Background
The incidence of colonic stenosis, primarily caused by colon cancer and Crohn’s disease, is increasing each year. The development of safer stents for colonic stenosis is required because ...perforation associated with cancer stent placement worsens the prognosis and stent placement for anastomotic stenosis due to Crohn’s disease or colectomy is not first choice due to the high migration rate. The wall of the large intestine where the stent is inserted receives the complex forces from the peristaltic movement of the large intestine and stool in addition to the reaction tension of the stent, causing perforation and migration. Animal models may help develop new and safe stents, but no animal model closely reproduces the condition of human colonic stenosis. Herein, we present a novel animal model of colonic stenosis, which closely replicates the human colonic size.
Methods
The artificial colonic stenosis model was developed by wrapping the porcine colon with a silicone sheet after laparotomy. The usefulness of the model was evaluated by investigating the availability of endoscopic stent placement, morphological maintenance of colonic stenosis, adverse effects on pigs, and modeling time. The first three and the last three modeling times were analyzed using Student’s
t
-test.
Results
Endoscopic stent placement was performed in all cases without intraoperative complications. There were no postoperative model complications or deaths. Adhesions to the surrounding tissue in the abdominal cavity of the artificial colon stenosis were slight. The morphology of the isolated artificial stenoses was completely maintained, and no necrosis or perforation was observed.
Conclusions
We developed a novel and feasible animal model of colonic stenosis using pigs. We believe that this animal model will be useful for developing a safer stent for obstruction caused by benign diseases and colon cancer.
Background
The occurrence of bile duct injury (BDI) during laparoscopic cholecystectomy (LC) is an important medical issue. Expert surgeons prevent intraoperative BDI by identifying four landmarks. ...The present study aimed to develop a system that outlines these landmarks on endoscopic images in real time.
Methods
An intraoperative landmark indication system was constructed using YOLOv3, which is an algorithm for object detection based on deep learning. The training datasets comprised approximately 2000 endoscopic images of the region of Calot's triangle in the gallbladder neck obtained from 76 videos of LC. The YOLOv3 learning model with the training datasets was applied to 23 videos of LC that were not used in training, to evaluate the estimation accuracy of the system to identify four landmarks: the cystic duct, common bile duct, lower edge of the left medial liver segment, and Rouviere’s sulcus. Additionally, we constructed a prototype and used it in a verification experiment in an operation for a patient with cholelithiasis.
Results
The YOLOv3 learning model was quantitatively and subjectively evaluated in this study. The average precision values for each landmark were as follows: common bile duct: 0.320, cystic duct: 0.074, lower edge of the left medial liver segment: 0.314, and Rouviere’s sulcus: 0.101. The two expert surgeons involved in the annotation confirmed consensus regarding valid indications for each landmark in 22 of the 23 LC videos. In the verification experiment, the use of the intraoperative landmark indication system made the surgical team more aware of the landmarks.
Conclusions
Intraoperative landmark indication successfully identified four landmarks during LC, which may help to reduce the incidence of BDI, and thus, increase the safety of LC. The novel system proposed in the present study may prevent BDI during LC in clinical practice.
Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional ...fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC.
In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis.
Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided
= .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration.
DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.
Background
Robotic gastrectomy (RG) has increased since being covered by universal health insurance in 2018. However, to ensure patient safety the operating surgeon and facility must meet specific ...requirements. We aimed to determine whether RG has been safely implemented under the requirements for universal health insurance in Japan.
Methods
Data of consecutive patients with primary gastric cancer who underwent minimally invasive total or distal gastrectomy—performed by a surgeon certified by the Japan Society for Endoscopic Surgery (JSES) endoscopic surgical skill qualification system (ESSQS) between October 2018 and December 2019—were extracted from the gastrointestinal surgery section of the National Clinical Database (NCD). The primary outcome was morbidity over Clavien–Dindo classification grade IIIa. Patient demographics and hospital volume were matched between RG and laparoscopic gastrectomy (LG) using propensity score-matched analysis (PSM), and the short-term outcomes of RG and LG were compared.
Results
After PSM, 2671 patients who underwent RG and 2671 who underwent LG were retrieved (from a total of 9881), and the standardized difference of all the confounding factors reduced to 0.07 or less. Morbidity rates did not differ between the RG and LG patients (RG, 4.9% vs. LG, 3.9%;
p
= 0.084). No difference was observed in 30-day mortality (RG, 0.2% vs. LG, 0.1%;
p
= 0.754). The reoperation rate was greater following RG (RG, 2.2% vs. LG, 1.2%;
p
= 0.004); however, the duration of postoperative hospitalization was shorter (RG, 10 8–13 days vs. LG, 11 9–14 days;
p
< 0.001).
Conclusions
Insurance-covered RG has been safely implemented nationwide.
Background
Laparoscopic distal gastrectomy (LDG) is becoming the standard procedure for gastric cancer. However, supporting evidence thus far has been derived primarily from randomized control trials ...conducted by centers of excellence. In the present study we used the National Clinical Database (NCD) in Japan to prospectively accumulate data from diverse types of hospitals and examine whether LDG is a safe and valid standard procedure.
Methods
From the NCD, 169 institutions were selected to form a cohort that was considered to be representative of Japan. From August 2014 to July 2015, 5288 patients who underwent LDG were registered prospectively, and clinical data were acquired through the NCD. To compare surgical outcomes between open distal gastrectomy (ODG) and LDG, we adjusted for confounding factors using propensity score matching, ultimately retrieving data from 1067 patients in each group.
Results
There were no significant differences in the number of in-hospital deaths in the ODG and LDG groups (3/1067 vs. 6/1067;
P
= 0.51) or in the number of reoperations (20/1067 vs. 29/1067;
P
= 0.19). However, the length of hospital stay was significantly shorter in the LDG. Although wound infection and dehiscence were more common in the ODG group, LDG was more often associated with grade B or higher pancreatic fistulas.
Conclusion
The safety and minimal invasiveness of LDG were confirmed in the present Japanese nationwide survey. However, care must be taken to prevent the formation of pancreatic fistulas with LDG, and further improvements in surgical quality are warranted in this regard.
Background
The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC.
...Methods
A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses.
Results
There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14–1.26,
P
= 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18–0.93,
P
= 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20–0.74,
P
= 0.004).
Conclusion
Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.
The shortage and aging of surgeons in regional surgical care has been remarkable, and the importance of surgical education for young surgeons in the region is only increasing. However, there are very ...few reports about regional surgical education. This study aimed to clarify the current status and issues regarding surgical education in regional surgical care and to examine the ideal way to provide surgical education in the region.
Two questionnaire surveys were carried out. (1) "Survey on the awareness regarding the education of young surgeons" was conducted by mail in institutions where surgeons worked. (2) "Survey on the current status of surgical education for young surgeons" was conducted via the Internet with surgeons under 40 years old and mentors at the same facility.
There were 175 respondents to survey (1), among whom 131 (75%) surgeons were interested in educating young surgeons, and 112 (64%) were actively participating in this educating. Regarding the best evaluation methods for mentors who are educating young surgeons, the most frequent answer was "I don't know (51%)". The number of respondents in survey (2) was 87, including 27 (31%) young surgeons and 60 (69%) mentors. Although there was no difference between young surgeons and mentors in the level of satisfaction with the current status of young surgeons, 37% of young surgeons in urban areas were dissatisfied with their current status, compared to 0% in the regional area (p < 0.05).
Although surgeons did not have confidence in their own education, the level of satisfaction among young surgeons was high even in those providing regional surgical care. Development of an evaluation system for surgical education is necessary for young surgeons to receive more effective surgical education in the region.
Chemotherapy‐induced alopecia is one of the most difficult adverse events of cancer treatment for patients. However, it is still unknown why anticancer drugs cause hair loss. We aimed to clarify the ...mechanism of chemotherapy‐induced alopecia in mice using an in vivo imaging technique with a two‐photon microscope, which enables observation of the deep reaction in the living body in real time. In this study, ICR mice were injected intraperitoneally with cyclophosphamide (120 µg/g). Changes in the hair bulb morphology, subcutaneous vessel permeability, and vessel density were evaluated by two‐photon microscopy and conventional methods. In order to determine whether there is a causal relationship between vascular permeability and hair loss, we combined cyclophosphamide (50 µg/g) with subcutaneous histamine. We found that the hair bulbs became smaller, blood vessels around the hair follicle decreased in diameter, and vascular permeability was confirmed by two‐photon microscopy and conventional examination at 24 h after cyclophosphamide injection. Apoptosis occurred in vascular endothelial cells around the hair follicle. Additionally, hair loss was exacerbated by temporarily enhancing vascular permeability with histamine. In conclusion, cyclophosphamide caused a decrease in vascular density and an increase in vascular permeability, therefore increased vascular permeability might be one of the causes of chemotherapy‐induced alopecia.
Chemotherapy‐induced alopecia is one of the most difficult adverse events, but it is still unknown why anticancer drugs cause hair loss. By using an in vivo imaging technique with a two‐photon microscope, we revealed that an anticancer drug caused a decrease in vascular density and increase in vascular permeability.
Chemotherapy‐induced alopecia is frequently induced by various regimens of chemotherapy and has a significant impact on mental health and quality of life. However, the effect of available current ...treatment for chemotherapy‐induced alopecia is not sufficient. This study aimed to clarify the therapeutic effects and mechanism of skin cooling and the antioxidant α‐lipoic acid derivative on chemotherapy‐induced alopecia. We developed a chemotherapy‐induced alopecia model of cyclophosphamide (120 μg/g) using Institute of Cancer Research mice. We used cooling therapy and α‐lipoic acid derivative application as the treatments. We compared the alopecia score, hair bulb diameter, insulin‐like growth factor‐1 level, vascular permeability, and apoptosis between the control and treatment groups. The alopecia score significantly improved in each treatment group compared with that in the cyclophosphamide group. Hair bulb diameter significantly improved in the cyclophosphamide + cooling group compared with that in the cyclophosphamide group. The insulin‐like growth factor‐1 level and vascular permeability level was significantly retained and suppressed, respectively, in each treatment group compared with that in the cyclophosphamide group. The number of apoptotic cells in the vascular endothelium significantly decreased in the cyclophosphamide + α‐lipoic acid derivative group compared with that in the cyclophosphamide group. In conclusion, cooling therapy and α‐lipoic acid derivative facilitated recovery from chemotherapy‐induced alopecia caused by cyclophosphamide through decreasing vascular permeability.
Chemotherapy‐induced alopecia is frequently induced by various regimens of chemotherapy and has a significant impact on mental health and quality of life. In this study, we demonstrated that cooling therapy and a‐lipoic acid derivative facilitated recovery from chemotherapy‐induced alopecia caused by cyclophosphamide through decreasing vascular permeability.
Altered glycosylation associated with hepatocellular carcinoma (HCC) is well documented. However, few reports have investigated the association between dedifferentiation and glycosylation. Therefore, ...the aim of this study was to analyze glycosylation associated with dedifferentiation of HCC within the same nodule and to investigate glycosyltransferase related to the glycosylation.
We analyzed resected HCC specimens (n = 50) using lectin microarray to comprehensively and sensitively analyze glycan profiles, and identify changes to glycosylation between well- and moderately-differentiated components within the same nodule. Moreover, we performed immunohistochemical staining of mannosyl(α-1,3-)-glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1), which is an essential glycosyltransferase that converts high-mannose glycans to complex- or hybrid-type N-glycans.
Four lectins from Narcissus pseudonarcissus agglutinin (NPA), Concanavalin A, Galanthus nivalis agglutinin, and Calystegia sepium agglutinin were significantly elevated in moderately-differentiated components of HCC compared with well-differentiated components, and all lectins showed binding specificity to high-mannose glycans. Therefore, these structures were represented to a greater extent in moderately-differentiated components than in well-differentiated ones. Immunohistochemical staining revealed significantly increased NPA expression and decreased MGAT1 expression in moderately-differentiated components. Low MGAT1 expression in moderately-differentiated components of tumors was associated with intrahepatic metastasis and had tendency for poor prognosis.
Dedifferentiation of well-differentiated HCC is associated with an increase in high-mannose glycans. MGAT1 may play a role in the dedifferentiation of HCC.