FBXW7 regulates the sensitivity of imatinib in gastrointestinal stromal tumors by targeting MCL1.

BACKGROUND: Imatinib contributes to improving prognosis of high-risk or unresectable gastrointestinal stromal tumors (GISTs). As therapeutic efficacy is limited by imatinib resistance and toxicity, the exploration of predictive markers of imatinib therapeutic efficacy that enables patients to utilize more effective therapeutic strategies remains urgent. METHODS: The correlation between FBXW7 and imatinib resistance via FBXW7-MCL1 axis was evaluated in vitro and in vivo experiments. The significance of FBXW7 as a predictor of imatinib treatment efficacy was examined in 140 high-risk patients with GISTs. RESULTS: The ability of FBXW7 to predict therapeutic efficacy of adjuvant imatinib in high-risk GIST patients was determined through 5-year recurrence-free survival (RFS) rates analysis and multivariate analysis. FBXW7 affects imatinib sensitivity by regulating apoptosis in GIST-T1 cells. FBXW7 targets MCL1 to regulate apoptosis. MCL1 involves in the regulation of imatinib sensitivity through inhibiting apoptosis in GIST-T1 cells. FBXW7 regulates imatinib sensitivity by down-regulating MCL1 to enhance imatinib-induced apoptosis in vitro. FBXW7 regulates imatinib sensitivity of GIST cells by targeting MCL1 to predict efficacy of imatinib treatment in vivo. CONCLUSIONS: FBXW7 regulates imatinib sensitivity by inhibiting MCL1 to enhance imatinib-induced apoptosis in GIST, and predicts efficacy of imatinib treatment in high-risk GIST patients treated with imatinib.

Management challenges and the role of adjuvant chemotherapy in remnant gastric cancer: an analysis of 313 patients from the KEGG multicenter observational study.

BACKGROUND: Clinical findings and postoperative follow-up data on remnant gastric cancer (RGC) are limited due to its rarity. Additionally, the preoperative staging, radical surgery, and managing recurrence in RGC present significant clinical challenges. METHODS: We analyzed the clinicopathological findings, adjuvant chemotherapy, and patterns of postoperative recurrence of 313 consecutive patients who underwent curative surgery for RGC at 17 Japanese institutions. This study investigated the optimal management of RGC and the impact of adjuvant chemotherapy (AC) on recurrence-free survival (RFS). RESULTS: Pathological stages I, II, and III were observed in 55.9% (N = 175), 24.9% (N = 78), and 19.2% (N = 60) of the patients, respectively. The overall concordance rate between clinical and pathological T staging was 58.3%, with a clinical T4 sensitivity of 41.4% for diagnosing pathological T4. During the median follow-up period of 4.6 years, disease recurrence occurred in 24.3% of patients. Most recurrences (over 80%) occurred within 2.5 years, and 96.1% within 5 years after RGC surgery. Peritoneal recurrence was the most common in patients with advanced RGC, accounting for 14.1% in stage II and 28.3% in stage III. Multivariable regression analysis showed that AC was significantly associated with a longer RFS, with a hazard ratio of 0.45 (95% confidence interval: 0.26-0.76). CONCLUSIONS: Our study underscores the importance of early detection, accurate preoperative staging, and postoperative surveillance in managing advanced RGC cases. Despite some limitations, our findings indicate that AC may provide survival benefits comparable to those seen in primary gastric cancer.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

Long-term adjuvant therapy for high-risk gastrointestinal stromal tumors in the real world.

PURPOSE: Three years of adjuvant imatinib is the standard therapy for gastrointestinal stromal tumors (GISTs) with high-risk features. The prognostic effects of long-term adjuvant therapy are unknown. PATIENTS AND METHODS: The prospective registry study recruited 515 patients with high-risk GISTs between Dec. 2012 and Dec. 2015 were analyzed. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints include overall survival (OS) and safety. The study was designed to compare RFS after 3.5 years of 3-year adjuvant therapy (3.0 ± 0.5 years: 3-year group) with that of more than 3.5 years (median 5.2 years: longer group). RESULTS: Five-year RFS and 5-year OS were 68.2% (95% confidence interval [CI] 63.8-72.1) and 92.3% (95% CI 89.5-94.4), respectively. The recurrence rate during adjuvant was estimated to be 2.9/100 person-years (95% CI 2.0-4.1) and those after the end of adjuvant, which appeared similar irrespective of the adjuvant duration or reason to stop adjuvant, were estimated 12.0/100 person-years (95% CI 10.2-14.0). The 5-year RFS rates of 3-year and longer groups were 78.7% (95% CI 70.8-84.7) and 92.7% (95% CI 85.2-96.4), respectively. RFS after 3.5 years of the longer group was significantly better than that of the 3-year group (adjusted hazard ratio [HR] 0.56; 95% CI 0.39-0.78; P < 0.001). CONCLUSION: The recurrence risk of high-risk GISTs after adjuvant therapy is similar irrespective of the adjuvant duration and imatinib adjuvant may not cure but may delay recurrence. RFS after long-term adjuvant therapy appeared better than that after 3-year adjuvant.

Survival analysis of a prospective multicenter observational study on surgical palliation among patients with malignant bowel obstruction caused by peritoneal dissemination of gastric cancer.

BACKGROUND: Our previous report showed that surgical palliation maintained quality of life (QOL), improved solid food intake, and had an acceptable surgical safety among patients with malignant bowel obstruction (MBO) caused by advanced gastric cancer. This study performed a survival analysis stratified by the patients' QOL to elucidate its impact on survival. METHODS: Patients who underwent resection or bypass of the small intestine/colon or ileostomy/colostomy for bowel obstruction caused by peritoneal dissemination of gastric cancer were included. Validated instruments (EuroQoL-5 Dimensions) were used to assess QOL at baseline and 2 weeks, 1 month, and 3 months following surgical palliation. Postoperative improvement in oral intake was also evaluated using the Gastric Outlet Obstruction Scoring System (GOOSS). Univariate and multivariate survival analyses were performed using baseline characteristics and changes in QOL and GOOSS scores 2 weeks after surgery to determine prognostic factors. RESULTS: We enrolled 60 patients with a median survival time of 6.64 (95% CI 4.76-10.28) months. Patients who received postoperative chemotherapy and had lower baseline C-reactive protein (CRP) levels, higher baseline albumin levels, better baseline EuroQoL-5 Dimensions (EQ-5D) scores, and improved oral intake after palliative surgery exhibited significantly better survival. Multivariate analysis identified postoperative chemotherapy, lower baseline CRP levels, and improved oral intake as independent prognostic factors. CONCLUSIONS: The current study revealed that baseline QOL and postoperative QOL changes did not affect survival. Moreover, improved oral intake, lower baseline CRP levels, and postoperative chemotherapy were significant prognostic factors in patients who underwent palliative surgery for advanced gastric cancer with MBO.

Safety assessment of robotic gastrectomy and analysis of surgical learning process: a multicenter cohort study.

BACKGROUND: The safety of robotic gastrectomy (RG) for gastric cancer in daily clinical settings and the process by which surgeons are introduced and taught RG remain unclear. This study aimed to evaluate the safety of RG in daily clinical practice and assess the learning process in surgeons introduced to RG. METHODS: Patients who underwent RG for gastric cancer at Kyoto University and 12 affiliated hospitals across Japan from January 2017 to October 2019 were included. Any morbidity with a Clavien-Dindo classification grade of II or higher was evaluated. Moreover, the influence of the surgeon's accumulated RG experience on surgical outcomes and surgeon-reported postoperative fatigue were assessed. RESULTS: A total of 336 patients were included in this study. No conversion to open or laparoscopic surgery and no in-hospital mortality were observed. Overall, 50 (14.9%) patients developed morbidity. During the study period, 14 surgeons were introduced to robotic procedures. The initial five cases had surprisingly lower incidence of morbidity compared to the following cases (odds ratio 0.29), although their operative time was longer (+ 74.2 min) and surgeon's fatigue scores were higher (+ 18.4 out of 100 in visual analog scale). CONCLUSIONS: RG was safely performed in actual clinical settings. Although the initial case series had longer operative time and promoted greater levels of surgeon fatigue compared to subsequent cases, our results suggested that RG had been introduced safely.

Mesenteric closure after laparoscopic total gastrectomy with Roux-en-Y reconstruction is effective for prevention of internal hernia: a multicenter retrospective study.

BACKGROUND: Internal hernia (IH) is one of the critical complications after gastrectomy with Roux-en-Y reconstruction, which can be prevented by closing mesenteric defects. However, only few studies have investigated the incidence of IH after laparoscopic total gastrectomy (LTG) with Roux-en-Y reconstruction for gastric cancer till date. This study aimed to assess the efficacy of defect closure for the prevention of IH after LTG. METHODS: This multicenter, retrospective cohort study collected data from 714 gastric cancer patients who underwent LTG with Rou-en-Y reconstruction between 2010 and 2016 in 13 hospitals. We evaluated the incidence of postoperative IH by comparing closure and non-closure groups of Petersen's defect, jejunojejunostomy mesenteric defect, and transverse mesenteric defect. RESULTS: The closure group for Petersen's defect included 609 cases, while the non-closure group included 105 cases. The incidence of postoperative IH in the closure group for Petersen's defect was significantly lower than it was in the non-closure group (0.5% vs. 4.8%, p < 0.001). The closure group for jejunojejunostomy mesenteric defect included 641 cases, while the non-closure group included 73 cases. The incidence of postoperative IH in the closure group of jejunojejunostomy mesenteric defect was significantly lower than that in the non-closure group (0.8% vs. 4.1%, p = 0.004). Out of 714 patients, 41 underwent retro-colic reconstruction. No patients in the transverse mesenteric defect group developed IH. CONCLUSION: Mesenteric defect closure after LTG with Roux-en-Y reconstruction may reduce postoperative IH incidence. Endoscopic surgeons should take great care to prevent IH by closing mesenteric defects.

Modeling Long-Range Dynamic Correlations of Words in Written Texts with Hawkes Processes.

It has been clarified that words in written texts are classified into two groups called Type-I and Type-II words. The Type-I words are words that exhibit long-range dynamic correlations in written texts while the Type-II words do not show any type of dynamic correlations. Although the stochastic process of yielding Type-II words has been clarified to be a superposition of Poisson point processes with various intensities, there is no definitive model for Type-I words. In this study, we introduce a Hawkes process, which is known as a kind of self-exciting point process, as a candidate for the stochastic process that governs yielding Type-I words; i.e., the purpose of this study is to establish that the Hawkes process is useful to model occurrence patterns of Type-I words in real written texts. The relation between the Hawkes process and an existing model for Type-I words, in which hierarchical structures of written texts are considered to play a central role in yielding dynamic correlations, will also be discussed.

QOL assessment after palliative surgery for malignant bowel obstruction caused by peritoneal dissemination of gastric cancer: a prospective multicenter observational study.

BACKGROUND: Patients with peritoneal dissemination of gastric cancer have poor oral intake caused by malignant bowel obstruction (MBO). Palliative surgery has often been undertaken to improve quality of life (QOL), but few prospective studies on palliative surgery in this patient population have been published. PATIENTS AND METHODS: We prospectively investigated the significance of palliative surgery using patient-reported QOL measures. Patients underwent palliative surgery by small intestine/colon resection or small intestine/colon bypass or ileostomy/colostomy for MBO. The primary endpoint was change in QOL assessed at baseline, 14 days, 1 month, and 3 months following palliative surgery using the Euro QoL Five Dimensions (EQ-5D™) questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire gastric cancer module (QLQ-STO22). Secondary endpoints were postoperative improvement in oral intake and surgical complications. RESULTS: Between April 2013 and March 2018, 63 patients were enrolled from 14 institutions. The mean EQ-5D™ utility index baseline score of 0.6 remained consistent. Gastric-specific symptoms mostly showed statistically significant improvement from baseline. Forty-two patients (67%) were able to eat solid food 2 weeks after palliative surgery and 36 patients (57%) tolerated it for 3 months. The rate of overall morbidity of ≥ grade III according to the Clavien-Dindo classification was 16% (10 patients) and the 30-day postoperative mortality rate was 3.2% (2 patients). CONCLUSIONS: In patients with MBO caused by peritoneal dissemination of gastric cancer, palliative surgery did not improve QOL while improving solid food intake, with an acceptable postoperative morbidity and mortality rate.

Survival analysis of a prospective multicenter observational study on surgical palliation among patients receiving treatment for malignant gastric outlet obstruction caused by incurable advanced gastric cancer.

BACKGROUND: We had previously reported that surgical palliation could maintain quality of life (QOL) while improving solid food intake among patients with malignant gastric outlet obstruction (GOO) caused by advanced gastric cancer. The present study aimed to perform a survival analysis according to the patients' QOL to elucidate its impact on survival. METHODS: Patients with GOO who underwent either palliative gastrectomy or gastrojejunostomy were included in this study. A validated QOL instrument (EQ-5D) was used to assess QOL at baseline and 2 weeks, 1 month, and 3 months following surgical palliation. Postoperative improvement in oral intake was also evaluated using the GOO scoring system (GOOSS). Thereafter, univariate and multivariate survival analyses were performed to determine independent prognostic factors. RESULTS: The median survival time of the 104 patients included herein was 11.30 months. Patients who received postoperative chemotherapy, PS 0/1, baseline EQ-5D ≥ 0.75, improved or stable EQ-5D, and improved oral intake expressed as GOOSS = 3 had significantly better survival. Multivariate analysis identified postoperative chemotherapy, a better baseline PS, a better baseline EQ5D, improved or stable EQ5D scores, and improved oral intake 3 months after surgical palliation as independent prognostic factors. CONCLUSION: Apart from preoperative PS and postoperative chemotherapy, the present study identified better baseline QOL, improvement in postoperative QOL, and improvement in oral intake as prognostic factors among patients who underwent palliative surgery for advanced gastric cancer with GOO.

Changes in the sexual function of male patients with rectal cancer over a 2-year period from diagnosis to 24-month follow-up: A prospective, multicenter, cohort study.

BACKGROUND AND OBJECTIVES: This prospective study aimed to identify long-term changes in sexual function of men with rectal cancer from point of diagnosis to 24 months postoperatively. METHODS: Male patients undergoing laparoscopic rectal cancer surgery were prospectively enrolled. International Index of Erectile Function (IIEF) Questionnaire scores were collected at diagnosis; first follow-up; and 6, 12, and 24 months postoperatively. Missing values were managed via multiple imputations using the propensity score method. Paired t tests were applied to examine changes in IIEF scores over time. RESULTS: This study analyzed 115 patients. For erectile function, there were no significant changes in scores from the point of diagnosis to first treatment (9.4 vs. 9.8 as mean scores; p = .227). Scores deteriorated postoperatively and recovered until 12 months post-surgery, but did not improve significantly from 12 months to 24 months post-surgery (8.7 vs. 8.2 as mean scores; p = .440). This pattern of change was observed in all other domains: orgasmic function, sexual desire, orgasmic satisfaction, and overall satisfaction. CONCLUSIONS: Sexual function was not influenced by a rectal cancer diagnosis. Sexual function deteriorated following surgery and recovered until 12 months post-surgery; however, it did not significantly improve from 12 months to 24 months postoperatively.

Linear or circular stapler? A propensity score-matched, multicenter analysis of intracorporeal esophagojejunostomy following totally laparoscopic total gastrectomy.

BACKGROUND: Presently, there is no consensus as to what procedure of intracorporeal esophagojejunostomy (EJS) in totally laparoscopic total gastrectomy (TLTG) is best to reduce postoperative complications. The aim of this study was to demonstrate the superiority of linear stapled reconstruction in terms of anastomotic-related complications for EJS in TLTG. METHODS: We collected data on 829 consecutive gastric cancer patients who underwent TLTG reconstructed by the Roux-en-Y method with radical lymphadenectomy between January 2010 and December 2016 in 13 hospitals. The patients were divided into two groups according to reconstruction method and matched by propensity score. Postoperative EJS-related complications were compared between the linear stapler (LS) and the circular stapler (CS) groups. RESULTS: After matching, data from 196 patients in each group were analyzed. The overall incidence of EJS-related complications was significantly lower in the LS group than in the CS group (4.1% vs. 11.7%, p = 0.008). The incidence of EJS anastomotic stenosis during the first year after surgery was significantly lower in the LS group than in the CS group (1.5% vs. 7.1%, p = 0.011). The incidence of EJS bleeding did not differ significantly between the groups, although no bleeding was observed in the LS group (0% vs. 2.0%, p = 0.123). The incidence of EJS leakage did not differ significantly between the groups (2.6% vs. 3.6%, p = 0.771). CONCLUSION: The use of linear stapled reconstruction is safer than the use of circular stapled reconstruction for intracorporeal EJS in TLTG because of its lower risks of stenosis.

Comparison between anatomical subsegmentectomy and nonanatomical partial resection for hepatocellular carcinoma located within a single subsegment: a single-center retrospective analysis.

BACKGROUND/AIMS: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy. METHODOLOGY: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28). RESULTS: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008). CONCLUSIONS: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.

The preventive surgical site infection bundle in patients with colorectal perforation.

BACKGROUND: Incisional surgical site infection (SSI) is one of the most frequent complications that occur after colorectal surgery. Surgery for colorectal perforation carries an especially high risk of incisional SSI because fecal ascites contaminates the incision intraoperatively, and in patients who underwent stoma creation, the incision is located near the infective origin and is subject to infection postoperatively. Although effectiveness of the preventive SSI bundle of elective colorectal surgery has been reported, no study has focused exclusively on emergency surgery for colorectal perforation. METHODS: Patients with colorectal perforation who underwent emergency surgery and stoma creation from 2010 to 2015 at our center were consecutively enrolled in the study. In March 2013, we developed the preventive incisional SSI bundle for patients with colorectal perforation undergoing stoma creation. The effectiveness of the bundle in these patients was determined and the rates of incisional SSI between before and after March 2013 were compared. RESULTS: We enrolled 108 patients with colorectal perforation who underwent emergency operation during the study period. Thirteen patients were excluded because they died within 30 days after surgery, and 23 patients without stoma were excluded; thus, 72 patients were analyzed. There were 47 patients in the pre-implementation group and 25 patients in the post-implementation group. The rate of incisional SSI was significantly lower after implementation of preventive incisional SSI bundle (43% vs. 20%, p = 0.049). Postoperative hospital stay was significantly shorter after implementation of the bundle (27 vs. 18 days respectively; p = 0.008). CONCLUSIONS: The preventive incisional SSI bundle was effective in preventing incisional SSI in patients with colorectal perforation undergoing emergency surgery with stoma creation.

Efficacy of surgical staple line reinforcement in Glissonean stapling: A single-center pilot study.

Vascular staplers are routinely used in laparoscopic liver resection, which has become a standard procedure in advanced medical facilities. Although previous reports have outlined the benefits of staple line reinforcement (SLR), its application in Glissonean pedicle transection during hepatic resection remains poorly studied. This study investigated surgical SLR as a tool to enhance staple line strength and improve perioperative hemostasis. Here, 10 patients who underwent laparoscopic liver resection using the Tri-StapleTM2.0 Reinforced Reload were included. Patient characteristics, surgical details, and outcomes were assessed. The results demonstrated successful outcomes with no complications related to bile leakage or injuries during staple insertion. Overall, our findings suggest that SLR can be safely utilized in Glissonean pedicle transection during laparoscopic liver resections. Further studies are required to comprehensively evaluate its benefits compared with conventional surgical staplers.

The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.

BACKGROUND: Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL. METHODS: This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis. DISCUSSION: This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer. TRIAL REGISTRATION: jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.

Promotion of hair growth by Rosmarinus officinalis leaf extract.

Topical administration of Rosmarinus officinalis leaf extract (RO-ext, 2 mg/day/mouse) improved hair regrowth in C57BL/6NCrSlc mice that experienced hair regrowth interruption induced by testosterone treatment. In addition, RO-ext promoted hair growth in C3H/He mice that had their dorsal areas shaved. To investigate the antiandrogenic activity mechanism of RO-ext, we focused on inhibition of testosterone 5α-reductase, which is well recognized as one of the most effective strategies for the treatment of androgenic alopecia. RO-ext showed inhibitory activity of 82.4% and 94.6% at 200 and 500 µg/mL, respectively. As an active constituent of 5α-reductase inhibition, 12-methoxycarnosic acid was identified with activity-guided fractionation. In addition, the extract of R. officinalis and 12-methoxycarnosic acid inhibited androgen-dependent proliferation of LNCaP cells as 64.5% and 66.7% at 5 µg/mL and 5 µM, respectively. These results suggest that they inhibit the binding of dihydrotestosterone to androgen receptors. Consequently, RO-ext is a promising crude drug for hair growth.

[A case of recurrent colon cancer developed thrombosis in superior mesenteric vein after chemotherapy].

A 48-year-old man was administered bevacizumab+FOLFOX for lymph node recurrence of colon cancer in the abdominal cavity, and developed serious thrombosis of the portal system after 6 courses of the chemotherapy. We discontinued it promptly and anticoagulant therapy with urokinase was started immediately, but a complete dissolution was not achieved. Preservation therapy using anticoagulants for a long duration was effective for controling the of clinical symptom of thrombosis. The result of 6 courses of chemotherapy was CR, and the effect continues today, without further treatment 2 years later.

Impact of intravenous injection of glucagon on anastomotic leakage in esophagectomy.

Background: Anastomotic leakage after esophagectomy affects the early postoperative state and prognosis. However, effective measures to prevent anastomotic leakage in esophagogastric anastomosis have not been established. Methods: This single-center, retrospective, observational study included 147 patients who underwent esophagectomy for esophageal cancer between 2010 and 2020. Glucagon was administered to extend the gastric tube in patients who underwent esophagectomy from January 2016. The patients were divided into two groups: a glucagon-treated group (2016-2020) and a control group (2010-2015). The incidence of anastomotic leakage was compared between the two groups for evaluation of the preventive effects of glucagon administration on anastomotic leakage. Results: The length of the gastric tube from the pyloric ring to the final branch of the right gastroepiploic artery was extended by 2.8 cm after glucagon injection. The incidence of anastomotic leakage was significantly lower in the glucagon-treated group (19% vs. 38%; p = 0.014). Multivariate analysis showed that glucagon injection was the only independent factor associated with a reduction in anastomotic leakage (odds ratio, 0.26; 95% confidence interval, 0.07-0.87). Esophagogastric anastomosis was performed proximal to the final branch of the right gastroepiploic artery in 37% patients in the glucagon-treated group, and these cases showed a lower incidence of anastomotic leakage than did those with anastomosis distal to the final branch of the right gastroepiploic artery (10% vs. 25%, p = 0.087). Conclusions: Extension of the gastric tube by intravenous glucagon administration during gastric mobilization in esophagectomy for esophageal cancer may be effective in preventing anastomotic leakage.