ac.jp/ctr/index.htm ).

Initial experience with the transanal approach for lateral pelvic lymph node dissection in rectal cancer.

BACKGROUND: The efficacy and safety of transanal lateral pelvic lymph node dissection (TaLPLND) in rectal cancer has not yet been clarified. The aim of the present study was to evaluate the short-term results as an initial experience of TaLPLND. METHODS: This retrospective study included patients with middle to lower rectal cancer who underwent TaLPLND from July 2018 to July 2021. Our institutions targeted lymph nodes in the internal iliac area and the obturator area for lateral pelvic lymph node dissection (LPLND). RESULTS: A total of 30 consecutive patients with rectal cancer were included in this analysis. The median age was 60 years (range, 36-83 years), and the male-female ratio was 2:1. The median operative time was 362 min (IQR, 283-661 min), and the median intraoperative blood loss was 74 ml (IQR, 5-500 ml). Intraoperative blood transfusion was required in one case. No cases required conversion to laparotomy. TaLPLND was performed bilaterally in 13 patients (43.3%). Five patients (16.7%) underwent LPLND with combined resection of the internal iliac vessels. The median distance of the distal margin from the anal verge was 20 mm. The pathological radial margin (pRM) was positive in one case, and the negative pRM rate was 96.7%. Short-term postoperative complications (Clavien-Dindo classification grade ≥ II) were observed in nine cases (30.0%). There were no cases of reoperation or mortality. The median number of harvested lateral pelvic lymph nodes was 11 (range, 3-28). On pathological examination, lateral pelvic lymph nodes were positive for metastasis in seven cases (23.3%). CONCLUSIONS: TaLPLND appeared to be beneficial from an oncological point of view because it was close to the upstream lymphatic drainage from the tumor. The short-term outcomes of this initial experience indicate that this novel approach is feasible.

SWI by 7T MR Imaging for the Microscopic Imaging Diagnosis of Astrocytic and Oligodendroglial Tumors.

BACKGROUND AND PURPOSE: Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. MATERIALS AND METHODS: 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. RESULTS: Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. CONCLUSIONS: Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.

Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study.

BACKGROUND: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. PATIENTS AND METHODS: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. RESULTS: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P = 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). CONCLUSION: Our study confirmed the usefulness of the 12-RS assay in aiding the physician-patient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.

Phase II study of trifluridine/tipiracil plus bevacizumab by RAS mutation status in patients with metastatic colorectal cancer refractory to standard therapies: JFMC51-1702-C7.

BACKGROUND: Although the efficacy of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) against metastatic colorectal cancer (mCRC) has been demonstrated, little is known about its effectiveness upon disease stratification by RAS mutations. In this phase II study, we investigated the efficacy and safety profiles of FTD/TPI in mCRC according to RAS mutation status. PATIENTS AND METHODS: Eligible patients were mCRC refractory or intolerant to all standard therapies other than FTD/TPI and regorafenib. Patients received 4-week cycles of treatment with FTD/TPI (35 mg/m2, twice daily, days 1-5 and 8-12) and bevacizumab (5 mg/kg, days 1 and 15). The primary endpoint was disease control rate (DCR). The null hypothesis of DCR in both RAS wild-type (WT) and mutant (MUT) cohorts was 44%, assuming a one-sided significance level of 5.0%. The necessary sample size was estimated to be 49 patients (target sample size: 50 patients) for each cohort. RESULTS: Between January and September 2018, 102 patients were enrolled, and 97 patients fulfilled the eligibility criteria (48 in the RAS WT cohort and 49 in the RAS MUT cohort). DCRs in the RAS WT and MUT cohort were 66.7% [90% confidence interval (CI), 53.9%-77.8%, P = 0.0013] and 55.1% (90% CI, 42.4%-67.3%, P = 0.0780), respectively. The median progression-free survival (PFS) and overall survival (OS) were 3.8 and 9.3 months, respectively, in the RAS WT cohort and 3.5 and 8.4 months, respectively, in the RAS MUT cohort. The most common grade 3 or higher adverse event in both cohorts was neutropenia (46% in the RAS WT cohort and 62% in the RAS MUT cohort), without unexpected safety signals. CONCLUSIONS: FTD/TPI plus bevacizumab showed promising activity with an acceptable safety profile for pretreated mCRC, regardless of RAS mutation status, although the efficacy outcomes tended to be better in RAS WT.

S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial.

BACKGROUND: The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy. PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020. RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31). CONCLUSION: Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.

A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience.

PURPOSE: Eribulin methylate (eribulin) improved the overall survival (OS) of HER2-negative advanced breast cancer (HER2-ABC) patients; however, the mechanism underlying the OS improvement has not been clarified. Several reports suggest that eribulin promotes antitumor immunity via tumor micro-environment conditioning. Recently, a maintained baseline lymphocyte count was proposed as predictive marker for eribulin therapy in HER2-ABC patients; however, no associations with the OS have been noted. We retrospectively investigated the neutrophil-to-lymphocyte ratio and absolute lymphocyte count (ALC) in HER2-ABC patients receiving eribulin and assessed the utility of eribulin re-administration for further OS improvement. METHODS: HER2-ABC patients who received eribulin therapy at Shizuoka Cancer Center between November 2011 and December 2018 were retrospectively analyzed. RESULTS: A total of 144 HER2-ABC (108 estrogen receptor-positive [ER+], 36 ER-) patients were identified, and 32 patients (28 ER+ , 4 ER-) were re-administered with eribulin. In the ER+ subgroup, a multivariate analysis showed that an ALC ≥ 1000/µL and re-administration were significantly associated with the OS (hazard ratio [HR] 0.503; P = 0.034 and HR 0.366; P < 0.0001, respectively), and an ALC ≥ 1000/µL was also identified as the only predictive factor for re-administration (HR 0.329; P = 0.033). In contrast, a multivariate analysis in the ER- subgroup identified no predictive markers. CONCLUSION: In HER2-ER + ABC patients, ALC was identified as a predictive marker for eribulin therapy, and the re-administration of eribulin is considered a valid therapeutic option for further improvement of the OS.

Extracellular Vesicles of Stem Cells to Prevent BRONJ.

Extracellular vesicles (EVs), several tens to hundreds of nanometers in size, are vesicles secreted by cells for intercellular communication. EVs released from mesenchymal stem cells (MSC-EVs) have the potential to treat multiple diseases. This study aimed to determine the effects of MSC-EVs on bisphosphonate-related osteonecrosis of the jaw (BRONJ), whose pathogenesis and treatment are not yet established. To this end, zoledronic acid (ZOL) was administered to bone marrow cells and fibroblasts in vitro. In vivo, a BRONJ model was produced by administering ZOL to rats and extracting teeth. Each MSC-EV-treated and nontreated group was compared histologically and molecularly. In vitro, the nontreated group showed an increased number of ß-galactosidase-positive cells and expression of senescence-associated genes p21, pRB and senescence-related inflammatory cytokines. Conversely, MSC-EV administration decreased the number of senescent cells and expression levels of p21, pRB and inflammatory cytokines. In vivo, in the nontreated group, the socket was partially uncovered by the oral epithelium, leaving an exposed bone. Conversely, in the MSC-EV-treated group, the socket was healed. Besides, in the nontreated group, ß-galactosidase-positive cells existed in the socket and colocalized with the CD90 and periostin-positive cells. However, there were few ß-galactosidase-positive cells in the MSC-EV-treated group. Furthermore, gene expression of stem cell markers Bmi1 and Hmga2 and the vascular endothelial marker VEGF was significantly increased in the MSC-EV-treated group, compared with that in the nontreated group. These results indicate that MSC-EVs prevent ZOL-induced senescence in stem cells, osteoblasts, and fibroblasts and reduce inflammatory cytokines. Furthermore, administration of MSC-EVs prevented senescence of cells involved in wound healing and the spread of chronic inflammation around senescent cells, thereby promoting angiogenesis and bone regeneration and preventing BRONJ.

Correction: Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Owing to the insufficient specificity of the anti-myeloproliferative leukemia protein (MPL) antibody in the original version of this Article, Figure 6 and parts of Figures 2a, 4e, and 5a do not represent the correct information. The corrected version of Figure 6 is in this correction and those of Figures 2a, 4e, and 5a are shown in the supplemental information.

Randomized clinical trial of high versus low inferior mesenteric artery ligation during anterior resection for rectal cancer.

BACKGROUND: The optimal level for inferior mesenteric artery ligation during anterior resection for rectal cancer is controversial. The aim of this randomized trial was to clarify whether the inferior mesenteric artery should be tied at the origin (high tie) or distal to the left colic artery (low tie). METHODS: Patients were allocated randomly to undergo either high- or low-tie ligation and were stratified by surgical approach (open or laparoscopic). The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were duration of surgery, blood loss and 5-year overall survival. RESULTS: Some 331 patients entered the trial between June 2006 and September 2012. The trial was stopped prematurely as recruitment was slow. Seven patients were excluded after randomization but before operation because of procedural changes. High tie and low tie were performed in 164 and 160 patients respectively. The incidence of anastomotic leakage was not significantly different (17·7 versus 16·3 per cent respectively; P = 0·731). The incidence of severe complications requiring intervention was 2·4 versus 5·0 per cent for high and low tie respectively (P = 0·222). In multivariable analysis, risk factors for anastomotic leakage included male sex (odds ratio 4·36, 95 per cent c.i. 1·56 to 12·18) and distance of the tumour from the anal verge (odds ratio 0·99, 0·98 to 1·00). At 5 years there were no significant differences in overall (87·2 versus 89·4 per cent respectively; P = 0·386) and disease-free (76·3 versus 77·6 per cent; P = 0·765) survival. CONCLUSION: The level of ligation of the inferior mesenteric artery does not significantly influence the rate of anastomotic leakage. Registration number: NCT01861678 ( https://clinicaltrials.gov).

Myeloproliferative leukemia protein activation directly induces fibrocyte differentiation to cause myelofibrosis.

Myelofibrosis (MF) may be caused by various pathogenic mechanisms such as elevation in circulating cytokine levels, cellular interactions and genetic mutations. However, the underlying mechanism of MF still remains unknown. Recent studies have revealed that fibrocytes, the spindle-shaped fibroblast-like hematopoietic cells, and the thrombopoietin (TPO)/myeloproliferative leukemia protein (MPL; TPO receptor) signaling pathway play a certain role in the development of MF. In the present study, we aimed to investigate the relationship between fibrocytes and MPL activation. We showed that TPO or a TPO receptor agonist directly induces fibrocyte differentiation using murine fibrocyte cell lines and a murine MF model. Conversely, elimination of macrophages expressing MPL by clodronate liposomes reversed the MF phenotype of the murine model, suggesting that fibrocyte differentiation induced by MPL activation contributes to the progression of MF. Furthermore, we revealed that SLAMF7high MPLhigh monocytes in human peripheral blood mononuclear cells were possible fibrocyte precursors and that these cells increased in number in MF patients not treated with ruxolitinib. Our findings confirmed a link between fibrocytes and the TPO/MPL signaling pathway, which could result in a greater understanding of the pathogenesis of MF and lead to the development of novel therapeutic interventions.

Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion.

BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is required. Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits pleiotropic functions that are mediated via its receptors [PACAP-specific receptor (PAC1R), vasoactive intestinal peptide (VIP) receptor type 1 (VPAC1R) and VPAC2R]. Although some studies have suggested a role for PACAP in the skin and several exocrine glands, the effects of PACAP on the process of eccrine sweat secretion have not been examined. OBJECTIVES: To investigate the effect of PACAP on eccrine sweat secretion. METHODS: Reverse transcriptase-polymerase chain reaction and immunostaining were used to determine the expression and localization of PACAP and its receptors in mouse and human eccrine sweat glands. We injected PACAP subcutaneously into the footpads of mice and used the starch-iodine test to visualize sweat-secreting glands. RESULTS: Immunostaining showed PACAP and PAC1R expression by secretory cells from mouse and human sweat glands. PACAP immunoreactivity was also localized in nerve fibres around eccrine sweat glands. PACAP significantly promoted sweat secretion at the injection site, and this could be blocked by the PAC1R-antagonist PACAP6-38. VIP, an agonist of VPAC1R and VPAC2R, failed to induce sweat secretion. CONCLUSIONS: This is the first report demonstrating that PACAP may play a crucial role in sweat secretion via its action on PAC1R located in eccrine sweat glands. The mechanisms underlying the role of PACAP in sweat secretion may provide new therapeutic options to combat sweating disorders.

Randomized clinical trial of single-incision versus multiport laparoscopic colectomy.

BACKGROUND: The efficacy and safety of single-incision laparoscopic colectomy (SILC) for colonic cancer remain unclear. The aim of this study was to determine the outcomes of SILC compared with multiport laparoscopic colectomy (MPLC) for colonic cancer. METHODS: Patients with histologically proven colonic carcinoma located in the caecum, ascending, sigmoid or rectosigmoid colon, clinically diagnosed as stage 0-III by CT, were eligible for this study. Patients were randomized before surgery and underwent tumour dissection with complete mesocolic excision. Safety analyses were conducted according to randomization groups. RESULTS: A total of 200 patients were enrolled and randomized to the MPLC (100 patients) or SILC (100 patients) arm. Surgical outcomes were similar between the MPLC and SILC arms, including duration of operation (mean 162 versus 156 min respectively; P = 0·273), blood loss (mean 8·8 versus 21·4 ml; P = 0·102), conversion to open laparotomy (2·0 versus 1·0 per cent; P = 0·561), reoperation (3·0 versus 3·0 per cent; P = 1·000), time to first flatus (both median 1 day; P = 0·155) and postoperative hospital stay (both median 6; P = 0·372). The total skin incision length was significantly shorter in the SILC arm (mean 4·4 cm versus 6·8 cm in the MPLC arm; P < 0·001). The median duration of analgesia use was 5 days in the MPLC and 4 days in the SILC arm (P = 0·485). Overall complication rates were equivalent (15·0 versus 12·0 per cent respecitvely; P = 0·680). CONCLUSION: SILC is not superior to MPLC. REGISTRATION NUMBER: UMIN000007220 (http://www.umin.ac.jp/ctr/index.htm).

Nutritional management of anastomotic leakage after colorectal cancer surgery using elemental diet jelly.

BACKGROUND/AIMS: Anastomotic leakage is major complication of colorectal surgery. Total parenteral nutrition (TPN) and fasting are conservative treatments for leakage in the absence of peritonitis in Japan. Elemental diet (ED) jelly is a completely digested formula and is easily absorbed without secretion of digestive juices. The purpose of this study was to assess the safety of ED jelly in management of anastomotic leakage. METHODOLOGY: Six hundred and two patients who underwent elective surgery for left side colorectal cancer from January 2008 to December 2011 were included in the study. Pelvic drainage was performed for all patients. Sixty-three (10.5%) patients were diagnosed with an anastomotic leakage, and of these, 31 (5.2%) without diverting stoma were enrolled in this study. RESULTS: Sixteen patients received TPN (TPN group) and 15 patients received ED jelly (ED group). The duration of intravenous infusion was significantly shorter in the ED group than in the TPN group (15 days versus 25 days, P= 0.008). In the TPN group, catheter infection was occurred in 2 patients who required re-insertion of the catheter. CONCLUSION: Conservative management of anastomotic leakage after colorectal surgery with ED jelly appears to be a safe and useful approach.

An open-label, dose-escalation, safety, and pharmacokinetics phase I study of ombrabulin, a vascular disrupting agent, administered as a 30-min intravenous infusion every 3 weeks in Japanese patients with advanced solid tumors.

PURPOSE: To determine ombrabulin's maximum tolerated dose and dose recommended for Japanese patients with advanced solid tumors and to assess its antitumor activity and overall safety and pharmacokinetic profiles. METHODS: This was a multi-center, open-label, sequential-cohort, dose-escalation phase I study of ombrabulin, a vascular disrupting agent, administered once every 3 weeks. Patients were treated with 15.5, 25, 35, or 50 mg/m(2) ombrabulin over a 30-min intravenous infusion. The recommended dose was the highest dose at which <33 % of all evaluable patients experienced dose-limiting toxicities (DLTs) during the first treatment cycle or 50 mg/m(2) (recommended in Caucasian patients) if the previous definition was not met. RESULTS: Fifteen patients were treated. No DLT occurred with 15.5, 25, or 35 mg/m(2) ombrabulin. In the 50 mg/m(2) group, one patient had Grade 3 lymphopenia, and another experienced Grade 2 hypertension and Grade 3 diarrhea judged as DLTs. The most frequent related adverse events in this group were diarrhea, nausea, and hypertension. Two patients had Grade 3 anemia, one at the 15.5 mg/m(2) and the other at the 50 mg/m(2). No AEs necessitating dose reduction or Grade 4 AEs were observed. Overall, five patients had stable disease. Pharmacokinetic parameters were comparable to those in non-Japanese patients. CONCLUSIONS: Ombrabulin treatment once every 3 weeks was well tolerated in Japanese patients with advanced solid tumors. The dose recommended is 50 mg/m(2), as in Caucasian patients. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients (funded by Sanofi; ClinicalTrials.gov number, NCT00968916).

An unusual case of subclinical diffuse glucagonoma coexisting with two nodules in the pancreas: characteristic features on computed tomography.

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT.