Downregulation of dual-specificity phosphatase 4 enhances cell proliferation and invasiveness in colorectal carcinomas.

It is widely accepted that aberrant activation of the Wnt signaling pathway is responsible for the development of precursor lesions of colorectal cancer (CRC). However, the molecular mechanisms involved in the process of progression from these precursor lesions to invasive lesions of CRC are not fully understood. Recently, we reported that constitutive activation of MAPK accompanied by downregulation of dual-specificity phosphatase 4 (DUSP4), a MAPK phosphatase, contributes to the progression of precursor lesions in the pancreas. In this study, we found that downregulation of DUSP4 was related to constitutive activation of ERKs in CRC cells. Restoration of DUSP4 resulted in inactivation of ERKs, leading to suppression of both proliferation and invasiveness, as shown by treatment with an MEK inhibitor. Furthermore, immunohistochemistry revealed that DUSP4 expression was upregulated in the superficial region of CRC tissue, whereas it was significantly downregulated in the deep region. In contrast, ERKs in the deep region were markedly hyperactivated compared to those in the superficial region. These results suggest that activation of the MAPK signaling pathway caused by downregulation of DUSP4 is responsible for progression of CRCs and would be a promising therapeutic target.

Control of inferior vena cava injury during laparoscopic surgery using a double balloon-equipped central venous catheter: proof of concept in a live porcine model.

BACKGROUND: Iatrogenic inferior vena cava (IVC) injury is a rare but potentially life-threatening complication during laparoscopic surgery. This experimental study aimed to assess the hemostatic ability of a new device, double balloon-equipped central venous (DB-CV) catheter, for IVC injury. METHODS: The DB-CV catheter comprises a triple-lumen sphincterotome combined with two dilating balloons having a diameter of 25 mm. The experimental procedures were performed in five pigs. The DB-CV catheter was inserted via the right femoral vein. For the IVC occlusion test, correct placement of the balloons was confirmed by indocyanine green fluorescence imaging, and hemodynamic data were recorded. For the IVC injury test, a 3- to 4-mm circumferential incision was created in IVC, and hemostasis was initiated using balloon inflation 5 s after the injury. RESULTS: Hemodynamic changes were minimal, with a 20 mmHg reduction in the mean arterial pressure because of IVC occlusion. All bleeding from IVC injuries was successfully temporarily stopped by direct balloon compression, with a mean time to hemostasis of 69 s and mean blood loss of 32 ml. Subsequently, the positioning of IVC injuries between two balloons made it possible to suture the injured IVC. CONCLUSIONS: Balloon occlusion using the DB-CV catheter provides a rapid temporal hemostatic effect and can overcome the serious condition of massive hemorrhage from IVC injuries.

Characteristics of advanced gastric cancer with negative or only perigastric lymph node metastasis in elderly patients.

OBJECTIVES: After gastrectomy with extended lymph node (LN) dissection, the damage of celiac plexus seems to cause of disorder of eating habits. To clarify the indication of gastrectomy with limited LN dissection for elderly patients, the pathological characteristics of advanced gastric cancer in elderly patients were examined in this study. METHODS: Forty-seven patients aged ≥80 years with advanced gastric cancer (deeper than pT2) who underwent curative gastrectomy from 1998 to 2015 were enrolled. Patients were classified into two groups by extent of LN metastasis: Group A, with N0 or only perigastric LN metastasis (n = 33); Group B, LN metastasis beyond the perigastric area (n = 14). Pathological factors were then evaluated. RESULTS: No significant differences were observed in age, sex, body mass index, American Society of Anesthesiologists physical status classification, serum level of carcinoembryonic antigen, surgical procedure, extent of LN dissection, and number of dissected LNs. Pathological findings showed no significant differences in tumor location, macroscopic type, histologic type, and lymphovascular invasion. However, significant differences were observed in tumor maximum diameter at the cut-off level of 40 mm (Group A: ≤40 mm, n = 10 and >40 mm, n = 23; Group B: ≤40 mm, n = 0 and >40 mm, n = 14; P = 0.02). CONCLUSION: In the elderly patients, LN metastasis in advanced gastric cancer of ≤40 mm in diameter was limited to be within the perigastric area. Gastrectomy with only perigastric LN dissection may be adopted in these patients.

Gluteal muscle metastasis with peritoneal dissemination from gastric cancer during postoperative adjuvant chemotherapy: a case report.

BACKGROUND: Skeletal muscle metastasis from gastric cancer is rare and has a poor prognosis. We reported a case of gluteal muscle metastasis with peritoneal dissemination from gastric cancer during postoperative adjuvant chemotherapy. CASE PRESENTATION: A 64-year-old man with gastric cancer underwent distal gastrectomy with D2 lymph node resection. The pathological diagnosis was poorly differentiated adenocarcinoma and signet cell carcinoma, T3N3bM0, Stage IIIC. Metastases were found in all regional lymph nodes, except 11p. The resection margin was negative. S-1 plus docetaxel therapy was administered as postoperative adjuvant chemotherapy. Six month post-operation, the patient presented with right gluteal muscle tenderness and abdominal distension. Computed tomography revealed a solid mass in the right gluteal muscle, a disseminated nodule on the abdominal wall, and massive ascites. Pathological examination of the gluteal muscle revealed signet cell carcinoma, similar to the resected gastric cancer. The tumor was diagnosed as gastric cancer metastases. Ascites cytology was class V. Thereafter, the patient underwent one course of capecitabine plus cisplatin combined with trastuzumab. Radiation therapy was also administered to relieve the pain of gluteal muscle metastasis. However, chemoradiotherapy was ineffective, and the patient died 2 months after the recurrence. CONCLUSIONS: Skeletal muscle metastasis and peritoneal dissemination during adjuvant chemotherapy indicated a poor prognosis.

Successful Conversion Surgery Following Chylous Ascites After Nivolumab for Advanced Gastric Cancer.

CASE REPORT: A 75-year-old man who underwent nivolumab as the third-line chemotherapy for advanced gastric cancer had chylous ascites (CA) after the primary tumor shrank remarkably. Total parenteral nutrition and subcutaneous octreotide were initiated, and CA disappeared. Nivolumab was continued for a total of 23 courses. Computed tomography showed lymph node swelling; however, staging laparoscopy showed that peritoneal metastasis had disappeared. Therefore, conversion surgery and distal gastrectomy with D1+ dissection were performed. RESULTS: The pathological diagnosis was type IV, poorly differentiated adenocarcinoma (por2) with signet ring cells, ypT2 (muscularis propria), without lymphatic or venous invasion, and no involvement of the proximal and distal margins. After the operation, no recurrence was observed over 7 months with no adjuvant chemotherapy. CONCLUSION: Nivolumab has the potential to lead to R0 resection for patients with peritoneal carcinomatosis gastric cancer. To our knowledge, this is the first report of successful conversion surgery after nivolumab-related chylous ascites.