The probability of double-strand breaks in giant DNA decreases markedly as the DNA concentration increases

DNA double-strand breaks (DSBs) represent a serious source of damage for all living things and thus there have been many quantitative studies of DSBs both in vivo and in vitro. Despite this fact, the processes that lead to their production have not yet been clearly understood, and there is no established theory that can account for the statistics of their production, in particular, the number of DSBs per base pair per unit Gy, here denoted by P1, which is the most important parameter for evaluating the degree of risk posed by DSBs. Here, using the single-molecule observation method with giant DNA molecules (166 kbp), we evaluate the number of DSBs caused by gamma-ray irradiation. We find that P1 is nearly inversely proportional to the DNA concentration above a certain threshold DNA concentration. A simple model that accounts for the marked decrease of P1 shows that it is necessary to consider the characteristics of giant DNA molecules as semiflexible polymers to interpret the intrinsic mechanism of DSBs

Sidedness of CRC on tumor immunity

Background Clinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity. Methods A total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined. Results Clinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS. Conclusions The prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients

Desmoid-type fibromatosis in abdomen

Background : Desmoid-type fibromatosis is a very rare disease that has no characteristic image findings, so it is often difficult to differentiate from gastrointestinal stromal tumor (GIST). A case of desmoid-type fibromatosis that was difficult to differentiate from GIST is reported. The decisive factor in the diagnosis was positive nuclear immunostaining for β-catenin nucleus. Case presentation : A man is his 30s had no significant past medical history, including no abdominal surgery. A medical check-up found a large tumor in the right lateral abdomen. After some examinations, a preoperative diagnosis of GIST was made, and open ileocecal resection was performed. However, the final diagnosis based on the pathological findings was desmoid-type fibromatosis. Conclusions : We should consider desmoid-type fibromatosis when we find a large abdominal mass, but it may be difficult to diagnose based only on imaging findings. Immunohistochemical examination of the specimen may make the diagnosis

TAPP with liquid-injection and gauze dissection

Purpose : This report describes a novel technique for trans-abdominal pre-peritoneal (TAPP) inguinal hernia repair using liquid injection and gauze dissection. Methods : Twenty-five cases underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection. Before the initial peritoneal incision, liquid injection was performed percutaneously into the pre-peritoneal space at the outside of the internal inguinal ring and the inside of the seminal duct. Especially, at the inside of the seminal duct, the liquid was injected into the space between the superficial and deep lobe of pre-peritoneal fascia. Gauze was effectively used to dissect this liquid-injected space. Results : In comparison with the cases of inguinal hernia repair without liquid-injection and gauze dissection, the cases who underwent TAPP inguinal hernia repair with liquid-injection and gauze dissection experienced shorter operation times and no complications or recurrence. Conclusions : TAPP inguinal hernia repair with liquid-injection and gauze dissection appears to be a safe and feasible procedure

Pre-operative weight loss program

Background : The aim of this study was to investigate the influence of obesity and the usefulness of a pre-operative weight loss program (PWLP) for obese patients undergoing laparoscopic gastrectomy (LG) for gastric cancer (GC). Materials and Methods : Study1 : 219 patients who underwent laparoscopic distal gastrectomy (LDG) for GC were divided into 2 groups : body mass index (BMI) ≧ 28 and BMI < 28kg / m2. The influence of BMI in LG surgery was investigated. Study2 : The BMI ≧ 28 kg / m2 patients with a planned LG (n = 8) undertook a PWLP including calorie restriction and exercise. The effects of this program were evaluated. Results : Study1 : The BMI ≧ 28kg / m2 group showed significantly longer operation times, more blood loss and a higher frequency of post-operative complications than that of the BMI < 28kg / m2 group. Study 2 : The patients achieved a weight loss of 4.2%. The visceral fat area (VFA) was significantly decreased by 10.6%, whereas skeletal muscle mass was unaffected. The PWLP group showed shorter operation times, less blood loss and a lower frequency of post-operative complications compared with that of the BMI ≧ 28kg / m2 group. Conclusion : Obesity is an important risk factor and a pre-operative weight loss program is useful for obese patients undergoing a LG

The influence and countermeasure of obesity in laparoscopic colorectal resection

Background: The aim of this study was to investigate the influence of obesity and the usefulness of a preoperative weight loss program (PWLP) for obese patients undergoing laparoscopic colorectal resection (LCR). Methods: Study 1: 392 patients who underwent LCR for colorectal cancer were divided into two groups: those with a body mass index (BMI) ≥25 kg/m2 (n = 113) and those with a BMI <25 kg/m2 (n = 279). The influence of BMI on LCR was investigated. Study 2: Patients with a BMI ≥28 kg/m2 who were scheduled to undergo LCR (n = 7, mean body weight 87.0 kg, mean BMI 33.9 kg/m2) undertook a PWLP including caloric restriction and exercise for 29.6 (15–70) days. The effects of this program were evaluated. Results: Study 1: The BMI ≥25 kg/m2 group had a prolongation of operation time and hospital stay than the BMI <25 kg/m2 group. Study 2: The patients achieved a mean weight loss of 6.9% (−6.0 kg). The mean visceral fat area was significantly decreased by 18.0%, whereas the skeletal muscle mass was unaffected. The PWLP group had a significantly lower prevalence of postoperative complications compared with the BMI ≥25 kg/m2 group. Conclusion: Obesity affected the surgical outcomes in LCR. A PWLP may be useful for obese patients undergoing LCR

Immunoescape in CRLM

The expression of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) indicate the efficacy of anti-PD-1/PD-L1 therapy in colorectal cancer (CRC), but are less useful for monitoring the efficacy of therapy of CRC liver metastasis (CRLM). This study investigated the effects of immune molecules on the prognosis of CRLM. We enrolled 71 patients with CRLM who underwent curative resection for CRC. We used immunohistochemistry to analyze the expression of PD-1, PD-L1, indoleamine-pyrrole 2,3-dioxygenase (IDO), and CD163 (a marker of tumor-associated macrophages [TAMs]) in metastatic tumors. The immune molecules PD-1, PD-L1, IDO, and TAMs were expressed in 32.3%, 47.8%, 45.0%, and 47.9% of metastatic CRC samples, respectively. The 5-year overall survival rates associated with immune molecule-positive groups were significantly better than in the negative groups (PD-1: 87.7% vs 53.2%, p = 0.023; PD-L1: 82.4% vs 42.3%, p = 0.007; IDO: 80.7% vs 43.5%, p = 0.007; TAMs: 82.6% vs 48.0%, p = 0.005). Multivariate analysis revealed PD-1 expression (p = 0.032, hazard ratio: 0.19), IDO expression (p = 0.049, hazard ratio: 0.37), and tumor differentiation (p<0.001, hazard ratio: 0.02) as independent prognostic indicators. PD-1 and TAMs in metastases were associated with less aggressive features such as smaller tumors. Furthermore, TAMs positively and significantly correlated with PD-1 expression (p = 0.011), PD-L1 expression (p = 0.024), and tended to correlate with IDO expression (p = 0.078). PD-1, PD-L1, IDO, and TAMs in CRLM were associated with less aggressive features and better prognosis of patients with CRC, indicating adaptive antitumor immunity vs immune tolerance. These molecules may therefore serve as prognostic markers for CRLM

CMTM6 is a Prognostic Factor in GC

Background : CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1 (PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods : A total of 105 patients who had undergone curative surgical resection for stage II / III GC at Tokushima University Hospital were included in this study. The expression of CMTM6 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results : CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS : 57.2% vs. 79.2%, respectively ; p < 0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS : 52.8% vs. 72.4%, respectively ; p < 0.05). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p < 0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p = 0.07). Conclusions : CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC