The impact of staple transection of the dorsal venous complex and urethra on intraoperative blood loss in cooperative laparoscopic and transperineal endoscopic pelvic exenteration.

PURPOSE: While laparoscopic pelvic exenteration reduces intraoperative blood loss, dorsal venous complex bleeding during this procedure causes issues. We previously introduced a method to transect the dorsal venous complex and urethra using a linear stapler during cooperative laparoscopic and transperineal endoscopic (two-team) pelvic exenteration. The present study assessed its effectiveness in reducing intraoperative blood loss by comparing it with conventional laparoscopic pelvic exenteration. METHODS: This retrospective cohort study was conducted at a Japanese tertiary referral center. Eleven cases of two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex (T-PE group) were compared to 25 cases of conventional laparoscopic pelvic exenteration (C-PE group). The primary outcome measure was intraoperative blood loss. RESULTS: There were no significant between-group differences in patient background. The mean intraoperative blood loss was significantly lower in the T-PE group than in the C-PE group (200 vs. 850 mL, p = 0.01). The respective mean operation time, postoperative complication rate, and R0 resection rate were similar between the T-PE and C-PE groups (636 min vs. 688 min, p = 0.36; 36% vs. 44%, p = 0.65; 100% vs. 100%, p = 1.00). CONCLUSIONS: Two-team laparoscopic pelvic exenteration with staple transection of the dorsal venous complex reduced intraoperative blood loss from the dorsal venous complex in a technically safe and oncologically feasible manner.

Incidence and risk factors of bowel dysfunction after minimally invasive rectal cancer surgery and discrepancies between the Wexner score and the low anterior resection syndrome (LARS) score.

PURPOSE: Bowel dysfunction after sphincter-preserving-surgery (SPS) impacts quality of life. The Wexner score (WS) and the low anterior resection syndrome (LARS) score (LS) are instruments for assessing postoperative bowel dysfunction. We analyzed the incidence of and risk factors for each symptom and examined the discrepancies between the two scores. METHODS: A total of 142 patients with rectal cancer, who underwent minimally invasive SPS between May, 2018 and July, 2019, were included. A questionnaire survey using the two scores was given to the patients 2 years after SPS. RESULTS: Tumor location and preoperative radiotherapy were independent risk factors for major LARS. Intersphincteric resection with a hand-sewn anastomosis (HSA) was an independent risk factor for high WS. Among the patients who underwent HSA, 82% experienced incontinence for liquid stools, needed to wear pads, and suffered lifestyle alterations. Of the 35 patients with minor LARS, only 1 had a high WS, and 80.0% reported no lifestyle alterations. Among the 75 patients with major LARS, 58.7% had a low WS and 21.3% reported no lifestyle alterations. CONCLUSION: The results of this study provide practical data to help patients understand potential bowel dysfunction after SPS. The discrepancies between the WS and LS were clarified, and further efforts are required to utilize these scores in clinical practice.

Risk Factors for Lymph Node Metastasis of Rectal Neuroendocrine Tumor and Its Prognostic Impact: A Single-Center Retrospective Analysis of 195 Cases with Radical Resection.

PURPOSE: The incidence of rectal neuroendocrine tumors (NETs) has been steadily increasing. The risk factors for and prognostic impact of lymph node (LN) metastasis were analyzed in 195 patients with stage I-III rectal NET who underwent radical surgery. METHODS: This retrospective, single-center study analyzed risk factors for LN metastasis focusing on previously identified factors and a novel risk factor: multiple rectal NETs. The association between LN metastasis and the prognosis was also analyzed. RESULTS: Pathologically, the LN metastasis rate (also the rate of stage III disease) was 39%, which was higher than the clinical LN metastasis rate of 14%. Tumor size > 10 mm, presence of central depression, tumor grade G2, depth of invasion, LN swelling on preoperative imaging (cN1), venous invasion and multiple NETs were identified as risk factors for LN metastasis. As the tumor size and risk factors increased, the rate of LN metastasis increased. Among these 7 factors, venous invasion, cN1, and multiple NETs were identified as independent predictors of LN metastasis. LN metastasis of rectal NETs was associated with significantly poor disease-free and disease-specific survival. CONCLUSIONS: As risk factors increase, the potential for rectal NETs to metastasize to the LNs increases and LN metastasis is associated with a poor prognosis. This is the first study to report multiple NETs as a risk factor for LN metastasis. A future study examining the survival benefit of radical surgery accompanying LN dissection compared with local resection is warranted.

Adding Induction Chemotherapy Before Chemoradiotherapy with Total Mesorectal Excision and Selective Lateral Lymph Node Dissection for Patients with Poor-Risk, Locally Advanced, Mid-to-Low Rectal Cancer May Improve Oncologic Outcomes: A Propensity Score-Matched Analysis.

BACKGROUND: This study aimed to investigate whether the addition of induction chemotherapy before chemoradiotherapy (CRT) and total mesorectal excision (TME) with selective lateral lymph node dissection improves disease-free survival for patients with poor-risk, mid-to-low rectal cancer. METHODS: The authors' institutional prospective database was queried for consecutive patients with clinical stage II or III, primary, poor-risk, mid-to-low rectal cancer who received neoadjuvant treatment followed by TME from 2004 to 2019. The outcomes for the patients who received induction chemotherapy before neoadjuvant CRT (induction-CRT group) were compared (via log-rank tests) with those for a propensity score-matched cohort of patients who received neoadjuvant CRT without induction chemotherapy (CRT group). RESULTS: From 715 eligible patients, the study selected two matched cohorts with 130 patients each. The median follow-up duration was 5.4 years for the CRT group and 4.1 years for the induction-CRT group. The induction-CRT group had significantly higher rates of 3-year disease-free survival (83.5 % vs 71.4 %; p = 0.015), distant metastasis-free survival (84.3 % vs 75.2 %; p = 0.049), and local recurrence-free survival (98.4 % vs 94.4 %; p = 0.048) than the CRT group. The pathologically complete response rate also was higher in the induction-CRT group than in the CRT group (26.2 % vs 10.0 %; p < 0.001). Postoperative major complications (Clavien-Dindo classification ≥III) did not differ significantly between the two groups (12.3 % vs 10.8 %; p = 0.698). CONCLUSIONS: The addition of induction chemotherapy to neoadjuvant CRT appeared to improve oncologic outcomes significantly, including disease-free survival, for the patients with poor-risk, mid-to-low rectal cancer who underwent TME using selective lateral lymph node dissection.

Geriatric nutritional risk index after neoadjuvant chemoradiotherapy and survival in older patients with advanced rectal cancer.

PURPOSE: To investigate the clinical impact of malnutrition on the survival of older patients with advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. METHODS: We investigated the clinical significance of the geriatric nutritional risk index (GNRI) in 237 patients aged over 60 years with clinical stage II/III rectal adenocarcinoma who were treated with neoadjuvant long-course chemoradiotherapy or total neoadjuvant therapy followed by radical resection from 2004 to 2017. Pre-treatment and post-treatment GNRI were evaluated, with patients split into low (< 98) and high (≥ 98) GNRI groups. The prognostic impact of pre-treatment and post-treatment GNRI levels on overall survival (OS), post-recurrence survival (PRS), and disease-free survival (DFS) was evaluated using univariate and multivariate analyses. RESULTS: Fifty-seven patients (24.1%) before neoadjuvant treatment and 94 patients (39.7%) after neoadjuvant treatment were categorized with low GNRI. Pre-treatment GNRI levels were not associated with OS (p = 0.80) or DFS (p = 0.70). Patients in the post-treatment low GNRI group had significantly poorer OS than those in the post-treatment high GNRI group (p = 0.0005). The multivariate analysis showed that post-treatment low GNRI levels were independently associated with poorer OS (hazard ratio, 3.06; 95% confidence interval, 1.55-6.05; p = 0.001). Although post-treatment GNRI levels were not associated with DFS (p = 0.24), among the 50 patients with recurrence, post-treatment low GNRI levels were associated with poorer PRS (p = 0.02). CONCLUSION: Post-treatment GNRI is a promising nutritional score associated with OS and PRS in patients over 60 years with advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

Inferior versus medial approach in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer: A propensity-score-matched analysis.

AIM: In laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer, either an inferior approach (IA) or a medial approach (MA) is selected in our institution based on the surgeon's preference. The present study compared the treatment outcomes between IA and MA. METHOD: This retrospective, single-centre study using propensity score matching analysed the short- and long-term outcomes of laparoscopic surgery in patients with right-sided colon cancer from 2010 to 2019 at Cancer Institute Hospital. RESULTS: After patient selection, 1011 patients remained for the analysis, of which 67% underwent IA surgery and 33% underwent MA surgery. After propensity score matching (1:1), 325 patients in each group were analysed. Regarding the short-term outcomes, there were no significant differences in the operation time, rate of conversion to open surgery or postoperative complication rate (Clavien-Dindo Grade ≥ III) between the two groups, although the intra-operative median blood loss was significantly less in the IA group than in the MA group (IA, 13 ml vs. MA, 20 ml, P < 0.0001). Regarding the long-term outcomes, the relapse-free survival, liver-relapse-free survival, cancer-specific survival and overall survival were all similar between groups. CONCLUSION: Both the IA and MA in laparoscopic colectomy with complete mesocolic excision and D3 lymphadenectomy for right-sided colon cancer are safe and feasible approaches; the IA may have an advantage over the MA in terms of reduced intra-operative blood loss. Based on their similar oncological outcomes, either the IA or MA can be selected, based on one's preference.

The impact of the advanced lung cancer inflammation index on the outcomes of patients with metastatic colorectal cancer who receive chemotherapy.

BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.

The evaluation of postoperative bowel dysfunction in Japanese patients with rectal cancer.

PURPOSE: The present study assessed postoperative bowel dysfunction in Japanese patients with rectal cancer, including patients who underwent preoperative radiotherapy (RT). METHODS: A total of 277 rectal cancer patients who underwent primary resection were included in the analyses. A questionnaire survey was administered using the low anterior resection syndrome (LARS) score and Wexner score. Scores were determined one year after rectal surgery or diverting ileostomy closure. The LARS score was categorized as minor LARS (21-29) and major LARS (30-42). RESULTS: The proportions of patients with minor and major LARS were significantly larger and Wexner scores significantly higher in patients with distal tumors and a lower anastomosis level than in those with proximal tumors and a higher anastomosis level. Among the patients with lower rectal cancer, the proportions with minor and major LARS were similar between those with and without preoperative RT. The Wexner scores in patients with preoperative RT were significantly higher than in patients without RT. A distal tumor location and lower anastomosis level were independent risk factors of major LARS in multivariate analyses. CONCLUSION: A distal tumor location, low anastomosis level, and preoperative RT might be associated with postoperative bowel dysfunction in rectal cancer patients.

Novel mobilization of the medial approach without changing the position for robotic right hemicolectomy.

Conventional laparoscopic or robotic surgery for right-sided colon cancer often requires intraoperative repositioning and removal of the bowel. Changing positions during robotic surgery can be troublesome and robotic removal of the small intestine carries a risk of unexpected injury because robotic devices have a strong grasping force and no sense of touch. Herein, we introduce a novel mobilization of the medial approach without changing the position for robotic right hemicolectomy. Using this technique, mobilization is performed in counterclockwise succession, allowing all mobilizations and bowel removal to be completed sequentially, without positional change.

Advantages of the umbilical minilaparotomy-first approach in robotic rectal cancer surgery.

BACKGROUND: Since 2018, we have performed robotic rectal cancer surgery at our institution via the umbilical mini-laparotomy-first approach. In the present technical note, we introduce the advantages of this approach. METHODS: In this approach, a 3-cm mini-laparotomy and the wound protector attachment are performed prior to port placement for the da Vinci® Xi system. During robotic surgery, the assistant can adjust the location of the camera port within the wound protector. RESULTS: This approach is only different from the standard port placement in terms of the timing of minilaparotomy; therefore, there is no additional cost. This approach has several advantages. 1: Intraabdominal adhesion around the umbilicus can be dissected under direct vision. 2: Robot arm collision can be diminished. 3: The diverting stoma can be located just at the preoperative stoma-site marking. 4: The da Vinci® camera is less likely to be dirty. 5: Assistant ports can be added through the wound protector. However, sometimes interference between the wound protector extends inside the abdomen and other ports can be a problem, especially in small patients. A smaller-size wound protector is thus recommended in such cases. CONCLUSIONS: The umbilical minilaparotomy-first approach in robotic rectal cancer surgery is a simple and feasible technique with great advantages for not only ensuring successful robotic surgery but also reducing the stoma-associated complications.

Laparoscopic extraperitoneal colostomy has a lower risk of parastomal hernia and bowel obstruction than transperitoneal colostomy.

PURPOSE: Several studies indicate that an extraperitoneal colostomy can prevent the development of a parastomal hernia (PSH) as compared to a transperitoneal colostomy. However, the clinical value of laparoscopic extraperitoneal colostomy, and its influence on bowel obstruction and PSH remain unclear. The present study aimed to clarify the impact of laparoscopic extraperitoneal colostomy on the development of a PSH and bowel obstruction. METHODS: This study included 327 consecutive patients who underwent laparoscopic abdominoperineal resection or Hartmann's procedure between January 2013 and December 2019 after fulfilling selection criteria. The incidence of a PSH (Clavien-Dindo classification ≥ grade I) and bowel obstruction (≥ grade IIIa) in the transperitoneal and extraperitoneal route groups were analyzed using univariate and multivariate analysis. RESULTS: The patients were classified into transperitoneal (n = 222) and extraperitoneal (n = 105) route groups. The patient characteristics, except for body mass index and operative time, were comparable between the groups. A PSH and bowel obstruction occurred more frequently in the transperitoneal than in the extraperitoneal route group (17.1% vs. 1.9% and 15.3% vs. 6.7%, respectively; p < 0.01 and p = 0.03, respectively). The multivariate analysis showed that age ≥ 70 years, body mass index ≥ 22.4 kg/m2, and a transperitoneal route were independent risk factors for the development of a PSH, and a transperitoneal route was an independent risk factor for bowel obstruction. CONCLUSIONS: The transperitoneal route was identified as a risk factor for the development of both a PSH and bowel obstruction after laparoscopic abdominoperineal resection or Hartmann's procedure.

Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis.

Fusobacterium nucleatum has been detected in 8%-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumors in animal models. Thus, we hypothesized that the presence of F. nucleatum might be associated with reduced T cell density in colorectal cancer liver metastases (CRLM). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative PCR assay. The densities of CD8+ T cells, CD33+ cells (marker for myeloid-derived suppressor cells [MDSCs]), and CD163+ cells (marker for tumor-associated macrophages [TAMs]) in CRLM tissue were determined by immunohistochemical staining. Fusobacterium nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLM, F. nucleatum-positive CRLM showed significantly lower density of CD8+ T cells (P = .033) and higher density of MDSCs (P = .001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = .70). The presence of F. nucleatum is associated with a lower density of CD8+ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings could provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLM.

Trastuzumab upregulates programmed death ligand-1 expression through interaction with NK cells in gastric cancer.

BACKGROUND: The predictive significance of programmed death ligand 1 (PD-L1) for programmed death 1 (PD-1) inhibitors remains unclear in gastric cancer (GC) due to the dynamic alteration by treatments. We aimed to elucidate the effects of trastuzumab (Tmab) on PD-L1 expression in GC. METHODS: PD-L1 expression was evaluated by multicolour flow cytometry analysis after co-culturing GG cell lines and immune cells with Tmab. IFN-γ in the co-culture experiments was quantified. Immunohistochemistry (IHC) for PD-L1 expression using clinical samples was also performed to confirm PD-L1 alteration by Tmab. RESULTS: PD-L1 expression was significantly upregulated by Tmab in HER2-amplified GC cell lines co-cultured with peripheral blood mononuclear cells (PBMCs). PD-L1 upregulation by Tmab was also observed in the GC cells co-cultured with NK cells in time-dependent manner, but not with monocytes. IFN-γ concentration in conditioned media from co-cultured PBMCs and NK cells with Tmab was significantly higher and anti-IFN-γ significantly suppress the Tmab-induced PD-L1 upregulation. IHC also suggested PD-L1 upregulation after Tmab treatment. CONCLUSIONS: Tmab can upregulate PD-L1 expression on GC cells through interaction with NK cells. These results suggest clinical implications in the assessment of the predictive significance of PD-L1 expression for PD-1 inhibitors.

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.

BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC). METHODS: We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance. RESULTS: ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens. CONCLUSIONS: F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.

Systemic Inflammatory Markers Combined with Tumor-Infiltrating Lymphocyte Density for the Improved Prediction of Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

BACKGROUND: Previous studies have reported the utility of systemic inflammatory markers and CD8+ tumor-infiltrating lymphocyte (TIL) separately in predicting response to chemoradiotherapy (CRT) in rectal cancer; however, the efficacy of combining these markers remains unclear. OBJECTIVE: This study aimed to elucidate the predictive efficacy of systemic inflammatory markers combined with CD8+ TIL density on response to neoadjuvant CRT in locally advanced rectal cancer. METHODS: Ten systemic inflammatory markers and CD8+ TIL density were assessed in 267 patients with rectal cancer using pretreatment clinical data and biopsy samples. Response to CRT was determined using the Dworak tumor regression grade (TRG), with good responders classified as TRG3-4. RESULTS: Receiver operating characteristic curve analysis showed high areas under the curve for the lymphocyte-to-C-reactive protein ratio (LCR) and neutrophil × monocyte (N × M) value (0.58 and 0.62, respectively). In the multivariate analysis, LCR, N × M value, and CD8+ TIL density were independently associated with good responders (p = 0.016, 0.005, and 0.002, respectively). Stratified analysis with these three markers showed a positive correlation between TRG3-4 ratio and the number of positive predictive factors (8.2%, 20.0%, 34.2%, and 59.1% in patients with 0, 1, 2, and 3 predictors, respectively). Overall and disease-free survival were significantly worse in patients with zero factors present compared with those with one to three factors present. CONCLUSIONS: LCR, N × M value, and CD8+ TIL density are independently associated with response to CRT. Assessing local TIL density along with systemic inflammatory markers may be useful for selecting a multimodal neoadjuvant approach in rectal cancer therapy.

Treatment outcome of laparoscopic surgery after self-expandable metallic stent insertion for obstructive colorectal cancer.

BACKGROUND: We assessed the technical and oncological safety of self-expandable metallic stent (SEMS) insertion followed by laparoscopic colorectal surgery as a bridge to surgery (BTS) for obstructive colorectal cancer (CRC). METHODS: A retrospective, single-center study analyzed the short- and long-term outcomes of SEMS insertion followed by laparoscopic colorectal surgery in patients with stage II/III/IV obstructive CRC from 2012 to 2020 at Cancer Institute Hospital. RESULTS: In 66 patients, including 28 stage IV patients, the clinical success rates of SEMS insertion were 97%. In laparoscopic surgery, primary anastomosis was performed in 61 patients (92%), and open conversion was required in 2 patients (3%). Postoperative complications were seen in 9 patients (13%); however, there was no anastomotic leakage or mortality. Curative resection was achieved in all 38 stage II/III patients and 15 of 28 (54%) stage IV patients. Stage IV patients had a longer operation time and greater blood loss than stage II/III patients; however, the open conversion and postoperative complication rates were similar between the groups. In stage II/III patients, 3-year disease-free survival and 3-year overall survival [OS] were 87.1 and 89.5%, respectively. The median OS of stage IV patients was 34.9 months, and stage IV patients who underwent R0 resection showed a significantly better OS (P = 0.0011) than those with R2 resection. CONCLUSION: SEMS insertion followed by laparoscopic surgery is a feasible treatment strategy that achieves a high-primary anastomosis rate without severe postoperative complication in not only stage II/III but also stage IV obstructive CRC patients.

Preoperative iron status is a prognosis factor for stage II and III colorectal cancer.

BACKGROUND: Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection. METHODS: We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60 µg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis. RESULTS: Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron. CONCLUSION: Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.

Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers.

BACKGROUND: The PD-1/PD-L1 pathway plays critical roles in tumour immunology, and serves as an immune-based therapeutic target. Less is known regarding PD-L2, another ligand of PD-1, and its relation to clinical outcome in human cancers. METHODS: We used a database of 437 surgically and 100 endoscopically resected oesophageal cancers (squamous cell carcinoma, n = 483; adenocarcinoma, n = 36; others, n = 18) to evaluate PD-L2 and PD-L1 expression by immunohistochemistry. RESULTS: Compared with PD-L2-negative cases (n = 366, 83.8%), PD-L2-positive cases (n = 71, 16.2%) had worse overall survival (P = 0.011, log-rank test). There was not a significant correlation between PD-L2 and PD-L1 expression. Multiplex immunofluorescence revealed that there was variability in the expression pattern of PD-L2 and PD-L1. In early-stage tumours, PD-L2 expression was more frequently observed compared with PD-L1. CONCLUSIONS: PD-L2 as well as PD-L1 were associated with an unfavourable prognosis in oesophageal cancer, supporting the role of PD-L2 as a prognostic biomarker. Considering that PD-L2 and PD-L1 had different features in terms of expression timing and responses to chemotherapeutic drugs, evaluation of both PD-L2 and PD-L1 expression may be clinically important.

Clinical Importance of Mean Corpuscular Volume as a Prognostic Marker After Esophagectomy for Esophageal Cancer: A Retrospective Study.

OBJECTIVE: To elucidate the clinical value of mean corpuscular volume (MCV) for prognostic prediction in patients with esophageal cancer who underwent radical esophagectomy. BACKGROUND: High MCV is suggested to be relevant to the incidence and prognosis of several malignancies. However, few studies investigating the correlation between MCV and survival outcome of esophageal cancer have been conducted. METHODS: This study included 570 patients with esophageal cancer who underwent radical esophagectomy between April, 2005 and December, 2017. Patients were divided into 2 groups according to the standard value of pretreatment MCV: normal (83-99 fL) and high (>99 fL) groups. Clinical backgrounds, short-term outcomes, and prognostic outcomes postesophagectomy were retrospectively compared between the groups. RESULTS: Of all patients, 410 (71.9%) had normal MCV, and 160 (28.1%) had high MCV. High MCV was significantly associated with lower body mass index, higher frequency of habitual alcohol and tobacco use, and higher incidence of multiple primary malignancies other than esophageal cancer. High MCV also correlated with higher incidence of postoperative morbidity of the Clavien-Dindo classification ≥II and pulmonary morbidity. Overall survival was significantly worse in patients with high MCV. Multivariate analysis suggested that high MCV was an independent risk factor for worse survival outcome (hazard ratio 1.54, 95% confidence interval 1.098-2.151, P = 0.012). CONCLUSIONS: Patients with high MCV have various disadvantages in clinical background that can adversely affect both short-term and long-term outcomes after esophagectomy. MCV can become a predictive marker to estimate survival outcome after esophagectomy for esophageal cancer.

Wives as Key Persons Positively Impacting Prognosis for Male Patients Undergoing Esophagectomy for Esophageal Cancer: A Retrospective Study from a Single Japanese Institute.

BACKGROUND: Identification of a key person for supporting patients with activities of daily living after esophagectomy can contribute to patients' nutrition, rehabilitation, mental status, and determination of treatments for cancer. It may also affect the patients' prognostic outcomes. PATIENTS AND METHODS: This retrospective study included 504 patients who underwent three-incisional esophagectomy for esophageal cancer between June 2005 and June 2018 at the Kumamoto University Hospital. The association between the type of key person identified and overall survival (OS) was investigated. The impact of the key person on postoperative nutrition and survival after recurrence was also examined. RESULTS: Clinical backgrounds in patients with and without wife as their key person were equivalent. OS among male patients who identified their wife as their key person was significantly better than that in those without their wife as key person (P = 0.0035). Cox regression analysis showed that absence of a wife was an independent risk factor for worse survival outcomes (hazard ratio, 0.62; 95% confidence interval, 0.393-0.987; P = 0.044) along with age, clinical stage, severe postoperative morbidity, and pathological curability. Presence of a wife did not affect postoperative nutritional status. Incidence of death due to other causes and OS after recurrence were better in male patients with a wife than in those without; however, this difference was not significant. CONCLUSIONS: Among males with esophageal cancer, their wives may be a significant contributor to extension of survival after surgery, via various support mechanisms.