Role of Collagen Gel Droplet-Embedded Culture-Drug Sensitivity Testing (CD-DST) for Assessing the Sensitivity of Gastric Cancer to Chemotherapy Drugs Combined with Other Cancer Therapeutic Drugs.

BACKGROUND: Chemosensitivity tests have long been a widely discussed research topic. Our group performed collagen gel droplet-embedded culture-drug sensitivity testing (CD-DST) of patients with advanced gastric cancer during the period from December 2012 to December 2017. To verify how CD-DST should be used, we invested correlations of sensitivities to cisplatin (CDDP), docetaxel (DOC), paclitaxel (PTX), and CPT11 with clinical outcome. METHODS: Patients with advanced gastric cancer underwent gastrectomy with lymph node dissection at Nippon Medical School Tama Nagayama Hospital, and surgical samples were retrospectively examined by CD-DST to assess chemosensitivity. The patients later received adjuvant chemotherapy as standard adjuvant therapy or chemotherapy. The CD-DST test was not performed for S-1 because it is commonly used in chemotherapy for gastric cancer. Although oxaliplatin has also recently become a key drug for advanced gastric cancer, it had not been adopted for gastric cancer in 2012, so CD-DST testing was not performed. The χ2 test was used for all statistical analyses. A p-value of <0.05 was assumed to indicate statistical significance. Three-year survival rates were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the obtained curves. RESULTS: Of the tumors from gastric cancer patients, 67.0% (77/115) could be cultured. The rate of sensitivity was 41.1% (30/73) for CDDP, 82.6% (57/69) for DOC, 82.8% (58/70) for PTX, and 49.2% (33/67) for CPT11. CDDP sensitivity and outcome were not correlated in patients who received CDDP. Sensitivities to CDDP, DOC, PTX, and CPT11 were not correlated with any patient characteristic. Patients with poorly differentiated adenocarcinoma tended to be sensitive to CDDP (P=0.051). CONCLUSIONS: No difference between CDDP sensitivity or outcome was observed in patients receiving CDDP. The CD-DST showed a high sensitivity to DOC and PTX in the present patients.

Small bowel GIST with hemorrhagic shock diagnosed by capsule endoscopy and double-balloon endoscopy, angiography-guided hemostasis, and laparoscopic-assisted resection.

Small bowel tumors presenting with hemorrhagic shock require urgent treatment with angiographic embolization to achieve hemostasis. Capsule endoscopy and double-balloon endoscopy are useful for localizing the tumor, diagnosis, and guiding surgery.

Cholecyst-jejunostomy for palliative surgery.

INTRODUCTION AND IMPORTANCE: Many cases of unresectable cancer that cause obstructive jaundice require treatment. Depending on the patient's condition in these cases, surgery may be performed to treat jaundice. The main goal of palliative surgery is to improve the quality of life. Therefore, palliative surgery for obstructive jaundice must be performed safely and quickly. CASE PRESENTATION: This case presents a 45-year-old man with fever and back pain who was diagnosed with pancreatic head cancer and multiple liver metastases. Chemotherapy was initiated; however, during the course of treatment, the patient developed hemorrhage from pancreatic cancer that had invaded the duodenum caused hematemesis and melena. Therefore, the chemotherapy could not be continued. Because the patient also developed obstructive jaundice and cholangitis, a gastrojejunostomy and cholecyst-jejunostomy was performed. The surgery was successful; however, the cancer continued to progress, and patient died 31 days after surgery. CLINICAL DISCUSSION: Biliary reconstruction can be difficult to perform safely and quickly due to many factors. This study shows that cholecyst-jejunostomy is effective for patients with end-stage cancer. In the long term, cholecyst-jejunostomy is not suitable for biliary reconstruction due to the possibility of bile congestion and cholecystitis. However, this easy and quick procedure is well indicated for emergency patients with a short life expectancy. CONCLUSION: As an easy and quick procedure for emergency patients with a short life expectancy, jejunal anastomosis of the gallbladder is an appropriate palliative surgery that is indicated for jaundice treatment.

A case of hepatic portal venous gas that resolved with conservative treatment.

Hepatic portal venous gas (HPVG) is a potentially fatal condition. If vital signs are normal and laboratory data are not suggestive of any necrotic changes, a follow-up computed tomography after a conservative procedure can be performed at short intervals to conservatively monitor the patient.

Excision of a huge adrenal pheochromocytoma resembling a pancreatic tumor: A case report.

INTRODUCTION: Pheochromocytoma is a rare disease. Adrenal gland tumors make intraoperative blood pressure control difficult. If the tumor is large, it may need to be differentiated from pancreatic tumors and may require combined resection of other organs. PRESENTATION OF CASE: A 73-year-old Japanese woman presented to our hospital with abdominal pain. Computed tomography revealed a left abdominal tumor of 15 cm diameter. Magnetic resonance imaging, abdominal ultrasonography, and fractionated catecholamine test results led to strong suspicions of pheochromocytoma. A surgery was performed to remove the large tumor while controlling the blood pressure in the perioperative period and preparing for the possibility of combined resection of other organs. DISCUSSION: Left adrenal tumors can be difficult to differentiate from pancreatic tumors if the lesion is large. Pheochromocytoma is a catecholamine-producing tumor, and surgery to remove the tumor can be risky if the blood pressure is not controlled in the perioperative period. CONCLUSION: Careful preparations must be made to resect a giant pheochromocytoma. Adrenal tumors should always be considered as a differential diagnosis for any lesion suspected of being a large pancreatic body tail tumor.

Superficial anorectal abscess resembling a lipoma: A case report.

Perianal abscesses exist in various forms depending on the location. Clinical examination and endorectal ultrasound (EUS) may be useful for the diagnosis of anal tumor.

A case of transverse colon cancer with a large liver abscess that could be treated with a radical operation after infection control.

INTRODUCTION: Advanced colorectal cancer is known to be associated with liver abscesses. A strategy to treat liver abscesses as early as possible is necessary to ensure high surgical curability before the cancer progresses and to prevent worsening nutritional status of the patient during surgery. PRESENTATION OF CASE: An 82-year-old woman was hospitalized due to fever. A 10 cm in diameter liver abscess and advanced colon cancer were diagnosed. After conservative treatment of the liver abscess with antibiotics and puncture drainage, colorectal cancer surgery was performed on a standby basis. DISCUSSION: We propose that empiric antibiotic therapy should be administered early in cases of liver abscesses that may require early colorectal surgery. Abscess drainage should be performed promptly if the abscess is of a size that can be punctured easily. CONCLUSION: In patients with advanced colorectal cancer complicated by liver abscesses that required early surgery, prompt drainage of the liver abscesses is mandatory.

A combination of check-point blockade and α-galactosylceramide elicits long-lasting suppressive effects on murine hepatoma cell growth in vivo.

Immunotherapy for cancer cells induced by interfering with PD-1/PD-L1 engagement via check-point blockades was initiated by tumour-specific PD-1+ CD8+ cytotoxic T lymphocytes (CTLs) within a tumour mass and eliminate the tumour. Here, we used C57BL/6 (B6) mice implanted with the syngeneic hepatoma cell line Hepa1-6-1, and confirmed that the dendritic cells (DCs) within Hepa1-6-1 tumour mass were tolerogenic with downmodulated co-stimulatory molecules by tumour-derived factors. Although Hepa1-6-1 cells did not prime tumour-specific CTLs within the tumour, specific CTLs primed in the regional lymph nodes seemed to be invaded into the tumour mass. The specific CTLs gained PD-1+ expression when associated with PD-L1+ Hepa1-6-1 cells within the tumour mass. Their cytotoxic activity in vivo was revitalised after intraperitoneal (i.p.) administration of the anti-PD-1 monoclonal antibody (mAb), indicating that PD-1/PD-L1 engagement within the tumour was abrogated by check-point blockade. Nonetheless, the tolerogenic DCs within the Hepa1-6-1 tumour mass remained tolerogenic even after three shots of PD-1-blockade administration, and the suppressed Hepa1-6-1 growth was revisited. In this study, we show here an excellent therapeutic effect consisting of three injections of anti-PD1 mAb and the sequential administration of the CD1d molecule-restricted ligand α-galactosylceramide (α-GalCer), an immuno-potent lipid/glycolipid, which converts tolerogenic DCs into immunogenic DCs with upregulated expression of co-stimulatory molecules. The α-GalCer-activated DCs secreted a large amount of IL-12, which can activate tumour-specific CTLs in vivo. The check-point blockade was not sufficiently effective, but the dose needed for tumour eradication was reduced by 90% when tumour-bearing mice were also administered i.p. α-GalCer.

Single-port laparoscopic-assisted resection for a large abdominal cystic lymphangioma: a case report.

BACKGROUND: We report the case of a young woman with a large abdominal cystic lymphangioma that was successfully resected using single-port laparoscopic-assisted cystectomy. This avoided the need for a large surgical incision, as would result during conventional laparotomy. CASE PRESENTATION: A 17-year-old young woman was admitted to our hospital complaining of abdominal pain that had persisted for 3 days. Computed tomography revealed a 10 × 10 × 10-cm low-density area in the mid-abdomen, and magnetic resonance imaging showed a large abdominal cystic lesion. A mesenteric cyst was suspected, and single-port laparoscopic-assisted resection was performed. The cyst fluid was aspirated using a tissue adhesive, a suction tube with negative pressure, and a 16-gage over-the-needle catheter and syringe. The tumor size was reduced without any spillage of cyst fluid into the abdominal cavity. Then, the shrunken cystic tumor was successfully removed via the small wound and resected outside the abdomen. Pathological findings revealed an abdominal cystic lymphangioma derived from the greater omentum. CONCLUSIONS: Our procedure was easy to perform and required no special materials. Therefore, it could be applied to various cases, such as for abdominal cystic diseases.

Successful abdominal wound closure for treatment of severe peritonitis using negative pressure wound therapy with continuous mesh fascial traction: a case report.

BACKGROUND: Surgery for severe peritonitis often entails difficult wound closure and may require open abdominal management due to gut edema and/or concern of abdominal compartment syndrome. Negative pressure wound therapy (NPWT) is known to have good outcomes for wound closure after surgery for severe peritonitis. NPWT with continuous mesh fascial traction may result in even better outcomes, especially for fascial closure. CASE PRESENTATION: An 81-year-old man was hospitalized for abdominal pain. At admission, computed tomography (CT) demonstrated multiple liver metastases and a tumor perforating the sigmoid colon. Acute peritonitis due to perforated sigmoid colon cancer was diagnosed, and emergency peritonitis surgery and Hartmann's operation were performed. However, at the end of the operation, the surgical abdominal wound could not be closed due to gut edema and concern of abdominal compartment syndrome. Thus, the abdominal wound was left open and NPWT was performed in the primary operation. In the second and subsequent operations, NPWT with mesh fascial traction was performed. The wound was ultimately closed in the fifth operation, which took place 9 days after the primary operation. CONCLUSIONS: Treatment of severe peritonitis requires that gastroenterological surgeons learn some form of open abdominal management. This case suggests that NPWT with fascial mesh traction is a suitable solution. Furthermore, it does not require any special materials, and surgeons will find it easy to perform. In sum, NPWT with fascial mesh traction may be the preferred method of open abdominal management over other techniques currently available.

Suppression of murine tumour growth through CD8+ cytotoxic T lymphocytes via activated DEC-205+ dendritic cells by sequential administration of α-galactosylceramide in vivo.

Cancer immunity is mediated through the effective priming and activation of tumour-specific class I MHC molecule-restricted CD8+ cytotoxic T lymphocytes (CTLs). DEC-205+ dendritic cells (DCs) can cross-present the epitope(s) of captured tumour antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumour-specific CD8+ CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction. Hepa1-6-1 cells were established from the mouse hepatoma cell line Hepa1-6; these cells grow continuously after subcutaneous implantation into syngeneic C57BL/6 (B6) mice and do not prime CD8+ CTLs. In this study, we show that the growth of ongoing tumours was suppressed by activated CD8+ CTLs with tumour-specific cytotoxicity through the administration of the glycolipid α-galactosylceramide (α-GalCer), which is a compound known to stimulate invariant natural killer T (iNKT) cells and selectively activate DEC-205+ DCs. Moreover, we demonstrated that sequential repetitive intraperitoneal inoculation with α-GalCer every 48 hr appeared to convert tolerogenic DEC-205+ DCs into immunogenic DCs with a higher expression of co-stimulatory molecules and a stronger cross-presentation capacity, which primed CTL precursors and induced tumour-specific CD8+ CTLs within the tumour environment without activating iNKT cells. These findings provide a new basis for cancer immunotherapy to convert tolerogenic DEC-205+ DCs within tumours into immunogenic DCs through the sequential administration of an immuno-potent lipid/glycolipid, and then activated immunogenic DCs with sufficient expression of co-stimulatory molecules prime and activate tumour-specific CD8+ CTLs within the tumour to control tumour growth.

Successful percutaneous ultrasound-guided drainage for treatment of a splenic abscess.

We report a case of splenic abscess that was successfully treated with percutaneous ultrasound-guided drainage and without splenectomy. A 40-year-old woman was admitted to Nippon Medical School Hospital because of pyrexia and left upper quadrant pain, which had persisted despite antibiotic treatment. On admission, computed tomography demonstrated a low-density area in the spleen, which had been been seen on computed tomography 3 months earlier. Ultrasonography demonstrated a hypoechoic area in the spleen. Initial laboratory tests revealed a serum C-reactive protein concentration of 19.7 mg/dl and a white blood cell count of 15,800 /microl. The serum glucose concentration was 267 mg/dl, and the glycolated hemoglobin value was 7.7%. A splenic abscess was diagnosed and was treated with percutaneous drainage. Milky yellow fluid was obtained, and the patients left upper quadrant abdominal pain and pyrexia resolved. A culture of the drainage fluid yielded Escherichia coli. The drainage catheter was removed 12 days after insertion. The patient was discharged 6 days later. The splenic abscess has not recurred during 3 months of follow-up. Our results suggest that ultrasound-guided percutaneous drainage is a safe and effective alternative to surgery for the treatment of splenic abscess and allows preservation of the spleen.