Japanese multicenter experience of endoscopic necrosectomy for infected walled-off pancreatic necrosis: The JENIPaN study.

BACKGROUND AND STUDY AIMS: Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled-off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. PATIENTS AND METHODS: A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011. The follow-up data were also reviewed to determine the long-term outcomes of the procedures. RESULTS: Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory - Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. CONCLUSIONS: Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality.

Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss.

Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%), while no interferon-gamma production was observed in non-responders (NR) (n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells specific for all the peptides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-gamma production by CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8(+) T cell response in controlling HCV infection.

[A case of multiple liver metastases from sigmoid colon cancer effectively treated by hepatic intra-arterial administration of levoforinate and 5-fluorouracil].

A 62-year-old female patient, who was diagnosed with sigmoid colon cancer with multiple liver metastases, was admitted to our hospital. She underwent sigmoidectomy with D3 lymph node dissection on January 31, 2000. In addition to that, she received hepatic intra-arterial infusion of levoforinate (l-LV) 250 mg and 5-fluorouracil (5-FU) 500 mg for combined multiple hepatic metastases starting on postoperative day 14, and these medications were administered over 48 hours once weekly by infuser pump. The tumor diminished by 59% 2 months after the start of administration and further diminished at 4 months. PR was achieved. Cancer metastasis to the cerebellum and metastasis to the lung were detected at month 9 and month 11, respectively, but the liver metastatic tumor continued to diminish in size, ultimately becoming undetectable by CT scan at month 10. Surgery and radiotherapy were performed for the cerebellar metastasis, and intravenous administration of a combination of l-LV and 5-FU was performed systemically for the pulmonary metastatic tumor. At present, the patient receives regular outpatient treatment continuously. To our knowledge, there has been no report on the combination therapy with l-LV and 5-FU through the hepatic artery. Since good antitumor efficacy was demonstrated in the present patient, this case is described in this report together with four other cases of hepatic metastasis from colorectal cancer.

Neuromagnetic localization of N15, the initial cortical response to lip stimulus.

The initial cortical response of the trigeminal somatosensory evoked magnetic fields was measured for electrical stimulation of the lower lip in eleven subjects. The stimulus frequency was 0.7 Hz and stimulus intensity was nine times sensory threshold. The initial contralateral response was detected in 20 hemispheres at a latency of 14.6+/-1.3 ms and was named N15m. The equivalent current dipole of N15m was localized at the posterior bank of the central sulcus with anterior-superior orientation, and inferior to the dipole of N20m for median nerve stimulation.

Marked therapeutic effect of dimyristoylphosphatidylcholine liposomes on carcinoma mice model in vivo.

Significantly prolonged survival rate was obtained for the first time using carcinoma mice models after the administration of single-component liposomes of dimyristoylphosphatidylcholine (DMPC) without any drug. An increase in lymphocytes under optical microscope was observed without any increase in the neutrophils count, suggesting that the DMPC liposomes might inhibit the tumor growth as well as increase in lymphocytes in vivo.

[A patient with multiple pulmonary metastases from colonic cancer who survived for 5 years by effectual administration of 5'-DFUR].

The patient was a 69-year-old woman who had been diagnosed with a bowel obstruction due to colonic cancer, with simultaneous multiple pulmonary metastases. The primary lesion was resected and 5'-DFUR was administered for 2 years at an out-patient clinic. During those 2 years, there was no change in CEA value and the pulmonary lesions were fading on the roentogenograms. It then became doubtful whether the pulmonary shadows were real metastases or not, and 5'-DFUR administration was discontinued. After stopping the medication, her CEA value rose and the tumor shadows increased in intensity. 5'-DFUR was therefore re-administrated and her CEA value declined. Afterwards, a re-elevation in CEA value was seen, and low-dose FP therapy was added on an out-patient basis. Anti-cancer chemotherapy of 5'-DFUR (oral) and low-dose FP (i.v.) was contributed to her 5-year survival.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

[A case report: disappearance of cancer cells confirmed by surgical resection after transcatheter hepatic artery embolization (TAE) for ruptured hepatocellular carcinoma].

The patient was a 74-year-old man. He had received medical treatment for liver cirrhosis (C types) and elevated AFP. Abdominal ultrasonography (US) revealed a 150 mm size tumor in the right lobe of the liver. After admission, anemia progressed rapidly, and we recognized bloody ascites by abdominal punction. Thus, diagnosis was a tumor rupture. Emergency angiography was performed. Farmorubicin and Lipiodol were injected, and complete TAE was added. After two TAE treatments CT-scan showed a remarkable decrement of the tumor and hypertrophy of the left lobe in the liver. Right lobectomy of the liver was then done because reserve function of the liver was good. Cancer cells changed into hyaline body and mecrotic focus. In the pathological examination of the extirpated sample, no viable tumor cells were detected.

[Long partial response (PR) in a case of multiple liver metastasis from colon cancer effectively treated by continuous hepatic intra-arterial infusion chemotherapy].

The patient was a 69-year-old man who had undergone a sigmoidectomy for cancer of the sigmoid colon on March 25, 1993. We detected the elevation of CEA after the operation. Computed tomography revealed multiple metastasis of the liver on September 3, 1996. After beginning 48-hour continuous hepatic arterial infusion using 5-FU 1,000 mg and Leucovorin 30 mg, we recognized a decrement of metastatic liver tumor. We could not detect cancer cells by needle biopsy for liver tumors on February 19, 1998. This case is maintaining good quality of life by hepatic artery infusion using 5-FU and Leucovorin, showing a long PR for about two years. We think that this case shows ideal clinical progress from chemotherapy for cancer of the digestive organs.

Chemotherapy with hybrid liposomes for melanomatosis.

The inhibitory effects of the hybrid liposomes on the growth of B-16 melanoma cells in vitro and in vivo were examined. The 50% inhibitory concentration of the hybrid liposomes composed of 90 mol% dimyristoylphosphatidylcholine (DMPC) and 10 mol% polyoxyethylenedodecyl ether (C12(EO)10) was one-twelfth of that of DMPC liposomes. It was noteworthy that for the first time significantly prolonged survival was obtained using a mouce model of carcinoma after the administration of the hybrid liposomes of 90 mol% DMPC/10 mol% C12(EO)n (n=10 or 23) without antitumor drugs.

[Medical support system to enable advanced cancer patients to die at home].

Among 207 advanced cancer patients that received home care during the period from April, 1987 to December, 1998, 144 died in their own house, and 129 people were confirmed dead by a doctor of this department. Eighty (62%) of these 129 people died outside the hospital working hours. Moreover, 47 people (36%) died on a day the hospital was closed. The time difference between the actual death time and the doctor's death confirmation time was less than 60 minutes for 88 people, over 60 minutes for 41 people, over 120 minutes for 17 people, and over 180 minutes for seven people. The doctor in charge performed the death confirmation for 107 people (83%). Forty-seven people had received a visit by the doctor or nurse on the day of death, and 57 people had received a visit on the day before death. The existence of the medical support system of 24 hour correspondence and various guidance for the family on the method of making urgent reports when near death, how to spend the last hours, and the postmortem procedures were especially important in making home death possible.

[Home anti-cancer chemotherapy with continuous infusion of 5-FU combined with low-dose cisplatin injection via implantable venous port with portable balloon pump].

Home anti-cancer chemotherapy was performed for patients with advanced cancer of the digestive plantable venous port placed beneath the skin via the subclavian vein. 128 patients under 75 years old (enrolled: 6 patients with esophageal, 65 with gastric, 44 with colorectal, 5 with cholangio, 5 with pancreatic, one with hepatic and one with ileal cancer) were treated. Continuous intravenous infusion of 5-FU (300-400 mg/body/day) combined with low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 23.6% in 72 patients with valuation of tumor mass. In 83 patients for whom a tumor marker evaluation was also performed, an effect was seen in 30.1%. No severe side effects such as renal dysfunction were observed, and no special infusions were needed. Therefore, a quality of life was maintained in which bathing was possible and patients were released from the hospital. Hyperalimentation through the venous port, and palliation during the terminal stage, is easily accomplished. It is useful method for surgery, chemotherapy and palliative therapy in the treatment of cancer.

A transient emergence of hepatic granulomas in a patient with chronic hepatitis B.

So far there were no reports but one on a hepatic granuloma in chronic hepatitis B virus (HBV) infection. We present a case of chronic hepatitis B with a transient emergence of hepatic granulomas. The case was a 35-year-old male who had chronic hepatitis with persistent hepatitis B surface antigen in the sera. A liver biopsy showed noncaseating granulomas in the parenchyma and a mild portal enlargement with mononuclear cell infiltration. The cellular components of the granulomas were mainly cluster of differentiation 68-positive macrophages with a few lymphocytes in the periphery. However, no granulomas were found in a liver specimen obtained three weeks after the first liver biopsy. Possible disorders causing hepatic granulomas such as tuberculosis, sarcoidosis, drugs and other infectious diseases were ruled out by clinical, serological and histopathological examination. Thus it is possible that the transient emergence of hepatic granulomas is a phenomenon related to chronic HBV infection.

[Home care for terminally ill cancer patients in 1997].

In 1997, home care was provided for thirty-seven terminally ill cancer patients, fifteen patients with gastric cancer, nine patients with colorectal cancer, four patients with breast cancer, and nine patients with other miscellaneous cancer. The shortest period of home care was three days, the longest was six hundred seventeen days, and the average was one hundred eight days. Medical treatment at home consisted of dosage of morphine for 30 patients, parenteral nutrition for 30 patients, dosage of steroids for 29 patients, infusion of haloperidol for 8 patients, continuous draining of ascites for 6 patients, and continuous draining of intestinal fluid through nasogastric tube for 3 patients. As of May 31, 1998, 3 patients were alive but 34 patients had died, 31 of them at home. The characteristic trends in this year were reinforcement of the home care system in our hospital, prolongation of mean at-home days, inhalation of nebulized morphine for management of dyspnea, restriction of indication of home infusion therapy and active cooperation with public health center and welfare office.

Serological and histological features of anti-HCV-positive individuals without serum HCV RNA.

Antibody to hepatitis C virus (anti-HCV) in patients who are negative for HCV RNA in serum may indicate a memory of past infection of HCV. However, their clinical features have not been well understood. Fourteen anti-HCV-positive but HCV RNA-negative individuals were examined for serological and histological features. As a result, it was found that they had only antibody to HCV core antigen C22-3 with or without antibody to nonstructural viral antigen C33c on a recombinant immunoblot assay (RIBA), and that an concentration of anti-C22 was low. Liver biopsy showed two having no evidence of an obvious hepatic injury, two having a minimal change, and two having portal fibrosis. HCV RNA was not found in the liver. These results corroborate an idea that the anti-HCV in HCV RNA-negative individuals implies a past infection of HCV. Furthermore, it is suggested that a combination of an appearance pattern of antibody to HCV antigens on RIBA and anti-C22 titer are an useful marker to distinguish anti-HCV-positive individuals without viremia from those with viremia.

[Postoperative normalization of prolonged P100m latency in the visual evoked magnetic field in a patient with occipital meningioma].

A 49-year-old female with a left occipital parasagittal meningioma was found to have prolonged P100m latency of the pattern reversal visual evoked magnetic field only in the hemisphere containing the lesion. After total removal of the tumor, the P100m latency was normalized in the affected hemisphere. Based on current dipole models, all the P100m dipoles were localized at the lateral bottom of the calcarine fissures bilaterally, as indicated by our previous study with normal subjects. Since the tumor was located near the parietoocipital sulcus and distant from the primary visual cortex, disturbance of the higher visual cortex probably affected the P100m latency.

Neuromagnetic evaluation of cortical auditory function in patients with temporal lobe tumors.

The N100m wave response of the auditory evoked magnetic field originates in the posterior part of the bilateral superior temporal planes for either contra- or ipsilateral ear stimulus. Cortical auditory function was evaluated in 14 patients with temporal lobe tumors using a magnetic resonance (MR) imaging-linked whole-head magnetoencephalography (MEG) system. Before surgery, seven patients had normal N100m latency (within the range of the mean +/- 2 standard deviations of 37 normal volunteers) in both normal hemispheres and in those with lesions, and MR imaging indicated no tumor invasion or edema in the posterior one-third of the superior temporal planes, even when the sylvian fissure was shifted upward due to the mass effect. Seven patients had prolonged N100m latency or absence of N100m in the hemisphere containing the lesion, and the posterior portion of the superior temporal plane was involved by the tumor or perifocal edema. Prolonged N100m latency recovered to the normal range after removal of tumors in two of four patients investigated postoperatively. The MEG system can be used to evaluate cortical auditory function noninvasively before and after surgical treatment of temporal lobe tumors.

[Ten years experience of home parenteral nutrition or hydration in advanced cancer patients].

From April 1987 to May 1997, ninety-six advanced cancer patients including ninety-one among 159 home care patients and five outpatients were administered parenteral nutrition or hydration. Eventually, 67 patients died at home. We concluded through our experience that advanced cancer patients who were unable to eat or drink might live at home with the support of parenteral nutrition or hydration. But four conditions are needed for satisfactory home care of these patients. First, patients understanding their disease condition therefore together with their family hope for home care. Second, the home care support team is organized in an institution. Third, the home care support team is on call for emergencies. Fourth, the home care support team can not only manage home parenteral nutrition but also provide palliative care, including pain control.

[Trial of home anti-cancer chemotherapy with infusion of 5-FU and low-dose cisplatin].

We tried home anti-cancer chemotherapy for patients with advanced or recurrent cancer of the digestive system, using two disposable balloon pumps connected to an implantable drug delivery system via central venous line. There were 33 patients under 75 years old, including 20 cases of gastric cancer, 9 cases of colorectal cancer, 2 cases of cholangiocarcinoma and 2 cases of esophageal cancer enrolled in this study. The protocol was combined chemotherapy with continuous intravenous infusion of 5-FU (300 mg/body/day) and low-dose intravenous injection of cisplatin (5 mg/body/day) in 10-day courses for two weeks, and it was repeated 3 times for 6 weeks. Because of side effects such as nausea, vomiting and bone marrow suppression, treatment was discontinued in 12 cases with peritoneal cancer infiltration. In two of 10 with estimable disease, the reduction of the metastatic lymph node was observed, but no effect was shown in the colorectal metastatic liver tumor. Thanks to the portability of the pump with this method, the patient need not undergo hospitalization. Moreover, there is no renal dysfunction or other major side effects, quality of life is not compromised and a return to family and social life is possible. Thus, if the patient cannot take the oral nutrition, it is easy to start home hyper-alimentation.

[How to palliate the symptoms of terminally ill patients at home].

We reported the kind of symptoms and how they could be palliated in terminally ill patients at home based on our experience of about 9 years. Cancer pain, which was the most frequent symptom, appeared in 67 among 126 patients receiving home care, and it could be effectively controlled with morphine; no patient returned to the hospital because of aggravation of pain. Very few patients stayed in the hospital and never returned home due to uncontrollable pain. Home parenteral infusion was done for 63 patients who were unable to eat or drink because of peritonitis carcinomatosa or cancer cachexia. High fever in the tumor mass was controlled by glucocorticoid hormone, and ascites was drained continuously when the patients suffered from abdominal distension. From analysis of the cases in which home care was interrupted or those in which patients were unable to transfer to home care, symptoms that were difficult to palliate at home were nausea caused by bowel obstruction, acute symptoms (bleeding, disturbance of consciousness, and so on), and dyspnea. But if the patients and family are eager for home care and an adequate medical support system is in place, home care may be possible despite these symptoms.