Predictive value of immuno-inflammatory and nutritional measures modulated by neoadjuvant chemotherapy on the response of neoadjuvant chemotherapy and long-term outcomes in patients with esophageal cancer.

It has been reported that immuno-inflammatory and nutritional parameters are associated with long-term survival in various malignancies. However, little is known regarding the associations between alterations of these parameters during neoadjuvant chemotherapy (NAC) and the response to NAC in patients with esophageal cancer. The present study examined the clinical significance of alterations in these parameters during NAC in terms of the response to NAC and the long-term outcomes in patients with esophageal cancer. Various systemic immuno-inflammatory and nutritional measures including the systemic neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP)-to-albumin ratio (CAR) and psoas muscle index (PMI) were examined before and after NAC. Statistical analyses were performed to determine the significance of immuno-inflammatory and nutritional parameters prior to NAC and alterations during NAC regarding the response to NAC and long-term outcomes. The NLR, PMI, neutrophil count and platelet count declined significantly following NAC, whereas no alterations in PLR, CAR, lymphocyte counts, CRP levels and albumin concentration were observed. The decreases in NLR and neutrophil counts following NAC were strongly associated with a favorable overall survival (P=0.006). In conclusion, decreases in NLR and neutrophil counts following NAC were clinically significant predictors of the response to NAC and of survival in esophageal cancer, respectively.

Risk factors for nonalcoholic fatty liver disease after gastrectomy for gastric cancer.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to hepatic steatosis caused by something other than alcoholic liver injury, and often occurs after gastrointestinal surgeries such as pancreatoduodenectomy and gastrectomy. This study aimed to identify the risk factors for NAFLD after gastrectomy for gastric cancer. METHODS: A total of 721 patients who underwent gastrectomy for gastric cancer and plane abdominal computed tomography (CT) preoperatively and 1 year after surgery were included in this study. NAFLD was defined as having a mean hepatic CT attenuation value of < 40 Hounsfield units. We retrospectively examined the relationship between the onset of NAFLD and clinicopathological findings to identify the risk factors associated with the development of NAFLD after gastrectomy. RESULTS: The incidence of postoperative NAFLD was 4.85% (35/721). The univariate analysis identified the following factors as being significantly associated with the incidence of NAFLD: age, preoperative BMI ≥ 25 kg/m2, tumor depth of pT3 ≤, lymph node metastasis grade of pN2 ≤, cholecystectomy, D2 lymphadenectomy, adjuvant chemotherapy, high preoperative cholinesterase serum level, and low grade of preoperative FIB-4 index. Adjuvant chemotherapy (p < 0.001) and high preoperative cholinesterase serum level (p = 0.021) were identified as independent risk factors for NAFLD 1 year after gastrectomy. CONCLUSION: Our study showed that adjuvant chemotherapy with S-1 and high level of serum cholinesterase were considered as the risk factors for NAFLD occurring after gastrectomy for gastric cancer.

Nutritional benefit of laparoscopic jejunostomy during neoadjuvant chemotherapy for obstructing esophageal cancer.

Neoadjuvant chemotherapy (NAC) confers a survival benefit in esophageal carcinoma, but it is difficult to perform in patients who cannot receive enteral feeding due to an esophageal obstruction. In the current study, the nutritional benefit of laparoscopic jejunostomy (Lap-J) was evaluated in patients with NAC for obstructing esophageal cancer. A total of 91 patients with esophageal cancer who received NAC between 2009 and 2017 were included in the present study. Lap-J was performed prior to NAC in 15 patients (16.5%) with an obstructing tumor. Patients with NAC without Lap-J were used as the control group (n=76). Nutritional parameters and surgical outcomes of the two groups were compared retrospectively. In the patients with Lap-J, 14 of the 15 patients (93.3%) did not experience any procedure-associated complications. No mortalities were associated with Lap-J. Significant decreases in total serum protein, albumin, hemoglobin concentrations and prognostic nutritional index (PNI) occurred following NAC in the control but not in the Lap-J group. Serum albumin and the improved modified Glasgow prognostic score increased significantly after NAC in the Lap-J group but not in the control group. In conclusion, perioperative nutritional support with Lap-J was safe and effective in patients with NAC for obstructing esophageal cancer.

Successful resection of a granulocyte colony-stimulating factor-producing carcinoma of the pancreas: A case report.

Granulocyte colony-stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation of precursor cells in the bone marrow and their maturation into fully differentiated neutrophils. G-CSF-producing cancers rarely occur in the digestive system, particularly the pancreas. Herein we report the rare case of a G-CSF-producing pancreatic carcinoma associated with severe anemia due to bleeding in the duodenum, which was successfully treated with surgery. A 79 year-old man presented with epigastralgia and anemia at our institution. Esophagogastroduodenoscopy revealed a duodenal tumor, which was diagnosed as a poorly differentiated adenocarcinoma. To control breeding, subtotal stomach-preserving pancreaticoduodenectomy was performed. The excised tumor measured 86×55×54 mm. It was primarily located in the pancreas and compressed the pancreatic parenchyma and main bile duct. It comprised poorly differentiated adenocarcinoma, and prominent neutrophil infiltration was noted around the tumor. Immunohistochemical examination revelaed that the tumor was positive for G-CSF expression. Based on these results, a final diagnosis of G-CSF-producing primary pancreatic cancer was made. At 18 months following surgery, the patient was alive without recurrence.

Long-term outcome following sentinel node navigation surgery for cT1 gastric cancer.

Sentinel node navigation surgery (SNNS) has become a standard procedure for early-stage melanoma and breast cancer. However, very few studies have evaluated the long-term clinical outcomes following SNNS for gastric cancer. The present study analyzed 51 patients with cT1 gastric cancer who underwent SNNS at our hospital. Sentinel nodes (SNs) were identified using the dual tracer method. Patients underwent limited gastrectomy with SN station dissection when the SNs were reported as pathologically negative during surgery. When SNs were pathologically positive, standard gastrectomy with D2 lymphadenectomy was performed. Out of the 51 cases, 42 cases (82%) were pathologically diagnosed as SN-negative using a frozen section. The surgical procedures included segmental gastrectomy (n=33) and local resection (n=9). A total of 9 patients (18%) had lymph node metastasis in SNs. The mean observation period was 3,125±167 days, and the 5-year overall survival rate was 98%. There was no recurrence, and body weight loss was minimal following the SNNS. Remnant gastric cancer developed in 4 (8%) of the 50 patients except total gastrectomy. Thus, SNNS was a useful procedure for cT1 gastric cancer from the long-term clinical outcomes, though metachronous gastric cancer should paid further attention to.

A case of intrahepatic cholangiocarcinoma that was difficult to diagnose prior to surgery: A case report.

The present study reports a case of mass-forming intrahepatic cholangiocarcinoma (ICC), which mimicked cholangiocellular carcinoma (CoCC) during imaging and a needle biopsy examination. A 51-year-old female with no relevant medical history was referred to the National Defense Medical College hospital with an intrahepatic tumor. Computed tomography demonstrated non-homogeneous enhancement in the early arterial phase and persistent enhancement in the portal and equilibrium phases, together with notable swelling of the para-aortic lymph nodes. Gadolinium-ethoxybenzyl diethylenetriamine-pentaacetic acid-enhanced magnetic resonance imaging revealed low signal intensity in the hepatobiliary phase. The liver tumor and lymph nodes exhibited increased radiotracer uptake (maximum standardized uptake value=14.0) with positron emission tomography. A histological examination of a percutaneous needle biopsy specimen of the liver tumor indicated a diagnosis of CoCC. The patient underwent left hepatectomy and lymphadenectomy. The surgical specimen contained a poorly differentiated adenocarcinoma with anaplastic changes, which was immunohistochemically positive for epithelial membrane antigen (at the luminal membrane), cytokeratins 7 and 19, and negative for α-fetoprotein, hepatocyte-specific antigen, cluster of differentiation 56 and KIT. Based on these histopathological and immunohistochemical findings, the patient was diagnosed with ICC.

Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis.

Surgical injury can be a life-threatening complication, not only due to the injury itself, but also due to immune responses to the injury and subsequent development of infections, which readily result in sepsis. Sepsis remains the leading cause of death in most intensive care units. Unfavorable outcomes of several high-profile trials in the treatment of sepsis have led researchers to state that sepsis studies need a new direction. The immune response that occurs during sepsis is characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immunosuppressive phase. Therefore, therapies that improve host immunity might increase the survival of patients with sepsis. Many mechanisms are responsible for sepsis-induced immunosuppression, including apoptosis of immune cells, increased regulatory T cells and expression of programmed cell death 1 on CD4+ T cells, and cellular exhaustion. Immunomodulatory molecules that were recently identified include interleukin-7, interleukin-15, and anti-programmed cell death 1. Recent studies suggest that immunoadjuvant therapy is the next major advance in sepsis treatment.

Impact of reduced skeletal muscle volume on clinical outcome after esophagectomy for esophageal cancer: A retrospective study.

The aim of the study was to clarify the impact of reduced skeletal muscle volume on the morbidity of patients who underwent esophagectomy for esophageal cancer.Malnutrition and reduced skeletal muscle volume, that is, presarcopenia, are reportedly associated with a high frequency of postoperative complications after esophagectomy. However, it remains unclear whether the reduction of skeletal muscle volume following esophagectomy may affect clinical outcomes including pneumonia occurred beyond the preoperative period.From February 2009 to June 2015, in 123 patients, we retrospectively evaluated the postoperative changes of the psoas muscle index (PI) on computed tomography and assessed their impact on the incidence of pneumonia after esophagectomy.There was a significant reduction in the PI 6 months after surgery compared to the preoperative value. The incidence of pneumonia as of 6 months after surgery was 23.6%, which was higher in patients of advanced age (P = .02), those with a lower body mass index (P = .02), and those with a greater reduction of PI during 6 months after surgery (P = .03). It was not associated with preoperative nutritional data, pulmonary function, operative procedure, and preoperative PI. Multivariate analysis demonstrated that age and postoperative PI reduction were independently associated with the incidence of pneumonia 6 months after surgery (hazard ratio [HR] = 2.92, 95% confidence interval [CI] 1.16-7.32, P = .02; HR = 3.25, 95% CI 1.15-9.15, P = .03, respectively). Patients with pneumonia 6 months after surgery had significantly poorer overall survival than those without pneumonia at that time.Postoperative reduction of skeletal muscle volume was independently associated with the occurrence of pneumonia beyond the preoperative period, which might indicate the importance of a postoperative nutritional support after perioperative period in esophageal cancer patients.

Prognostic Value of Preoperative Systemic Immunoinflammatory Measures in Patients with Esophageal Cancer.

BACKGROUND: It is reported that several systemic immunoinflammatory measures, including systemic immune-inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and C-reactive protein (CRP)-to-albumin ratio (CAR), are associated with survival in patients with various types of cancer. OBJECTIVE: The aim of the present study was to clear which systemic immunoinflammatory measures had the greatest prognostic values. In addition, we examined which component had the greatest prognostic power in patients with esophageal cancer. METHODS: Preoperative systemic immunoinflammatory measures were evaluated in 143 patients undergoing esophageal resection for esophageal cancer from 2009 to 2014. Univariate and multivariate analyses were performed to determine the prognostic significance of these markers. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curves (AUROCs) were compared to verify the accuracy of each measure in predicting overall survival (OS). RESULTS: In univariate analysis, preoperative SII, NLR, and CAR were the predictors of OS in patients who underwent esophagectomy for esophageal cancer (p < 0.05, respectively), whereas in multivariate analysis, CAR and pathological tumor depth were the significant predictors of OS (hazard ratio [HR] 1.994, p = 0.03 vs. HR 1.967, p = 0.02, respectively). According to AUROC, the CRP (0.66) and albumin levels (0.66) were more important systemic immunoinflammatory measures than neutrophil (0.58), lymphocyte (0.63), and platelet (0.56) levels. CONCLUSION: Among systemic immunoinflammatory measures, CAR was the most significant predictor of OS in patients with esophageal cancer. CRP and albumin levels were more important components of systemic immunoinflammatory measures.

Diagnostic accuracy of T stage of gastric cancer from the view point of application of laparoscopic proximal gastrectomy.

The preoperative diagnosis of T stage is important in selecting limited treatments, such as laparoscopic proximal gastrectomy (LPG), which lacks the ability to palpate the tumor. Therefore, the present study examined the accuracy of preoperative diagnosis of the depth of tumor invasion in early gastric cancer from the view point of the indication for LPG. A total of 193 patients with cT1 gastric cancer underwent LPG with gastrointestinal endoscopic examinations and a series of upper gastrointestinal radiographs. The patients with pT1 were classified into the correctly diagnosed group (163 patients, 84.5%), and those with pT2 or deeper were classified into the underestimated group (30 patients, 15.5%). Factors that were associated with underestimation of tumor depth were analyzed. Tumor size in the underestimated group was significantly larger; the lesions were more frequently located in the upper third of the stomach and were more histologically diffuse, scirrhous, with infiltrative growth, and more frequent lymphatic and venous invasion. For upper third lesions, in univariate analysis, histology (diffuse type) was associated with underestimation of tumor depth. Multivariate analysis found that tumor size (≥20 mm) and histology (diffuse type) were independently associated with underestimation of tumor depth. gastric cancer in the upper third of the stomach with diffuse type histology and >20 mm needs particular attention when considering the application of LPG.

A case of pneumatosis intestinalis during neoadjuvant chemotherapy with cisplatin and 5-fluorouracil for esophageal cancer†.

Pneumatosis intestinalis (PI) is a relatively rare disease. A 70-year-old man with stage II squamous cell carcinoma of the middle thoracic esophagus was administered cisplatin plus 5-fluorouracil (CF) therapy as neoadjuvant chemotherapy. On Day 14 of the first course of CF therapy, he complained of acute abdominal pain. Computed tomography (CT) revealed PI of the entire colon and a small air bubble in the mesentery. A colonoscopy revealed that there was no finding suggestive of ischemia. Because there was no sign of peritoneal irritation, conservative treatment was selected. On Day 7 after PI diagnosis, CT indicated the disappearance of PI. The patient underwent a radical esophagectomy. Intraoperative laparoscopic findings showed the serosa of the colon to be intact. The patient was discharged without any complications. It is important to take into account that CF therapy may cause PI and that PI can be treated conservatively.

Weekly paclitaxel therapy for gastric cancer in patients with renal dysfunction: A case report.

A 57-year-old woman was admitted to National Defense Medical College hospital for treatment of gastric cancer with pyloric stenosis. She had been diagnosed with chronic kidney disease (CKD) 10 years prior, but received no hemodialysis. Because of peritoneal dissemination, a palliative distal gastrectomy was performed. In consideration of renal dysfunction, we decided for chemotherapy with paclitaxel, but not S-1 plus cisplatin regimen which is renal toxic agents. On the 29th postoperative day, chemotherapy using paclitaxel was initiated at a dose of 80 mg/m(2). Paclitaxel was administered weekly on days 1, 8, and 15 on a 28-day cycle. The patient tolerated 13 courses of this treatment without any severe adverse effect, such as exacerbation of renal function. Despite the gradual increase in the level of tumor markers, metastases were not detected via radiography during the clinical course. Moreover, renal function was maintained for the duration of the clinical course. To date, standard chemotherapeutic treatment for patients with CKD has not been established. We conclude that weekly paclitaxel is a suitable treatment regimen for patients with renal failure requiring chemotherapy for advanced gastric cancer.

Efficacy of totally laparoscopic distal gastrectomy for gastric cancer in elderly patients.

Elderly patients are often considered as high-risk for major abdominal surgery due to reduced functional reserve and increased comorbidities. We herein evaluated the efficacy of totally laparoscopic distal gastrectomy (TLDG) in elderly patients with gastric cancer by measuring the postoperative systemic responses and postoperative analgesic consumption. A total of 102 patients with gastric cancer [57 who underwent TLDG and 45 who underwent laparoscopy-assisted distal gastrectomy (LADG)] were enrolled in this study. The patients were classified as elderly (aged ≥75 years) and non-elderly (aged <75 years) groups. The surgical outcome and postoperative analgesic consumption were evaluated. The elderly group exhibited a higher incidence of comorbidities and a longer postoperative hospital stay compared with those of younger patients, although there was no difference in the incidence of postoperative complications. In addition, the total consumption of additional analgesics until postoperative day 5 in patients who underwent TLDG was significantly lower compared with that in patients who underwent LADG in the elderly group; there was no such difference in the non-elderly group. The results suggested that TLDG was better for the management of postoperative pain in elderly patients with gastric cancer, who exhibit the highest mortality rates in the adult surgical population.

Successful laparoscopic repair of an incarcerated Bochdalek hernia associated with increased intra-abdominal pressure during use of blow gun: A case report.

BACKGROUND: Bochdalek hernia is a congenital diaphragmatic hernia, and adult cases are rare, with a reported frequency of 0.17%-6% among all diaphragmatic hernias. PRESENTATION OF CASE: A 78-year-old man was referred to our hospital with a sudden onset of whole abdominal pain after playing with a blow gun. Chest radiography and computed tomography revealed diaphragmatic hernia with the small intestine. We therefore diagnosed him with an incarcerated Bochdalek hernia associated with increased intra-abdominal pressure during use of blow gun. Laparoscopic repair was performed. The omentum, transverse colon, and small intestine were located in the left thoracic cavity, without ischemic change. After placing the herniated organs into the abdominal cavity, we performed a primary closure of the diaphragmatic defect with interrupted non-absorbable sutures. DISCUSSION: It is generally recommended that all adult Bochdalek hernia patients undergo surgical repair to prevent life-threatening complications due to incarceration. Recently, laparoscopic techniques for repair the hernia have gained popularity, especially in elective cases. In our case, we could successfully perform emergency laparoscopic repair, as it is associated with a shorter inpatient hospitalization period. CONCLUSION: An incarcerated Bochdalek hernias associated with increased intra-abdominal pressure is an uncommon clinical finding in an adult, and laparoscopic repair of an incarcerated Bochdalek hernia is safe, feasible, and an excellent option as it is minimally invasive.

Pneumatosis intestinalis with obstructing intussusception: A case report and literature review.

Pneumatosis intestinalis (PI) often represents a benign condition that should not be considered as an argument for surgery. We report a patient with PI and obstructing intussusception who underwent urgent colectomy and review the literatures regarding PI with intussusception. A 20-year-old man presented at our hospital with a 3-d intermittent lower abdominal pain history. He underwent steroid therapy for membranoproliferative glomerulonephritis for 4 years. Computed tomography revealed ascending colon intussusception with air within the wall. Intraoperative colonoscopy revealed numerous soft polypoid masses with normal overlying mucosa and right hemicolectomy was performed. Histological examination of colonic wall sections revealed large cysts in the submucosal layer. The pathological diagnosis was PI. Nine cases of intussusception associated with primary PI have been reported. Although primary PI often represents a benign condition that should not be considered as an argument for surgery, if the case involves intussusception and obstruction, emergent laparotomy should be considered.

In vivo evaluation of a modified linear stapling device designed to facilitate accurate pathologic examination of the surgical margin.

BACKGROUND: Microscopic involvement of the resection margin could influence the long-term outcome of patients undergoing curative surgery for gastric cancer. Linear staplers, commonly used for gastrectomies, are often equipped with three lines of staples on either side of the resection line. Although multiple lines of staples reinforce closure of the gastric or intestinal stump, they could hinder accurate histopathologic evaluation of the surgical margin of the resected specimen. METHODS: We modified a linear stapling device by removing one line (stapler E2) or two lines (stapler E1) of staples on the specimen side, and attempted to dissect a silicon film and then the stomach from a porcine model using the stapling device and examined the distances between the cutting edge and the nearest staple line. RESULTS: The distance between the cutting edge and the staple line for stapler E1 was significantly greater than the distance between the cutting edge and the nearest staple line for stapler E2 or the control device. Consequently, specimens of exemplary quality were available for pathologic examination of the surgical margin. Moreover, the lack of multiple layers of staples did not result in contamination of the abdominal cavity with gastric juice during laparoscopic procedures in the porcine model. CONCLUSIONS: Stapler E1 is safe and could be useful for the pathologic evaluation of the true surgical margin.

Abdominal Infection Suppresses the Number and Activity of Intrahepatic Natural Killer Cells and Promotes Tumor Growth in a Murine Liver Metastasis Model.

BACKGROUND: Increasing evidence suggests that postoperative infection is associated with poorer long-term outcome in various malignancies. However, the mechanism of poor prognosis induced by postoperative infection has not been clearly explained. We sought to determine whether abdominal infection promotes cancer metastases in a murine liver metastasis model, and to investigate the role of liver natural killer (NK) cells on antitumor immunity during abdominal infection. METHODS: Female BALB/c (8-10 weeks old) mice were inoculated with NL-17 colon cancer cells into the spleen and then subjected to abdominal infection induced by cecal ligation and puncture (CLP) or sham treatment. The extent of liver metastases and cytokine production in the serum and liver were investigated. Cell fraction and cytotoxic activities of liver mononuclear cells (MNCs) were elucidated. RESULTS: CLP mice had poorer survival and their serum levels of IL-6, -10, and -12p70 were significantly elevated on day 1 compared with sham-treated and control mice. No obvious differences in cytokine levels of the liver homogenates were identified among the three groups, except IL-12p70 levels in CLP mice on day 7 significantly decreased. The cytotoxic activities of liver MNCs were significantly suppressed in CLP mice soon after tumor inoculation. Flow cytometry revealed a decrease in NK cells in the liver and perforin and granzyme B expression levels. CONCLUSIONS: Abdominal infection promoted liver metastases in a murine liver metastasis model, which may be partially caused by a decrease in the number and activity of NK cells during abdominal infection.

Preferentially examined sentinel nodes for sentinel node navigation surgery in gastric cancer.

The intraoperative examination of the sentinel nodes (SNs) is crucial for correctly performing SN navigation surgery (SNNS). Frozen-section diagnosis is ordinarily used; however, when several SNs are being assessed in gastric cancer, which has numerous regional lymph nodes, it is difficult to examine them all correctly within the short duration of surgery. In the present study, we aimed to determine the SNs that should be preferentially examined during SNNS in gastric cancer. A total of 824 SNs were examined in 113 patients with clinically determined T1-2 gastric cancer and no apparent lymph node metastasis. We focused on the accumulation of tracers expressed by hot nodes (HNs) using the radioisotope (RI) method and green nodes (GNs) using the dye-guided method and measured the radioactivity count of the HNs (RI count). We compared these parameters between 35 metastatic and 789 non-metastatic SNs. The percentage of metastasis-positive SNs that were radioactively 'hot' and dyed green was higher compared with that of the negative SNs (89 vs. 43%, respectively; P<0.01). The RI counts of the metastasis-positive SNs were higher compared with those of the negative SNs [median (range): 361 (0-10,670) vs. 53 (0-9,931), respectively; P<0.01]. The area under the receiver operating characteristic curve of the RI count was 0.69 (95% CI: 0.60-0.78). Therefore, when assessing several SNs, those with higher RI counts (HNs and GNs) should be preferentially examined. Further accumulation of cases is required to establish the cut-off value for the diagnosis of metastasis based on the RI count.

CD47 is an adverse prognostic factor and a therapeutic target in gastric cancer.

CD47 is an antiphagocytic molecule that acts via ligation to signal regulatory protein alpha on phagocytes; its enhanced expression and therapeutic targeting have recently been reported for several malignancies. However, CD47 expression in gastric cancer is not well documented. Immunohistochemical expression of CD47 in surgical specimens was investigated. Expression of CD47 and CD44, a known gastric cancer stem cell marker, were investigated in gastric cancer cell lines by flow cytometry. MKN45 and MKN74 gastric cancer cells were sorted by fluorescence-activated cell sorting according to CD44 and CD47 expression levels, and their in vitro proliferation, spheroid-forming capacity, and in vivo tumorigenicity were studied. In vitro phagocytosis of cancer cells by human macrophages in the presence of a CD47 blocking monoclonal antibody (B6H12) and the survival of immunodeficient mice intraperitoneally engrafted with MKN45 cells and B6H12 were compared to experiments using control antibodies. Immunohistochemistry of the clinical specimens indicated that CD47 was positive in 57 out of 115 cases, and its positivity was an independent adverse prognostic factor. Approximately 90% of the MKN45 and MKN74 cells expressed CD47 and CD44. CD47(hi) gastric cancer cells showed significantly higher proliferation and spheroid colony formation than CD47(lo) , and CD44(hi) CD47(hi) cells showed the highest proliferation in vitro and tumorigenicity in vivo. B6H12 significantly enhanced in vitro phagocytosis of cancer cells by human macrophages and prolonged the survival of intraperitoneal cancer dissemination in mice compared to control antibodies. In conclusion, CD47 is an adverse prognostic factor and promising therapeutic target in gastric cancer.

Theranostic Photosensitive Nanoparticles for Lymph Node Metastasis of Gastric Cancer.

BACKGROUND: Preoperative and intraoperative diagnoses of lymph node (LN) metastasis in patients with gastric cancer is essential to determine the extent of LN dissection in order to establish individualized treatment strategies. We investigated the theranostic value of a newly developed drug delivery system employing nanoparticles loaded with the indocyanine green (ICG) derivative ICG-loaded lactosome (ICGm) using a murine draining LN metastasis model of gastric cancer. METHODS: In the experimental draining LN metastasis model of human gastric cancer, the right hind footpads of nude mice were injected with cancer cells. Three weeks later, either ICGm or ICG solution was injected through the tail vein. Forty-eight hours after the administration of a photosensitizer, in vivo and ex vivo imaging and photodynamic therapy (PDT) were performed, and size of the LNs was measured. RESULTS: In vivo imaging revealed metastatic LNs in the ICGm-treated mice but not in the ICG-treated mice. PDT using ICGm induced apoptosis and significantly inhibited the growth of metastatic LNs. CONCLUSIONS: ICGm presents a novel theranostic nanodevice for LN metastasis of gastric cancer.