CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery.

BACKGROUND/AIM: The role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence. MATERIALS AND METHODS: Gastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed. RESULTS: CD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells. CONCLUSION: CD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.

Successful treatment of rectal cancer with pelvic abscess using transrectal drainage followed by laparoscopic radical resection: a case report.

The incidence of rectal cancer with a pelvic abscess is rare; hence, treatment strategies are difficult because both malignant and infectious inflammation need to be addressed. Here, we report the case of a 53-year-old man diagnosed with rectal cancer accompanied by a pelvic abscess. We performed transrectal drainage of the abscess, and a transanal rectal drainage tube was inserted into the abscess cavity. His symptoms rapidly improved, and computed tomography showed that the pelvic abscess had disappeared. Six weeks after drainage, radical laparoscopic Hartmann's procedure with resection of the rectal cancer and incision drainage scar was performed. After adjuvant chemotherapy, laparoscopic stoma closure was performed a year after the operation. The patient showed no evidence of cancer recurrence 1.5 years after radical surgery. Transrectal drainage followed by laparoscopic radical resection can be a less invasive and effective treatment for rectal cancer accompanied by a pelvic abscess.

Postoperative analgesic effect of ultrasound-guided rectus sheath block and local anesthetic infiltration after laparoscopic cholecystectomy: Results of a prospective randomized controlled trial.

INTRODUCTION: Even if laparoscopic cholecystectomy (LC) has lower invasiveness through small incisions compared with laparotomy, postoperative pain control is important. METHODS: This prospective, randomized, single-blinded, interventional, single-center study was conducted from December 2016 to March 2018 at the Shiga University of Medical Science Hospital in Japan. Enrolled patients were assigned to either a rectus sheath block (RSB) group or an infiltrative local anesthesia (LA) group. After LC, the RSB group received bilateral RSB with 10 mL of 0.375% ropivacaine and the LA group received subcutaneous and fascial injection with 10 mL of 0.75% ropivacaine at the umbilical wound. The primary endpoint was a visual analog scale (VAS) score on postoperative day (POD) 1. RESULTS: This study enrolled 62 patients (RSB group = 31, LA group = 31). On POD1, the mean VAS scores were 36.4 ± 18.9 and 29.4 ± 15.4 in the RSB group and LA groups, respectively, showing that the LA group tended to describe lesser postoperative pain than the RSB group (P = 0.062). CONCLUSIONS: VAS scores on POD1 were not different between the groups. LC patients might obtain postoperative pain control via long-acting local analgesia.

The impact of blood type on the mortality of patients with severe abdominal trauma: a multicenter observational study.

Few studies have investigated the relationship between blood type and trauma outcomes according to the type of injury. We conducted a retrospective multicenter observational study in twelve emergency hospitals in Japan. Patients with isolated severe abdominal injury (abbreviated injury scale for the abdomen ≥ 3 and that for other organs < 3) that occurred between 2008 and 2018 were divided into four groups according to blood type. The association between blood type and mortality, ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate regression models. A total of 920 patients were included, and were divided based on their blood type: O, 288 (31%); A, 345 (38%); B, 186 (20%); and AB, 101 (11%). Patients with type O had a higher in-hospital mortality rate than those of other blood types (22% vs. 13%, p < 0.001). This association was observed in multivariate analysis (adjusted odds ratio [95% confidence interval] = 1.48 [1.25-2.26], p = 0.012). Furthermore, type O was associated with significantly higher cause-specific mortalities, fewer VFD, and larger transfusion volumes. Blood type O was associated with significantly higher mortality and larger transfusion volumes in patients with isolated severe abdominal trauma.

Successful laparoscopy-assisted repair of a rectovaginal fistula after low anterior resection for rectal cancer: a report of two cases.

BACKGROUND: Rectovaginal fistula (RVF) after low anterior resection for rectal cancer is troublesome and refractory. Although various surgical procedures have been previously described, no definitive procedure has shown a satisfactory outcome. We present two consecutive Japanese patients who underwent successful surgery for an RVF after low anterior resection. CASE PRESENTATION: The patients were two women (61-year-old and a 64-year-old). They were admitted to our hospital with a chief complaint of fecal discharge from the vagina after low anterior resection using the double-stapling technique for rectal cancer. They were diagnosed with RVF. Local surgical procedures, including diverting ileostomy, were unsuccessful in previous hospitals. Therefore, we performed laparoscopy-assisted repair of the RVF. In both patients, laparoscopically robust pelvic adhesions were dissected, and the sigmoid colon was transected at just oral side to the RVF. Thereafter, in combination with a perineal approach, the rectum, along with a previous anastomosis and fistula, were completely removed. Surgeries were completed after vaginal repair, redo coloanal anastomosis, and interposition of the dissected connective tissue. In both patients, the postoperative courses were uneventful. They complained of neither recurrence of any RVF nor fecal incontinence 1 year and 10 months after diverting stoma closure. CONCLUSIONS: A laparoscopy-assisted procedure with reanastomosis and interposition of the perineal connective tissue can be an effective treatment for RVF after low anterior resection for rectal cancer.

Gastric volvulus and giant Bochdalek hernia in an adult patient that were safely repaired by endoscopic reduction and elective laparoscopic surgery.

A Bochdalek hernia (BH) is a congenital abnormality with incomplete closure of the diaphragm. It is usually manifested in infants but rarely in adults. Here, we report an adult patient with gastric volvulus and giant BH that were safely repaired by endoscopic reduction and elective laparoscopic surgery, respectively. A 79-year-old woman presented with left upper abdominal pain but no history of trauma. CT revealed a giant BH with gastric volvulus. After emergency endoscopic reduction of the volvulus, elective laparoscopic repair of the BH was performed. The 8 × 8-cm defect was repaired with interrupted nonabsorbable sutures and a mesh. The patient's postoperative course was uneventful, and no complications or recurrence were observed in the 6 months that followed.

Perioperative tight glycemic control using artificial pancreas decreases infectious complications via suppression of inflammatory cytokines in patients who underwent pancreaticoduodenectomy: A prospective, non-randomized clinical trial.

BACKGROUND: We sought to investigate the efficacy of perioperative tight glycemic control (TGC) in reducing of postoperative infectious complications (POICs) and study its impact on early inflammatory mediators in patients who underwent pancreaticoduodenectomy. METHODS: In this non-randomized trial, the artificial pancreas (AP) group received TGC (target glucose range of 80-110 mg/dL; n = 14), while the control group received conventional glycemic control (range of 80-180 mg/dL; n = 15). The primary endpoint was POICs. RESULTS: The AP group had a markedly decreased POIC rate (28.6% vs. 73.3%; P = 0.027), mean glycemic variability (13.5 ± 3.5% vs. 16.4 ± 5.9%; P = 0.038), and plasma interleukin-6 level (26.3 ± 33.8 vs 98.3 ± 89.1 pg/ml; P = 0.036) compared to the control group, but insulin dosage (27.0 ± 13.4 vs. 10.2 ± 16.2 U; P = 0.002) and the adiponectin ratio (i.e., postoperative/preoperative adiponectin; 0.8 ± 0.2 vs. 0.6 ± 0.3; P = 0.021) were markedly higher in the AP group. CONCLUSIONS: Among patients undergoing PD with impaired glucose tolerance, AP facilitated strict glycemic control and resulted in a reduction of anti-inflammatory mediators and POICs. SUMMARY: Perioperative hyperglycemia increases postoperative infectious complications; however, tight glycemic control using artificial pancreas can reduce them via a dual effect. Artificial pancreas facilitates strict and safe glycemic control while reducing anti-inflammatory mediators, including adiponectin, following pancreaticoduodenectomy.

Interval between hepatocellular carcinoma treatment and interferon-free direct-acting antiviral agents against hepatitis C is necessary to suppress tumor recurrence.

Interferon (IFN) has been identified to suppress carcinogenesis when used for treating hepatitis C virus (HCV) infections. Treatment with IFN-free direct-acting antiviral agents (DAAs) is an acceptable alternative, even in elderly patients or patients who have been treated for hepatocellular carcinoma (HCC), because it has a lower incidence of side effects and higher sustained virological response (SVR) rate compared with IFN treatment. However, the suppression of carcinogenesis by DAAs is unclear. In the present study, 19 patients who underwent DAA treatment following treatment for HCC between January 2015 and March 2017 were retrospectively investigated. The clinical data were compared between 9 patients with HCC recurrence following DAA treatment (recurrence group) and 10 patients without HCC recurrence (no-recurrence group). The 1-year cumulative recurrence rate of HCC following SVR was as high as 50.2%. Age and sex did not significantly differ between the two groups, and the average number of HCC treatments prior to DAA treatment was also not significantly different between the recurrence and no-recurrence groups (3.2 and 2.2, respectively). The median interval between the final HCC treatment and the commencement of DAA treatment was 88 days in the recurrence group, which was significantly less compared with 790 days in the no-recurrence group (P=0.018). An interval of 120 days or more from final HCC treatment to the commencement of DAA treatment was a significant independent factor of no HCC recurrence following DAA treatment (P=0.028). A high HCC recurrence rate was identified following DAA treatment in patients with a history of HCC treatment. Therefore, there should be at least a 4-month interval from the final HCC treatment to the commencement of DAA treatment to ensure no HCC recurrence.

Postoperative Pancreatic Swelling Predicts Pancreatic Fistula after Pancreaticoduodenectomy.

Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy. However, the criteria for prompting drainage have not been clarified yet. We evaluated 80 patients who underwent pancreaticoduodenectomy between 2011 and 2016. Clinically relevant POPF (International Study Group of Postoperative Pancreatic Fistula grade B or C) was evaluated on the basis of the following parameters: changes in pancreatic thickness between preoperation and postoperative day (POD) 4 identified via enhanced CT, drain amylase level, laboratory data, and operative factors. POPF occurred in 21 patients (26.3%). The median change in pancreatic thickness before and after operation was 8.33 mm in the POPF-positive group, which was significantly larger than that in the POPF-negative group (3.79 mm, P <0.001). In addition, operation time, pancreatic texture, main pancreatic duct diameter, WBC count, C-reactive protein level, and drain amylase level demonstrated significant differences between the groups. In the multivariate analysis, operation time, C-reactive protein level on POD 3, drain amylase level on POD 1, and the change in pancreatic thickness before and after operation were independent risk factors of POPF. The drastic change in pancreatic thickness before and after operation predicted POPF in this study. This might be one of the factors that determine the requirement for drainage.

Computed Tomography Enhancement Pattern of the Pancreatic Parenchyma Predicts Postoperative Pancreatic Fistula After Pancreaticoduodenectomy.

OBJECTIVE: The aim of this study was to assess the relationship between the computed tomography (CT) pancreatic parenchyma attenuation value and clinically relevant postoperative pancreatic fistula (POPF). METHODS: The medical records of 115 patients who underwent pancreaticoduodenectomy and preoperative dynamic CT were retrospectively reviewed. The CT attenuation values of the nonenhanced (N), arterial (A), portal venous (P), and late (L) phase in the pancreatic parenchyma were determined via CT, and the A/N, A/P, and P/L ratios were calculated. The CT attenuation values and value ratios were compared between the POPF and non-POPF groups. RESULTS: Thirty-two patients (28%) were categorized in the POPF group. On univariate analysis, the A/P ratio (P < 0.001) and P/L ratio (P = 0.018) were significantly higher in the POPF group. On receiver operating characteristic curve analysis, the A/P and P/L ratio cutoff values for predicting POPF were 1.19 and 1.17, respectively. Of the preoperative evaluable factors, A/P ratio of 1.19 or greater (P < 0.001; odds ratio, 10.3) and P/L ratio of 1.17 or greater (P = 0.049; odds ratio, 3.23) were independent predictive factors for POPF, and the combination of the 2 ratios was useful in detecting POPF preoperatively. CONCLUSIONS: The enhancement pattern of the pancreatic parenchyma is associated with the development of clinically relevant POPF.

[Study of Eight Cases of Retroperitoneal Liposarcoma].

Retroperitoneal liposarcoma is a relatively rare disease, with a high recurrence rate and poor prognosis. We encountered 8 patients with retroperitoneal liposarcoma who underwent surgery in Shiga University of Medical Science Hospital. We often encounter elderly male patients without symptoms. Of the 8 patients, 6 received extensive resection that included the surrounding organs or tissues; however, 3 patients demonstrated positive surgical margins, which resulted in liposarcoma recurrence. Despite the additional resection in the 3 recurrent cases, all the patients had a tumor relapse. One patient with an unresectable tumor received chemotherapy. The other patients received surgical treatment 3 times. One patient developed an unresectable relapse after receiving chemotherapy. Another patient attained long-term survival by adjuvant chemoradiotherapy combined with 3 surgeries. Aggressive surgical resection to achieve a negative surgical margin and careful postoperative follow-up seem important for the treatment of retroperitoneal liposarcoma. This study suggests that postoperative adjuvant therapy may contribute to the improvement of prognosis. Further findings must be accumulated to clarify the significance of postoperative adjuvant therapies in the future.

A pilot study: The association between physical activity level using by accelerometer and postoperative complications after hepatic resection.

Recently, accelerometers measuring physical activity level have been available to the public. In the present study, it was examined whether the accelerometer could evaluate postoperative outcomes for 12 patients subjected to hepatic resection from August-November 2016. The association was evaluated between the changing pattern of activity level until the postoperative day (POD) 7 and the occurrence of postoperative complications. The median age of patients was 79 years (range, 58-85). Postoperative complications were identified in 6 patients. The activity level in patients with complications was low from POD 1 and was significantly lower than patients without complications following POD 6. The changing pattern of activity level with all included patients could be divided into the following 3 types: Increase type, bell curve type and flat type. Patients without complications exhibited an accelerated increase of postoperative activity level, categorized as increase type. Bell curve type and flat type demonstrated delay of recovery in postoperative activity levels, and were suggested to be associated with the occurrence of postoperative complications. These findings may provide rationale for larger sample studies to evaluate whether physical activity level measured via accelerometer may be a surrogate marker for postoperative complications.

[A Case of Gastric Cancer Underwent Two-Stage Gastrectomy after Chemotherapy-Induced Perforation].

A 70's man presenting with a chief complaint of stomachache was found to have advanced gastric cancer with a deep ulcer and some lymph-node metastases. We decided performing a curative operation after 2 courses of S-1 plus cisplatin. On the first course day 13 of chemotherapy, he complained of severe epigastralgia, and we diagnosed as generalized peritonitis due to perforation of gastric cancer. We performed an urgent laparoscopic operation, which made perforation simple closure and omentopexy. Curative distal gastrectomy with D2 lymph node dissection was successfully performed on postoperative day 16.

In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro.

Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor-specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine. The cells were then incubated for 7 days in vitro with a major histocompatibility complex (MHC) class I peptide derived from neu, in the presence or absence of an agonistic anti-OX40 monoclonal antibody, before CD8+ T cells were isolated for use in ACT therapy. The proliferative ability of OX40-driven tumor Ag-specific effector CD8+ T-cells in vitro was less than that of non-OX40-driven tumor Ag-specific effector CD8+ T-cells, but they expressed significantly more early T-cell differentiation markers, such as CD27, CD62L and CCR7, and significantly higher levels of Bcl-2, an anti-apoptotic protein. These OX40-driven tumor Ag-specific effector CD8+ T-cells, when transferred into tumor-bearing recipients, demonstrated potent proliferation capability and successfully eradicated the established tumor. In addition, these cells exhibited long-term antitumor function, and appeared to be established as memory T-cells. Our findings suggest a possible in vitro approach for improving the efficacy of ACT, which is simple, requires only a small amount of modulator, and can potentially avoid several toxicities associated with co-stimulation in vivo.

[A Surgically Resected Case of Retroperitoneal Liposarcoma with Metastasis].

An 80s man presenting with general malaise and anorexia was referred for treatment of abdominal tumor. Abdominal contrast-enhanced CT revealed a tumor in the left renal cavity. The inside of the tumor coexisted with a fat component and a solid component having a contrast effect. In addition, 2 solid tumors were found to be in contact with the stomach, away from the primary lesion. Based on these findings, retroperitoneal liposarcoma with intraperitoneal metastases was diagnosed. The patient underwent excision of the retroperitoneal tumor and local gastrectomy. The size of the main tumor was 21×18 cm, and the weight was 2.0 kg. Histopathology of the resected specimen showed dedifferentiated liposarcoma and its metastases. The resected margin of the excised tumor was negative. Liposarcoma has a high local recurrence rate, and the status of a resected margin of the tumor is an important factor for prognosis. Here, we report a case of dedifferentiated liposarcoma with metastatic lesions that could be completely resected.

[Prognosis of Patients after Palliative Stoma Creation].

INTRODUCTION: We evaluated the effectiveness of palliative stomas created to resolve symptoms of bowel obstruction. METHODS: We retrospectively evaluated patient characteristics and outcomes in 16 cases of palliative enterostomy performed to resolve malignant bowel obstruction. RESULTS: The median age of the patients was 64 years, and the most common original cancer was colorectal cancer(11 cases, 69%). Oral intake was recovered in 15 patients after the surgery(94%), and the colorectal obstruction scoring system(CROSS)score improved from 2 to 4. Postoperative complications(Clavien-Dindo grade Ⅱ or higher)were observed in 8 cases(50%), in which serum albumin levels were less than 3.5 g/dL(p=0.077), resulting in longer hospital stays(p=0.041). The median overall survival time was 107 days, and longer survival time was achieved in patients aged younger than 70 years, with CA19-9 levels C37.7 U/mL and postoperative CROSS score of 4, who were administered postoperative chemotherapy. The chemotherapy was feasible after surgery when CROSS scores improved to 4(p=0.019). CONCLUSION: Palliative stomas contributed to the improvement in oral intake of patients with terminal cancer. This improvement may allow patients to receive postoperative chemotherapy, which leads to longer survival times.

Synchronous primary gallbladder and pancreatic cancer associated with congenital biliary dilatation and pancreaticobiliary maljunction.

INTRODUCTION: Synchronous double cancer of the gallbladder and pancreas that is associated with congenital biliary dilatation (CBD) and pancreaticobiliary maljunction (PBM) is extremely rare. PBM is frequently reported in Asia, particularly in Japan. We report a surgical case of synchronous double cancer in a patient with primary gallbladder and pancreatic cancer. PRESENTATION OF CASE: A 72-year-old woman with epigastralgia underwent subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection for synchronous primary gallbladder and pancreatic head cancer. Histopathological examination revealed moderately differentiated ductal adenocarcinoma of the pancreatic head and well-differentiated tubular adenocarcinoma at the bottom of the gallbladder. CONCLUSION: Synchronous gallbladder and pancreatic cancer is extremely rare. It is necessary to determine the optimal surgical course taking into consideration the degree of tumor progression. This is the second case of synchronous primary gallbladder and pancreatic cancer associated with CBD accompanied by PBM.

Endotoxin adsorption: Direct hemoperfusion with the polymyxin B-immobilized fiber column (PMX).

Toraymyxin® is a medical device developed to adsorb circulating endotoxins in the blood using direct hemoperfusion therapy for patients with septic shock. In 1994, the Japanese National Health Insurance system approved the use of Toraymyxin for the treatment of endotoxemia and septic shock. Since then, Toraymyxin has been safely used in more than 100,000 cases in emergency and intensive care units in Japan. Toraymyxin is currently available for use in the clinical setting in 14 countries worldwide. In this study, we reviewed and introduced the development, clinical use, and efficacy of Toraymyxin and commented on its anticoagulant use and cartridge clotting issue in the treatment of severe sepsis and septic shock. We also highlighted potential new applications of Toraymyxin for longer duration therapy and pulmonary diseases.

[A Case of Small Intestinal GIST with Long-Term Survival after Tumor Resection for Repeated Peritoneal Recurrence].

A 70-year-old woman presenting with abdominal pain was admitted to our hospital. Abdominal contrast CT revealed a small intestine tumor of 10 cm with active bleeding and performed partial resection of the small intestine including tumor. Pathological findings were high risk GIST of the small intestine because of spindle cells and c-kit positive. Imatinib 400mg/day as adjuvant chemotherapy was administered. However administration was stopped for 15 days because of the Grade 4 erythema multiforme. Recurrence of peritoneal dissemination was observed in 2 years after surgery and tumor resection was performed, but complete resection was difficult. Within 5 years after surgery, tumor resection was performed on a total of 5 times peritoneal disseminative recurrences, and it was possible to avoid the appearance of symptoms due to tumor augmentation.