Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2. Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

Knowledge-Embedded Message-Passing Neural Networks: Improving Molecular Property Prediction with Human Knowledge.

The graph neural network (GNN) has become a promising method to predict molecular properties with end-to-end supervision, as it can learn molecular features directly from chemical graphs in a black-box manner. However, to achieve high prediction accuracy, it is essential to supervise a huge amount of property data, which is often accompanied by a high property experiment cost. Prior to the deep learning method, descriptor-based quantitative structure-property relationships (QSPR) studies have investigated physical and chemical knowledge to manually design descriptors for effectively predicting properties. In this study, we extend a message-passing neural network (MPNN) to include a novel MPNN architecture called the knowledge-embedded MPNN (KEMPNN) that can be supervised together with nonquantitative knowledge annotations by human experts on a chemical graph that contains information on the important substructure of a molecule and its effect on the target property (e.g., positive or negative effect). We evaluated the performance of the KEMPNN in a small training data setting using a physical chemistry dataset in MoleculeNet (ESOL, FreeSolv, Lipophilicity) and a polymer property (glass-transition temperature) dataset with virtual knowledge annotations. The results demonstrate that the KEMPNN with knowledge supervision can improve the prediction accuracy obtained from the MPNN. The results also demonstrate that the accuracy of the KEMPNN is better than or comparable to those of descriptor-based methods even in the case of small training data.

[A Case of Laparoscopic Hartmann's Procedure for Rectal Cancer with Inferior Mesenteric Vein-Left Ovarian Vein Shunt].

A 77-year-old woman presented with a chief complaint of bloody stools. Detailed examination revealed a semi-circumferential type 2 tumor in the lower rectum, and a diagnosis of Group 5, tub1-2, cT3N2aM0, cStage Ⅲb rectal cancer was made. Preoperative abdominal CT scans revealed a shunt in the inferior mesenteric vein and left ovarian vein. Laparoscopic Hartmann's procedure was performed, and when the sigmoid mesentery was moved from the inner side, a shunt flowing from the left ovarian vein to the inferior mesenteric vein in the sigmoid mesentery was found, which was then dissected. The operating time was 253 min, and blood loss was approximately 140 g. There was no postoperative liver dysfunction, and the patient was transferred to another hospital on postoperative day 36. Causes of portal-systemic shunts are portal hypertension occurring due to liver cirrhosis or congenital causes and organ adhesion from abdominal surgery. In this case, there was no liver cirrhosis, and the blockage of the left renal vein perfusion by the superior mesenteric artery may have resulted in congestion and varicose of the left ovarian vein. Furthermore, the shunt with the inferior mesenteric vein may have been formed due to the adhesion of the left ovarian vein after ovariectomy. If preoperative tests reveal varices, a surgical treatment is recommended while keeping in mind the possibility of shunt formation as in this case.

[A Case of Pancreatotomy of the Pancreatic Tail with a Preserved Residual Stomach Using ICG Fluorescence Method for Pancreatic Cancer after Gastrectomy of the Pyloric Side].

A 53-year-old male had a history of gastrectomy of the pyloric side for gastric cancer and Billroth Ⅰ reconstruction done 20 years ago. The patient visited the gastrointestinal internal medical department of our hospital with abdominal pain as the chief complaint. Pancreatic cancer was diagnosed with the help of an abdominal CT, and he was then referred to our department. The preoperative disease stage was cT3, N0, M0, Stage ⅡA. As it was over 20 years since the previous surgery and the preoperative CT showed cardiac branches of the left inferior phrenic artery, we inferred that the residual stomach can be preserved. The blood flow was confirmed by the intraoperative ICG fluorescence method, and we then performed pancreatotomy of the pancreatic tail, preserving the stomach and a splenectomy. The pathologic findings were invasive ductal carcinoma, pT3, N1a, M0, Stage ⅡB, and R0. S-1 was administered orally as postoperative adjunctive chemotherapy. The postoperative course has been favorable without recurrence for 2 years. In case a pancreatotomy of the pancreatic tail is performed for cancer of the pancreatic body after gastrectomy of the pyloric side, it was considered that the intraoperative ICG fluorescence method was useful to confirm the blood flow of the residual stomach.

[Laparoscopic Gastrectomy for Early Gastric Cancer in a Patient with an Adachi Type â ¥ Arterial Variant-A Case Study].

We report successfull aparoscopic distalgastrectomy in a patient with early gastric cancer and an Adachi type Ⅵ arterial variant. The case is a male in his 50's who was detected a type 0-Ⅱc lesion on the antrum of the stomach and diagnosed as tub2. Laparoscopic distalgastrectomy was performed, with the pathologic diagnosis of cT1bN0M0, cStage Ⅰ. MD-CT showed absence of the common hepatic artery ventralto the portalvein, consistent with an Adachi type Ⅵ arterialvariant. The interface between pancreatic and fatty tissue was separated in suprapancreatic dissection, and was extended between the hepatoduodenal ligament and splenic artery, with exposure of the surface of the portal vein. Thus, safe dissection of No. 8a area was achieved. Discussion: Adachi classified the celiac artery branches into 6 types and 28 groups. Type Ⅵ, a variant of the common hepatic artery located on the dorsalaspect of the portalvein, has a reported frequency of 2%. Because it is a variant of the hepatic artery, a landmark of suprapancreatic dissection, careful observation is required to determine the anatomy. Although tactile sensation is limited in laparoscopic surgery, arterial pulsation is clearly visible. To ensure a safe procedure, it is important to identify vesselanatomy both pre- and intraoperatively.

[Metachronous Gastric Intramural Metastasis following Esophageal Cancer ESD-A Case Study].

We report a case of metachronous gastric intramural metastasis following esophageal cancer endoscopic submucosal dissection( ESD). The patient was an 80s man who was referred to the department of gastroenterology of our hospital for earlystage esophageal cancer by a local physician. ESD was performed for a lesion(Lt, 0-Ⅱa+Ⅱc, cT1N0M0, StageⅠ)located 35- 38 cm from the incisors. Pathologic diagnosis revealed that the lesion was a 2.5×2.0 cm-sized, pSM2, 506 mm, well-differentiated squamous cell carcinoma, ly+, v-, pHM0, pVM0. The patient was indicated for additional treatment, but because the patient requested not to undergo operative treatment, radiation therapy, or chemotherapy, strict follow-upwas performed. Upper endoscopy performed 1 year after ESD revealed the presence of a submucosal tumor(diameter of 5 cm)accompanied by ulceration in the gastric cardia, and biopsy findings led to the diagnosis of squamous cell carcinoma. The patient was referred to our department for operative treatment, and considering the possibility of primary squamous cell carcinoma of the stomach, we performed total gastrectomy(D2 dissection, Roux-en-Y)and cholecystectomy. The pathologic diagnosis was well-differentiated squamous cell carcinoma, ly1, v0, SE, N1. Because esophageal cancer and the tissue type were consistent and the primary locus of the tumor was the submucosal layer, the patient was diagnosed with esophageal cancer with gastric intramural metastasis. We report a rare case of metachronous gastric intramural metastasis of esophageal cancer along with a review of the literature.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

[A Case of Laparoscopic Resection for Locally Advanced Primary Rectal Cancer after Neoadjuvant Chemotherapy].

We treateda 70-year-oldfemale patient with locally advancedrectal cancer accompaniedby metastases to other organs. Three courses of S-1 plus oxaliplatin(SOX)therapy were administered as neoadjuvant chemotherapy(NAC), andthe cancer was subsequently treatedwith laparoscopic rectal resection. She hadvisiteda physician with a chief complaint of melena. A type 2 tumor located in the rectum Rb was found during the lower gastrointestinal endoscopy, which was diagnosed as an adenocarcinoma by biopsy. Vaginal invasion andlymph node metastasis were observedon CT andMRI. After 3 courses of SOX therapy(NAC), her condition was categorized as SD. Laparoscopic rectal amputation(D3)combinedwith resection of the ovary, uterus, and vagina was performed. On histopathological examination, the tumor was an adenocarcinoma, muc> tub2, ypT4b(AI, vaginal wall), int, INF b, ly1, v2, EX(-), PN1a, grade 1, pPM0, pDM0, pRM0 and pStage Ⅲa. The histological analysis demonstrated that the therapeutic effect of chemotherapy was grade 1a. Laparoscopic surgery, which is a relatively safe procedure, may be useful after NAC for an R0 resection.

[A Case of Neuroendocrine Carcinoma of the Esophagus Treated with Neoadjuvant Chemotherapy Comprising 5-Fluorouracil plus Cisplatin].

Esophageal neuroendocrine carcinoma is relatively rare and the prognosis is poor owing to its aggressive malignancy. We experienced a case of neuroendocrine carcinoma of the esophagus treated with neoadjuvant chemotherapy of 5-fluorouracil plus cisplatin. A 71-year-old man was diagnosed with esophageal carcinoma(clinical T3N1M0, Stage III ). He received neoadjuvant chemotherapy comprising 5-fluorouracil plus cisplatin, followed by subtotal esophagectomy with dissection of 3 regional lymph nodes. Immunohistochemical findings were synaptophysin-positive, CD56-positive, Ki-67(labeling index) B90%. The final diagnosis was neuroendocrine carcinoma, categorized as CT-pT1a-MM, pN0, Stage 0. The pathological response to neoadjuvant chemotherapy was Grade 2. The patient is alive 8 months after esophagectomy without metastasis.

[Laparoscopic Lateral Lymph Node Dissection for Rectal Cancer with Lateral Lymph Node Metastasis - A Case Report].

BACKGROUND: Lateral lymph node dissection(LLND)for locally advanced lower rectal cancer is the standard treatment procedure in Japan. We performed LLND with an extraperitoneal approach. Recently, we introduced laparoscopic surgery for locally advanced rectal cancer and laparoscopic LLND. We performed laparoscopic LLND in a patient havinglower rectal cancer with lateral lymph node metastasis that was detected via preoperative imaging. CASE PRESENTATION: The patient was a woman in her 50s who experienced melena and visited a physician. Colonoscopy revealed a tumor in the lower rectum and computed tomography showed lateral lymph node swelling and liver metastasis. The patient was referred to our institution and she was diagnosed with lower rectal cancer having lateral lymph node and synchronous liver metastases. We performed laparoscopic abdominoperineal resection and laparoscopic LLND. The operatingtime was 260 min, and the blood loss was 60g. CONCLUSION: The magnification of laparoscopy enables precision in the surgical operation of the narrow pelvis during lymph node dissection, allowingautonomic nerve preservation. Therefore, laparoscopic LLND is a helpful procedure in the treatment of locally advanced rectal cancer with a lateral lymph node metastasis.

Risk Factors for Anastomotic Leakage After Intersphincteric Resection Without a Protective Defunctioning Stoma for Lower Rectal Cancer.

BACKGROUND: Intersphincteric resection (ISR) is performed as an alternative to abdominoperineal resection for super-low rectal cancer. The purpose of this study was to evaluate risk factors for anastomotic leakage (AL) after ISR without a defunctioning stoma for lower rectal cancer. METHODS: Between 1995 and 2012, 135 consecutive patients with lower rectal cancer underwent curative ISR without a protective defunctioning stoma. Univariate and multivariate analyses were performed to determine the risk factors for AL. RESULTS: The radiological and symptomatic AL rate was 17.0 % (23/135). Univariate analysis demonstrated that male sex (P = 0.030), preoperative chemotherapy (P = 0.016), partial ISR (P < 0.001), lateral lymph-node dissection (P = 0.042), distal tumor distance from the dentate line (P = 0.007), and straight reconstruction (P < 0.001) were significantly associated with AL. Severe AL requiring re-laparotomy developed in 13 (9.6 %) patients. Univariate analysis demonstrated that male sex (P = 0.006), partial ISR (P < 0.001), distal tumor distance from the dentate line (P = 0.002), and straight reconstruction (P < 0.001) were significantly associated with AL requiring relaparotomy. Multivariate analysis demonstrated that partial ISR [odds ratio (OR) 6.701; P = 0.001] and straight reconstruction (OR 5.552; P = 0.002) were independently predictive of AL. CONCLUSIONS: Partial ISR and straight reconstruction increased the risk of AL after ISR without a protective defunctioning stoma. A defunctioning stoma might be mandatory in patients with the risk factors identified in this analysis.

[Surgical treatment outcomes of multimodality therapy for locally recurrent rectal cancer].

The aim of this study was to clarify the status of multimodality therapy for locally recurrent rectal cancer. Between 2000 and 2012, 27 patients with locally recurrent rectal cancer underwent surgical resection. We examined 18 patients treated with preoperative chemo-radiotherapy (CRT group) and 9 patients treated with surgery alone (surgical group). The rate of R0 - resection was 89% in the CRT group and 78% in the surgical group. The mean operative durations for the CRT and surgical groups were 323 min and 289 min, respectively. The mean amount of bleeding was 1,462 g for the CRT group and 2,846 g for the surgical group. There was no significant difference in the rate of postoperative complications between both groups (CRT group: 78%, surgical group: 78%). Regarding local recurrences, the recurrence rate of the CRT group was 28%, whereas that of the surgical group was 67%. The 3-year and 5-year overall survival rates of the CRT group were 71%and 44%, respectively, whereas those of the surgical group were 58% and 22%, respectively. These results showed that CRT treatment was associated with an improvement in prognosis. Preoperative CRT and surgical resection should be the standard treatment for patients with local recurrence.

[A review of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer].

We retrospectively analyzed the efficacy of stereotactic radiotherapy (SRT) for lung metastasis of colon cancer, with particular emphasis on local tumor control. Seven patients with 8 lesions underwent SRT for lung metastasis of colon cancer in our institution between February 2012 and February 2014. We judged the curative effect of SRT on the basis of tumor shrinkage observed on computed tomography (CT) scans. All lung metastases decreased in size, and local recurrence was not observed. SRT is a technique involving three-dimensional radiation, which decreases radiation exposure to neighboring normal tissues. The 2-year local tumor control rate for lung metastasis of colon cancer with SRT is 77.9%, and the 2-year survival rate is 53.7%. Our results, in which all patients achieved local control, suggest that SRT is a minimally aggressive treatment option for lung metastasis of colon cancer in cases where a pneumonectomy is difficult to perform. In the future, results from long-term studies are needed to validate our findings.

Association between concentration of trace elements in serum and bronchial asthma among Japanese general population.

BACKGROUND AND AIMS: A number of previous studies had revealed the association between trace elements in serum and bronchial asthma. However, only a few researches had focused on serum concentration of trace elements in a general population. In this study, an association between trace elements in serum and bronchial asthma was investigated in a general population. METHODS: Subjects were 1025 volunteers (385 males and 640 females between ages 19 and 82 years old) who had participated in the Iwaki Health Promotion Project 2005. Bronchial asthma was diagnosed based on the European Community Respiratory Health Survey II according to the self-questionnaires on health conditions of subjects. The serum concentrations of certain trace elements (manganese, copper, zinc, selenium and iron) were measured and compared. Also, an association between serum trace elements level and neutrophil-related functions (oxidative burst activity, phagocytic activity, serum opsonic activity) were determined. RESULTS: In males, no significant differences were seen in any serum trace elements concentrations. In females, serum zinc level was significantly higher in bronchial asthma group than in control. A positive correlation was seen between serum concentration of zinc and serum opsonic activity in both genders. CONCLUSIONS: In female asthmatics, increase of oxidative stress was suggested to be caused by superoxide dismutase pathway (elimination system of reactive oxygen species) rather than serum opsonic activity (production system of reactive oxygen species from neutrophils) pathway, as the zinc concentration in bronchial asthma group was higher than that in control.

[Predictive factors for histopathological liver injury in the patients who received preoperative systemic chemotherapy for colorectal liver metastases].

The operation for liver metastases from colorectal cancer is increasing due to a progress of chemotherapy. On the other hand, the live damage induced by chemotherapy affects on post operative course. We studied histopathological liver injury on the patients who received preoperative chemotherapy. Between January 2004 and May 2009, forty seven patients underwent hepatectomy for colorectal liver metastases after systemic chemotherapy, and the remnant liver was histopathologically investigated about sinusoidal dilatation and non-alcoholic steatohepatitis. As a result, chemotherapy including irinotecan or oxaliplatin was significantly associated with sinusoidal dilatation, and female gender or higher body mass index was correlated with non-alcoholic steatohepatitis. These results should be taken into consideration before liver resection in patients who have received preoperative chemotherapy.