Clinical Significance of Adjuvant Surgical Resection for Initially Unresectable Pancreatic Cancer Responsive to Arterial Infusion Chemotherapy.

BACKGROUND/AIMS: We have reported a clinically meaningful local-control effect and a hepatic metastatic tumor-regression effect of transcatheter peripancreatic arterial embolization-hepatic and splenic arterial infusion chemotherapy (TPPAE-HSAIC) for unresectable advanced pancreatic cancer. The aim of this study was to evaluate the clinical significance, of adjuvant surgical resection after TPPAE-HSAIC. METHODOLOGY: We assessed histopathological findings and outcomes of 6 patients who underwent surgical resection of tumors judged to be radically resectable after attaining tumor down-staging or long-term tumor control following TPPAE-HSAIC for pancreatic cancer initially diagnosed as unresectable. RESULTS: Clinical stage at the initial diagnosis was T4N0M0 Stage III in 4 patients and T4N0M1 Stage IV in 2 patients. The durations of TPPAE-HSAIC ranged from 5 to 46 months with a median of 19 months. An R0 resection was performed in 5 of the 6 patients (83%) and pathological down-staging, from the viewpoint of clinical stage, was observed in 4 patients. Of the 5 patients with R0 resection, one died from a postoperative complication at 7 months and another from pulmonary metastasis at 30 months post-operatively, while the other 3 patients have survived for 45 to 83 months to date. CONCLUSIONS: If surgical resection of pancreatic cancer initially diagnosed as unresectable can be carried out in patients responding favorably to TPPAE-HSAIC, the likelihood of long-term survival might be increased.

[Intraperitoneal and intrapleural gemcitabine in patients with advanced pancreatic cancer].

We performed intraperitoneal and intrapleural dosing gemcitabine (GEM) to eight patients with advanced pancreatic cancer having peritoneal or pleural carcinomatosis and evaluated its actions and safety. GEM (500 mg/m2) was infused into the abdominal cavity or thoracic cavity after drainage of peritoneal or pleural effusion. We checked the change of serum GEM concentration and the side effects after the GEM administration. Then, we repeated the GEM administration observing their systematic symptoms and evaluated the alteration of peritoneal or pleural effusion and cytology. Plasma concentration of GEM by infusing into the abdominal cavity or thoracic cavity was lower than by intravenous injection. In three of the five cases of peritoneal carcinomatosis, intraperitoneal administration revealed a decrease of peritoneal effusion. In two of the three cases of pleural carcinomatosis, intrapleural administration revealed a decrease of pleural effusion. Four cases had leukocytopenia of grade 1/2, three cases had thrombocytopenia, and two cases had alopecia as side effects, although all of them were minor side effects. Intraperitoneal and intrapleural dosing GEM had minor side effects and could improve QOL for the patients with advanced pancreatic cancer associated with peritoneal or pleural carcinomatosis.

Mechanisms for increment of platelet associated IgG and platelet surface IgG and their implications in immune thrombocytopenia associated with chronic viral liver disease.

In addition to hypersplenism, immunological destruction of platelets by elevated platelet associated IgG (PAIgG) and platelet surface IgG (PSIgG) has been proposed as a causative factor for thrombocytopenia in chronic liver disease (CLD), although the implication of PAIgG may be debatable since recent investigations on idiopathic thrombocytopenic purpura disclosed the fact that PAIgG largely relates to the intra-platelet IgG in alpha-granules and not to PSIgG. Further, with regard to the elevated PSIgG of CLD, characterization as to whether it mainly represents anti-platelet glycoprotein (GP) antibodies or IgG contained in the immune complex has not been elucidated. Thirty-seven patients with chronic viral liver disease (CVLD); 31 hepatitis C and 6 hepatitis B were included in this study. First we monitored the changes in levels of PAIgG, alpha-granule IgG, PSIgG and mean platelet volume (MPV) during the course of partial splenic arterial embolization (PSE). The elevated level of PAIgG decreased after PSE, paralleling that of alpha-granule IgG, while PSIgG showed no change; MPV decreased reciprocally with the increase of platelet count. These results indicate that the increment of PAIgG in CVLD may be caused by accelerated destruction of platelets; this generally evokes hyperproduction of large-sized thrombocytes, which have an increased capability to uptake circulating IgG. To characterize PSIgG, we then tested CVLD patients for antiplatelet GP antibodies and found only a 5.4% positivity. It was also found that circulating immune complex levels in CVLD patients were clearly elevated, correlating with the levels of PSIgG. Thus, it was surmised that immune complexes bound to the platelet surface, and not platelet specific GP antibodies, may be playing a crucial role in platelet destruction of CVLD, possibly through phagocytosis by macrophages.

A comparative randomized trial of intermittent intrahepatic arterial carboplatin- versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage IV).

BACKGROUND/AIMS: The study was performed to investigate the anti-tumor effect, survival rate, and toxicity of intermittent intrahepatic infusion chemotherapy with carboplatin suspended in lipiodol. METHODOLOGY: We conducted a randomized controlled study containing either doxorubicin or carboplatin in 65 patients with advanced hepatocellular carcinoma. RESULTS: The results observed in the carboplatin- and doxorubicin-lipiodol groups included: response rates, 29.0 and 20.6% respectively, 1-year survival rates of, 60.4% and 40.4%, respectively, and the difference achieved statistical significance (p=0.025). The median survival of 31 patients who received carboplatin emulsified with lipiodol was 16.9 months, 34 patients who received doxorubicin was 12.1 months. The difference achieved statistical significance. CONCLUSIONS: Compared with doxorubicin, carboplatin caused neither cardiotoxicity nor nephrotoxicity, and side effects of nausea and vomiting were less severe. Therefore, carboplatin is effective and preferable for repeated intrahepatic arterial administration to treat advanced hepatocellular carcinoma over a relatively long period.

Superselective transcatheter embolization for acute lower gastrointestinal hemorrhage after endoscopic mucosal resection: a report of 3 cases.

One of the most common complications related to endoscopic mucosal resection is hemorrhage; in almost every case, the bleeding is endoscopically managed, but some cases are unresponsive to the treatment. We have encountered three cases of endoscopically uncontrollable lower gastrointestinal hemorrhage after endoscopic mucosal resection in the colon which we successfully treated by urgent superselective transcatheter embolization. In our three cases, massive hemorrhage occurred immediately after endoscopic mucosal resection of a sessile polyp 25-40 mm in diameter, two cases in the ascending colon and one in the rectum. Although hemoclip placement was attempted in every case, hemostasis was not achieved. Emergency angiography disclosed massive extravasation of the contrast material in the colon. Hemostasis was achieved immediately after superselective transcatheter arterial embolizations with microcoils, with no observable ischemic complications and without the need of transfusions. In conclusion, superselective transcatheter embolization with microcoils should be considered a safe and efficient treatment option for endoscopically uncontrollable lower gastrointestinal hemorrhage occurring after endoscopic mucosal resection.

[A devised method of hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization for patients with advanced pancreatic cancer].

We previously reported the clinical efficacy based on hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer after transcatheter peripancreatic arterial embolization (TPPAE). However, this medical treatment pointed out a few problems in which the method had its complexity and a limited use of embolus micro-coil numbers. Then, we tried to improve the method in solving those problems. In order to reduce the embolus micro-coil numbers for TPPAE, we divided the micro-coil into several parts. We also devised the method of HSAIC. We used one catheter with a side hole, so that the catheter was able to supply a therapeutic drug for arterial infusion chemotherapy, both to the common hepatic artery and splenic artery. The effective rate for eleven cases was 72.7%, and there were no significant differences from the cases treated with the conventional method of TPPAE-HSAIC. Therefore, the devised treatment was considered to be an easy and useful method for TPPAE and HSAIC.

[A case of gastric carcinoma with multiple skin, bone, and bilateral ovary metastasis; effective treatment by chemotherapy].

A 40-year-old female visited our hospital with general malaise. She was diagnosed with gastric carcinoma with multiple skin, bone, and bilateral ovary metastases. Chemotherapy with 5-FU (1,000 mg/w) and cisplatin (10 mg/w) was performed in the outpatient clinic. Two years after the initial diagnosis, CEA was elevated. She then was given chemotherapy of CPT-11 (40 mg/w) in the outpatient clinic after 1 cycle of combined chemotherapy of CPT-11 and cisplatin. She died 38 months after the initial diagnosis. Weekly 5-FU/CDDP or low-dose CPT-11 appear to be effective for such a gastric carcinoma with systemic metastases without impairing quality of life.

[Usefulness of CT arteriography for transcatheter peripancreatic arterial embolization to patients with advanced pancreatic cancer].

We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.

[Three cases of multiple liver metastases of carcinoid tumor responding to hepatic arterial infusion chemotherapy using degradable starch microspheres].

We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.

Long-term clinical and radiological improvement of chronic acquired hepatocerebral degeneration after obliteration of portosystemic shunt: Report of a case.

Neurological manifestations are common in patients with decompensated cirrhosis. The majority of these patients show hepatic encephalopathy or chronic acquired (non-Wilsonian) hepatocerebral degeneration (CAHD). They characteristically present with dysarthria, ataxia, involuntary movements, and altered mental status. Neuroradiological examination in patients with hepatic encephalopathy often shows abnormal signals in multiple regions of the brain, such as the pallidum, putamen, caudate nucleus, hemispheric white matter, and ventral midbrain. The pathogenesis of hepatic encephalopathy and CAHD is poorly understood and the response to conventional therapies is often poor. We report a male patient with cirrhosis of unknown cause, who developed slowly progressive cerebellar truncal and limb ataxia and slurred speech. Magnetic resonance imaging (MRI) showed focal T2 hyperintensity in bilateral dentate nuclei and middle cerebellar peduncles (MCPs). After treatment by obliteration of the portosystemic shunt, clinical manifestations and MRI abnormalities were dramatically improved. He was followed for six years until he died of uncontrollable bleeding due to hepatocellular carcinoma. At the last examination 9 months before death, he showed no apparent aggravation of neurological symptoms, and no abnormal signal intensities in the MCPs and supratentorial compartment. The clinical course and changes of brain MRI findings of this case are extremely rare, suggesting that obliteration of the portosystemic shunt may be effective for CAHD over long term.

Selective embolization of the splenic vein in patients with hepatic encephalopathy and splenorenal shunt.

Obliteration of portal-systemic shunts is effective for portosystemic encephalopathy but is often associated with complications such as retention of ascites and worsening of esophageal varices. Selective embolization of the splenic vein was performed on six patients with hepatic encephalopathy and splenorenal shunts. Hepatic encephalopathy was not observed in four patients after the procedure. Neither retention of ascites nor rupture of esophageal varices was observed because postoperative elevation of portal venous pressure was not as great as that seen when shunt obliteration is performed. This procedure can be an effective and safe treatment option for hepatic encephalopathy with a splenorenal shunt.

Advanced pancreatic carcinoma showing a complete response to arterial infusion chemotherapy.

We report a patient with advanced carcinoma of the pancreatic body and tail with multiple liver metastases who showed a complete response to hepatic and splenic arterial infusion chemotherapy (HSAIC) with gemcitabine and 5-fluorouracil, following transcatheter peripancreatic arterial embolization (TPPAE) and partial splenic embolization (PSE). Nonresectable advanced pancreatic carcinoma tends to have a low response to medical treatment, with the median survival time being 6 months or less for stage IV cases. We disclose herein that the median survival time of patients receiving HSAIC after TPPAE is more than three times longer than the survival time attained with conventional treatments. However, in patients with advanced carcinoma of the pancreatic tail, for which TTPAE is not applicable, survival times remain low. Thus, in the patient described here, we also performed embolization of the left gastric and short gastric arteries as well as PSE to increase the flow within the great pancreatic and caudal pancreatic arteries via the splenic artery, and gemcitabine and 5-fluorouracil were administered via the splenic artery. As a result of these procedures, marked reduction in the advanced carcinoma of the pancreatic body and tail and of liver metastases was attained.