Learning organo-transition metal catalyzed reactions by graph neural networks.

Chemical reaction outcome prediction presents a fundamental challenge in synthetic chemistry. Most existing machine learning (ML) approaches focus on chemical reactions of typical elements. We developed a simple ML model focused on organo-transition metal-catalyzed reactions (OMCRs). Instead of overall reactions observed in experiments, we let the ML model learn the sequence of simplified elementary reactions. This drastically reduced the complexity of the model and helped it find common patterns from distinct reactions. We let a graph neural network learn the reactivity index of a pair of atoms. The model was able to learn a wide variety of OMCRs, and the accuracy of reaction prediction reached 97%, even though the model has extremely fewer learnable parameters than other standards. The learned reactivity indices of bonds nicely summarize the knowledge of reactions in the dataset.

[A Case of Interstitial Pneumonia Induced by Immune Checkpoint Inhibitors for Gastric Cancer During the COVID- 19 Pandemic].

BACKGROUND: The novel coronavirus disease(corona virus disease 2019: COVID-19)has calmed down worldwide, and the severity of the disease is decreasing. On the other hand, due to the emergence of strain mutations, the number of infected people shows a wavy course. I have experienced a case of gastric cancer that underwent chemotherapy including an immune checkpoint inhibitors(ICI) early after COVID-19, so I will report it including a discussion. CASE: A 71-year-old man. The patient visited our hospital with a chief complaint of stomach discomfort, and gastrointestinal endoscopy revealed advanced gastric cancer accompanied by narrowing of the gastric lumen. The histopathological examination showed a poorly differentiated adenocarcinoma. A CT scan of the chest and abdomen showed thickening of the entire gastric wall, indicating the presence of enlarged adjacent lymph nodes and infiltration into adjacent organs. No other obvious distant metastases were observed. Staging laparoscopy was performed, it revealed infiltration of the posterior wall of the stomach into the celiac artery and anterior surface of the pancreas. We determined that curative resection would be difficult. As a result of planning chemotherapy for locally advanced gastric cancer, the patient contracted COVID-19 due to a hospital- acquired infection. The patient's COVID-19 infection was managed with supportive care alone without severe complications, and they recovered within the course of treatment. Two weeks after the onset of the infection, chemotherapy(FOLFOX+ Nivo)was initiated. The patient completed up to 9 courses of chemotherapy, and the treatment response was determined to be stable disease(SD). Due to a tendency of stenosis in the gastric lumen, the possibility of future dilation procedures was considered. As a result, the patient underwent second-line chemotherapy with a combination of wPTX+RAM. After completing 1 course of treatment, the patient developed drug-induced interstitial pneumonia, which was managed with intensive care and steroid pulse therapy, resulting in improvement. There was progression of gastric lumen stenosis, and an endoscopic dilation procedure/stent placement was performed. Subsequently, there was a rapid increase in malignant ascites and a decline in activities of daily living(ADL), leading to palliative care. Unfortunately, the patient succumbed to cancer-related complications 10 months after the diagnosis. DISCUSSION: In this case, the serial antibody titers of COVID-19 also indicated the sustained effectiveness of the multi-drug combination chemotherapy. The treatment course suggests a suspicion of drug-induced interstitial pneumonia due to PTX/RAM, but the long-term imaging follow-up implies that ICI may be the cause. When using ICI, COVID-19 infection alone may pose a potential risk factor.

[A Case of Long-Term Remission with Surgical Therapy and Chemoradiotherapy for a Rapidly Increasing Large Cell Neuroendocrine Carcinoma(LCNEC)].

BACKGROUND: Large cell neuroendocrine carcinoma(LCNEC)is a relatively rare disease classified as a subtype of neuroendocrine tumor. LCNEC has clinical and histological similarities to small cell lung cancer, both of which have a similarly poor prognosis. There are also unclear points regarding treatment. CASE: 43-years-old, male. He had repeated intermittent fever from 1 month before the consultation. Cough appeared 4 days before the consultation, and the family doctor pointed out an abnormal shadow in the right lung field, and the patient was referred. Blood test showed increased CRP 1.34 mg/dL and mild inflammatory response. Chest CT showed an increased tumor with a major axis of 16 cm in the right thoracic cavity compared to 6 months ago. FDG-PET showed accumulation of SUVmax 11.83 in the same area. A CT-guided needle biopsy was performed, and although tumor cell hyperplasia of like a plasma cells was suspected, but most of them were coagulative necrotic images and could not be diagnosed. After hospitalization, fever continued and the general condition became poor, so surgery was performed for the purpose of diagnostic treatment. Preoperatively, Interventional Radiology was used to embolize the tumor-feeding blood vessels. Intrathoracic tumor resection and partial upper and lower lobe resection were performed under thoracotomy. Postoperative histopathological examination revealed that large round to polyhedron tumor cells proliferated in sheet-like or intercellular binding sparsely, and synaptophysin was positive, which was a diagnosis of large cell neuroendocrine cell carcinoma. The general condition improved promptly after the operation, and the patient was discharged 14 days after the operation without any complications. After discharge, 4 courses of adjuvant chemotherapy (CDDP plus CPT-11)were performed. Six months after the operation, the disseminated nodule recurred in the right thoracic cavity. Chemotherapy(CBDCA plus PTX plus BEV)and radiation therapy were performed and the patient was in remission. It has been 5 years since the operation and has not recurred. SUMMARY: We report a case of rapidly increasing LCNEC with long-term remission by surgical treatment and chemoradiotherapy, with some review of the literature.

Adsorption Behavior of TEMPO-Based Organic Friction Modifiers during Sliding between Iron Oxide Surfaces: A Molecular Dynamics Study.

Organic friction modifiers (OFMs) added to lubricating oils to reduce friction and wear are crucial for reducing energy loss and CO2 emissions. In our previous studies, we have developed N-(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl)dodecaneamide, referred to as C12TEMPO, as a new type of OFM and experimentally demonstrated its superior performance to conventional OFMs of stearic acid and glycerol monooleate. However, the behavior of C12TEMPO adsorbing onto solid surfaces from base oil during sliding, which largely dictates the lubrication performance, is yet to be elucidated. Here, we performed molecular dynamics simulations for confined shear of a C12TEMPO solution in poly-α-olefin between hematite surfaces. Unlike conventional OFMs, which typically have one functional group or multiple functional groups of the same type, C12TEMPO features two functional groups of different types: one amide and one terminal free oxygen radical. The results showed that adsorbed boundary films with a double-layer structure form stably during sliding, owing to double- or single-site surface adsorption and interlayer hydrogen bonding via the two functional groups. Additionally, some molecules in each of the first and second layers also form intralayer hydrogen bonding. Such multitype adsorption is unique and favorable for enhancing the strength of boundary films to withstand heavily loaded and prolonged sliding. The velocity distribution indicates that the first and second layers are solid- and liquid-like, respectively. The second layer could act as a buffer for the first layer, which is the last barrier to prevent solid-solid contact, against shear. We also found that the second layer can act as a reservoir to rapidly repair the once depleted region in the first layer because of the interlayer hydrogen bonding. The combination of the high strength and self-repair ability of the C12TEMPO boundary films can rationally explain the experimentally observed properties of high load-carrying capacity, excellent antiwear effect, and high stability of friction over time.

[A Case of Preoperative Diagnosis of Intraductal Papillary Tumor with Good Course after Surgical Resection].

BACKGROUND: Intraductal papillary neoplasm of bile duct(IPNB)is a papillary tumor that develops in the bile duct inside and outside the liver, and is a relatively new disease concept recognized as a precancerous/early cancer lesion of bile duct cancer. CASE: A 74-year-old woman. A nearby doctor pointed out liver dysfunction in a medical examination, and he was introduced for the purpose of detailed examination. No subjective symptoms were observed. The blood sampling test showed no increase in tumor markers. Abdominal CT/MRI examination and abdominal echo examination showed multiple nodules from the origin of the left intrahepatic bile duct and intrahepatic bile duct dilation predominantly on the left side. No other findings indicating metastasis were found, including the PET-CT test. Endoscopic retrograde cholangiography revealed a poorly contrast-enhanced area in the B3 region, and intraluminal ultrasonography confirmed a mass that coincided with the poorly contrast-enhanced area and grew papillary. No tumor growth was observed in the other branches or common bile ducts, but all ducts were filled with suspended matter, which was thought to be mucus. Histopathological examination of the tumor biopsy revealed atypical epithelium with papillary structure and moderate nuclear atypia. A diagnosis of intraductal papillary tumor was made, and left hepatic lobectomy was performed. Postoperative histopathological examination revealed a complex papillary growth of highly dysplastic mucus-producing epithelium similar to the pancreatic duct/bile duct epithelium, and no obvious infiltrative growth. The postoperative course was uneventful, and the patient was discharged 16 days after the operation. Currently, 6 months after the operation, he is outpatient without recurrence. We report a case of intraductal papillary tumor that had a favorable course after surgical resection in the preoperative diagnosis, with some review of the literature.

[A Case of Lung Adenocarcinoma with Pulmonary Hypertrophic Osteoarthropathy].

BACKGROUND: Hypertrophic osteoarthropathy(HOA)is a syndrome that has three signs, the digital finger, periosteal neoplasia of the iliac bone, and arthritis. Among them, the secondary 1 associated with lung disease is called pulmonary hypertrophic osteoarthropathy(PHO). It is reported that many of the underlying diseases are associated with primary lung cancer, but in Japan, this is a rare condition with about 0.2 to 5.0%. CASE: A 68-year-old man. The patient was complaining of an arthralgia, and treated by the department of rheumatology. The thoracic CT scan for a screening pointed out a tumor in the right lower lobe, and referred to the department of surgery. Blood test showed CEA 21.8 ng/mL and LH 10.2 mIU/mL, FSH 23.1 mIU/mL. Chest CT showed a lung mass measuring 6.5×3.5 cm in the right lower lobe, and tracheobronchial lymph- node swelling. Bone scintigraphy showed abnormal accumulations in the long bones. We performed right lower lobectomy by thoracoscope. The pathological results were adenocarcinoma, G2, pT3, pN1, pm0, pl1, Ly1, V1, stage ⅢA. The arthralgia was relieved early after surgery. The patient recovered uneventfully and was discharged after the operation. Adjuvant chemotherapy was started, he was been well without recurrence.

QseC inhibition as an antivirulence approach for colitis-associated bacteria.

Hosts and their microbes have established a sophisticated communication system over many millennia. Within mammalian hosts, this dynamic cross-talk is essential for maintaining intestinal homeostasis. In a genetically susceptible host, dysbiosis of the gut microbiome and dysregulated immune responses are central to the development of inflammatory bowel disease (IBD). Previous surveys of stool from the T-bet-/-Rag2-/- IBD mouse model revealed microbial features that discriminate between health and disease states. Enterobacteriaceae expansion and increased gene abundances for benzoate degradation, two-component systems, and bacterial motility proteins pointed to the potential involvement of a catecholamine-mediated bacterial signaling axis in colitis pathogenesis. Enterobacteriaceae sense and respond to microbiota-generated signals and host-derived catecholamines through the two-component quorum-sensing Escherichia coli regulators B and C (QseBC) system. On signal detection, QseC activates a cascade to induce virulence gene expression. Although a single pathogen has not been identified as a causative agent in IBD, adherent-invasive Escherichia coli (AIEC) have been implicated. Flagellar expression is necessary for the IBD-associated AIEC strain LF82 to establish colonization. Thus, we hypothesized that qseC inactivation could reduce LF82's virulence, and found that an absence of qseC leads to down-regulated flagellar expression and motility in vitro and reduced colonization in vivo. We extend these findings on the potential of QseC-based IBD therapeutics to three preclinical IBD models, wherein we observe that QseC blockade can effectively modulate colitogenic microbiotas to reduce intestinal inflammation. Collectively, our data support a role for QseC-mediated bacterial signaling in IBD pathogenesis and indicate that QseC inhibition may be a useful microbiota-targeted approach for disease management.

[A Case of Gastrointestinal Stromal Tumor in the Rectum with Preservation of Anal Function after Neoadjuvant Chemotherapy UsingImatinib].

A n 81-year-old woman was admitted to our institution. Computed tomography performed before transcatheter aortic valve implantation(TAVI)for aortic stenosis revealed a tumor in the rectum. Lower endoscopy revealed that the tumor was a 60mm submucosal tumor and located 2 cm from the anal verge. Abiopsy revealed the diagnosis to be gastrointestinal stromal tumor(GIST). Although the tumor was located near the anal verge and might have invaded the surrounding organs, neoadjuvant chemotherapy(NAC) with 400mg/day of imatinib was initiated to preserve anal function as requested by the patient and her family. After 3 months, the tumor size decreased by 36.6% and there was a decrease in rate of tumor shrinkage. We performed transanal tumor resection and temporary colostomy. After 6 months, we performed colostomy closure, and the patient has remained recurrence-free and is continuing chemotherapy.

[A Case of Advanced Gastric Cancer with Liver Metastases Treated with Curative Conversion Therapy after S-1 plus Oxaliplatin].

An 81-year-old man was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 2 tumor in the antrum of the stomach. The histopathological findings showed a moderately differentiated HER2-negative adenocarcinoma. Two low-density areas of 17mm and 26mm in diameter were observed in the liver S6 and S8respectively at the CT scan. Nine courses of S-1 plus oxaliplatin(SOX)therapy were administered to this patient with gastric cancer and liver metastases. Since both the primary tumor and the liver metastases were significantly reduced by the chemotherapy, distal gastrectomy(D2 dissection)and partial liver resection(liver S6, S8)were performed. The histopathological findings revealed no tumor cells in the primary tumor, lymph nodes, and liver metastases, with a histologic effect of Grade 3. The patient underwent adjuvant therapy with S-1. He has been alive without recurrence for 11 months post-surgery.

[Two Cases of Advanced Gastric Cancer with Simultaneous Liver Metastasis with Long-Term Recurrence-Free Survival].

We report 2 cases of postoperative long-term survival of gastric cancer with synchronous liver metastasis. Case 1 was a 65- year-old man. Examination for anemia revealed advanced type 5 cancer in the antrum and suspected invasion of the transverse colon. A nodule 15mm in diameter suspected to be metastasis was also found in the liver S2. As no unresectable factors were present, partial hepatectomy, partial transverse colon resection, and distal gastrectomy were performed. Postoperatively, S-1 chemotherapy was administered for 14 months. Seven years after surgery, the patient is alive without recurrence. Case 2 was a 67-year-old woman. Examination for anemia revealed advanced type 2 cancer in the lower gastric body and a nodule 12mm in diameter suspected to be liver metastasis in the liver S8. Partial resection of the liver, total gastrectomy, cholecystectomy, and splenectomy were performed because no unresectable factors were observed. Postoperatively, chemotherapy with S-1 was administered for 38 months. Six years after surgery, she is alive without recurrence. Although there is no clear evidence for radical surgery for gastric cancer with simultaneous liver metastases, these results indicate that resection may be considered in cases with small numbers of metastases.

Impact of Primary Tumor Location on Postoperative Recurrence and Subsequent Prognosis in Nonmetastatic Colon Cancers: A Multicenter Retrospective Study Using a Propensity Score Analysis.

OBJECTIVE: We aimed to clarify the prognostic impact of primary tumor location on recurrence after curative surgery and subsequent survival in patients with nonmetastatic colon cancer. SUMMARY OF BACKGROUND DATA: Right and left colon cancers are suggested to be oncologically different; however, their prognostic differences have been conflictingly reported. METHODS: A total of 5664 patients with curatively resected stage II-III colon cancer were reviewed, retrospectively. Relapse-free survival (RFS) after primary surgery and cancer-specific survival (CSS) after recurrence were compared between patients with right and left colon cancer. Patients' backgrounds were matched using propensity scores. RESULTS: Although patients with right colon cancer had more advanced disease, their 5-year RFS rate was significantly superior compared with that in those with left colon cancer (83.9% vs 81.1%, P = 0.019). However, the 5-year CSS after recurrence rate was significantly inferior in patients with right colon cancer compared with that in those with left colon cancer (30.6% vs 43.6%, P = 0.016). CONCLUSIONS: The primary tumor location of nonmetastatic colon cancer might have different prognostic implications for the rates of recurrence after curative resection and cancer-specific mortality after recurrence.

Successful Management of a Positive Air Leak Test during Laparoscopic Colorectal Surgery.

BACKGROUND/AIMS: Anastomotic leakage remains the most serious complications of colorectal surgery. To prevent colorectal anastomotic leakage (CAL), an air leak test (ALT) with intraoperative colonoscopy (IOCS) is performed to detect mechanically insufficient colorectal anastomoses. The approaches to an intraoperative anastomotic air leak (IOAL) have not been fully investigated. This study aimed to clarify the safe management of an IOAL in laparoscopic colorectal surgery. METHODS: One hundred forty-eight consecutive patients who underwent laparoscopic resection with double-stapling technique (DST) anastomosis for left-sided colorectal cancer between April 2015 and June 2016 were included and retrospectively reviewed. RESULTS: Intraoperative anastomotic ALT yielded positive results in 7 patients. In all 7 patients, reanastomoses were performed, and diverting stomas were constructed to protect the anastomosis in 2 patients whose reanastomosis sites were close to the anus. Three of the revised DST anastomoses showed air leakage on the repeat ALT; these sites underwent suturing repair and were confirmed to be airtight. None of the patients with a positive intraoperative ALT had postoperative CAL. The overall CAL rate was 1.4%. CONCLUSIONS: Combination management using DST revision, direct suturing repair, and a diverting stoma is recommended for intraoperative repair of anastomotic defects detected by IOCS.

Different Impacts of Preoperative Radiotherapy and Chemoradiotherapy on Oncological Outcomes in Patients with Stages II and III Lower Rectal Cancer: A Propensity Score Analysis.

BACKGROUND/AIMS: The neoadjuvant therapy for locally advanced rectal cancer has been changed from radiotherapy (RT) to chemoradiotherapy (CRT). This study is aimed at evaluating the benefit of CRT in patients with stage II or III lower rectal cancer, with regard to the impact on recurrence. METHODS: A total of 474 patients with clinical stage II or III lower rectal cancer who received either preoperative RT (n = 221) or CRT (n = 253) followed by total mesorectal excision were identified from our institutional database. Propensity score analysis was performed to mitigate selection biases. RESULTS: Among stage II patients, the CRT group showed a significantly lower 5-year local recurrence rate than the RT group (3.0 vs. 14.8%, p = 0.002). In contrast, among stage III patients, the CRT group showed a significantly lower 5-year distant recurrence rate than the RT group (27.8 vs. 42.6%, p = 0.04) and also a better 5-year recurrence-free survival (64.2 vs. 48.3%, p = 0.03). CONCLUSIONS: Addition of concurrent chemotherapy to preoperative RT significantly enhanced the local control in stage II patients and decreased distant recurrence in stage III patients. The oncological benefit of CRT may differ between patients with stage II or III rectal cancer.

Results of a 36-year surveillance program for ulcerative colitis-associated neoplasia in the Japanese population.

BACKGROUND AND AIM: Surveillance colonoscopy has been carried out for patients with long-standing ulcerative colitis who have an increased risk for colorectal cancer. The aim of the present study was to determine the incidence of and the risk factors for neoplasia. METHODS: We evaluated 289 ulcerative colitis patients who underwent surveillance colonoscopy between January1979 and December 2014. Cumulative incidence of neoplasia and its risk factors were investigated. Clinical stage and overall survival were compared between the surveillance and non-surveillance groups. RESULTS: Cumulative risk of dysplasia was 3.3%, 12.1%, 21.8%, and 29.1% at 10, 20, 30 and 40 years after the onset of ulcerative colitis, respectively. Cumulative risk of colorectal cancer was 0.7%, 3.2%, 5.2%, and 5.2% at 10, 20, 30 and 40 years from the onset of ulcerative colitis, respectively. Total colitis was a risk factor for neoplasia (P = 0.015; hazard ratio, 2.96). CONCLUSIONS: Our surveillance colonoscopy program revealed the incidence and risk factors of ulcerative colitis-associated neoplasias in the Japanese population. Total colitis is a risk factor for neoplasia.

Survival and Prognostic Factors for Metachronous Peritoneal Metastasis in Patients with Colon Cancer.

BACKGROUND: The clinical course of metachronous peritoneal metastasis of colorectal origin is poorly understood. In this retrospective study, we aimed to elucidate survival and prognostic factors for metachronous peritoneal metastasis. METHODS: Patients with metachronous peritoneal metastasis after curative resection for stage I-III colon cancer were retrospectively reviewed, and the incidence and prognosis of metachronous peritoneal metastasis were investigated. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: Among 1582 surgically resected stage I-III colon cancer patients, 65 developed metachronous peritoneal metastasis. The 5-year cumulative incidence rate was 4.5%, and the median survival after diagnosis of peritoneal metastasis was 29.6 months. None of the patients underwent peritonectomy or intraperitoneal chemotherapy. Independent prognostic factors included right colon cancer [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.26-5.64; p = 0.011], time to metachronous peritoneal metastasis of <1 year (HR 2.02, 95% CI 1.04-3.87; p = 0.040), Peritoneal Cancer Index (PCI) >10 (HR 3.68, 95% CI 1.37-8.99; p = 0.012), concurrent metastases (HR 4.09, 95% CI 2.02-8.23; p < 0.001), and peritoneal nodule resection (HR 0.31, 95% CI 0.13-0.65; p = 0.002). CONCLUSIONS: A proportion of colon cancer patients with metachronous peritoneal metastasis may benefit from combined peritoneal nodule resection and systemic chemotherapy. Right colon cancer, early peritoneal metastasis, a high PCI, and concurrent metastases negatively affected prognosis in patients with metachronous peritoneal metastasis.

Characterization of Conversion Chemotherapy for Secondary Surgical Resection in Colorectal Cancer Patients with Lung Metastases.

OBJECTIVE: Clinical trials demonstrated that 6-37% of the patients with colorectal liver-limited metastases underwent surgical resection after first-line chemotherapy. However, limited information is available on the conversion of colorectal cancer patients with lung metastases to resection by systemic chemotherapy. METHODS: We retrospectively investigated 156 patients with unresectable colorectal cancer who received oxaliplatin- or irinotecan-based first-line systemic chemotherapy with or without antibodies in our department between January 2007 and December 2015. The conversion rate to surgery and chemotherapeutic regimens and periods were analyzed with respect to the target organ. RESULTS: In addition to 4 patients who achieved complete response, 73 exhibited tumor shrinkage of any extent. Twenty patients underwent secondary surgery, all of whom received targeting antibodies. In 75 patients with liver metastases, 18 (24%) were converted to resection after chemotherapy for a median of 110 days. In contrast, 4 (7%) out of 56 patients with lung metastases underwent resection after chemotherapy for a median of 449 days. Conversion was an independent prognostic factor in patients with lung metastases. CONCLUSION: The conversion rate to resection was lower for colorectal cancer patients with lung metastasis by systemic chemotherapy, which required a longer duration than for those with liver metastases.

Prognostic Value of Pre- and Postoperative Anti-p53 Antibody Levels in Colorectal Cancer Patients: A Retrospective Study.

OBJECTIVE: To determine the utility of the post-/preoperative anti-p53 antibody (p53 Ab) ratio as a prognostic factor for colorectal cancer (CRC) recurrence. METHODS: A total of 737 nonmetastatic CRC patients who had undergone R0 resection were retrospectively analyzed. p53 Ab levels were measured within 1 month prior to and at least every 3 months after surgery. Post-/preoperative p53 Ab ratios were calculated, and the optimal ratio cutoff values for predicting recurrence were determined using the Kaplan-Meier method and the log-rank test. RESULTS: Preoperative p53 Ab elevation was observed in 194 patients (pre-p53 high). Preoperative p53 Ab levels correlated with TNM stage. Re-elevation of p53 Ab levels occurred on recurrence in the pre-p53 high group, but not in the pre-p53 low group (n = 543). In the pre-p53 high group, patients who experienced tumor recurrence exhibited a slow postoperative reduction of p53 Ab levels, and a post-/preoperative p53 Ab ratio >0.4 at postoperative 3 months predicted relapse-free survival. In other words, a p53 Ab level remaining higher than 40% of the preoperative level was an independent and strong risk factor for recurrence in multivariate analyses. CONCLUSION: In CRC patients with preoperative p53 Ab elevation, the rate of p53 Ab reduction in the early postsurgical period is a promising prognostic factor for recurrence.

A high preoperative carbohydrate antigen 19-9 level is a risk factor for recurrence in stage II colorectal cancer.

BACKGROUND: Many risk factors for recurrence in stage II colorectal cancer (CRC) have been proposed, and the efficacy of adjuvant chemotherapy is still controversial. This study aimed to identify risk factors for tumor recurrence and assess whether they are related to the benefits of adjuvant chemotherapy in stage II CRC. MATERIAL AND METHODS: Patients with stage II CRC that was curatively operated on in a tertiary hospital between 2005 and 2014 were analyzed. Cox's proportional hazards models were applied to identify risk factors for recurrence and overall mortality. Kaplan-Meier methods were used to evaluate whether adjuvant chemotherapy was beneficial in terms of recurrence-free survival (RFS). RESULTS: A total of 384 patients were identified, among whom 38 (10%) received adjuvant chemotherapy. In a median follow-up of 48.6 months, 52 patients (14%) developed recurrence. Multivariate analyses identified two independent parameters that significantly decreased RFS; pathological T4 [hazard ratio (HR), 2.34; 95% confidence interval (CI), 1.31-4.15; p = .0045) and preoperative carbohydrate antigen (CA) 19-9 > 37 U/ml (HR 1.96; 95% CI 1.02-3.58; p = .045). These factors also inversely correlated with overall survival; T4: HR 2.10, p = .019) and CA 19-9 > 37 U/ml (HR 2.15, p = .025). The combination of T4 and CA 19-9 > 37 U/ml resulted in an increased HR (3.52) for recurrence. However, adjuvant chemotherapy did not improve RFS in patients with these features. CONCLUSION: The present study demonstrated elevated CA 19-9 levels as well as T4 independently predicted worse long-term outcomes in patients with stage II CRC. However, the characterization of patients who gain survival advantages by adjuvant chemotherapy requires further investigation.

Adiponectin and colorectal cancer.

Colorectal cancer is an obesity-related malignancy. Adiponectin is an adipokine produced exclusively by adipose tissue, and its concentration in the serum is reduced in obesity. A low serum level of adiponectin is associated with an increased risk of various types of malignancies including colorectal cancer. These facts suggest that the epidemiological link between obesity and cancer may have a significant association with adiponectin. Although numerous studies of colorectal cancer have been reported, the results are conflicting about the anti-cancer effect of adiponectin, and how adiponectin affects carcinogenesis or cancer development remains controversial. Because adiponectin has multiple systemic effects and exists as a high serum concentration protein, the main role of adiponectin should be regulation of homeostasis, and it would not likely act as an anti-cancerous hormone. However, as epidemiological evidence shows, a low adiponectin level may be a basic risk factor for colorectal cancer. We speculate that when the colonic epithelium is stimulated or damaged by another carcinogen under the condition of a low adiponectin level, carcinogenesis is promoted and cancer development is facilitated. In this report, we summarize recent findings of the correlation between adiponectin and colorectal cancer and investigate the effect of adiponectin on colorectal cancer.

Laparoscopic versus open surgery for obese patients with rectal cancer: a retrospective cohort study.

PURPOSE: To evaluate the advantages of laparoscopic surgery for rectal cancer in obese patients. METHODS: We collected clinical data from consecutive patients who underwent anterior resection for rectal cancer between 2008 and 2015 to compare the surgical outcomes of a laparoscopic surgery group (LG) with those of an open surgery group (OG) stratified by obesity. Obesity was defined as a body mass index ≥25. RESULTS: A total of 268 patients were analyzed, with 157 in the LG (44 obese and 113 non-obese) and 111 in the OG (25 obese and 86 non-obese). The rates of complications between the LG and the OG were 18.5 vs. 11.6 % (p = 0.18) for the non-obese patients and 18.2 vs. 20.0 % (p = 1.0) for the obese patients, respectively, without a significant difference. Operative time was longer in the LG than in the OG, but the difference between the non-obese and obese patients was not significant, being 266 vs. 189 min (p < 0.0001) and 260 vs. 254 min (p = 0.96), respectively. Blood loss was much lower in the LG for both obese and non-obese patients, being 10 vs. 435 mL (p < 0.0001) and 10 vs. 275 mL (p < 0.0001), respectively. CONCLUSION: There were no significant differences between LG and OG in operative time or complications for obese patients with rectal cancer, and blood loss was much lower in the LG. Thus, laparoscopic surgery is a safe and minimally invasive approach for obese patients with rectal cancer.