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 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.
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.
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.
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.
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.
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.
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.
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.
Summary 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 alpha-galactosylceramide (alpha-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 alpha-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.
Summary
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.
The growth of ongoing tumours was suppressed by activated CD8+ cytotoxic T lymphocytes (CTLs) with tumour‐specific cytotoxicity through the administration of the glycolipid α‐galactosylceramide (α‐GalCer). Sequential repetitive intraperitoneal inoculation with α‐GalCer every 48 hr appeared to convert tolerogenic DEC‐205+ dendritic cells (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. 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.
•DCs in Hepa1-6-1 tumours remained tolerogenic even after blockade of PD-1.•Combination therapy with anti-PD-1 mAb and α-GalCer showed an excellent effect.•The amount of anti-PD-1 mAb could be ...reduced by 90% when used with α-GalCer.
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.
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