Clinical Utility of ypTNM Stage Grouping in the 8th Edition of the American Joint Committee on Cancer TNM Staging System for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. OBJECTIVE: This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). METHODS: We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. RESULTS: Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. CONCLUSIONS: ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

Anatomic location of residual disease after initial cholecystectomy independently determines outcomes after re-resection for incidental gallbladder cancer.

PURPOSE: This study aimed to elucidate the impact of anatomic location of residual disease (RD) after initial cholecystectomy on survival following re-resection of incidental gallbladder cancer (IGBC). METHODS: Patients with pT2 or pT3 gallbladder cancer (36 with IGBC and 171 with non-IGBC) who underwent resection were analyzed. Patients with IGBC were classified as follows according to the anatomic location of RD after initial cholecystectomy: no RD (group 1); RD in the gallbladder bed, stump of the cystic duct, and/or regional lymph nodes (group 2); and RD in the extrahepatic bile duct and/or distant sites (group 3). RESULTS: Timing of resection (IGBC vs. non-IGBC) did not affect survival in either multivariate or propensity score matching analysis. RD was found in 16 (44.4%) of the 36 patients with IGBC; R0 resection following re-resection was achieved in 32 patients (88.9%). Overall survival (OS) following re-resection was worse in group 3 (n = 7; 5-year OS, 14.3%) than in group 2 (n = 9; 5-year OS, 55.6%) (p = 0.035) or in group 1 (n = 20; 5-year OS, 88.7%) (p < 0.001). There was no survival difference between groups 1 and 2 (p = 0.256). Anatomic location of RD was independently associated with OS (group 2, HR 2.425, p = 0.223; group 3, HR 9.627, p = 0.024). CONCLUSION: The anatomic location of RD independently predicts survival following re-resection, which is effective for locoregional disease control in IGBC, similar to resection for non-IGBC. Not all patients with RD have poor survival following re-resection for IGBC.

Long-Term Trends in Respiratory Function After Esophagectomy for Esophageal Cancer.

BACKGROUND: Esophagectomy for esophageal cancer is known to lead to deterioration in respiratory function (RF). The aim of this study was to assess long-term trends in RF after esophagectomy and the impact of different operative procedures. METHODS: A total of 52 patients with thoracic esophageal cancer who were scheduled for esophagectomy from 2003 to 2012 were enrolled. We prospectively evaluated patients for vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and 6-min walk distance (6MWD) before and after esophagectomy at 3, 6, 12, 24, and 60 mo. RESULTS: Patients had mostly recovered their VC and FEV1.0 after 12 mo. After that point, VC and FEV1.0 declined again, reaching levels lower than baseline at 60 mo, with a median change ratio of 0.85 and 0.86, respectively. Although the 6MWD after open esophagectomy declined, patients treated with transhiatal esophagectomy and minimally invasive esophagectomy maintained above baseline levels throughout the follow-up period. Furthermore, we identified transhiatal esophagectomy (odds ratio [OR] = 0.03, 95% confidence interval [CI] 0.002-0.43, P = 0.01) and minimally invasive esophagectomy (OR = 0.14, 95% CI 0.02-0.94, P = 0.04) as favorable factors and postoperative pulmonary complication (OR = 9.14, 95% CI 1.22-68.6, P = 0.03) as an unfavorable factor for RF after 12 mo. Operative procedures had no significant impact on RF after 60 mo. CONCLUSIONS: Our results support the notion that RF does not recover to the baseline level, and operative procedures have no significant impact on RF at late phase after esophagectomy.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Palliative interventions for patients with incurable locally advanced or metastatic thoracic esophageal carcinoma.

BACKGROUND: The aim of this study was to assess the clinical outcomes of palliative interventions for patients with incurable locally advanced or metastatic esophageal carcinoma. METHODS: A total of 131 patients with thoracic esophageal carcinoma who underwent palliative interventions were enrolled. Insertion of a self-expandable metallic stent (SEMS), tube enterostomy for enteral nutrition (EN), and palliative esophagectomy (PE) were performed in 38, 65, and 28 patients, respectively. The clinicopathological characteristics and clinical outcomes of each group were retrospectively reviewed. RESULTS: Patients in the EN group frequently received chemoradiotherapy (P < 0.01). SEMS insertion, but not PE or EN, improved the mean dysphagia score after the intervention (P < 0.01). For the SEMS, EN, and PE groups, the occurrence of intervention-related complications was 31.6, 10.8, and 96.4%, respectively, the median survival time was 88, 208, and 226 days (P < 0.01), and the mean ratio of duration of home care to survival time was 28.9, 38.5, and 39.6% (P = 0.95). CONCLUSIONS: SEMS insertion effectively relieved obstructive symptoms, but had no survival benefit. Tube enterostomy showed a low complication rate and has the potential to improve survival in combination with additional treatment, with no palliation of obstructive symptoms.

Association between poorly differentiated clusters and efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer.

OBJECTIVE: Although poorly differentiated cluster has been reported to be a useful grading system for predicting prognosis in colorectal cancer, its relationship to chemotherapy efficacy has not been demonstrated. We aimed to investigate the association between poorly differentiated cluster and the efficacy of 5-fluorouracil-based adjuvant chemotherapy in stage III colorectal cancer. METHODS: This retrospective study enrolled 131 patients with stage III colorectal cancer who underwent curative resection: 72 received 5-fluorouracil-based adjuvant chemotherapy (chemotherapy group) and 59 did not (surgery-alone group). Poorly differentiated cluster was defined as a cancer cluster of ≥5 cancer cells without gland-like structure, and was classified into poorly differentiated cluster G1, G2 and G3 according to the number of clusters. The benefit of 5-fluorouracil-based adjuvant chemotherapy was evaluated based on poorly differentiated cluster grade. RESULTS: Thirty-nine, 40 and 52 patients were classified as poorly differentiated cluster G1, G2 and G3, respectively. Significant differences in the 5-year cumulative recurrence rate and relapse-free survival were observed between poorly differentiated cluster G1/G2 and G3 (26.7% vs. 47.5%, P = 0.010; 66.0% vs. 43.9%, P = 0.004). A comparison of cumulative recurrence rate and relapse-free survival between the chemotherapy and surgery-alone groups showed a significant benefit of adjuvant chemotherapy in poorly differentiated cluster G1/G2 patients (cumulative recurrence rate: 17.4% vs. 37.3%, P = 0.035; relapse-free survival: 79.5% vs. 51.9%, P = 0.002), but not in poorly differentiated cluster G3 patients (cumulative recurrence rate: 48.6% vs. 44.8%, P = 0.885; relapse-free survival: 51.4% vs. 32.7%, P = 0.068). CONCLUSIONS: In stage III colorectal cancer, poorly differentiated cluster G1/G2 predicts a significant benefit from 5-fluorouracil-based adjuvant chemotherapy, whereas poorly differentiated cluster G3 predicts a poor response to it.

Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma.

BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.

Clinical Significance of Extramural Tumor Deposits in the Lateral Pelvic Lymph Node Area in Low Rectal Cancer: A Retrospective Study at Two Institutions.

BACKGROUND: The presence of extramural tumor deposits without lymph node structure (EX) is an important prognostic factor for patients with colorectal cancer. However, the clinical significance of EX in the lateral pelvic lymph node area (LP-EX) remains unclear. This study aimed to determine the prognostic implications of LP-EX for patients with low rectal cancer. METHODS: This retrospective study involved 172 consecutive patients with stage 2 or 3 low rectal cancer who underwent curative surgery including lateral pelvic lymph node (LPLN) dissection. The patients were classified into the following three groups according to the metastatic status of the LPLN area: patients without metastasis (no-LP-M group), patients with lymph node metastasis (LP-LNM group), and patients with EX (LP-EX group). Potential prognostic factors of overall survival (OS) and relapse-free survival (RFS) were identified in uni- and multivariate analyses. RESULTS: Classification assigned 131 patients (76 %) to the no-LP-M group, 27 patients (16 %) to the LP-LNM group, and 14 patients (8 %) to the LP-EX group. The 5-year OS rate was 80.3 % in the no-LP-M group, 61.1 % in the LP-LNM group, and 34.9 % in the LP-EX group (P < 0.001). The corresponding 5-year RFS rates were 62.2, 33.8, and 14.3 %, respectively (P < 0.001). A multivariate Cox proportional hazards regression analysis showed that the presence of LP-EX was an independent prognostic factor for OS (P = 0.006) and RFS (P = 0.001). CONCLUSIONS: The LP-EX classification is a useful pathologic parameter that can be used to stratify patients with metastasis in the LPLN area.

Tumor Budding Detection by Immunohistochemical Staining is Not Superior to Hematoxylin and Eosin Staining for Predicting Lymph Node Metastasis in pT1 Colorectal Cancer.

BACKGROUND: Tumor budding is recognized as an important risk factor for lymph node metastasis in pT1 colorectal cancer. Immunohistochemical staining for cytokeratin has the potential to improve the objective diagnosis of tumor budding over detection based on hematoxylin and eosin staining. However, it remains unclear whether tumor budding detected by immunohistochemical staining is a significant predictor of lymph node metastasis in pT1 colorectal cancer. OBJECTIVE: The purpose of this study was to clarify the clinical significance of tumor budding detected by immunohistochemical staining in comparison with that detected by hematoxylin and eosin staining. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at Niigata University Medical & Dental Hospital. PATIENTS: We enrolled 265 patients with pT1 colorectal cancer who underwent surgery with lymph node dissection. MAIN OUTCOME MEASURES: Tumor budding was evaluated by both hematoxylin and eosin and immunohistochemical staining with the use of CAM5.2 antibody. Receiver operating characteristic curve analyses were conducted to determine the optimal cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining. Univariate and multivariate analyses were performed to identify the significant factors for predicting lymph node metastasis. RESULTS: Receiver operating characteristic curve analyses revealed that the cutoff values for tumor budding detected by hematoxylin and eosin and CAM5.2 staining for predicting lymph node metastases were 5 and 8. On multivariate analysis, histopathological differentiation (OR, 6.21; 95% CI, 1.16-33.33; p = 0.03) and tumor budding detected by hematoxylin and eosin staining (OR, 4.91; 95% CI, 1.64-14.66; p = 0.004) were significant predictors for lymph node metastasis; however, tumor budding detected by CAM5.2 staining was not a significant predictor. LIMITATIONS: This study was limited by potential selection bias because surgically resected specimens were collected instead of endoscopically resected specimens. CONCLUSIONS: Tumor budding detected by CAM5.2 staining was not superior to hematoxylin and eosin staining for predicting lymph node metastasis in pT1 colorectal cancer.

Risk Factors and Clinical Outcomes of Recurrent Laryngeal Nerve Paralysis After Esophagectomy for Thoracic Esophageal Carcinoma.

BACKGROUND: The objectives of this study were to assess the incidence of recurrent laryngeal nerve paralysis (RLNP) using laryngoscopy after esophagectomy for thoracic esophageal carcinoma and to clarify the risk factors influencing postoperative RLNP. METHODS: A total of 299 patients who underwent laryngoscopic examination after esophagectomy were retrospectively reviewed. Patients who were found to have postoperative RLNP were followed up every 1­3 months, with a median follow-up period of 3 months. Recovery from paralysis was also evaluated on the basis of each affected nerve. Multivariate analyses using logistic regression were used to identify independent risk factors for RLNP. Cumulative recovery rate was calculated using Kaplan­Meier method. RESULTS: A total of 178 (59.5%) patients were diagnosed with RLNP by first laryngoscopy [bilateral in 59 (33.1%) patients, right in 15 (8.4%), and left in 104 (58.4%)]. In 206 patients who underwent transthoracic and thoracoscopic esophagectomy, independent risk factors for RLNP were lymph node dissection along the right RLN (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.06­8.54, P = 0.04) and cervical anastomosis (OR 5.94, 95% CI 1.78­19.80, P < 0.01). Cumulative recovery rate from RLNP was 61.7% at 12 months after esophagectomy with 91 nerves eventually recovering from paralysis. Median recovery time was 6 months. CONCLUSIONS: RLNP developed in 60 % of patients after esophagectomy and may be associated with lymphadenectomy around the right RLN and cervical esophageal mobilization. Although 62% of affected nerves recovered within 12 months, great attention should be given when performing these procedures.

Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors.

BACKGROUND: Patients undergoing imatinib therapy for gastrointestinal stromal tumors (GISTs) show drug resistance during treatment in the late stages. The aims of this study were to determine survival after the appearance of imatinib secondary resistance (ISR) and to identify the prognostic factors. METHODS: Eligible were patients with unresectable and metastatic GISTs who were diagnosed with ISR and/or underwent treatment for ISR in our institution between 2001 and 2012. A total of 48 patients were enrolled and overall survival was retrospectively analyzed. The Cox proportional hazards model was used to identify the independent prognostic factors. Median follow-up time was 58 months. RESULTS: As of the cutoff date, 41 of the 48 patients with ISR had died, of which 39 died of GISTs. The overall 1-, 3-, and 5-year survival rates of the 48 patients were 64.6, 32.8, and 20.4 %, respectively, and median survival time was 22 months. The favorable independent prognostic factors identified were long progression-free survival in first-line imatinib therapy (P = 0.04), small diameter of progressive disease (PD) (P = 0.02), and surgical resection of PD (P = 0.01). CONCLUSION: Surgical resection of PD in selected cases could improve prognosis in ISR patients undergoing GIST treatment.

DNA damage response and sphingolipid signaling in liver diseases.

Patients with unresectable hepatocellular carcinoma (HCC) cannot generally be cured by systemic chemotherapy or radiotherapy due to their poor response to conventional therapeutic agents. The development of novel and efficient targeted therapies to increase their treatment options depends on the elucidation of the molecular mechanisms that underlie the pathogenesis of HCC. The DNA damage response (DDR) is a network of cell-signaling events that are triggered by DNA damage. Its dysregulation is thought to be one of the key mechanisms underlying the generation of HCC. Sphingosine-1-phosphate (S1P), a lipid mediator, has emerged as an important signaling molecule that has been found to be involved in many cellular functions. In the liver, the alteration of S1P signaling potentially affects the DDR pathways. In this review, we explore the role of the DDR in hepatocarcinogenesis of various etiologies, including hepatitis B and C infection and non-alcoholic steatohepatitis. Furthermore, we discuss the metabolism and functions of S1P that may affect the hepatic DDR. The elucidation of the pathogenic role of S1P may create new avenues of research into therapeutic strategies for patients with HCC.

Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis.

Prognostic markers are urgently needed to optimize the postoperative treatment strategies for gastrointestinal stromal tumors (GIST). GIST of the small intestine (I-GIST) show more aggressive behavior than those of the stomach (S-GIST), and the molecular background of the malignancy in I-GIST may include potential prognostic biomarkers. We conducted integrated proteomic and transcriptomic analysis to identify genes showing differential expressions according to the tumor site. We generated protein expression profiles for four cases each of surgically resected I-GIST and S-GIST using label-free proteomic analysis. For proteins showing differential expressions, global mRNA expression was compared between 9 I-GIST and 23 S-GIST. Among the 2555 genes analyzed, we found that promyelocytic leukemia (PML), a tumor suppressor gene, was significantly downregulated in I-GIST at both the protein and mRNA levels (P < 0.01; fold difference ≥2.0). Immunohistochemistry of 254 additional cases from multiple clinical facilities showed that PML-negative cases were significantly frequent in the I-GIST group (P < 0.001). The 5-year recurrence-free survival rate was significantly lower in the PML-negative than in the PML-positive cases (60.1% vs 91.7%; P < 0.001). Multivariate analysis revealed that downregulation of PML was an independent unfavorable prognostic factor (hazard ratio = 2.739; P = 0.001). Our study indicated that prognostication based on PML expression may have potential for optimizing the treatment strategy for GIST patients. Further validation studies of PML for clinical application, and investigation for the mechanistic significance of PML to clarify the molecular backgrounds of malignancy in GIST are warranted.

Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303).

Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

Incidence and Risk Factors for Anastomotic Stricture after Esophagectomy with Gastric Tube Reconstruction.

BACKGROUND/AIMS: The aim of this study was to investigate the incidence and risk factors for anastomotic stricture after esophagectomy with gastric tube reconstruction. METHODOLOGY: A total of 150 consecutive patients with esophageal cancer who underwent esophagectomy with gastric tube reconstruction were analyzed in this study. Anastomotic stricture was de fined as disturbance of the passage of a standard endo scope, with no evidence of locoregional cancer recurrence. Cumulative incidence was calculated using the Kaplan-Meier method. A total of 38 clinicopathological variables were assessed to elucidate the risk factors by univariate and multivariate analyses. RESULTS: Anastomotic stricture developed in 61 of 150 patients 41%). The cumulative incidences were 34.2% at 6 months, and 37.9% at 12 months. Fifty-seven patients (93%) developed anastomotic stricture within 12 months after esophagectomy. A low preoperative partial pressure of arterial oxygen (odds ratio, 2.23; 95% confidence interval, 1.10-4.55; p = 0.027) and the presence of postoperative complications of Grade 3 or higher (3.05; 1.04-9.00; p = 0.043) were identified as the independent risk factors. CONCLUSIONS: The incidence of anastomotic stricture after esophagectomy was high. A modification of anastomotic procedure may be necessary for patients with a low preoperative partial pressure of arterial oxygen to prevent the development of stricture.

Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer.

PURPOSE: Perineural invasion (PN) diagnosed by hematoxylin-eosin (HE) staining is an important prognostic factor after curative-intent surgery in patients with colorectal cancer. However, the clinical significance of PN diagnosed by immunohistochemistry (IHC) has not been investigated. The present study assessed the clinical significance of PN diagnosed by IHC with an anti-S100 antibody in patients with colorectal cancer. METHODS: We retrospectively enrolled 184 consecutive patients with stage I-III colorectal cancer who had undergone curative-intent surgery. We analyzed the absence/presence of PN diagnosed by HE staining (HE-PN) compared to that diagnosed by IHC with the anti-S100 antibody (S100-PN). Potential prognostic factors were identified by univariate and multivariate analyses of the overall and relapse-free survival. The [Formula: see text] statistics were used to assess the inter-observer reproducibility. RESULTS: The incidence of HE-PN and S100-PN among the 184 patients was 60 patients (32.6%) and 113 patients (61.4%), respectively (P < 0.001). A multivariate Cox proportional hazards regression model analysis indicated that S100-PN was an independent prognostic factor for both the overall and relapse-free survival. The [Formula: see text] value was 0.77 for S100-PN and 0.47 for HE-PN. CONCLUSION: PN diagnosed by IHC is an important prognostic factor in patients with colorectal cancer. An inter-observer assessment showed superior judgment reproducibility for S100-PN compared with HE-PN.

[Usefulness of Palliative Gastrojejunal Bypass Surgery].

OBJECTIVES: The aim of this study was to evaluate the usefulness of gastrojejunal bypass surgery performed in patients presenting with upper gastrointestinal tract obstruction due to unresectable advanced cancer. SUBJECTS AND METHODS: The subjects were 21 patients who underwent gastrojejunal bypass surgery at our division between 2010 and 2014 for symptom palliation. We retrospectively evaluated the operative outcomes, whether chemotherapy was administered, the oral ingestion period, and survival time. RESULTS: The median postoperative day of starting oral ingestion was 6 (range: 2-42), and the median period from decreased oral ingestion to death was 4 (range: 0-26) days. Twelve patients (57%) were discharged. Postoperative chemotherapy was prescribed to all the 9 patients who desired treatment. The median duration of oral digestion time was 61 days, and the median overall survival time was 92 days. CONCLUSION: Gastrojejunal bypass surgery is found to have the potential to not only make relatively long-term oral ingestion possible, but also broaden available treatment options, such as home care or chemotherapy, thereby contributing to improved quality of life.

[A Case of Long-Term Survival Following Metastasectomies of Liver Metastasis, Lung Metastasis, and Peritoneal Dissemination of Cecal Cancer].

The patient was a 73-year-old woman. She underwent right hemicolectomy and D3 lymph node dissection for cecal cancer in June 2003. Although a peritoneal dissemination was intraoperatively noted around the primary tumor lesion, it was resected concurrently and thus R0 surgery was accomplished. Postoperative adjuvant chemotherapy was not performed. During the follow-up on an outpatient basis, a solitary left lung metastasis was found and partial left upper lobectomy of the lung was performed in December 2004. A solitary liver metastasis was identified in the liver (S3), and lateral segmentectomy of the liver was performed in June 2007. The patient was alive with no evidence of recurrence 11 years and 9 months after resection of the primary lesion and 7 years and 9 months after the hepatectomy. Long-term survival can be achieved by performing resection without residual cancer even in some cases with metachronous metastatic recurrences in multiple organs. Metastasectomy should be considered proactively when the patient is in a good general condition and R0 resection is possible.