The association between surgical site infection and postoperative colorectal cancer recurrence and the effect of laparoscopic surgery on prognosis.

PURPOSE: Studies have shown that surgical site infection (SSI) incidence is lower in patients undergoing laparoscopic surgery. Therefore, we reported the SSI countermeasures adopted by our institution and aimed to evaluate the association between SSI occurrence and postoperative colorectal cancer recurrence and the usefulness of laparoscopic surgery for prognosis. METHODS: Among the patients with colorectal cancer who underwent radical surgery at our hospital between January 2015 and December 2017, 197 with stage I-III cancer without distant metastases were included. We retrospectively analyzed patients' electronic medical records and classified them into the non-SSI (without SSI, n = 159) and SSI (with SSI, n = 38) groups. We calculated and compared the 5-year relapse-free survival (RFS) and overall survival (OS) rates. Additionally, we assessed the relationship between prognosis in the non-SSI, incisional SSI, and organ/space SSI groups and the usefulness of laparoscopic surgery. RESULTS: The 5-year RFS and OS were 80.5% versus 63.2% (P = 0.024; hazard ratio [HR], 2.065; 95% confidence interval [CI], 1.099-3.883) and 88.7% versus 84.2% (P = 0.443; HR, 1.436; 95% CI, 0.570-3.617), respectively. The SSI group had a significantly worse 5-year RFS prognosis. Regarding the relationship with laparoscopic surgery, the SSI incidence was 45.0% (9/20 cases) and 16.4% (29/177 cases) with laparotomy and laparoscopic surgery, respectively, indicating a significantly reduced SSI occurrence with laparoscopic surgery (P = 0.005). CONCLUSION: Patients with SSI were at high risk for colorectal cancer recurrence, and laparoscopic surgery may be useful for reducing SSI.

The Association Between Surgical Site Infection and Prognosis of T4 Colorectal Cancer.

OBJECTIVES: Patients with T4 colorectal cancer have poor prognosis, wherein no prognostic factors have been established. Surgical site infection (SSI) has been reported to be one of the risk factors for colorectal cancer recurrence. In this study, we evaluated the relationship between SSI occurrence and prognosis of T4 colorectal cancer and the prognostic impact of the site of SSI occurrence. METHODS: We examined 100 patients with T4 colorectal cancer who underwent radical surgery between April 2002 and December 2017, in a retrospective case-control study, excluding stage IV cases, and classified them into two groups: without SSI (non-SSI) and with SSI (SSI). The five-year relapse-free survival (RFS) and overall survival (OS) were calculated and compared between the two groups. The relationship between prognosis and the SSI site was also assessed according to the SSI site in the incisional/deep and organ/space SSI groups.  Results: The without SSI and with SSI groups included 73 and 27 patients, respectively. The five-year RFS was 55.1% and 22.2% in the without SSI and with SSI groups, respectively (hazard ratio (HR), 2.224; 95% confidence interval (CI), 1.269-3.898; P=0.005). The five-year OS was 67.0% and 38.4% in the without SSI and with SSI groups, respectively (HR, 2.366; 95% CI, 1.223-4.575; P=0.010). The patients in the with SSI group had a significantly poorer prognosis compared with the without SSI group. By SSI site, the prognosis was significantly worse in patients with SSI in the incisional/deep SSI group. CONCLUSIONS: In T4 colorectal cancer, SSI occurrence was a high-risk factor for recurrence and may be a prognostic factor. This result suggested that patients with SSI occurrence may require close postoperative follow-up and appropriate adjuvant chemotherapy.

SpiB regulates the expression of B-cell-related genes and increases the longevity of memory B cells.

Generation of memory B cells is one of the key features of adaptive immunity as they respond rapidly to re-exposure to the antigen and generate functional antibodies. Although the functions of memory B cells are becoming clearer, the regulation of memory B cell generation and maintenance is still not well understood. Here we found that transcription factor SpiB is expressed in some germinal center (GC) B cells and memory B cells and participates in the maintenance of memory B cells. Overexpression and knockdown analyses revealed that SpiB suppresses plasma cell differentiation by suppressing the expression of Blimp1 while inducing Bach2 in the in-vitro-induced germinal center B (iGB) cell culture system, and that SpiB facilitates in-vivo appearance of memory-like B cells derived from the iGB cells. Further analysis in IgG1+ cell-specific SpiB conditional knockout (cKO) mice showed that function of SpiB is critical for the generation of late memory B cells but not early memory B cells or GC B cells. Gene expression analysis suggested that SpiB-dependent suppression of plasma cell differentiation is independent of the expression of Bach2. We further revealed that SpiB upregulates anti-apoptosis and autophagy genes to control the survival of memory B cells. These findings indicate the function of SpiB in the generation of long-lasting memory B cells to maintain humoral memory.

Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow.

The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located in the bone marrow. Here, by employing a traceable method to label recently generated plasma cells, we showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220hiMHC-IIhi populations that progressively differentiated into B220loMHC-IIlo long-lived plasma cell (LLPC) populations. We also found that, in the bone marrow, germinal center (GC)-independent and GC-dependent plasma cells decayed similarly upon NP-CGG engagement, and both entered the B220loMHC-IIlo LLPC pool. Compared with NP+B220hiMHC-IIhi plasma cells, NP+B220loMHC-IIlo cells were more immobilized in the bone marrow niches and showed better survival potential. Thus, our results suggest that the adhesion status of bone marrow plasma cells is dynamically altered during their differentiation and is associated with provision of survival signals.

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.

Scatter patterns in lymph node metastases as a novel prognostic indicator in patients with stage III/N2 colorectal cancer.

To classify patients with stage III/N2 colorectal cancer into high- and low-risk groups for recurrence, the present study compared clinicopathological features by immunohistochemical staining. The single-center analysis included 53/668 patients (7.9%) with stage III/N2 colorectal cancer who underwent radical resection between January 2006 and December 2014. The present study examined cancer cell distribution in metastatic lymph nodes and classified patients into a group with circumferential localization patterns like a cystic mass (CLP) and a group with scatter patterns like fireworks (SPF). Subsequently, 5-year relapse-free survival (5Y-RFS) and 5-year overall survival (5Y-OS) rates were compared and the histological type (differentiation degree) of the primary adenocarcinoma was included. The CLP group included 16 patients (30.2%) and the SPF group included 37 patients (69.8%). The 5Y-RFS rates in these groups were 75.0 vs. 37.8%, respectively (P=0.021), and the 5Y-OS rates were 81.3 vs. 48.6% (P=0.033). Patient clinicopathological characteristics exhibited no significant differences between groups. The adenocarcinoma was well differentiated in 14 patients (Well; 26.4%) and moderately (Mod; n=37) or poorly (Por; n=2) differentiated in 39 patients (Mod+Por; 73.6%). Patients were further classified into four groups: Well/CLP (n=6), Well/SPF (n=8), Mod+Por/CLP (n=10) and Mod+Por/SPF (n=29). For Well/CLP vs. Well/SPF, the 5Y-RFS rates were 66.7 vs. 25.0%, respectively (P=0.293), and for Mod+Por/CLP vs. Mod+Por/SPF (80.0 vs. 41.4%; P=0.052), the respective values for 5Y-OS were 66.7 vs. 50.0% (P=0.552) and 90.0 vs. 48.3% (P=0.059). Based on the aforementioned results, the CLP group was considered a low-risk group for recurrence with a relatively good prognosis; however, the SPF group was considered a high-risk group for recurrence with a poor prognosis, suggesting a need for more potent multi-combination chemotherapy in these patients from the early postoperative period.

Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer. METHODS: A retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery. RESULTS: The 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months). CONCLUSIONS: This modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.

Pelvic local recurrence as first relapse predicts prognosis for clinical stage II/III lower rectal cancer: A clinicopathological investigation.

The present study investigated the association between the mode of tumor recurrence and prognosis in 123 patients with clinical stage II/III rectal cancer. In the past 10 years, patients received systemic chemotherapy following radical (R0, with no macroscopic residual tumor lesions) resection using total or tumor-specific mesorectal excision. Patients with rectosigmoid cancer and T4 + chemoradiation therapy were excluded from the present study. The 5-year relapse-free survival rate (5Y-RFS), 5-year overall survival rate (5Y-OS), and associations between early post-operative complications, recurrence mode and prognosis, as well as the 5Y-OS of patients with relapsed cancer, were calculated. The overall 5Y-RFS and 5Y-OS were 71.4 and 83.5%, respectively, and the overall recurrence rate was 22.8% (28/123 patients). Among relapses, remote metastases were observed in 17/123 patients (13.8%): The lung in 8 patients (6.5%), the liver in 5 patients (4.1%) and elsewhere in 4 patients (3.3%). A total of 11 patients (8.9%) had pelvic local recurrence as the first relapse, which was located anterior to the sacrum in 7 patients (5.7%), at the anastomosis site in 2 patients (1.6%), and in the inner pelvis in 2 patients (1.6%). Among relapsed patients, the 5Y-OS was 69.3% in those with distant metastases and 27.3% in those with local relapse (P=0.02; no significant differences in patient demographics). The results indicated that advanced rectal cancer and control of pelvic local recurrence are manageable by R0 resection and postoperative chemotherapy. However, for patients whose initial relapse was pelvic local recurrence, the relapsed tumor initiated a new metastatic cascade to organs, such as the lung and liver, and affected prognosis.

[Response to S-1+paclitaxel in far-advanced gastric cancer].

The patient was a 55-year-old man who was treated with S-1 and paclitaxel(PTX)combination chemotherapy for inoperable advanced gastric cancer in whom an abdominal CT examination had revealed peritoneal dissemination, pancreatic invasion, and ascites. A total of 15 courses of S-1 120 mg/day for 2 weeks followed by a 2-week rest period and PTX 90 mg/ body on day 1, 8, and 15 were administered. The CT examination after the completion of chemotherapy showed resolution of the ascites, and no evidence of peritoneal dissemination was observed on the images. The tumor marker values had also decreased, but because of severe manifestations of pyloric stenosis, distal gastrectomy and D1 lymph node dissection were performed. Intraoperative exploration revealed total scarring of the peritoneal dissemination and no evidence of pancreatic invasion. We reported this case because of the long-term combination chemotherapy with no major adverse effects and the fact that resection was possible.

The quantity of CD40 signaling determines the differentiation of B cells into functionally distinct memory cell subsets.

In mice, memory B (Bmem) cells can be divided into two subpopulations: CD80hi Bmem cells, which preferentially differentiate into plasma cells; and CD80lo Bmem cells, which become germinal center (GC) B cells during a recall response. We demonstrate that these distinct responses can be B-cell-intrinsic and essentially independent of B-cell receptor (BCR) isotypes. Furthermore, we find that the development of CD80hi Bmem cells in the primary immune response requires follicular helper T cells, a relatively strong CD40 signal and a high-affinity BCR on B cells, whereas the development of CD80lo Bmem cells does not. Quantitative differences in CD40 stimulation were enough to recapitulate the distinct B cell fate decisions in an in vitro culture system. The quantity of CD40 signaling appears to be translated into NF-κB activation, followed by BATF upregulation that promotes Bmem cell differentiation from GC B cells.

Two Cases of Laparoscopic Diagnosis and Treatment of Intersigmoid Hernia.

We present two cases of intestinal obstruction due to intersigmoid hernia that were diagnosed and treated laparoscopically. The first case was a 42-year-old woman with no surgical history. She was treated conservatively with the insertion of an ileus tube. Although the intestinal obstruction improved temporarily, since it subsequently worsened, laparoscopic surgery was performed, which revealed incarceration of the ileum in the intersigmoid fossa. Although there were no signs of necrosis after intestinal release, partial resection of the small bowel was performed before the hernial orifice was closed due to the evidence of serous damage. The second case was a 53-year-old man with no surgical history. An ileus tube was inserted for intestinal decompression, following which laparoscopic surgery was performed. Operative findings revealed incarceration of the ileum in the intersigmoid fossa, and, since there were no signs of necrosis after intestinal release, the hernial orifice was closed without performing intestinal resection. This condition is a good indication for laparoscopic surgery, given that intestinal necrosis is frequently absent and the operation can usually be completed simply by release of the incarcerated intestine and closure of the hernia orifice. Intersigmoid hernia should be suspected in cases of intestinal obstruction with no surgical history.