5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence Imaging for Tumor Detection: Recent Advances and Challenges.

5-Aminolevulinic acid (5-ALA) is a natural amino acid and a precursor of heme and chlorophyll. Exogenously administered 5-ALA is metabolized into protoporphyrin IX (PpIX). PpIX accumulates in cancer cells because of the low activity of ferrochelatase, an enzyme that metabolizes PpIX to heme. High expression of 5-ALA influx transporters, such as peptide transporters 1/2, in cancer cells also enhances PpIX production. Because PpIX radiates red fluorescence when excited with blue/violet light, 5-ALA has been used for the visualization of various tumors. 5-ALA photodynamic diagnosis (PDD) has been shown to improve the tumor removal rate in high-grade gliomas and non-muscular invasive bladder cancers. However, 5-ALA PDD remains a challenge as a diagnostic method because tissue autofluorescence interferes with PpIX signals in cases where tumors emit only weak signals, and non-tumorous lesions, such as inflammatory sites, tend to emit PpIX fluorescence. Here, we review the current outline of 5-ALA PDD and strategies for improving its diagnostic applicability for tumor detection, focusing on optical techniques and 5-ALA metabolic pathways in both viable and necrotic tumor tissues.

Accumulation of Uroporphyrin I in Necrotic Tissues of Squamous Cell Carcinoma after Administration of 5-Aminolevulinic Acid.

5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.

Rapid fluorescence imaging of human hepatocellular carcinoma using the ß-galactosidase-activatable fluorescence probe SPiDER-ßGal.

Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescence probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a ß-galactosidase (ß-Gal)-activatable fluorescence probe SPiDER-ßGal was examined. ß-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-ßGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, ß-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-ßGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-ßGal. SPiDER-ßGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-ßGal would help surgeons detect tumours rapidly and achieve complete liver resection.

Matrix metalloprotease-14 is a target enzyme for detecting peritoneal metastasis in gastric cancer.

BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.

Impact of Inferior Mesenteric Artery Lymph Node Metastasis on the Prognosis of Left-sided Colorectal Cancer.

BACKGROUND/AIM: This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC). PATIENTS AND METHODS: A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included. RESULTS: IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]. CONCLUSION: The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM).

ß-Galactosidase is a target enzyme for detecting peritoneal metastasis of gastric cancer.

Diagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and ß-galactosidase (ß-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. ß-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-ßGal, a fluorescent probe that can be activated by ß-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-ßGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-ßGal. The human GC samples showed significantly higher fluorescence than NP samples. ß-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.

Clinical Significance of Prognostic Nutritional Index in the Treatment of Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The prognostic nutritional index (PNI) is reported to affect postoperative complications and survival of patients with esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the clinical significance of PNI in treatment of ESCC. PATIENTS AND METHODS: Two hundred and sixty-three patients who underwent radical esophagectomy were retrospectively analyzed. PNI was calculated in the pretreatment (pre-Tx), post-neoadjuvant chemotherapy (post-NAC), and postoperative periods. RESULTS: Pre-Tx PNI positively correlated with prognosis irrespective of undergoing NAC (p<0.05). In the patients with NAC, pre-Tx PNI was one of the independent prognostic factors (p=0.04). In patients with low pre-Tx PNI, the prognosis was improved by increase of PNI after NAC (p=0.08), and two cycles of NAC significantly correlated with high post-NAC PNI (p=0.04). CONCLUSION: Pre-Tx PNI is an independent prognostic factor irrespective of NAC. Patients in whom the post-NAC PNI can be improved have a high probability of obtaining a good prognosis.

Efficacy of 5-aminolevulinic acid-mediated photodynamic therapy in a mouse model of esophageal cancer.

5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a minimally invasive therapeutic modality used in the management of various cancers, but to a lesser extent for esophageal cancer (EC). The current study investigated the antitumor effects of ALA-PDT. Human EC cells were treated with ALA, after which ALA-induced fluorescence was examined under a fluorescence microscope. The cytotoxic effects of ALA-PDT were assessed using three types of LEDs (blue, green and red) in vitro and in vivo. Subcutaneous tumor model mice was constructed with KYSE150 cells. ALA-PDT was performed once a week for 4 weeks and tumor weights were measured. A popliteal lymph node (PLN) metastasis murine model was generated using KYSE150 cells. KYSE150 cells were inoculated into the left footpad of nude mice. ALA-PDT was performed on the footpad once a week for 4 weeks. PLNs were then removed 3 weeks after the last treatment. The lymph nodes were evaluated by hematoxylin and eosin staining. Red fluorescence of protoporphyrin IX (PpIX) was observed in all EC cell lines. ALA-PDT using LEDs exerted significant antitumor effects in vitro and in vivo. The antitumor effects of ALA-PDT with blue LED were the strongest, followed by green and red LEDs. The number of metastasized PLNs was significantly smaller in the ALA-PDT group (0%) than in the control group (37.5%). The present results indicated that ALA-PDT is effective for EC.

Clinical significance of the distance between the cricoid cartilage and upper edge of the tumor using PET-CT in cervical esophageal cancer.

Cervical esophageal squamous cell carcinoma (CESCC) is less common compared with thoracic esophageal cancer, and few studies have investigated the clinicopathological features of CESCC. The present study analyzed 69 patients with CESCC who underwent various therapies at the University Hospital of Kyoto Prefectural University of Medicine between January 2000 and December 2016. The distance between the inferior border of the cricoid cartilage and upper edge of the tumor was evaluated using positron emission tomography and computed tomography. Positive and negative values indicated oral and anal directions, respectively. Using receiver operating characteristic curves, the cut-off value for laryngeal preservation was calculated as -5 mm. According to this value, the patients were divided into two groups: The short group (distance from the cricoid cartilage ≥-5 mm) and long group (distance from the cricoid cartilage <-5 mm). There were no significant differences in clinicopathological factors between the two groups except for body mass index. In univariate analysis, the 3-year overall survival rate was significantly lower in short group (45.4 vs. 79.6%; P=0.009). In multivariate analysis, short group was an independent prognostic risk factor (hazard ratio=2.65; P=0.039). This may be due to lymphatic flow around the cervical esophagus.

5-ALA-assistant automated detection of lymph node metastasis in gastric cancer patients.

BACKGROUND: 5-aminolevulinic acid (5-ALA) has been utilized for cancer diagnosis as a fluorescence probe. We have reported the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence for detecting lymph node (LN) metastasis in gastrointestinal malignancies. However, a major barrier to the fluorescence diagnosis has been that the evaluation has been highly dependent on the observers. In this study, we examined the validity of a developed device for automated detection without subjectivity. METHODS: Gastric cancer patients who received oral administration of 5-ALA (20 mg/kg) prior to surgery were enrolled. For a total of 323 LNs obtained from 64 patients, the diagnostic results of the device were compared to those of conventional histopathological examination based on hematoxylin-and-eosin-stained slides. The accuracy with the device was compared to that of stereoscopic detection with conventional fluorescence microscopy for 211 LNs from 42 patients. We used two types of image processing that we previously developed to eliminate autofluorescence of background tissues: differential and ratio methods. RESULTS: For detection of metastasis in 323 LNs, the areas under the receiver operating characteristic curves with the differential method and ratio method were 0.921 and 0.909, respectively. The sensitivity, specificity, and accuracy with the differential method were 78.0%, 96.8%, and 94.4%; while those with the ratio method were 78.0%, 96.1%, and 93.8%, respectively. In 211 LN analysis, the diagnostic accuracy with the device was comparable to that of stereoscopic examination. CONCLUSION: Our device for automated detection of LN metastasis using 5-ALA can be a useful tool for intraoperative diagnosis.

Utility of continuous glucose monitoring following gastrectomy.

BACKGROUND: Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. METHODS: We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. RESULTS: We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CONCLUSIONS: CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

Value of intra-tumor heterogeneity evaluated by diffusion-weighted MRI for predicting pathological stages and therapeutic responses to chemoradiotherapy in lower rectal cancer.

Aim: Diffusion-weighted MRI (DWI) has the potential to reveal intra-tumor structural heterogeneity consisting of stroma through an evaluation of uniformity on DWI. In present study, we examined the diagnostic value of intra-tumor heterogeneity evaluated by DWI in lower rectal cancer (LRC). Patients and Methods: A total of 172 LRC patients underwent radical surgery between 2009 and 2017. T1 tumors and cases without pre-operative MRI were excluded. Twenty-nine primary resection cases (PR) and 37 pre-operative chemoradiotherapy followed by radical surgery cases (pCRT) were targeted. Intra-tumor heterogeneity on DWI was quantified using a specific formula (HSD). Structural heterogeneity was objectively quantified by an image analysis of resected specimens using a digital microscope (HSP). The relationships between HSD and HSP, pathological factors, and tumor regression grades (TRG) of pCRT were evaluated. Results: The relationship between HSD and HSP was analyzed by a linear regression model in PR cases, revealing a positive correlation (R2=0.43). PR cases were divided into HSD-high and HSD-low according to the median. There were more pT3 or N(+) cases in HSD-high (p=0.038, 0.095). HSD before pCRT correlated with TRG (grade 1 versus 2/3) in pCRT cases (p=0.001). The diagnostic accuracy of HSD for predicting T and N stages and therapeutic grades was evaluated by cut-off values calculated using a ROC curve and revealed that each factor may be accurately diagnosed. Conclusion: Intra-tumor heterogeneity on DWI corresponded with stromal pathological heterogeneity. It is useful for predicting T3 or deeper tumor invasion, pathological N(+), and the therapeutic effects of pCRT.

The impact of postoperative inflammation on recurrence in patients with colorectal cancer.

BACKGROUND: Systemic inflammatory response is strongly linked to among cancer development, progression and poor prognosis. The aim of this study was to clarify the impact of postoperative serum C-reactive protein (CRP) levels on the prognoses of patients with colorectal cancer (CRC). METHODS: A total of 467 patients with stage I-III CRC who underwent curative surgery were retrospectively analyzed. To precisely evaluate the effect of postoperative inflammatory status on prognosis in CRC patients, we excluded patients with postoperative complication or elevated preoperative CRP level (CRP > 1.0 mg/dL). Patients were divided into two groups based on their highest post-resection CRP levels (max CRP): the low CRP group (LCG; < 9.0 mg/dL, n = 385) and high CRP group (HCG; ≥ 9.0 mg/dL, n = 82). Furthermore, the effect of inflammation on malignant potential of CRC cells was evaluated using in vitro peritoneal dissemination model. RESULTS: HCG patients showed significantly worse recurrence-free survival (RFS) than LCG patients (p = 0.012). Multivariate analysis revealed that a higher max CRP was an independent prognostic factor for RFS (HR: 2.07, 95% CI 1.04-3.96, p = 0.038). Concerning the risk factors for high max CRP level, multivariate analysis revealed that older age (p < 0.001), male sex (p < 0.001), higher BMI (p = 0.005), right-sided colorectal cancer (p = 0.008), and longer operative time (p = 0.007) were independent risk factors. A higher max CRP was also significantly associated with peritoneal recurrence (p < 0.001). Additionally, recombinant cytokines enhanced the adhesive ability of CRC cells to mesothelial cell in vitro (p < 0.05). CONCLUSIONS: Postoperative inflammation may be a possible mechanism portending the poor prognosis of CRC patients.

Clinical significance of neutrophil-to-lymphocyte ratio as a predictor of lymph node metastasis in gastric cancer.

BACKGROUND: Precise staging is indispensable to select the appropriate treatment strategy for gastric cancer (GC); however, the diagnostic accuracy of conventional modalities needs to be improved. This study investigated the clinical significance of the preoperative neutrophil-to-lymphocyte ratio (NLR) for the prediction of pathological lymph node metastasis (pN+) in GC. METHODS: This was a retrospective study of 429 patients with GC who underwent curative gastrectomy. The predictive ability of NLR for pN+ was examined in comparison with that of computed tomography. RESULTS: The preoperative NLR ranged from 0.6 to 10.8 (median, 2.0), and the optimal cut-off value for predicting pN+ was 1.6 according to the receiver operating characteristic curve with the maximal Youden index. Multivariate analysis identified a NLR ≥ 1.6 (odds ratio (OR) 3.171; 95% confidence interval (CI) 1.448-7.235, p = 0.004) and cN+ (OR 2.426; 95% CI 1.221-4.958, p = 0.011) to be independent factors associated with pN+ in advanced GC (cT2-T4). On the other hand, a NLR ≥ 1.6 was not useful for predicting pN+ in early GC (cT1). In advanced GC, a NLR ≥ 1.6 detected pN+ with a higher sensitivity (84.9%) and negative predictive value (NPV) (63.9%) than conventional modalities (50.0 and 51.7%, respectively). When the subjects were limited to those with advanced GC with cN0, the sensitivity and NPV of a NLR ≥ 1.6 for pN+ increased further (90.7 and 81.0%, respectively). CONCLUSION: The preoperative NLR may be a useful complementary diagnostic tool for predicting pN+ in advanced GC because of its higher sensitivity and NPV than conventional modalities.

Value of Prognostic Nutritional Index as a Predictor of Lymph Node Metastasis in Gastric Cancer.

BACKGROUND/AIM: This study examined whether the prognostic nutritional index (PNI) is a useful predictor of pathological lymph node metastasis (pN+) in gastric cancer (GC). PATIENTS AND METHODS: This study retrospectively examined 167 patients with advanced GC (cT2-T4) undergoing curative gastrectomy. The predictive ability of PNI for pN+ was evaluated in comparison with that of clinical lymph node metastasis (cN+) determined by computed tomography (CT). RESULTS: The optimal cut-off value of PNI for predicting pN+ was 46 according to the receiver operating characteristic curve analysis. Multivariate analysis revealed a PNI<46 [odds ratio (OR)=2.905; 95% confidence interval (CI)=1.347-6.638, p=0.006], cN+ (OR=2.323; 95%CI=1.204-4.579, p=0.012), and undifferentiated-type adenocarcinoma (OR=2.032; 95%CI=1.060-3.947, p=0.033) to be independent predictors of pN+. PNI detected pN+ with a higher specificity (84.9%) and positive predictive value (PPV) (75.6%) than cN+ (68.5% and 68.1%, respectively). When the subjects were limited to patients with cN+, the specificity and PPV of a PNI<46 for pN+ became markedly high (91.3% and 90.5%, respectively). CONCLUSION: PNI predicts pN+ with a high specificity in patients with a clinical diagnosis of advanced GC; therefore, PNI may aid in the definitive diagnosis of pN+, especially in combination with CT findings.

[Prognostic Significance of Preoperative Neutrophil-Lymphocyte Ratio in Gastric Cancer].

BACKGROUND: This study examined the significance of preoperative neutrophil-lymphocyte ratio(NLR)as a predictor of postoperative outcomes of gastric cancer(GC). METHODS: NLR was calculated in 447 patients with GC undergoing curative gastrectomy, and its associations with postoperative short- and long-term outcomes were retrospectively examined. RESULTS: Patients were divided into high-(n=313)or low-(n=134)NLR groups using an optimal cut-off NLR value of 1.6 according to the ROC curve analysis. A high-NLR was significantly associated with other clinical factors such as undifferentiated histology, advanced cT, and cN+. There was no difference in the incidence of postoperative complications between the 2 groups. Meanwhile, a high NLR was associated with a poor 5-year overall survival. Multivariate analysis identified preoperative NLR to be an independent prognostic factor(hazard ratio: 2.77, 95% confidence interval: 1.39-6.33, p=0.003)along with performance status, tumor location, and cT. CONCLUSION: Preoperative NLR could be one of the useful predictors of postoperative long-term outcomes of GC.

[Prognostic Value of Preoperative Serum C-Reactive Protein Level in Gastric Cancer].

BACKGROUND: This study investigated the prognostic value of preoperative serum C-reactive protein(CRP)level in patients with gastric cancer(GC). METHODS: This retrospective study examined 446GC patients undergoing curative gastrectomy. The associations between preoperative CRP level and postoperative long-term outcomes were examined by univariate and multivariate analyses. RESULTS: The patients were divided into high(n=147)or low(n=299)CRP groups based on an optimal cut- off CRP value of 0.13mg/dL according to the ROC curve analysis. High CRP levels were significantly associated with other clinical factors such as older age(B65 years), high BMI(B25 kg/m2), poor performance status(PS), and advanced cT and cN+. In the survival analyses using only the clinical factors, high CRP levels were significantly associated with worse 5-year overall and cancer-specific survivals. The multivariate analysis for 5-year overall survival identified preoperative CRP to be an independent factor(HR: 1.95, 95%CI: 1.15-3.36, p=0.0129), as well as PS, tumor location, and cT. CONCLUSION: Preoperative CRP level could be a useful prognostic indicator in patients with GC undergoing curative gastrectomy.

Functional Outcomes of Billroth I Gastroduodenostomy Using Linear Staplers in Totally Laparoscopic Distal Gastrectomy.

BACKGROUND/AIM: This study examined whether functional outcomes of linear-stapled Billroth I (LS-BI) in totally laparoscopic distal gastrectomy (TLDG) are comparable to those of circular-stapled Billroth I (CS-BI) in laparoscopy-assisted distal gastrectomy (LADG). PATIENTS AND METHODS: This was a retrospective study of patients with gastric cancer undergoing TLDG with LS-BI (n=50) or LADG with CS-BI (n=50). Postoperative endoscopic findings of the remnant stomach and nutritional status were evaluated. RESULTS: The occurrence of grade 2 or more severe remnant gastritis in the LS-BI group (46.0%) was significantly higher than that in the CS-BI group (18.0%) (p=0.005), whereas there was no significant difference in the incidence of residual food and bile reflux between the two groups. Postoperative changes in body weight, and serum albumin and total protein levels were similar between the two groups. CONCLUSION: TLDG with LS-BI may be a good alternative to LADG with CS-BI because of its comparable nutritional outcomes, but with a higher occurrence of remnant gastritis.

Preoperative total cholesterol-lymphocyte score as a novel immunonutritional predictor of survival in gastric cancer.

PURPOSE: Immunonutritional status is a known prognostic correlate in the context of gastric cancer (GC). In the present study, we investigated the prognostic relevance of a lipid profile-based immunonutritional score in patients with GC. METHODS: Data pertaining to 224 patients with stage II and III GC who underwent curative gastrectomy were retrospectively analyzed. The total cholesterol-lymphocyte score (TL score) was defined as follows: patients with both low total cholesterol (TC) and total lymphocyte count were allocated a score of 2; patients with only one or none of these biochemical abnormalities were allocated a score of 1 or 0, respectively. RESULTS: Among the serum lipid indices, low TC was the strongest predictor of cancer-specific survival (CSS; p = 0.001). On multivariate analysis, both low prognostic nutritional index (PNI) (p < 0.001) and high TL score (p = 0.003) were independent prognostic factors. PNI was significantly associated with peritoneal recurrence (p = 0.047), while TL score was significantly associated with locoregional and distant metastasis (p = 0.004 and p = 0.003, respectively). CONCLUSIONS: TL score may facilitate risk stratification of patients based on CSS. TL score plus PNI may help predict the recurrence pattern in patients with stage II and III GC.

Preoperative inflammatory response as prognostic factor of patients with colon cancer.

PURPOSE: This study aimed to investigate the abilities of the modified Glasgow prognostic score (mGPS) and other inflammatory scores to predict recurrence-free survival (RFS) among patients with colon cancer (CC). In addition, we evaluated the abilities of the mGPS to predict recurrence of stage II disease and the efficacy of adjuvant chemotherapy (AC) for stage III disease. METHODS: This retrospective study evaluated 477 patients with stage I-III CC who underwent curative surgery. These patients were categorized as having a low mGPS (mGPS 0) or a high mGPS (mGPS 1-2). RESULTS: Patients in the high mGPS group had significantly poorer RFS than patients in the low mGPS group (p < 0.01). Multivariate analysis revealed that a high mGPS independently predicted poor RFS (p < 0.01). Among patients with stage II CC, multivariate analysis revealed that the independent predictors of poor RFS were pT4 status (p < 0.01) and a high mGPS (p = 0.04). Among patients with stage III CC, AC was not significantly associated with the 5-year RFS for patients with a low mGPS (p = 0.38), although AC significantly improved the 5-year RFS for patients with a high mGPS (p < 0.01). CONCLUSION: The preoperative mGPS significantly predicted recurrence among patients with CC, even among patients with stage II CC. In addition, mGPS may provide valuable information regarding subgroups of patients with stage III CC who might benefit from AC.