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Despite improvements in surgical technique and postoperative management, pancreatoduodenectomy (PD) is associated with high morbidity 1-3. The most frequent causes of morbidity after PD are anastomotic insufficiencies, particularly clinically relevant postoperative pancreatic fistula (CR-POPF). In a recent case series, the reported rates of such conditions ranged from 8.9% to 29.1% 2-7. Previous studies have reported a correlation between bacterial infection and the development of a pancreatic fistula after PD 8-12. In particular, during the earlier postoperative period, most bacteria isolated from abdominal fluid can be associated with bile infection. Therefore, intraoperative bile contamination may become a concern. Although bile contamination may supply microorganisms responsible for abdominal infection, previous studies have not provided definitive conclusions regarding the contribution of

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis because it is often detected at an advanced stage, and drug resistance interferes with treatment. However, the mechanism underlying drug resistance in PDAC remains unclear. Here, we investigated metabolic changes between a parental PDAC cell line and a gemcitabine (GEM)-resistant PDAC cell line. We established a GEM-resistant cell line, MIA-G, from MIA-PaCa-2 parental (MIA-P) cells using continuous therapeutic-dose GEM treatment. MIA-G cells were also more resistant to 5-fluorouracil in comparison to MIA-P cells. Metabolic flux analysis showed a higher oxygen consumption rate (OCR) in MIA-G cells than in MIA-P cells. Notably, OCR was suppressed by GEM treatment only in MIA-G cells. GEM treatment increased mitochondrial membrane potential and mitochondrial reactive oxygen species (ROS) in MIA-P cells, but not in MIA-G cells. Glutamine uptake and peroxidase levels were elevated in MIA-G cells. The antioxidants N-acetyl-L-cysteine and vitamin C increased the sensitivity to GEM in both cell lines. In MIA-G cells, the expression of the mitochondrial transcription factor A also decreased. Furthermore, rotenone reduced the sensitivity of MIA-P cells to GEM. These findings suggest that the suppression of oxidative phosphorylation contributes to GEM resistance by reducing ROS production. Our study provides a new approach for reducing GEM resistance in PDAC.

AIM:To evaluate the efficacy of technical modifications of total hepatic vascular exclusion (THVE) for hepatectomy involving inferior vena cava (IVC). METHODS:Of 301 patients who underwent hepatectomy during the immediate previous 5-year period, 8 (2.7%) required THVE or modified methods of IVC cross-clamping for resection of liver tumors with massive involvement of the IVC. Seven of the patients had diagnosis of colorectal liver metastases and 1 had diagnosis of hepatocellular carcinoma. All tumors involved the IVC, and THVE was unavoidable for combined resection of the IVC in all 8 of the patients. Technical modifications of THVE were applied to minimize the extent and duration of vascular occlusion, thereby reducing the risk of damage. RESULTS:Broad dissection of the space behind the IVC coupled with lifting up of the liver from the retrocaval space was effective for controlling bleeding around the IVC before and during THVE. The procedures facilitate modification of the positioning of the cranial IVC cross-clamp. Switching the cranial IVC cross-clamp from supra-to retrohepatic IVC or to the confluence of hepatic vein decreased duration of the THVE while restoring hepatic blood flow or systemic circulation via the IVC. Oblique cranial IVC cross-clamping avoided ischemia of the remnant hemi-liver. With these technical Retrocaval liver lifting maneuver and modifications of total hepatic vascular exclusion for liver tumor resection Retrospective Study ORIGINAL ARTICLEmodifications, the mean duration of THVE was 13.4 ± 8.4 min, which was extremely shorter than that previously reported in the literature. Recovery of liver function was smooth and uneventful for all 8 patients. There was no case of mortality, re-operation, or severe complication (i.e. , Clavien-Dindo grade of Ⅲ or more). CONCLUSION:The retrocaval liver lifting maneuver and modifications of cranial cross-clamping were useful for minimizing duration of THVE.