Phase II Study of Intraperitoneal Administration of Paclitaxel Combined with S-1 and Cisplatin for Gastric Cancer with Peritoneal Metastasis.

BACKGROUND: Intraperitoneal chemotherapy is promising for gastric cancer with peritoneal metastasis. Although a phase III study failed to show a statistically significant superiority of intraperitoneal paclitaxel combined with S-1 and intravenous paclitaxel, the sensitivity analysis suggested clinical efficacy. Thus, attempts to combine intraperitoneal paclitaxel with other systemic therapies with higher efficacy have been warranted. We sought to explore the efficacy of intraperitoneal paclitaxel with S-1 and cisplatin. PATIENTS AND METHODS: Gastric cancer patients with peritoneal metastasis were enrolled in the phase II trial. In addition to the established S-1 and cisplatin regimen every 5 weeks, intraperitoneal paclitaxel was administered on days 1, 8, and 22 at a dose of 20 mg/m2. The primary endpoint was overall survival rate at 1 year after treatment initiation. Secondary endpoints were progression-free survival and toxicity. RESULTS: Fifty-three patients were enrolled and fully evaluated for efficacy and toxicity. The 1-year overall survival rate was 73.6% (95% confidence interval 59.5-83.4%), and the primary endpoint was met. The median survival time was 19.4 months (95% confidence interval, 16.1-24.6 months). The 1-year progression-free survival rate was 49.6% (95% confidence interval, 34.6-62.9%). The incidences of grade 3/4 hematological and non-hematological toxicities were 43% and 47%, respectively. The frequent grade 3/4 toxicities included neutropenia (25%), anemia (30%), diarrhea (13%), and anorexia (17%). Intraperitoneal catheter and implanted port-related complications were observed in four patients. There was one treatment-related death. CONCLUSIONS: Intraperitoneal paclitaxel combined with S-1 and cisplatin is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Impact of comprehensive geriatric assessment on treatment strategies and complications in older adults with colorectal cancer considering surgery.

BACKGROUND AND OBJECTIVES: This study aimed to assess the effectiveness of Comprehensive Geriatric Assessment (CGA) in customizing care for elderly cancer patients, specifically focusing on colorectal cancer. The research compared treatment strategies and outcomes in older adults considered for surgery before and after the initiation of a Geriatric Oncology Service (GOS). METHODS: Conducting a comparative study, two cohorts of consecutive colorectal cancer patients aged 75 or older were examined: the control group (n = 156) and the GOS group (n = 158). Upon the treating surgeon's GOS consultation request, a geriatrician and an oncologist performed CGA, guiding treatment decisions and perioperative interventions. Postoperative complications were compared using propensity score matching (PSM). RESULTS: In the GOS group, 91% (n = 116) underwent CGA consultations, influencing decisions to forego surgery in 12 patients. After PSM for surgical cases (controls n = 146, GOS n = 146), each group comprised 128 patients. Perioperative physical therapy and pharmacist referrals were more frequent in the GOS group. The GOS group exhibited a significantly lower incidence of postoperative complications (22%) compared to the control group (33%) (p = 0.0496). CONCLUSION: Patients undergoing colorectal surgery post-GOS implementation experienced a notable reduction in postoperative complications, highlighting the positive impact of personalized geriatric assessment on surgical outcomes in the elderly.

Enhanced Clinical Utility of Molecular Budding Signature as a Recurrence Risk Determinant in Stage II and III Colon Cancer Patients.

BACKGROUND: A molecular budding signature (MBS), which consists of seven tumor budding-related genes, was recently presented as a prominent prognostic indicator in colon cancer (CC) using microarray data acquired from frozen specimens. This study aimed to confirm the predictive power of MBS for recurrence risk based on formalin-fixed, paraffin-embedded (FFPE) materials. METHODS: This research utilized the same microarray data from a prior multicenter study using FFPE whole tissue sections, which retrospectively reviewed 232 stage II CC patients without adjuvant chemotherapy and 302 stage III CC patients with adjuvant chemotherapy. All patients underwent upfront curative surgery without neoadjuvant therapy between 2009 and 2012. An MBS score was calculated using the mean of log2 [each signal] of seven genes (MSLN, SLC4A11, WNT11, SCEL, RUNX2, MGAT3, and FOXC1) as described before. RESULTS: The MBS-low group exhibited a better relapse-free survival (RFS) than the MBS-high group in stage II (P = 0.0077) and in stage III CC patients (P = 0.0003). Multivariate analyses revealed that the MBS score was an independent prognostic factor in both stage II (P = 0.0257) and stage III patients (P = 0.0022). Especially among T4, N2, or both (high-risk) stage III patients, the MBS-low group demonstrated markedly better RFS compared with the MBS-high group (P = 0.0013). CONCLUSIONS: This study confirmed the predictive power of the MBS for recurrence risk by employing FFPE materials in stage II/III CC patients.

Symptoms Contributing to the Diagnosis of Small Bowel Tumors.

INTRODUCTION: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. METHODS: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. RESULTS: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. CONCLUSION: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs.

Comprehensive registry of esophageal cancer in Japan, 2015.

BACKGROUND: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan. METHODS: We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification by the Union of International Cancer Control (UICC) for cancer staging. RESULTS: A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM). CONCLUSION: We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan.

RAD51 Expression as a Biomarker to Predict Efficacy of Preoperative Therapy and Survival for Esophageal Squamous Cell Carcinoma: A Large-cohort Observational Study (KSCC1307).

OBJECTIVE: The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). BACKGROUND: It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. METHODS: A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. RESULTS: In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (≥50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. CONCLUSIONS: In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression.

Comparison of laparoscopic surgery with open standard surgery for advanced gastric carcinoma in a single institute: a propensity score matching analysis.

BACKGROUND: Compared with open standard gastrectomy (OG), laparoscopic gastrectomy (LG) did not result in inferior disease-free survival for early-stage and locally advanced gastric cancer (AGC). However, whether LG for AGC in elderly patients is more beneficial than OG is unclear. METHODS: This study examined 458 patients with AGC. The mortality, morbidity, and prognosis were compared by age, gender, T and N factors, and pathological stage in the LG and OG groups using propensity score matching analysis. For the final analysis, 151 pairs of patients were selected from at each group. RESULTS: The results showed that no significant difference in mortality and morbidity existed between the two groups. The 5-year relapse-free survival (RFS) rates were 70% and 62% in the LG and OG groups, respectively (p = 0.104). The 5-year RFS rates in patients with pathological stages I, II, and III who had undergone LG were 84%, 80%, and 55%, respectively, and 78%, 70%, and 45%, respectively, in those who had undergone OG (p < 0.005). The 5-year RFS rates in nonelderly patients who underwent LG or OG were 75% and 68%, respectively, and 58% and 40%, respectively, in elderly patients who underwent LG or OG (p < 0.005). CONCLUSION: The 5-year RFS rates in patients with AGC at each stage did not significantly differ between LG and OG. However, the benefits at 5-year RFS in patients who underwent LG compared with OG were larger in elderly patients than those in nonelderly patients.

Indications for conversion hepatectomy for initially unresectable colorectal cancer with liver metastasis.

PURPOSE: Selected patients with initially unresectable colorectal cancer (CRC) and liver metastases undergo conversion surgery after appropriate chemotherapy. The prognosis of these patients is good, with some even cured of the disease. This retrospective, single-institution study analyzes the clinical importance of patient characteristics on the outcomes of conversion hepatectomy. METHODS: We evaluated 229 consecutive patients with initially unresectable CRC and liver metastasis, who underwent systemic chemotherapy. The patients were assigned to groups depending on conversion hepatectomy. RESULTS: Conversion hepatectomy was performed in 30 patients (13.1%). The proportion of patients with extrahepatic metastasis was significantly lower in the conversion group than in the unresectable group (30.0 vs. 66.8%; P < 0.01). The rate of left-sided primary colorectal tumors was significantly higher in the conversion group than in the unresectable group (96.7 vs. 65.8%; P < 0.01). Multivariate analyses identified that left-sided tumors, no extrahepatic metastasis, H1 or H2 grade CLM, and treatment with molecular-targeted agents were associated with conversion hepatectomy (odds ratios: 16.314, 4.216, 7.631, and 4.070; P < 0.01). Overall survival was significantly longer in the conversion group than in the unresectable group (MST: 50.0 versus 14.7 months; P < 0.01). CONCLUSION: Left-sided primary tumors, absence of extrahepatic metastases, H1 or H2 grade, and use of molecular-targeted agents were associated with successful conversion hepatectomy; thus, patients with these characteristics may be candidates for conversion therapy.

Clinicopathological features and prognosis of gastric tube cancer after esophagectomy for esophageal cancer: a nationwide study in Japan.

BACKGROUND: Survivors of esophageal cancer post-esophagectomy may sometimes develop gastric tube cancer (GTC). However, its clinical characteristics have not been elucidated. We conducted a retrospective nationwide survey of GTCs to clarify them. METHODS: A questionnaire on GTCs was sent by e-mail and mail to 116 institutions certified by the Japan Esophageal Society. A total of 608 GTC cases diagnosed and treated between 2001 and 2015 were registered from 62 institutions. RESULTS: The median age at diagnosis was 71 years, with 88.9% being diagnosed with stage I. Sixty percent of GTC cases were in the anal third of the gastric tube and 79.7% were differentiated adenocarcinomas. The median interval between esophagectomy and GTC diagnosis was 6 years, with approximately 25% of patients being diagnosed more than 10 years later. The 5-year overall survivals (5-OSs) after endoscopic and surgical treatments for GTC were 75.9% and 52.7%, respectively. Patients whose GTC was diagnosed without symptoms or by regular follow-up examination showed better 5-OSs compared to others (69.7% vs. 41.2%, p < 0.0001; and 71.4% vs. 41.8%, p < 0.0001, respectively). The prognosis of GTC cases diagnosed within 2 years of the preceding upper gastrointestinal endoscopy (UGI) was better than that in cases diagnosed longer than 2 years (5-OS: 73.4% vs. 48.8%, p < 0.05). CONCLUSION: This nationwide survey revealed the clinicopathological features of GTCs for the first time. Early detection is important in improving the prognosis of GTC, and it is recommended that UGI endoscopy be continued every 2 years for 10 or more years after esophagectomy.

Health-related quality of life after esophagectomy in patients with esophageal cancer.

Esophageal cancer is one of the malignant tumors with the poorest prognosis. Esophagectomy, which is the mainstay of curative-intent treatments, imposes excessive surgical stress on the patients, and postoperative morbidity and mortality rates after esophagectomy remain high. On the other hand, the number of survivors after esophagectomy for esophageal cancer is increasing due to recent improvements in surgical techniques and multidisciplinary treatments for this cancer. However, esophagectomy still has a great influence on the fundamental aspect of patients' lives, that is, the health-related quality of life (HR-QOL), including their physical, emotional, and social functions in the short- and long-term postoperatively. HR-QOL is a multifactorial concept used to assess the symptoms and functional changes caused by the disease itself and treatments from the patients' perspectives. Therefore, assessing the HR-QOL of patients with esophageal cancer after esophagectomy is becoming increasingly important. However, the status of HR-QOL changes after esophagectomy has not been satisfactorily evaluated, and there is no worldwide consensus as to how the postoperative HR-QOL can be improved. This review aimed to raise awareness of healthcare providers, such as surgeons and nurses, on the importance of HR-QOL in patients with esophageal cancer after curative-intent esophagectomy by providing multifaceted information concerning the short- and long-term HR-QOLs, including the status of changes and the determinants of HR-QOL after esophagectomy, and furthermore, essential points for improvement of HR-QOL after esophagectomy.

Nationwide survey of the follow-up practices for patients with esophageal carcinoma after radical treatment: historical changes and future perspectives in Japan.

BACKGROUND: No post-treatment follow-up methods have been established yet for patients with esophageal carcinoma who undergo radical esophagectomy (Surg) or who show complete response to definitive chemoradiotherapy (dCRT-CR). The purpose of this study was to investigate the current status of follow-up of the Surg and dCRT-CR patients in Japan, and understand the current reality and problems to establish an optimal follow-up method. METHODS: A questionnaire on the follow-up method adopted was sent by e-mail to 124 institutions approved by the Japan Esophageal Society as training institutions for board-certified esophageal surgeons; responses were received from 89 institutions. The data were compared with those obtained by a similar survey conducted in 2014. RESULTS: Follow-up methods markedly varied among institutions. Almost all institutions scheduled computed tomography and upper gastrointestinal endoscopy at least once a year up to postoperative year 5 for both the Surg and dCRT-CR groups. At least 70% of the institutions continued follow-up up to postoperative year 10, and this proportion had increased as compared to that reported from the 2014 survey. Only 25-30% of the institutions scheduled follow-up screening for metachronous head and neck cancer for both groups, and the health-related quality of life (HR-QOL) after the treatment were seldom assessed. These trends remained unchanged as compared to those reported from the 2014 survey. CONCLUSIONS: The results suggest that the consensus of follow-up protocol could not be established. More attention is required for detection of metachronous cancers and assessment of the HR-QOL. Establishment of a consensus-based follow-up system and verification of its effectiveness are required.

Immunogenic characteristics of microsatellite instability-low esophagogastric junction adenocarcinoma based on clinicopathological, molecular, immunological and survival analyses.

Microsatellite instability (MSI) is categorized by mutation frequency: high MSI (MSI-H), low MSI (MSI-L) and microsatellite stable (MSS). MSI-H tumors have a distinct immunogenic phenotype, with immunotherapies using checkpoint inhibitors already approved for the treatment of MSI-H gastroesophageal adenocarcinoma (GEA); this is not observed for MSI-L or MSS. Here, we tested the hypothesis that MSI-L tumors are also a distinct phenotype and potentially immunogenic. MSI-PCR assays (BAT25, BAT26, BAT40, D2S123, D5S346 and D17S250) were performed on 363 Epstein-Barr virus-negative, surgically resected esophagogastric junction (EGJ) adenocarcinoma samples. Tumors were characterized as MSI-H (≥2 markers), MSI-L (1 marker) or MSS (0 markers). CD8+ cell counts, PD-L1 and HER2 expression levels, TP53 mutations, epigenetic alterations and prognostic significance were also examined. All pathological and molecular experiments were conducted using serial, whole-tumor sections of chemo-naïve surgical specimens. MSI-H and MSI-L were assigned to 28 (7.7%) and 24 (6.6%) cases, respectively. Compared to MSS cases, MSI-L cases had significantly higher intratumoral CD8+ cell infiltration (P = .048) and favorable EGJ cancer-specific survival (multivariate hazard ratio = 0.35, 95% CI, 0.12-0.82; P = .012). MSI-L tumors were also significantly associated with TP53-truncating mutations as compared to MSI-H (P = .009) and MSS (P = .012) cases, and this trend was also observed in GEA data from The Cancer Genome Atlas (TCGA). Indel mutational burden among TCGA MSI-L tumors was significantly higher than that of MSS tumors (P = .016). These results suggest that MSI-L tumors may have a distinct tumor phenotype and be potentially immunogenic in EGJ adenocarcinoma.

A 10-Item Frailty Index Based on a Comprehensive Geriatric Assessment (FI-CGA-10) in Older Adults with Cancer: Development and Construct Validation.

BACKGROUND: A frailty index (FI) based on domain-level deficits identified through a comprehensive geriatric assessment (CGA) has been previously developed and validated in general geriatric patients. Our objectives were to construct an FI-CGA and to assess its construct validity in the geriatric oncology setting. METHODS: Five hundred forty consecutive Japanese patients with cancer who underwent a CGA on a geriatric oncology service were included (median age 80 years, range 66-96 years). We developed a 10-item frailty index based on deficits in 10 domains (FI-CGA-10): cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. Deficits in each domain were scored as 0 (no problem), 0.5 (minor problem), and 1.0 (major problem). Scores were calculated by dividing the sum of the scores for each domain by 10 and then categorized as fit (<0.2), pre-frail (0.2-0.35), and frail (>0.35). Construct validity was tested by correlating the FI-CGA-10 with other established frailty measures. RESULTS: FI-CGA-10 was well approximated by the gamma distribution. Overall, 20% of patients were fit, 41% were pre-frail, and 39% were frail. FI-CGA-10 was correlated with Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (r = 0.83), CSHA rules-based frailty definition (r = 0.67), and CSHA Function Score (r = 0.77). Increasing levels of frailty were significantly associated with functional and cognitive impairments, high comorbidity burden, poor self-rated health, and low estimated survival probabilities. CONCLUSION: The FI-CGA-10 is a user-friendly and construct-validated measure for quantifying frailty from a CGA. IMPLICATIONS FOR PRACTICE: This article describes the construction of a user-friendly 10-item frailty index based on a comprehensive geriatric assessment (FI-CGA-10) for older adults with cancer: cognition, mood, communication, mobility, balance, nutrition, basic and instrumental activities of daily living, social support, and comorbidity. The FI-CGA-10 simplifies the original FI-CGA used in the general geriatric setting while maintaining its content validity. The index's construct validity was demonstrated in a cohort of older adults with various cancer types. The advantage of the FI-CGA-10 is that a frailty score can be calculated more readily and interpreted in a more clinically sensible manner than the original FI-CGA.

Evaluation of a 55-gene classifier as a prognostic biomarker for adjuvant chemotherapy in stage III colon cancer patients.

BACKGROUND: Adjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. METHODS: We retrospectively identified patients aged 20-79 years, with stage III CC, who received adjuvant chemotherapy with or without oxaliplatin, between the years 2009 and 2012. RESULTS: Among 938 eligible patients, 203 and 201 patients who received adjuvant chemotherapy with and without oxaliplatin, respectively, were selected by propensity score matching. Of these, 95 patients from each group were analyzed, and their 5-year relapse-free survival (RFS) rates with and without oxaliplatin were 73.7 and 77.1%, respectively. The hazard ratios for 5-year RFS following adjuvant chemotherapy (fluoropyrimidine), with and without oxaliplatin, were 1.241 (95% CI, 0.465-3.308; P = 0.67) and 0.791 (95% CI, 0.329-1.901; P = 0.60), respectively. Stratification using the 55GC revealed that 52 (27.3%), 78 (41.1%), and 60 (31.6%) patients had microsatellite instability (MSI)-like, chromosomal instability (CIN)-like, and stromal subtypes, respectively. The 5-year RFS rates were 84.3 and 72.0% in patients treated with and without oxaliplatin, respectively, for the MSI-like subtype (HR, 0.495; 95% CI, 0.145-1.692; P = 0.25). No differences in RFS rates were noted in the CIN-like or stromal subtypes. Stratification by cancer sidedness for each subtype showed improved RFS only in patients with left-sided primary cancer treated with oxaliplatin for the MSI-like subtype (P = 0.007). The 5-year RFS rates of the MSI-like subtype in left-sided cancer patients were 100 and 53.9% with and without oxaliplatin, respectively. CONCLUSIONS: Subclassification using 55GC and tumor sidedness revealed increased RFS in patients within the MSI-like subtype with stage III left-sided CC treated with fluoropyrimidine and oxaliplatin compared to those treated without oxaliplatin. However, the predictive power of 55GC subtyping alone did not reach statistical significance in this cohort, warranting larger prospective studies. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Education Network (UMIN) clinical trial registry (UMIN study ID: 000023879 ).

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Feasibility of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma: a multi-center experience.

PURPOSE: Patients with liver metastasis of head-and-neck carcinoma and esophageal carcinoma are generally not treated with hepatic resection, but there are no established standard treatment methods. We report 11 cases of hepatic resection for liver metastasis of head-and-neck carcinoma or esophageal carcinoma performed at 5 Japanese institutions. METHODS: The subjects of this retrospective analysis were 11 patients who underwent hepatic resection for metastatic liver tumors, originating from head-and-neck carcinoma in 5 and from esophageal cancer in 6, between January, 2010 and March, 2020 RESULTS: There were nine men and two women (median age, 64 years; range 40-72 years). The primary disease was esophageal carcinoma in six patients and pharyngeal carcinoma in five patients. All cancers were squamous cell carcinoma. The time from the initial treatment to the diagnosis of liver metastasis was 15.3 months and the 1-year and 3-year overall survival rates after hepatic resection were 72% and 32%, respectively. The overall and disease-free survival rates after hepatic resection were significantly higher for patients who underwent hepatic resection more than 12 months after the initial treatment than for those who underwent hepatic resection within 12 months after the initial treatment (p = 0.0172 and p = 0.0120, respectively). CONCLUSIONS: Liver resection may prolong the survival of patients with liver metastases controlled for more than 12 months after the initial treatment of head and neck or esophageal carcinoma.

Altered serum profile of the interleukin-22 system in inflammatory bowel disease.

BACKGROUND AND AIM: Interleukin-22 (IL-22), plays a vital role in the mucosal repair of inflammatory bowel disease (IBD). Serum levels of IL-22 and IL-22 binding protein (IL-22BP), a soluble inhibitory IL-22 receptor, were measured in patients with IBD to investigate the profile of IL-22 in the systemic circulation. METHODS: Blood samples from 92 healthy subjects, 98 patients with ulcerative colitis (UC), and 105 patients with Crohn's disease (CD) were analyzed for serum levels of IL-22, IL-22BP, human ß-defensin 2 (hBD-2), and serum inflammatory parameters. Disease activity was assessed by the partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS: Serum IL-22 level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and its decrease was more pronounced in CD than in UC (P = 0.019). Serum IL-22BP level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and correlated with inflammatory parameters (albumin and C-reactive protein (CRP) in UC; hemoglobin, albumin, and CRP in CD). Serum IL-22/IL-22BP ratios were higher in UC (P = 0.009) vs control and correlated with inflammatory parameters (albumin and CRP). Serum hBD-2 level was higher only in CD (P = 0.015) but did not correlate with serum IL-22 levels, IL-22BP levels, IL-22/IL-22BP ratios, or inflammatory parameters. CONCLUSIONS: Dysregulation of the IL-22 system in the blood may play a role in the pathogenesis of IBD. Further studies are needed to understand the pathogenic and clinical significance of the blood IL-22 system in IBD.

A Validation Study for Recurrence Risk Stratification of Stage II Colon Cancer Using the 55-Gene Classifier.

INTRODUCTION: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). OBJECTIVE: Here, we validate the 55GC specifically for stage II CC and compare it with CMS categories. METHODS: Tissue sections from 232 stage II CC patients who underwent curative surgery without adjuvant chemotherapy between 2009 and 2012 were subjected to DNA microarray analysis. RESULTS: Based on the 55GC, patients were classified into microsatellite instability-like (27%), chromosomal instability-like (41%), and stromal (32%) subtypes with 5-year relapse-free survival (RFS) rates of 88.5, 83.3, and 71.2%, respectively (stromal vs. others: p = 0.0049). Multivariate analysis by Cox's proportional hazard model revealed that the stromal subtype, pT4, and the number of lymph nodes examined (<12) were independent poor prognostic factors. The overall concordance rate between 55GC and CMS was 72%, and 5-year RFS rates of patients with CMS1, CMS2, CMS3, and CMS4 cancers were 100, 85.5, 92.3, and 73.0%, respectively (p = 0.0113). CONCLUSIONS: We conclude that the 55GC is a useful and reproducible grading system for stage II CC recurrence risk stratification.

Prognostic Impact of the Neutrophil-to-Lymphocyte Ratio in Stage I-II Rectal Cancer Patients.

BACKGROUND: Systemic inflammation and immune response play crucial roles in tumor growth; neutrophil-to-lymphocyte ratio (NLR) is a known systemic inflammatory scoring system. Previous studies have reported that NLR is a prognostic biomarker in various human cancers. The aim of this study was to determine whether the NLR predicts tumor recurrence in patients with stage I-II rectal cancer after curative resection. METHODS: We retrospectively analyzed 130 consecutive patients with stage I-II rectal cancer who underwent curative resection between January 2006 and March 2015 at our institution without any preoperative treatment. We investigated whether clinicopathologic factors including NLR were associated with cancer recurrence after curative surgery. RESULTS: There were four cases (3.1%) of cancer-specific deaths and 16 cases (12.3%) of recurrence; the 5-year disease-free survival rate was 85.6%. NLR, pathologic T-category, and lymphatic invasion were significantly associated with disease-free survival. Multivariate analysis further showed that these three factors were independently associated with disease-free survival. CONCLUSIONS: Preoperative NLR could predict tumor relapse in stage I-II rectal cancer and might be a useful biomarker for predicting recurrence in patients undergoing curative resection.

Esophageal Position Affects Short-Term Outcomes After Minimally Invasive Esophagectomy: A Retrospective Multicenter Study.

BACKGROUND: Anatomical esophageal position may affect the short-term outcomes after minimally invasive esophagectomy (MIE). A previous single-institutional retrospective study suggested that the presence of a left-sided esophagus (LSE) made MIE more difficult and increased the incidence of postoperative complications. METHODS: The current study was a multicenter retrospective study of 303 patients with esophageal cancer who underwent MIE at six esophageal cancer high-volume centers in Kyushu, Japan, between April 2011 and August 2016. The patients were divided into the LSE (66 patients) and non-LSE groups (237 patients) based on the esophageal position on computed tomography images obtained with the patients in the supine position. RESULTS: Univariate analysis showed that patients with LSE were significantly older than those with non-LSE (69 ± 8 vs. 65 ± 9 years; P = 0.002), had a significantly greater incidence of cardiovascular comorbidity (65.2% vs. 47.7%; P = 0.013), and a significantly longer operating time (612 ± 112 vs. 579 ± 102 min; P = 0.025). Logistic regression analysis verified that LSE was an independent risk factor for the incidence of pneumonia (odds ratio 3.3, 95% confidence interval 1.254-8.695; P = 0.016). CONCLUSIONS: The presence of a LSE can increase the procedural difficulty of MIE and the incidence of morbidity after MIE. Thus, careful attention must be paid to anatomical esophageal position before performing MIE.