Abstract: Mortality and morbidity was assessed after adoption of a systematic care for patient with pancreatoduodenectomy starting from patient selection and preparation, operative technique, and postoperative care. In this prospective study seventy patients who underwent pancreatoduodenectomy for periampullary carcinoma with curative intent between January 2010 and December 2014 were carefully analyzed prospectively. Patients were selected those who had ampullary carcinoma, lower bile duct carcinoma and small size carcinoma head of pancreas without local invasion and distant metastasis, and the patient who did not have any major disabling comorbid diseases. All patients were assessed uniformly before surgery and deficiency were corrected up to normal level before operation. Pancreatoduodenectomy and standard lymphadenectomy was performed meticulously with minimum blood loss. The pancreatojejunal reconstruction was performed using duct-to-mucosa method mostly. A nasojejunal feeding tube was placed in most patients for starting postoperative early oral feeding. Broad spectrum antibiotics and the epidural analgesia were mostly prescribed for good control infection and pain. Proper nutrition was maintained in calculative way through central venous line and nasojejunal feeding tube in the early postoperative period. General care, early mobilization and chest physiotherapy were given routinely in each patient. Seventy-seven percent (n=54) patients did not have any postoperative complications and they were discharged from hospital within 12-14 postoperative days. The morbidity occurred in 16 patients (23%) and most common complication was wound infection (18%, n=9). The rest complications were pancreatojejunal anastomotic leakage – 2, hepaticojejunal anastomosis leakage – 1, melaena – 1, intra-abdominal abscess – 1, intra-abdominal hemorrhage – 1, and renal dysfunction – 1. The mortality rate was 5.7% (n=4), causes of death were massive myocardial infarction; 1, failure of reversal from anesthesia; 1, massive intraabdominal bleeding; 1 and CV catheter related severe sepsis; 1. Review of recent published literature revealed that mortality and morbidity our series is better than low volume center and almost similar with high volume center of pancreatoduodenectomy surgery. Our systematic management policy of careful patient selection, planned approach in the form of proper work up, meticulous conduction of the procedure, appropriate postoperative care provides an acceptable morbidity and mortality after pancreatoduodenectomy.

Abstract: BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.