Evaluation of bacterial contamination and medium-term oncological outcomes of intracorporeal anastomosis for colon cancer: A propensity score matching analysis.

BACKGROUND: Although intracorporeal anastomosis (IA) for colon cancer requires longer operative time than extracorporeal anastomosis (EA), its short-term postoperative results, such as early recovery of bowel movement, have been reported to be equal or better. As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum, there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells. However, intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified. AIM: To clarify the effects of bacterial and tumor cell contamination of the intra-abdominal cavity in IA. METHODS: Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020, 75 underwent EA (EA group), and 52 underwent IA (IA group). After propensity score matching, the primary endpoint was 3-year disease-free survival rates, and secondary endpoints were 3-year overall survival rates, type of recurrence, surgical site infection (SSI) incidence, number of days on antibiotics, and postoperative biological responses. RESULTS: Three-year disease-free survival rates did not significantly differ between the IA and EA groups (87.2% and 82.7%, respectively, P = 0.4473). The 3-year overall survival rates also did not significantly differ between the IA and EA groups (94.7% and 94.7%, respectively; P = 0.9891). There was no difference in the type of recurrence between the two groups. In addition, there were no significant differences in SSI incidence or the number of days on antibiotics; however, postoperative biological responses, such as the white blood cell count (10200 vs 8650/mm3, P = 0.0068), C-reactive protein (6.8 vs 4.5 mg/dL, P = 0.0011), and body temperature (37.7 vs 37.5 °C, P = 0.0079), were significantly higher in the IA group. CONCLUSION: IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

Clinical T2N0 Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy plus Local Excision.

INTRODUCTION: Total mesorectal excision is the standard treatment for clinical T2 (cT2) rectal cancer; however, this procedure can result in postoperative dysfunction, decreased quality of life, and stoma creation in some patients. We investigated neoadjuvant chemoradiotherapy (nCRT) plus local excision (LE) as an alternative treatment strategy for patients with cT2N0 rectal cancer. METHOD: Fifty-six patients with cT2N0M0 rectal cancer who exhibited the following characteristics (an anal verge of ≤8 cm, tumor size of <30 mm, well- or moderately differentiated adenocarcinoma on biopsy) underwent LE following nCRT. Chemoradiotherapy was administered at 40 or 45 Gy in 20-25 fractions with concurrent oral UFT (tegafur/uracil; 400 mg/m2) or S-1 (tegafur/gimeracil/oteracil; 80 mg/m2). RESULTS: Fifty-five patients (98%) completed nCRT as planned. Histologically, the excision margin was negative in all patients, and four patients with ypT3 disease underwent total mesorectal excision. Recurrence was observed in 15 patients (27%), local recurrence in 7 (13%), and distant recurrence in 10 (18%). The salvage surgery was possible for the local recurrence group. The 5-year disease-free and overall survival rates were 68.4% and 84.9%, respectively. Multivariate analysis showed that only the tumor regression grade (TRG) was an independent risk factor for recurrence (p = 0.025). Although 7 (26%) out of 27 patients with a TRG of 3 or 4 developed local recurrence and 6 (22%) had distant metastasis, 25 patients with a TRG of 1 or 2 did not exhibit local recurrence, and only 1 (4%) experienced distant metastasis. CONCLUSION: nCRT plus LE may be an alternative treatment for patients with cT2N0 rectal cancer who achieved a TRG of 1 or 2. However, additional treatment was required in patients who achieved a TRG of 3 or 4.

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer.

Background: From 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients). Methods: Data were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared. Results: Baseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80-92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80-88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027). Conclusions: Approximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.

Classification of rectal cancer according to recurrence types - comparison of Japanese guidelines and Western guidelines.

BACKGROUND: Rectal cancer is characterized by more local recurrence (LR) and lung metastasis than colon cancer. However, the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and classification. The classification of rectal cancer differs between Japanese and Western guidelines. AIM: To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of guidelines. METHODS: A total of 958 patients with Stage II and III colorectal cancer were included in the analysis: 607 with colon cancer and 351 with rectal cancer. Localization of rectal cancers was assessed by enema examination and rigid endoscopy. According to Japan guidelines, rectal cancer is classified as Rb (below the peritoneal inversion), Ra (between the inferior margin of second sacral vertebrae and Rb) or RS (between Ra and sacral promontory). RESULTS: There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or LR. Lung metastasis and LR were significantly more common among Rb rectal cancer (in Japan) than in colon cancer (P = 0.0043 and P = 0.0002, respectively). Lung metastases and LR occurred at significantly higher rates in rectal cancer measuring ≤ 12 cm and ≤ 10 cm than in colon cancers (P = 0.0117, P = 0.0467, P = 0.0036, P = 0.0010). Finally, the rates of liver metastasis, lung metastasis, and LR in rectal cancers measuring 11 cm to 15 cm were 6.9%, 2.8%, and 5.7%, respectively. These were equivalent to the rates in colon cancer. CONCLUSION: High rectal cancer may be treated with the same treatment strategies as colon cancer. There was no difference in the classification of colorectal cancer between Japan and Western countries.

Distal gastric tube resection with preservation of the right gastroepiploic artery for gastric tube cancer: a case report.

BACKGROUND: The incidence of gastric tube cancer is increasing because of improved survival rates in patients with esophageal cancer treated by esophagectomy. Total resection of the gastric tube is expected to be highly curative, but it is associated with a higher risk of severe postoperative complications. Herein we report a case of early gastric tube cancer that was successfully treated by distal gastric tube resection with preservation of the right gastroepiploic artery (RGEA). CASE PRESENTATION: An 82-year-old man was diagnosed as having gastric tube cancer, B-12-O, Type 0-IIc, T1b, N0, M0, cStage IA (Japanese Classification of Gastric Carcinoma). Upper gastrointestinal endoscopy showed a Type 0-IIc lesion measuring 30 mm in length in the lower part of the gastric tube, and histopathological examination of biopsy specimens revealed the features of poorly differentiated adenocarcinoma. The primary lesion could not be identified by computed tomography, and there was no obvious lymph node metastasis or distant metastasis. Considering that total resection of the gastric tube would have been highly invasive and that the gastric tube cancer was at a relatively early stage, we performed distal gastric tube resection with preservation of the RGEA. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. There has been no recurrence during the 17 months of follow-up. CONCLUSION: We successfully treated a patient with gastric tube cancer by distal gastric tube resection with preservation of the RGEA. This treatment strategy may be acceptable for patients with early gastric tube cancer without lymph node metastasis, considering the balance between the surgical invasiveness and curability of the tumor.

Prediction of Recurrence in Patients with Stage III Colon Cancer Using Conventional Clinicopathological Factors and Peripheral Blood Test Data: A New Analysis with Artificial Intelligence.

BACKGROUND: Survival rate may be predicted by tumor-node-metastasis staging systems in colon cancer. In clinical practice, about 20 to 30 clinicopathological factors and blood test data have been used. Various predictive factors for recurrence have been advocated; however, the interactions are complex and remain to be established. We used artificial intelligence (AI) to examine predictive factors related to recurrence. METHODS: The study group comprised 217 patients who underwent curative surgery for stage III colon cancer. Using a self-organizing map (SOM), an AI-based method, patients with only 23 clinicopathological factors, patients with 23 clinicopathological factors and 34 of preoperative blood test data (pre-data), and those with 23 clinicopathological factors and 31 of postoperative blood test data (post-data) were classified into several clusters with various rates of recurrence. RESULTS: When only clinicopathological factors were used, the percentage of T4b disease, the percentage of N2 disease, and the number of metastatic lymph nodes were significantly higher in a cluster with a higher rate of recurrence. When clinicopathological factors and pre-data were used, three described pathological factors and the serum C-reactive protein (CRP) levels were significantly higher and the serum total protein (TP) levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. When clinicopathological factors and post-data were used, three described pathological factors, serum CRP levels, and serum carcinoembryonic antigen levels were significantly higher and serum TP levels, serum albumin levels, and the percentage of lymphocytes were significantly lower in a cluster with a higher rate of recurrence. CONCLUSIONS: This AI-based analysis extracted several risk factors for recurrence from more than 50 pathological and blood test factors before and after surgery separately. This analysis may predict the risk of recurrence of a new patient by confirming which clusters this patient belongs to.

Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An Open-Label Randomized Phase II Trial.

BACKGROUND: FOLFIRI plus bevacizumab have been widely used as first-line treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab versus FOLFIRI plus bevacizumab. METHODS: The subjects comprised 120 chemotherapy-naïve patients with mCRC. The study group received a 24-h infusion of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). RESULTS: From December 2013 through January 2018, 120 patients were randomly assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 and 61.7%, respectively (p = 0.0053). AEs were similar. CONCLUSIONS: Our results show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated regimen for the first-line treatment of mCRC.

A prospective clinical study assessing the presence of exfoliated cancer cells and rectal washout including tumors in patients who receive neoadjuvant chemoradiotherapy for rectal cancer.

PURPOSE: Rectal washout is performed in rectal cancer surgery to eliminate exfoliated cancer cells. Before rectal washout, a cross-clamp should generally be placed distal to the tumor. In some patients with lower rectal cancer, however, the tumor cannot be adequately isolated. We, therefore, hypothesized that neoadjuvant chemoradiotherapy (nCRT) can decrease the number of exfoliated cancer cells even after the rectal washout including tumors. METHODS: We prospectively studied 86 patients with rectal cancer who underwent proctectomy after nCRT. A cross-clamp was applied proximal to the tumor, and the rectum was washed with 2000 mL of physiological saline solution. The initial 100 mL used to wash the rectum was collected as a pre-washout sample. After the rectum was washed with the remaining 1900 mL, the solution remaining in the rectum was collected as a post-washout sample. Cells classified as class IV or higher according to the papanicolaou classification were considered to indicate a positive diagnosis. RESULTS: The cytological diagnosis was positive in pre-washout samples in 21 patients (24%) and post-washout samples in two patients (2%). CONCLUSION: In patients with rectal cancer, nCRT may decrease the number of exfoliated cancer cells in the rectum, and rectal washout including the tumor may be oncologically acceptable.

Distribution of Neuroendocrine Marker-Positive Cells in Colorectal Cancer Tissue and Normal Mucosal Tissue: Consideration of Histogenesis of Neuroendocrine Cancer.

BACKGROUND: Colorectal neuroendocrine carcinoma (NEC) is a rare disease, and mixed cases with colorectal adenocarcinoma also exist. The histogenesis of this disease remains unclear. We studied the numbers of neuroendocrine marker-positive cells in adenocarcinoma tissue and in normal -mucosal tissue to investigate the relation between adenocarcinoma and NEC and to discuss the histogenesis of NEC. METHODS: We studied a total of 354 curatively resected cases of stage II or III colon cancer and 36 cases of rectal cancer treated at the Tokai University Hospital between 2007 and 2012. Adenocarcinoma tissue and normal mucosal tissue were immunohistochemically stained with chromogranin A, synaptophysin, and CD56. Cases in which neuroendocrine marker-positive cells were found in cancer tissue were defined as positive. In normal mucosa, the numbers of positive cells per 15 high-power fields (HPF) were counted. RESULTS: Among the 390 cases, 181 cases had right sided colon cancer, 173 cases had left sided colon cancer, and 36 cases had rectal cancer. The rates of positive staining for chromogranin A, synaptophysin, and CD56 were significantly higher in the right sided colon than in the left sided colon, consistent with the preferred sites of NEC as reported previously. Cells positive for chromogranin A and synaptophysin in normal mucosa were significantly more common in the rectum and the left sided colon than in the right sided colon. No site-specific differences were found for CD56. CONCLUSIONS: Neuroendocrine marker-positive cells in colorectal cancer tissue are more common in the right sided colon, whereas neuroendocrine marker-positive cells in normal mucosa are more common in the rectum. These results suggest that NEC may arise from preceding adenocarcinomas.

Induction of CD3+ and FoxP3+ T Cells in Left-sided Colorectal Tumors After UFT/LV Chemotherapy.

BACKGROUND/AIM: Immune checkpoint inhibitors are mainly used for right-sided, microsatellite instability-high colorectal tumors. In this study, the effects of oral uracil-tegafur plus leucovorin (UFT/LV) chemotherapy on the gene expressions of four immunotherapy targets and the amounts of tumor-infiltrating lymphocytes (TILs) were investigated. PATIENTS AND METHODS: Data of 260 patients with stage II or stage III colorectal cancer were analyzed. Gene expression and amount of TILs were evaluated using real-time reverse transcription polymerase chain reaction (CRT-PCR) assay and immunohistochemical staining, respectively. RESULTS: Expression of CTLA4 and LAG3 in tumor tissues was significantly increased after UFT/LV chemotherapy, but only in left-sided tumors. The percentage of high-TIL, high-CD3 and high-FoxP3 patients in the UFT/LV group was significantly higher than that in the control group, only in left-sided tumors. CONCLUSION: The increase in TILs count, especially of CD3+ T cells and FoxP3+ regulatory T cells, after UFT/LV chemotherapy were specific to left-sided colorectal cancers.

Chemoradiotherapy-induced Changes in Mucinous Components in Rectal Cancer Tissue: Evaluation on High Iron Diamine-alcian Blue and Mucin 1 Staining.

BACKGROUND/AIM: The standard treatment for rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Mucinous carcinoma responds poorly to nCRT. In some patients, mucin lakes (MLs) are induced by nCRT. Identifying whether MLs are induced or originally present would be of great importance. PATIENTS AND METHODS: We studied 20 patients with MLs (CRT-MC group) among 205 patients who received nCRT. Among 88 patients who did not receive nCRT, we studied 9 patients with mucinous carcinoma (non-CRT-MC group) and 18 patients with MLs in differentiated adenocarcinoma (non-CRT-AC group). Tumors were stained with high iron diamine-Alcian blue (HID-AB) and MUC1 staining. RESULTS: Rate of AB>HID staining of cancer cells was significantly higher in the CRT-MC group than in non-CRT-MC group (p=0.0004). Rate of MUC1 staining in MLs was significantly higher in the CRT-MC group (p=0.0254). CONCLUSION: nCRT can induce qualitative changes in mucinous components, however, other methods are required to distinguish induced components from originally existing components.

Promising Cell Configuration for Next-Generation Energy Storage: Li2S/Graphite Battery Enabled by a Solvate Ionic Liquid Electrolyte.

Lithium-ion sulfur batteries with a [graphite|solvate ionic liquid electrolyte|lithium sulfide (Li2S)] structure are developed to realize high performance batteries without the issue of lithium anode. Li2S has recently emerged as a promising cathode material, due to its high theoretical specific capacity of 1166 mAh/g and its great potential in the development of lithium-ion sulfur batteries with a lithium-free anode such as graphite. Unfortunately, the electrochemical Li(+) intercalation/deintercalation in graphite is highly electrolyte-selective: whereas the process works well in the carbonate electrolytes inherited from Li-ion batteries, it cannot take place in the ether electrolytes commonly used for Li-S batteries, because the cointercalation of the solvent destroys the crystalline structure of graphite. Thus, only very few studies have focused on graphite-based Li-S full cells. In this work, simple graphite-based Li-S full cells were fabricated employing electrolytes beyond the conventional carbonates, in combination with highly loaded Li2S/graphene composite cathodes (Li2S loading: 2.2 mg/cm(2)). In particular, solvate ionic liquids can act as a single-phase electrolyte simultaneously compatible with both the Li2S cathode and the graphite anode and can further improve the battery performance by suppressing the shuttle effect. Consequently, these lithium-ion sulfur batteries show a stable and reversible charge-discharge behavior, along with a very high Coulombic efficiency.

[Au7](3+): a missing link in the four-electron gold cluster family.

Ligand-stabilized ultrasmall gold clusters offer a library of diverse geometrical and electronic structures. Among them, clusters with four valence electrons form an exceptional but interesting family because of their unique geometrical structures and optical properties. Here, we report a novel diphosphine-ligated four-electron Au7 cluster (2). In good agreement with previous theoretical predictions, 2 has a "core+one" structure to exhibit a prolate shape. The absorption spectrum showed an isolated band, similar to the spectra of Au6 and Au8 clusters with "core+two" structures. TD-DFT studies demonstrated that the attachment of only one gold atom to a polyhedral core is sufficient to generate unique electronic structures and characteristic absorptions. The present result fills the missing link between Au6 and Au8 in the four-electron cluster family, showing that the HOMO-LUMO gap increases with increasing nuclearity in the case of the tetrahedron-based "core+exo" clusters.

Protonation-induced chromism of pyridylethynyl-appended [core+exo]-type Au8 clusters. Resonance-coupled electronic perturbation through π-conjugated group.

A series of [core+exo]-type Au8 clusters bearing two alkynyl ligands on the exo gold atoms ([Au8(dppp)4(C≡CR)2](2+), 2-6) were synthesized by the reaction of [Au8(dppp)4](2+) (1) with alkynyl anions. Although the C≡C moieties directly attached to the Au8 units did not affect the optical properties arising from intracluster transitions, the pyridylethynyl-bearing clusters (4-6) exhibited reversible visible absorption and photoluminescence responses to protonation/deprotonation events of the terminal pyridyl moieties. The chromism behaviors and proton-binding constants of these clusters were highly dependent on the relative position of the pyridine nitrogen atom, such that the 2-pyridyl (4) and 4-pyridyl (6) isomers showed more pronounced responses than the 3-pyridyl isomer (5). These results suggest that the resonance-coupled movement of the positive charge upon protonation is involved in the optical responses, where the formation of extended charged resonance structures causes significant perturbation effects on the electronic properties of the Au8 unit and also contributes to the high binding affinities.

Unique [core+two] structure and optical property of a dodeca-ligated undecagold cluster: critical contribution of the exo gold atoms to the electronic structure.

A novel dodeca-ligated undecagold cluster having a nonagold core plus two exo-attached gold atoms was synthesized. Unlike the conventional icosahedron-based "core-only" isomer, the [9+2] cluster showed an intense visible absorption band. Theoretical calculation showed the involvement of the exo gold atoms in the generation of the unique electronic structure.