Preoperative Smoking Cessation and Prognosis After Curative Esophagectomy for Esophageal Cancer: A Cross-Sectional Study.

BACKGROUND: Several cohort studies have reported that post-esophagectomy morbidities may worsen prognosis. Smoking cessation is an effective prophylactic measure for reducing post-esophagectomy morbidity; however, whether smoking cessation can contribute to the improvement of prognosis is unknown due to the absence of reliable databases covering the cessation period. This study aimed to elucidate whether sufficient preoperative smoking cessation can improve prognosis after esophageal cancer surgery by reducing post-esophagectomy morbidity. METHODS: This study included 544 consecutive patients who underwent curative McKeown and Ivor-Lewis esophagectomies for esophageal cancer between May 2011 and June 2021. Data on smoking status and cessation period were prospectively accumulated. Survival data were finally updated on 30 January 2022. Receiver operating characteristic curve analysis for the cut-off value of appropriate cessation period in reducing post-esophagectomy respiratory morbidity as well as analyses for the association of cessation period with short- and long-term outcomes were performed. RESULTS: Post-esophagectomy morbidity significantly diminished overall survival (OS) after esophagectomy (p = 0.0003). A short preoperative smoking cessation period of ≤ 2 months was associated with frequent post-esophagectomy morbidity of Clavien-Dindo classification ≥IIIb (p = 0.0059), pneumonia (p = 0.016), respiratory morbidity (p = 0.0057), and poor OS in clinical stages II and III (p = 0.0015). Moreover, it was an independent factor for poor OS (hazard ratio 1.85, 95% confidence interval 1.068-3.197; p = 0.028), along with body mass index <18.5 and R1 resection. CONCLUSIONS: Sufficient preoperative smoking cessation > 2 months may be effective in improving not only short-term outcomes but also prognosis after esophagectomy for locally advanced esophageal cancer.

Clinical Significance of Pretreatment Red Blood Cell Distribution Width as a Predictive Marker for Postoperative Morbidity After Esophagectomy for Esophageal Cancer: A Retrospective Study.

BACKGROUND: Clinical significance of red blood cell distribution (RDW) as a predictive marker for the incidence of postoperative morbidity after esophagectomy for esophageal cancer has not been established. METHODS: This study included 634 consecutive patients who underwent three-incisional esophagectomy with lymphadenectomy for esophageal cancer between April 2005 and November 2020. Correlation between pretreatment RDW and patient background, cancer background, and short-term outcome after esophagectomy were retrospectively investigated. RESULTS: Eighty patients (12.6%) had a high pretreatment RDW (> 14.2), which correlated with malnutrition estimated by body mass index, hemoglobin, total lymphocyte count, albumin, and total cholesterol. High pretreatment RDW was an independent risk factor for postoperative severe morbidity of grade IIIb or higher based on the Clavien-Dindo classification (hazard ratio [HR] 3.90, 95% confidence interval [CI] 1.707-8.887; p = 0.0012) and reoperation (HR 4.39, 95% CI 1.552-12.390; p = 0.0053) after open esophagectomy (OE). However, RDW was not associated with postoperative morbidity incidence after minimally invasive esophagectomy (MIE). CONCLUSIONS: Pretreatment RDW may be a surrogate marker for nutritional status and could be a predictive marker for postoperative severe morbidity, reoperation, and possibly pneumonia after OE. On the contrary, the lower invasiveness of MIE may have reduced the effect of pretreatment malnutrition on morbidity incidence, which could explain the insignificant relationship between RDW and poor short-term outcomes in MIE.

Prognostic Impact of PD-1 on Tumor-Infiltrating Lymphocytes in 433 Resected Esophageal Cancers.

BACKGROUND: Immune checkpoint inhibitors targeting the programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway have demonstrated antitumor effects in patients with various malignancies, including esophageal cancer. Thus, a better understanding of local immunity in esophageal cancer is crucial for improving treatment and clinical outcomes. METHODS: We evaluated PD-1 expression on tumor-infiltrating lymphocytes (TILs), as well as PD-L1 expression on cancer cells, by immunohistochemistry and immunofluorescence using a nonbiased database of 433 curatively resected esophageal cancers. With the idea of application as liquid biopsy, PD-1 expression status on peripheral lymphocytes was evaluated by flow cytometry. RESULTS: The cutoff value of PD-1 expression was the median PD-1 count. Compared with cases of low PD-1 expression (n = 219), cases with high levels of PD-1 expression (n = 213) showed significantly worse overall survival (log-rank P = .0017). The prognostic effect of PD-1 differed according to the preoperative treatment status (P for interaction = .040); PD-1 expression was associated with high overall mortality among patients without preoperative therapy, while no such association was present among those with preoperative treatment. A stratification based on PD-1 and PD-L1 status was also significantly associated with overall survival (log-rank P = .0005). PD-1 expression on TILs was significantly associated with that on peripheral lymphocytes (P < .0001). CONCLUSIONS: PD-1 expression on TILs was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. The combination of PD-1 and PD-L1 expression enabled further classification of patients according to clinical outcome.

Oligometastatic recurrence as a prognostic factor after curative resection of esophageal squamous cell carcinoma.

PURPOSE: In recent years, the concept of oligometastasis, which represents limited metastatic disease, has gained much interest. This study focuses on the oligometastatic recurrence (OLR) of esophageal squamous cell carcinoma (ESCC) after esophagectomy. METHODS: From among 514 patients who underwent curative resection for ESCC at our hospital between April 2005 and December 2019, 97 patients with recurrence were enrolled in this study. OLR was defined as fewer than five recurrences in a single organ. We analyzed the prognostic factors for patients with OLR after curative resection of ESCC, especially the relationship between the recurrence pattern and prognosis according to treatment, defined as metastasis-directed therapy (MDT) and chemotherapy with local therapy as combined local therapy (CLT). RESULTS: OLR was identified in 43 (44%) of the 97 patients with recurrence. The OLR group had a significantly better prognosis than the non-OLR group (P = 0.003). Multivariate analysis revealed that OLR was a prognostic factor after recurrence (P = 0.007) and that CLT after recurrence was the only prognostic factor in the OLR group (P = 0.024). CONCLUSIONS: The findings of this study suggest that OLR is a prognostic factor after resection of ESCC and that CLT is a promising treatment modality for patients with OLR after curative resection of ESCC.

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.

Time trial of dry box laparoscopic surgical training improves laparoscopic surgical skills and surgical outcomes.

INTRODUCTION: The present study assessed the utility of a dry box time trial during laparoscopic surgical training to improve laparoscopic surgical skills and surgical outcomes. METHODS: In a monthly time trial, surgeon trainees twice completed a set task that involved grasping a suture, aligning a needle with a needle holder, passing the suture, making three knots, and cutting the two tails of the suture. The mean suturing time was then analyzed. To assess the utility of this time trial, we analyzed the short-term outcomes of patients with stage I to III colon cancer who had undergone laparoscopic colectomy before and after the introduction of the time trial. RESULTS: The monthly time trial was introduced in October 2018, and 52 surgeon trainees participated in the trials examined in this study. Within 6 months of the program's introduction, the mean suturing time had significantly declined to less than 70% of the time trial, while the standard deviations had declined to less than 30%. In comparisons of the short-term outcomes of laparoscopic colon cancer surgery before (n = 49) and after (n = 46) the introduction of the time trial, the operative time tended to decline (P = .074) after the introduction of the time trial, and blood loss was significantly reduced (P = .018). The rate of postoperative complications was similar before and after the introduction. CONCLUSION: Regular time trials of laparoscopic surgical suture training using a dry box can be useful for improving laparoscopic surgical skills and surgical outcomes. Moreover, time trials can keep trainees motivated.

Two Asian families with gastric adenocarcinoma and proximal polyposis of the stomach successfully treated via laparoscopic total gastrectomy.

Family 1: a 39-year-old woman and her sister were admitted to our hospital for fundic gland polyps (FGPs). Their mother died of gastric cancer with FGPs. We performed repeated biopsies at close intervals, suspecting gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). After a 1-year follow-up, the sisters were diagnosed with gastric cancer with FGP. We performed laparoscopic total gastrectomies with D1+lymph node dissection. Promoter 1B (exon 1B) of the APC gene (chr5: 112,043,224 T>C) contained a point mutation. The sisters were subsequently diagnosed with GAPPS as per the mutational analysis. Family 2 (unrelated to Family 1): a-24-year-old woman was referred for epigastralgia. EGD revealed FGPs localized in the proximal stomach. Pathological biopsy results showed severe dysplasia and adenocarcinoma in situ. Her father was simultaneously diagnosed with FGPs with GC localized in the proximal stomach. We performed laparoscopic total gastrectomies with D1+lymph node dissection. They had the same gene mutation as the family 1. Here, we report two Asian families with GAPPS successfully treated via laparoscopic total gastrectomy.

Total Lesion Glycolysis Ratio in Positron Emission Tomography/Computed Tomography Images During Neoadjuvant Chemotherapy Can Predict Pathological Tumor Regression Grade and Prognosis in Patients with Locally Advanced Squamous Cell Carcinoma of the Esophagus.

BACKGROUND: The usefulness of quantitating tumor lesion glycolysis (TLG) from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings as a tool for determining the effect of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) has not yet been established. METHODS: The cohort of this retrospective study comprised 46 patients who had undergone NAC and subsequent esophagectomy for locally advanced ESCC between January 2008 and December 2017. PET/CT was conducted before and after NAC to assess its therapeutic effect. Associations between changes in TLG values during NAC and clinicopathological findings, pathological tumor regression grade (TRG), and prognosis were assessed. RESULTS: Most patients received two courses of DCF (Docetaxel, Cisplatin, and Fluorouracil) as NAC. The mean TLG value of the primary tumor decreased significantly after NAC. The median follow-up period was 41 months. The Kaplan-Meier method, analyzed by log-rank test, showed that low TLG ratio (≤ 0.4) and low SUVmax ratio (≤ 0.6) were associated with favorable survival outcomes (P = 0.0073 and P = 0.032, respectively). Univariate and multivariate analysis revealed that TLG ratio and achievement of pathological cure were independent prognostic factors for overall survival. TLG ratio was also associated with pathological TRG (TRG 0-1a vs 1b-3) (P = 0.0016). CONCLUSIONS: TLG ratio before and after NAC is clinically useful in predicting both histological response and survival outcome after NAC and subsequent esophagectomy in patients with ESCC.

Preoperative C-reactive protein-to-albumin ratio and clinical outcomes after resection of colorectal liver metastases.

PURPOSE: Accumulating evidence suggests that the inflammatory tumor microenvironment can potentiate tumor progression and metastasis. The C-reactive protein-to-albumin ratio (CAR) is a novel inflammation-based prognostic score. This study was performed to examine the associations of the preoperative CAR with clinical outcomes in patients with colorectal liver metastases (CRLM) after curative resection. METHODS: We retrospectively assessed the preoperative CAR in 184 patients who underwent curative resection for CRLM from November 2001 to January 2018 at Kumamoto University (Kumamoto, Japan). The optimal cutoff level of the preoperative CAR was determined by survival classification and regression tree (CART) analysis. We compared clinicopathological factors and prognoses between the high-CAR and low-CAR groups. A Cox proportional hazards model was used to calculate hazard ratios (HRs), controlling for potential confounders. RESULTS: A higher preoperative CAR was associated with worse overall survival (OS) (p < 0.0001) and recurrence-free survival (RFS) (p = 0.003). Applying survival CART analysis, the high-CAR group comprised 33 patients (17.9%). In the multivariate analyses, a high CAR was independently associated with shorter OS (HR, 2.82; 95% confidence interval, 1.63-4.72; p = 0.0004) and RFS (HR, 1.62; 95% confidence interval, 1.02-2.49; p = 0.040). A high CAR was associated with a large tumor size, high serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, high intraoperative blood loss, and more postoperative complications. CONCLUSION: A high preoperative CAR is associated with shorter OS and RFS and might serve as a prognostic marker for patients with CRLM after curative resection.

Outcomes of esophageal bypass surgery and self-expanding metallic stent insertion in esophageal cancer: reevaluation of bypass surgery as an alternative treatment.

PURPOSE: Advanced esophageal cancer often results in esophageal stenosis or tracheoesophageal fistula. Esophageal bypass surgery and esophageal stent insertion are palliative treatments for esophageal cancer. With improvements in metallic stents and the stent insertion technique, esophageal stent insertion appears to be performed more frequently than bypass surgery, worldwide. The aim of this study was to evaluate the outcomes of bypass surgery and stent insertion in our hospital and reevaluate which patients would benefit from bypass surgery. METHODS: A total of 70 esophageal cancer patients who could not tolerate oral feeding due to esophageal stenosis or tracheoesophageal fistula underwent palliative treatment [esophageal bypass surgery (N = 34) and esophageal stent insertion (N = 36)] at Kumamoto University. We retrospectively investigated the clinicopathological factors, postoperative outcomes, and complications. RESULTS: Both treatments could significantly improve the amount of food intake and the dietary form (P < 0.01). The length of hospital stay was shorter (P < 0.01) and complications associated with treatment were reduced in the stent group (P = 0.03). The overall survival did not differ significantly between the groups (log rank P = 0.22). Importantly, in the bypass surgery group, the patients who received postoperative treatment had a better prognosis than those who did not receive postoperative treatment (log rank P < 0.01). CONCLUSION: Both bypass surgery and stent insertion allowed oral intake in patients who could not tolerate oral feeding because of esophageal stenosis or tracheoesophageal fistula. Considering that patients who undergo stent insertion have a shorter hospital stay and fewer complications, stent insertion may be a better first choice for treatment than bypass surgery. However, bypass surgery may be an option for patients who can tolerate postoperative treatment.

Fibrosis-4 Index, a Noninvasive Fibrosis Marker, Predicts Survival Outcomes After Hepatectomy for Colorectal Cancer Liver Metastases.

BACKGROUND: Liver fibrosis influences liver regeneration and surgical outcomes, and several noninvasive models based on laboratory data have been developed to predict liver fibrosis. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, a noninvasive fibrosis marker, can predict the prognosis in patients with colorectal liver metastases (CRLM) undergoing hepatectomy. METHODS: This retrospective study involved 193 consecutive patients with CRLM who underwent hepatectomy. The FIB-4 index was calculated by laboratory data and age before hepatectomy and before preoperative chemotherapy. The FIB-4 cut-off was determined using survival classification and regression tree analysis. Patients were divided into two groups (high and low FIB-4 index), and post-hepatectomy overall survival (OS) and recurrence-free survival (RFS) were investigated. RESULTS: In total, 193 patients were evaluated. Chemotherapy before hepatectomy was performed in 105 (54.4%) patients. A high FIB-4 index (> 2.736) was found in 39 (20.2%) patients. OS was significantly shorter in patients with a high FIB-4 index than those with a low FIB-4 index in the univariate (45.9 vs. 74.4 months, log-rank p = 0.007) and multivariate analysis (hazard ratio 2.28, 95% confidence interval 1.39-3.74; p = 0.001). Among patients who received chemotherapy before hepatectomy, those with a high FIB-4 index had significantly shorter RFS (6.9 vs. 45.3 months, log-rank p = 0.047) and OS (23.9 vs. 55.0 months, log-rank p = 0.003) than those with a low FIB-4 index. This association was also confirmed by multivariate analysis (hazard ratio 4.28, 95% confidence interval 1.46-12.6; p = 0.008). CONCLUSION: Both the preoperative and prechemotherapy FIB-4 index can predict long-term outcomes after hepatectomy in patients with CRLM.

IgG4-related disease presenting as a submucosal tumor of the stomach resected with laparoscopic endoscopic cooperative surgery: a case report.

BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated disorder in which abundant IgG4-positive plasma cells infiltrate affected organs. There have been reported four cases of probable IgG4-RD presenting as a submucosal tumor of the stomach. We herein report the first case of definite IgG4-RD presenting as a submucosal tumor of the stomach resected with laparoscopic endoscopic cooperative surgery (LECS). CASE PRESENTATION: A 70-year-old woman with a 6-year history of autoimmune pancreatitis was referred to our department because a 15-mm submucosal tumor in the greater curvature of the lower part of the stomach had been identified via upper gastrointestinal endoscopy. Endoscopic ultrasonography showed a 10-mm low-echoic lesion derived from the submucosal layer of the stomach. A fine-needle aspiration biopsy was attempted, but the tumor was too hard for sampling. F-fluorodeoxyglucose (FDG) positron emission tomography showed an FDG uptake, suggesting a possibility of malignant disease. As the diagnosis could not be confirmed, LECS for both the diagnosis and curative treatment was performed. A histopathological examination showed a tumor with IgG4-positive lymphoplasmacytic infiltration and fibrosis. The ratio of IgG4+/IgG+ lymphoplasmacytic cells was > 80%. A laboratory examination showed elevation of the serum IgG4 levels preoperatively. Thus, the final diagnosis was IgG4-RD of the stomach. No recurrence was observed within 1 year after surgery. CONCLUSIONS: We encountered a case of definite IgG4-RD presenting as a gastric SMT in which a correct diagnosis was achieved by a minimally invasive LECS technique. IgG4-RD may present as a gastric lesion and should be taken into consideration as a differential diagnosis.

Port site recurrence of esophageal adenocarcinoma after minimally invasive esophagectomy: a case report.

BACKGROUND: Port site recurrence has been observed after a variety of oncologic resection procedures. However, few have reported port site recurrence of esophageal cancer. CASE PRESENTATION: A 51-year-old man underwent minimally invasive esophagectomy for pT3(AD)N3M0 adenocarcinoma of the esophagus. One year after surgery, he presented with a rapidly growing tumor on the right thoracic wall. Contrast computed tomography demonstrated an enhancing tumor with uptake on positron emission tomography. We performed resection of the thoracic wall, including the skin and subcutis. The pathologic diagnosis was poorly differentiated adenocarcinoma, consistent with metastasis of esophageal origin. CONCLUSION: This was the first report on thoracic port site recurrence of esophageal adenocarcinoma. We recommend elimination of leakage around the thoracoscopic ports to prevent such recurrence. We should provide prudent postoperative clinical surveillance.

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.

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.

Synchronous NET and colorectal cancer development: a case report.

BACKGROUND: The incidence of synchronous gastrointestinal neuroendocrine tumors (GI-NETs) and colorectal cancer is very low. CASE PRESENTATION: We present a 72-year-old man diagnosed with a rectal neuroendocrine tumor (NET) with multiple organ metastases and simultaneous sigmoid colon cancer. Although the NET was his prognostic factor, he underwent a laparoscopic sigmoidectomy at first because it was expected that the colon cancer would cause obstruction or bleeding during NET treatment. Subsequently, he started taking everolimus. CONCLUSIONS: We should consider surgical resection of the synchronous cancer before systemic therapy for a GI-NET regardless of the difference in prognosis between synchronous tumors, if the cancer may impair the continuation of systemic therapy.

Prognostic significance of serum p53 antibody according to KRAS status in metastatic colorectal cancer patients.

BACKGROUND: Serum anti-p53 antibody is used clinically as a tumor marker of colorectal cancer. However, its prognostic significance in patients with metastatic colorectal cancer (mCRC) remains unclear. KRAS status may influence the host immune response against tumor progression. In the present study, we investigated the prognostic significance of serum anti-p53 in mCRC patients with wild-type KRAS and mutant KRAS treated with systemic chemotherapy. METHODS: A retrospective study of 150 mCRC patients in whom serum anti-p53 antibody was measured before first-line chemotherapy was conducted. The patients were divided into two groups, high p53 and low p53, based on their serum anti-p53 antibody levels. Associations between serum anti-p53 level and clinical outcomes were evaluated in conjunction with KRAS status. RESULTS: There were 97 (64.7%) patients with wild-type KRAS and 53 (35.3%) with mutant KRAS. In an analysis of all patients, there was no significant difference in overall survival (OS) between the high p53 and low p53 groups. In patients with mutant KRAS, those in the high p53 group exhibited significantly longer OS than those in the low p53 group (p = 0.017, log-rank test). In the multivariate analysis, serum p53 antibody level was an independent predictor of OS in mCRC patients (high vs. normal; hazard ratio 0.438, 95% confidence interval 0.178-0.974, p < 0.05). CONCLUSIONS: Serum anti-p53 antibody level may be an independent predictor of OS in mCRC patients with KRAS mutant tumors.