In contrast, the patients in our study received HIFU within 24 ho

In contrast, the patients in our study received HIFU within 24 hours of gemcitabine administration in every CCHT. According to our TTP, the CA 19-9 level and the CT findings, the period of growth inhibition appeared to extend beyond eight months from the time of initiating administering chemotherapeutic agents in all three patients, compound library which, in our opinion, contributed to their excellent survival times. In several animal studies, CCHT induced apoptosis and it inhibited tumor growth more than chemotherapy or HIFU alone (10-12, 18). The mechanistic rationale for the inhibition of tumor growth by CCHT is based on the thermal and non-thermal effects of pulsed HIFU.

Thermally, the pulsed HIFU induces an increase in blood flow to the target tissues by causing local hyperthermia, which increases drug delivery, and it also mechanically induces structural and molecular changes at the cellular and molecular levels due to acoustic cavitation, radiation force, shear stress and acoustic streaming/microstreaming, which all might enhance drug extravasation and sensitize the cancer cells to chemotherapeutic agents (1, 11). The median OS and TTP of our non-CCHT group are similar to the results of the previous studies, with considering that the median OSs and median TTPs of gemcitabine and gemcitabine-capecitabine chemotherapies are 6-10 months and 3.8-5.4 months, respectively, for patients with advanced pancreatic cancer (3-6). In terms of safety, no major complications, other than one event of pancreatitis, was encountered in either study group.

However, mild pain was not uncommon during treatment, but it was well controlled with analgesics. When energy of 900-1000 J/spot was initially administered at our center, four patients presented with severe abdominal pain during the HIFU treatment and another two patients experienced a subcutaneous burn. However, no severe pain or subcutaneous burn has been encountered during treatment since this dose was reduced to 800 J/spot or less. Given that all three patients in the CCHT group received a mean target energy/spot of less than 850 J, a target energy of less than 800 J/spot might well be advisable. HIFU carries a risk of biliary perforation or biliary duct damage by thermal injury when cancers are located in the head of the pancreas. To reduce the risk, a previous study recommended placing a biliary stent before HIFU in patients with cancer in the pancreatic head (2).

In this current study, two patients with invasion of the distal common bile duct in the CCHT group underwent metallic biliary stent insertion due to obstructive jaundice before the initiation of CCHT. The biliary stents were always included in the treatment territory Brefeldin_A in all the HIFU sessions, and there was no evidence of a biliary obstruction or leakage in both patients. This suggests that metallic stents can prevent biliary complications.

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