Therapeutic Targeting of Tumor Cells Rich in LGR Stem Cell Receptors.

LGR5 and LGR6 mark epithelial stem cells in many niches including the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. Human ovarian cancers express these receptors at high levels and express one of their ligands, RSPO1, at levels uniquely higher than all other tumor types except mesothelioma. Reasoning that these receptors are also important to tumor stem cells, arming the LGR binding domain of RSPO1 with a cytotoxin may permit depletion of the tumor stem cells. The Fu1-Fu2 receptor binding domain of RSPO1 (R1FF), containing a sortase recognition sequence at the C-terminal end, was produced in bacteria and a single molecule of MMAE was attached to each R1FF through a val-cit-PAB linker using the sortase reaction, thus producing a homogeneous population of armed molecules. R1FF-MMAE demonstrated (1) selective LGR-dependent binding, uptake, and cytotoxicity; (2) low nM cytotoxicity to multiple types of human tumor cell lines in vitro; (3) favorable plasma pharmacokinetic properties when administered iv with an elimination half-life of 27.8 h; (4) favorable absorption from the peritoneal cavity; and (5) therapeutic activity in aggressive xenograft models of ovarian cancer in the absence of any weight loss or other adverse events. These results demonstrate that the Fu1-Fu2 domain of RSPO1 can be exploited to deliver a potent cytotoxin to tumor cells that express the LGR4-6 family of stem cell receptors.

Decreased mean platelet volume predicts poor prognosis in patients with pancreatic cancer.

BACKGROUND: Decreased mean platelet volume (MPV) predicts poor prognosis in some cancers. However, its significance as a prognostic indicator in pancreatic cancer (PC) remains unclear. METHODS: A total of 91 PC patients who underwent pancreatectomy were included in this study. MPV and serum carbohydrate antigen 19-9 (CA19-9) were measured within 1 week before surgery. RESULTS: We divided patients into MPVhigh (≥ 8.65; n = 40), MPVlow (< 8.65; n = 51), CA19-9high (≥ 66.3; n = 47), and CA19-9low (< 66.3; n = 44) groups based on the optimal cut-off values determined from receiver operating characteristic curve analysis. The 5-year overall survival (OS) rates were significantly lower in the MPVlow than in the MPVhigh group (16.9% and 56.3%, respectively; P = 0.0038), and the 5-year disease-specific survival (DSS) rates in the MPVlow group and MPVhigh group were 20.5% and 62.2%, respectively (P = 0.0031). Multivariate analysis identified MPV as an independent prognostic indicator for both OS and DSS. The patients were then divided into groups A (MPVhigh and CA19-9low), B (MPVhigh and CA19-9high), C (MPVlow and CA19-9low), and D (MPVlow and CA19-9high), with 5-year OS rates of 73.2%, 40.4%, 25.8%, and 10.3%, respectively (P = 0.0002), and 5-year DSS rates of 80.8%, 44.9%, 27.3%, and 16.4%, respectively (P = 0.0003). CONCLUSIONS: Classification based on MPV and CA19-9 might be useful for predicting long-term outcomes in patients with PC.

Early vs. Delayed Feeding after Endoscopic Submucosal Dissection for Gastric Cancer: A Systematic Review and Meta-Analysis.

Background: Endoscopic submucosal dissection (ESD) for gastric cancer is increasingly performed worldwide due to its efficacy and safety. This study aimed to assess the evidence of the impact of early vs. delayed feeding after ESD on quality of care, which remains to be fully determined. Methods: Electronic databases (PubMed, the Cochrane Central Register of Controlled Trials, EMBASE) and the trial registries (the World Health Organization International Clinical Trials Platform Search Portal and ClinicalTrials.gov) were searched for studies performed prior to September 2020. Study selection, data abstraction, and quality assessment were independently performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Self-rated satisfaction and hospital stay were chiefly analyzed. Results: Two randomized controlled trials (239 patients) were included. The early and delayed post-ESD feeding groups had similar rates of post-ESD bleeding (risk ratio 1.90, 95% CI 0.42 to 8.63; I2 = 0%). Early post-ESD feeding resulted in increased patients' satisfaction in comparison to delayed post-ESD feeding (standard mean difference (MD) 0.54, 95% CI 0.27 to 0.81; I2 = 0%) and reduced the length of hospital stay (MD -0.83, 95% CI -1.01 to -0.65; I2 = 0%). Conclusion: Early post-ESD feeding was associated with increased patients' satisfaction and reduced hospital stay in comparison to delayed feeding, while the rate of complications did not differ to a statistically significant extent. As we must acknowledge the limited number of reviewed studies, various trials regarding the quality of care are further needed to determine the benefits of early feeding after ESD.

Avoidance of bile duct injury during laparoscopic liver cyst fenestration using indocyanine green: A case report.

By administering ICG test immediately before laparoscopic liver cyst fenestration, the biliary tract can be easily identified and intraoperative bile duct damage and postoperative bile fistula formation can be avoided, as demonstrated in this case.

Combined prognostic nutritional index ratio and serum amylase level during the early postoperative period predicts pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: The aim of this study was to investigate the usefulness of the range of change in prognostic nutritional index (PNI) during the early postoperative period as a predictor of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. METHODS: Data were retrospectively analyzed for 192 patients who underwent pancreaticoduodenectomy. Univariate and multivariate logistic regression analyses were used to evaluate perioperative variables. PNIP3-Pre ratio represented the range of change in PNI from before surgery to postoperative day (POD) 3, PNIP1-Pre ratio represented the range of change in PNI from before surgery to POD 1, and PNIP3-P1 ratio represented the range of change in PNI from POD 1 to POD 3. RESULTS: The area under the curve (AUC) for PNIP3-P1 for prediction of POPF following pancreaticoduodenectomy was 0.683 (P <  0.001), which was highest among PNI ratios and higher than PNI on POD 3. The AUC for serum amylase level on POD 1 was 0.704 (P <  0.001), which was superior to the corresponding AUC on POD 3. The AUC for the combination of PNIP3-P1 ratio and serum amylase level on POD 1 for prediction of POPF was higher than the AUC of either indicator alone (0.743, P <  0.001). The combination of PNIP3-P1 ratio and serum amylase level on POD 1 was an independent predictor of POPF following pancreaticoduodenectomy (P = 0.018). CONCLUSIONS: The combination of the range of change in PNI from POD 1 to POD 3 and serum amylase levels on POD 1 may be useful for prediction of POPF following pancreaticoduodenectomy.

The Advantages of Robotic Gastrectomy over Laparoscopic Surgery for Gastric Cancer.

BACKGROUND: We compared short- and long-term clinical outcomes including inflammatory marker levels between robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) to define the advantages of RG over LG. METHODS: We enrolled 209 patients with gastric cancer who underwent curative distal gastrectomy. We compared short- and long-term clinical outcomes including inflammatory marker levels between RG and LG to define the advantages of RG over LG. C-reactive protein (CRP) levels; the CRP-to-albumin, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios; and the prognostic nutritional index were compared as systemic inflammatory markers. RESULTS: RG was associated with a longer operative time. The incidence of postoperative infectious complications of grade II or higher according to the Clavien-Dindo classification was not significantly different between the two groups. Amylase levels in drainage fluid on postoperative days 1 and 3 were significantly lower in the RG group than in the LG group. The incidence of pancreatic fistula in the RG group (4.3%) was lower than that in the LG group (7.5%), albeit without significance. There were no significant differences in inflammatory marker levels either before or after surgery between the two groups. The 3-year overall survival rate did not significantly differ between the RG and LG groups (91.1% vs. 91.1%). Similar results were observed regarding the 3-year disease-specific survival rate (100% vs. 97.1%). CONCLUSION: RG might be feasible and safe for treating gastric cancer from both surgical and oncological perspectives. The use of robotic assistance is associated with decreased amylase levels in drainage fluid, which may reduce the risk of pancreatic fistula and prevent pancreatic injury.

Laparoscopically-Assisted Repair of a Small Bowel Perforation Secondary to Multiple Metastases of Undifferentiated Pleomorphic Sarcoma.

We present a very rare case of a laparoscopically-assisted repair of a small bowel perforation secondary to multiple metastases of undifferentiated pleomorphic sarcoma from the posterior mediastinum. A 46-year-old man presented with middle to upper abdominal pain during chemotherapy for lung metastases from undifferentiated pleomorphic sarcoma. Computed tomography revealed intra-abdominal free air, and emergency laparoscopy was performed. Consequently, a perforation was detected in the jejunum, and partial jejunal resection was performed by mini-laparotomy. Pathological examination demonstrated an ulcerated tumor with perforation and four additional tumors in the resected jejunum. Pathological examination also revealed undifferentiated pleomorphic sarcoma in all five tumors. To our knowledge, our case is the first report of a laparoscopically-assisted repair of a small bowel perforation secondary to metastasis of undifferentiated pleomorphic sarcoma. Although the perforation site was unclear preoperatively, laparoscopic observation readily identified the lesion in this patient. Therefore, minimally invasive surgery could be performed successfully with mini-laparotomy following laparoscopic observation. Laparoscopic techniques for the small intestine are viable options, even in acute and uncommon situations, and small bowel perforation secondary to metastasis should be considered in patients with undifferentiated pleomorphic sarcoma and acute abdomen.

A Novel Noninvasive Method for Predicting Liver Fibrosis by Quantifying the Estrangement of Indocyanine Green Retention Rate and Tc-99m-diethylenetriamine-penta-acetic Acid-galactosyl Human Serum Albumin Scintigraphy.

BACKGROUND/AIM: Indocyanine green (ICG) clearance test is one of the most popular dynamic methods for evaluating preoperative liver function to avoid posthepatectomy liver failure (PHLF). Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin scintigraphy (GSA) also facilitates the direct estimation of functional hepatocytes and can estimate the ICG retention rate (R15); however, in some cases, there is a discrepancy between results of a preoperative examination of ICG-R15 and the estimated ICG-R15 obtained by 99mTc-GSA (GSA-R15). This study evaluated the gap between ICG-R15 and GSA-R15 (ΔICG) for predicting background liver fibrosis in patients who underwent hepatectomy. PATIENTS AND METHODS: Sixty-four consecutive patients who underwent hepatectomy and preoperative ICG-R15 and GSA-R15 examinations from 2016 to 2019 were retrospectively evaluated. The gap between GSA-R15 and ICG-R15 was defined as ΔICG and the factors predicting liver fibrosis were investigated. RESULTS: In the pathologically-proven cirrhotic group, platelet counts were significantly lower and ΔICG values were significantly larger than those in the non-/early-cirrhotic group. A multivariate analysis identified a higher total bilirubin level, a higher AST level, and a larger ΔICG level as significant predictive factors for liver cirrhosis. CONCLUSION: Larger ΔICG was found to be an independent preoperative predictor of liver fibrosis and may positively contribute to decision-making before hepatectomy to avoid PHLF.

Successful treatment of peritoneal recurrence after gastric cancer surgery with intravenous and intraperitoneal paclitaxel combined with S-1 chemotherapy: a case report.

BACKGROUND: Despite recent advances in systemic chemotherapy, the prognosis of patients with peritoneal metastases from gastric cancer still remains poor. Nonetheless, several efficacious intraperitoneal chemotherapy regimens have recently been developed for patients with peritoneal metastases. However, no study has investigated the effectiveness of intraperitoneal chemotherapy for metachronous peritoneal metastases from gastric cancer after curative surgery. CASE PRESENTATION: We herein report a case of a 65-year-old man who had metachronous peritoneal metastases from gastric cancer after curative total gastrectomy who had been successfully treated with intraperitoneal chemotherapy. One month after surgery, adjuvant chemotherapy with S-1 was initiated given a final pathological stage of IIIB (pT4aN2M0). However, during adjuvant chemotherapy 12 months after surgery, tumor marker levels, which had been within normal range before surgery, increased with abdominal contrast-enhanced computed tomography (CT) revealing pelvic ascites. Thereafter, staging laparoscopy was performed, and the patient was diagnosed with peritoneal recurrence of gastric cancer. Following staging laparoscopy, an intraperitoneal access port was subcutaneously implanted for subsequent intraperitoneal chemotherapy. Combined chemotherapy with intraperitoneal and intravenous administration of paclitaxel and oral S-1 was then provided. After one course of combined chemotherapy, peritoneal lavage cytology was negative for malignancy. CT showed gradually decreasing ascites, whereas tumor marker levels returned to normal. The patient continued chemotherapy without major side effects and remained progression-free for 33 months with 36 chemotherapy cycles. CONCLUSIONS: A combination regimen including intraperitoneal chemotherapy could be a promising option for patients with peritoneal recurrence after gastric cancer surgery.

Small bowel stenosis after blunt abdominal trauma: a case report.

BACKGROUND: Small bowel stenosis after blunt abdominal trauma is relatively rare, and progression from trauma to bowel stenosis might sometimes be delayed. Herein, we report the case of a patient who was diagnosed with small bowel stenosis relatively early and received laparoscopic surgery. CASE PRESENTATION: An 18-year-old Japanese male was in a traffic accident and was urgently transported to our hospital. On arrival, he was admitted with right kidney and right adrenal injury and abdominal aortic aneurysm. On hospital day 13, he vomited during conservative treatment without surgery, and computed tomography revealed small bowel stenosis and dilatation of the oral-side small bowel. No improvement with the ileus tube occurred, and he received laparoscopic surgery on hospital day 21. Briefly, the abdominal cavity was observed with a laparoscope. The mesentery was congested, scarring around the stenotic small bowel regions was present, and three stenotic regions were observed 40-50 cm from the Treitz ligament. The patient received partial resection and anastomosis of the small bowel. The postoperative course was stable, and he was discharged on postoperative day eight. CONCLUSIONS: Most cases of bowel stenosis after abdominal trauma are irreversible and usually require surgical treatment. Therefore, small bowel stenosis should be considered in patients with abdominal symptoms after blunt abdominal trauma.

Successful preservation of the proximal stomach tube by evaluating blood flow using indocyanine green for gastric tube cancer: a case report.

BACKGROUND: There have been two reports on preserving the proximal gastric tube by using intraoperative indocyanine green (ICG)-based photodynamic detection to evaluate blood flow through the anastomosis for gastric tube cancer after esophagectomy. However, in those cases, the period since the first operation was > 3 years 11 months, and there have been no reports of cases with < 1-year periods after the first operation. CASE PRESENTATION: A 59-year-old man underwent video-assisted thoracic subtotal esophagectomy and gastric tube reconstruction after two courses of preoperative chemotherapy for middle thoracic esophageal cancer. After half a year, follow-up upper gastrointestinal endoscopy showed a submucosal tumor in the posterior wall of the pre-pyloric region. We performed a biopsy, and the results led to a diagnosis of gastric cancer (moderately differentiated adenocarcinoma: tub2). Clinically, the patient was described as having stage IB (cT2N0M0) gastric cancer of the reconstructed gastric tube. To avoid total gastrectomy, we tried to evaluate the blood flow of the proximal part of the gastric tube by intraoperative ICG-based photodynamic detection. Intraoperative findings confirmed neo-vascularization from the remnant cervical esophagus to the upper region of the gastric tube approximately 7 cm through the esophagogastric anastomosis. Therefore, we dissected the distal part of the gastric tube approximately 4 cm from the esophagogastric anastomosis and then performed Roux-en-Y gastro-jejunostomy via the ante-sternum route. The postoperative course was stable, and the patient was discharged on the 14th postoperative day. CONCLUSIONS: ICG-based photodynamic diagnosis was found to be simple and less invasive. Therefore, even if the postoperative period is short, this method should be considered for evaluation of blood flow prior to performing less invasive surgery.

Prognostic Impact of Pre- and Post-operative P-CRP Levels in Pancreatic Cancer Patients.

BACKGROUND: C-reactive protein (CRP) levels reflect ongoing inflammation and/or tissue damage, and studies suggest that platelets play a role in tumor invasion and metastasis. P-CRP is defined as the multiplied product of serum CRP and platelet levels. Here the prognostic value of pre- and post-operative P-CRP levels in pancreatic cancer (PC) patients was assessed. METHODS: This retrospective study used data from 107 consecutive PC patients who had undergone either pancreaticoduodenectomy or distal pancreatectomy. Clinicopathological parameters and pre/post-operative laboratory data derived from patient records were used for analyses. P-CRP was defined as the product of peripheral thrombocyte count (/uL) × serum CRP level (mg/dL) divided by 104; the optimal P-CRP cut-off value was defined using receiver operating characteristic curves. RESULTS: PC patients were classified as either P-CRPLow (< 1.782; n = 49) or P-CRPHigh (≥ 1.782; n = 58), based on the cut-off value of 1.782. Univariate analysis revealed that performance status, clinical stage, pathological T and N stages, P-CRP, and carbohydrate antigen 19-9 (CA19-9) significantly affected overall survival (OS). Multivariate analysis revealed that independent risk factors for OS were pathological N stage, P-CRP, and CA19-9. Additionally, 103 PC patients for whom postoperative data were available were classified into four groups (P-CRPLow-Down, P-CRPLow-Up, P-CRPHigh-Down and P-CRPHigh-Up), based on preoperative P-CRP and postoperative trend of P-CRP, and we found that prognosis, in terms of OS, was significantly different among these groups (P = 0.012). CONCLUSION: Pre- and post-operative P-CRP values are a potential predictor of prognosis in PC patients.

Prognostic Significance of Pre-surgical Combined Platelet Count and Neutrophil-Lymphocyte Ratio for Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: Recent studies have investigated a novel inflammation-based prognostic system using the combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR). As platelet count decreases with liver damage, we hypothesized that COP-NLR could indicate both inflammation and hepatic reserve in patients with hepatocellular carcinoma (HCC). This study was conducted to clarify the prognostic significance of preoperative COP-NLR in patients with HCC. PATIENTS AND METHODS: We enrolled 176 patients with histologically-proven HCC who underwent initial curative hepatectomy. Patients were assigned one point each for low platelet count (<15×104/µl) or for high NLR (≥2.0), for hepatic-COP-NLR scores (h-COP-NLR) of 0, 1 or 2. RESULTS: Five-year overall survival (OS) and recurrence-free survival (RFS) rates were 74.5±9%, and 62.2%±9.3% for score 0, 63.6±5.4% and 50.3%±5.6% for score 1, and 45.2±8.8% and 40.6±8.7% for score 2, respectively, and significantly differed (OS: p=0.01; RFS: p=0.03). In multivariate analysis, h-COP-NLR was an independent risk factor for tumor recurrence (HR=1.39, p=0.03) and death (HR=1.71, p=0.02). CONCLUSION: h-COP-NLR was an independent predictor for prognosis of HCC patients after hepatic resection.

Prognostic Value of DEPDC1 Expression in Tumor and Non-tumor Tissue of Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: To evaluate the impact of DEPDC1 expression on patient prognosis after hepatic resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We reviewed data from 75 patients who underwent hepatic resection for HCC between 2004 and 2013. Recurrence at 2 years following resection, which mainly included metastatic recurrence, was defined as late recurrence. RESULTS: DEPDC1 was up-regulated in HCC tissue and in non-tumor tissue of patients with HCC compared to normal liver (p<0.01 and p<0.01, respectively). High expression of DEPDC1 was associated with poor overall, disease-specific, and disease-free survival (p=0.02, p<0.01, and p<0.01, respectively). High DEPDC1 expression was an independent predictor of death and recurrence (p=0.03 and p<0.01, respectively). High expression of DEPDC1 in non-tumor liver was an independent risk factor for late recurrence (p=0.04). CONCLUSION: High expression of DEPDC1 in tumor tissue appears to be associated with tumor progression and poor prognosis.

Preoperative Albumin-Bilirubin Grade as a Useful Prognostic Indicator in Patients With Pancreatic Cancer.

BACKGROUND: The albumin-bilirubin (ALBI) grade assesses the severity of liver dysfunction in patients with hepatocellular carcinoma. Herein we investigated the prognostic significance of the combination of the ALBI grade with serum carbohydrate antigen 19-9 (CA 19-9) concentration, the most frequently used tumor marker in pancreatic cancer (PC) in resected patients with PC. MATERIALS AND METHODS: Included patients (n=100) had a histopathological diagnosis of pancreatic cancer and underwent pancreatectomy. Serum concentrations of albumin, bilirubin, and CA19-9 were measured within 5 days before surgery. Patients were divided into groups with high and low CA19-9 (cut-off ≥35 U/ml) and ALBI grade (2 and 3 vs. 1). RESULTS: The 5-year overall survival (OS) rates of the ALBIHigh and ALBILow groups were 21.6% and 35.3%, respectively (p=0.015). The 5-year OS rates of the CA19-9High and CA19-9Low groups were 22.2% and 41.5%, respectively (p=0.017). Patients were divided into groups A (ALBIHigh and CA19-9High), B (ALBIHigh and CA19-9Low or ALBILow and CA19-9High), and C (ALBILow and CA19-9Low). The 5-year OS rates of groups A, B, and C were 13.8%, 31.0%, and 43.3%, respectively (p=0.0006). Multivariate analysis revealed that the ALBI grade combined with the CA19-9 concentration, served as an independent prognostic indicator. CONCLUSION: The combination of ALBI grade and CA19-9 concentration predicted the prognosis of patients with PC.

Bacterial smear test of drainage fluid after pancreaticoduodenectomy can predict postoperative pancreatic fistula.

OBJECTIVES: It is widely accepted that postoperative pancreatic fistula (POPF) accompanied by bacterial infection results in a worse outcome than POPF alone. However, few studies evaluating predictive indicators of POPF have focused on bacterial infection. METHODS: A consecutive 100 patients who underwent pancreaticoduodenectomy at our institute for periampullary disease were enrolled. POPF was assessed according to the International Study Group of Pancreatic Fistula consensus guidelines; grades B and C were defined as clinically relevant POPF (CR-POPF). The patients' characteristics, perioperative surgical factors, and laboratory data including the results of culture and smear testing performed using drainage fluid on postoperative days (PODs) 1 and 3 were analyzed. RESULTS: The overall incidence of CR-POPF was 25%. Univariate analyses revealed that the factors associated with CR-POPF were male sex, soft pancreas, MPD diameter, higher serum C-reactive protein concentration and white blood cell count on POD 3, higher amylase concentration in drainage fluid, and culture and/or smear positivity of drainage fluid. Multivariate analysis newly revealed that the smear positivity of drainage fluid on POD 3 was the independent risk factors for CR-POPF (p = 0.027). CONCLUSIONS: Smear positivity of drainage fluid on POD 3 after pancreaticoduodenectomy may be a new predictor of CR-POPF.

Indirubin, a Constituent of the Chinese Herbal Medicine Qing-Dai, Attenuates Dextran Sulfate Sodium-induced Murine Colitis.

BACKGROUND: Indirubin, a constituent of the Chinese herbal medicine "Qing-Dai," has anti-cancer and anti-inflammatory activities. We aimed to evaluate the efficacy of indirubin for ameliorating colonic inflammation in a mouse model of inflammatory bowel disease. METHODS: Mice with dextran sulfate sodium (DSS)-induced acute and chronic colitis were treated with indirubin in their diet. Clinical and histologic changes were evaluated. In addition, colon levels of interleukin-6, a critical pro-inflammatory mediator, was detected by enzyme-linked immunosorbent assay. RESULTS: In the model of acute colitis, indirubin treatment improved the loss of body weight. Histology of colonic tissue revealed that indirubin treatment improved the histology grading of colitis (P = 0.02), the extent of submucosal fibrosis (P = 0.018), the number of mucosal toluidine blue-positive cells (P = 0.004) and colon length (P = 0.01). In the model of chronic colitis, indirubin treatment had no significant effect on pathologic findings except for colon length (P = 0.003). However, indirubin administration significantly reduced colon levels of interleukin-6 in the chronic-colitis model (P = 0.001). CONCLUSION: Our study clearly showed that oral intake of indirubin can improve murine DSS-induced colitis (which mimics human inflammatory bowel disease).

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis.

IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.

Prognostic indicators based on inflammatory and nutritional factors after pancreaticoduodenectomy for pancreatic cancer.

PURPOSE: We evaluated prognostic indicators based on inflammatory and nutritional factors, namely, the modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR), to determine their efficiency and significance after pancreaticoduodenectomy for pancreatic cancer. METHODS: The subjects of this study were 46 patients who underwent pancreaticoduodenectomy for pancreatic cancer between October 2007 and December 2014. Patients were divided into preoperative mGPS (0/1 and 2), PNI (<40 and ≥40), NLR (<2.5 and ≥2.5), and PLR (<200 and ≥200) groups, to evaluate various perioperative outcomes. RESULTS: Hemoglobin concentrations were significantly lower (P = 0.019), whereas intra-abdominal bleeding was significantly higher (P = 0.040) in the PNI (<40) group than in the PNI (≥40) group. The incidence of postoperative pneumonia was significantly higher in the mGPS (2) group (P = 0.009), and surgical complications greater than grade 3 (Clavien-Dindo classification) were significantly increased in the NLR (≥2.5) group (P = 0.041). Overall survival rates in the PNI (<40) (P = 0.019), NLR (≥2.5) (P = 0.001), and PLR (≥200) (P < 0.001) groups were significantly lower than those in the other groups. The PLR was the only independent prognostic indicator (P = 0.002) according to multivariate analysis. CONCLUSIONS: The mGPS, PNI, and NLR were effective predictive indicators of postoperative complications. The PLR was the most useful prognostic indicator for pancreatic cancer patients after pancreaticoduodenectomy.

TSLP Expression and High Serum TSLP Level Indicate a Poor Prognosis in Gastric Cancer Patients.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) plays an important role in promoting tumor survival, by manipulating the immune response and angiogenesis. However, the clinical significance of TSLP in gastric cancer is unclear. METHODS: Immunohistochemistry was used to investigate TSLP expression in non-cancerous gastric mucosa and gastric cancer tissue from patients with gastric cancer. Serum TSLP levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Tumors with TSLP expression were significantly larger than those without TSLP expression. TSLP expression was observed more frequently in advanced (T2/T3/T4) than in early (T1) gastric cancer and in stage 3/4 than in stage 1/2. Lymph node metastasis, liver metastasis, positive peritoneal lavage cytology, lymphatic invasion, and vascular invasion occurred significantly more often in TSLP-expressing than in non-expressing tumors. The prognosis of patients with TSLP-positive tumors was significantly worse than that of patients with TSLP-negative tumors. Patients with high serum TSLP concentrations also had a significantly worse prognosis than those with low concentrations. Multivariate analysis identified serum TSLP level as an independent prognostic indicator. CONCLUSION: TSLP is closely related to the progression of gastric cancer and may predict survival in these patients.