[Local Control with At-Home Mohs Paste Treatment for Malignant Tumor Exposed at the Skin].

Malignant tumors exposed at the body surface are often complicated by bleeding, effusion, infection, and offensive odor, which can lead to impairment of patients' QOL. Mohs paste has previously been used in the treatment of cutaneous malignant tumors as a local application for such symptoms during palliative care; some reports indicate that this procedure is effective. However, most of the cases were treated in hospital. We have performed this procedure as a part of home care. From January 2011 to December 2014, we studied Mohs paste treatment at home in 5 patients. In all cases, hemostasis and reduction of effusion were observed. To ensure a safe procedure, the patient is required to maintain the rest position during the treatment. We conclude that Mohs paste treatment is possible at home and that this procedure is an effective means to support the patients hoping for home care.

[A case of gastric cancer accompanied by disseminated carcinomatosis of bone marrow wherein long-term chemotherapy was enabled by early supportive palliative care].

Here we report gastric cancer accompanied by bone marrow carcinomatosis in a patient for whom long-term chemotherapy was enabled by early pain-relief therapy. A 45-year-old man was admitted to our hospital because of back pain associated with multiple spinal tumors in June 2011. Blood tests showed a trend toward disseminated intravascular coagulation(DIC) and gastric cancer was suspected as the primary lesion. Because pain was severe, emergency pain relief was provided by flurbiprofen axetil and a continuous subcutaneous infusion of fentanyl citrate. After bone marrow examination gave a diagnosis of poorly differentiated adenocarcinoma, we performed sequential methotrexate(MTX)and 5-fluorouracil(5-FU)therapy. The therapy successfully decreased tumor marker levels, and alkaline phosphatase and lactate dehydrogenase levels normalized. Finally, gastric cancer accompanied by bone marrow carcinomatosis was diagnosed. Because the patient had anxiety and spiritual pain from the time of admission, psychiatric care was also required. In November 2011, the tumor recurred, and we switched therapy to a combination of S-1 and cisplatin. The patient's pain was controlled by combined treatment with a fentanyl patch and etodolac, and he was discharged in December 2011. However, severe pain recurred and pain therapy was continued. DIC developed in February 2012 and transiently resolved after resuming combination therapy with MTX and 5-FU; however, it subsequently recurred, leading to the patient's death in May 2012.

[Decision making support for chemotherapy outpatients and their families: role of the home care professional].

The intervention of palliative care from the early stages of cancer is advocated, however, current situation remains virtually unchanged. Since the Baptist Home Hospice Palliative Care Clinic opened, the percentage of patients who have been introduced to the clinic during chemotherapy and have received home-visit care is 16.1%. Of those, the percentage of patients who passed away more than two months since the start of home-visit care is 45.7%. We determine the direction in care by listening closely to our patients and their families, and putting advance care planning (ACP) into effect. One of our roles is to offer support in deciding to discontinue the treatment in the final stages of chemotherapy. It is recognized that a number of patients are undergoing ineffective chemotherapy, despite the strong side effects. Our clinic strives to help these patients spend time the way they want by providing home-visit care and home-visit nursing.

[Palliative care for patients with hematological malignancies in the Japan Baptist Medical Foundation].

The Japan Baptist Medical Foundation has established a "hospice triangle" system consisting of the hospice ward, general ward, and home hospice. Palliative care is provided for patients with various types of cancer, including hematological malignancies, in the place where they desire to receive care. From December 2010 to December 2013, 37 patients with hematological malignancies received palliative care and died at our foundation. Eleven (30%) patients died in the hospice ward, 24 (65%) in the general ward, and 2 (5%) at home. The median interval between the final dose of chemotherapy and death was 12 (1- 88) days. Twenty (54%) patients received transfusions during the last 2 weeks prior to death. Quick response to patient situations and early introduction of palliative care are essential to support end-of-life decision-making processes, because the clinical course of hematological malignancies generally differs from that of other cancers.

[The role of cooperating hospitals in homecare].

The Japan Baptist Medical Foundation forms a so-called hospice triangle, with a general ward, a hospice ward, and home hospice, and it is possible to provide palliative care in the desired place. The ratio of homecare is 65.0%, and there were 2 cases in which a physician was present at the time of death. The average number of home-visit medical treatments during the week prior to death was 3.7. The median value of the period of home-visit medical treatment is 36 days. The group of homecare patients who were temporarily hospitalized during the period of home-visit medical treatment was 17.1%, and the most common reason was exacerbation of symptoms related to the primary disease. The group of patients who were hospitalized in a hospice ward was 17.0%, and many were for the purpose of respite care or trial hospitalization. Because some patients are reluctant to be hospitalized in a hospice ward, it was thought that adding an option of hospitalizing in a cooperating hospital to the homecare support system would give patients peace of mind. In order to increase the use of homecare from now on, it was thought that even further education about homecare is necessary in addition to a support system of cooperating hospitals.

[Aging problem in the home hospice care].

Home hospice care is not merely an extension of hospital-based medical care administered at the hospital, but refers to hospice care for patients with life-threatening diseases that can only be given at their homes. The rapid growth of the elderly population in Japan has led to not only the need for home hospice care, but also social problems such as living alone, living with only one elderly family member, and problems that are particularly acute in cancer patients with dementia. We analyzed data for 262 patients for whom home hospice care was provided by our clinic. Overall, elderly persons with dementia tended to request admission before death, but most elderly persons living alone preferred home hospice care. We found that 58% of the patients living with only one elderly family member requested admission before death, which was lower than the rate of the study group as a whole. We further performed an in-depth analysis of the current situation in order to improve home hospice care of terminally ill patients in Japan, focusing on problems related to the aging population.

[Development of a cooperative system for palliative care among a hospice ward, general ward, geriatric health services facility, and home in Japan Baptist Hospital-provision of home-based care by hospice physicians].

In November 2009, a home hospice palliative care clinic(clinic)was opened in addition to a hospice ward, general ward, and geriatric health services facility at our hospital. This marked the initiation of a health care system able to provide the palliative care desired by patients and families. We studied the characteristics and hospitalization status of 514 patients with cancer who died at the hospice ward, general ward, or their homes from November 2009 through December 2011. Overall, 373 patients died at the hospice ward, 11 at the general ward, and 130 at home. Hospice physicians participated in the home care of 20 patients. Hospice physicians provide home-based care in cooperation with clinic physicians, facilitating the palliative care of patients who initially do not have a place to receive terminal care and the prompt discharge of patients who want to live at home.

[A case of gastric cancer accompanied by disseminated carcinomatosis of bone marrow with DIC, and subdural hematoma successfully treated with sequential methotrexate and 5-fluorouracil therapy].

A 44-year-old man visited a nearby hospital because of severe headache. Brain MRI revealed a subdural hematoma, and he was transferred to the Department of Neurosurgery of our hospital. Burr hole surgery was performed on the second day of hospitalization because of an enlargement of the hematoma. Laboratory data on admission showed the presence of a disseminated intravascular coagulation(DIC). Bone marrow aspiration revealed metastases of signet ring cell carcinoma, and abdominalCT showed gastric cancer. He was diagnosed as having DIC with bone marrow metastases of advanced gastric cancer. Despite anti-DIC therapy and blood transfusion, his systemic bleeding tendency was not improved. The neurosurgeon therefore consulted with a palliative care team. Since the patient was still young, we considered that he should be treated with anti-cancer drugs. At first, his family did not accept chemotherapy because they were pessimistic about his prognosis. However, after he regained his consciousness, we were able to perform sequential MTX and 5-FU therapy with the consent of the patient and his family. The therapy was successful, and he recovered from DIC and was discharged on the 57th hospital day.

[Two cases of primary unresectable and/or recurrent gastrointestinal stromal tumors of small intestine presenting hemoperitoneum caused by administration of imatinib mesylate].

Case1 was a 52-year-old man who had recurrence of postoperative intra-abdominal disseminations from gastrointestinal stromal tumor (GIST) of the jejunum. Case2 was a 66-year-old man who had GIST of the jejunum with multiple liver metastases. Two cases presented hemoperitoneum caused by administration of imatinib mesylate, and we conducted emergent surgery. In spite of surgically non-curative cases, it is suggested that the surgical management for GIST of high grade group with peritoneal exposure should be followed by the administration of imatinib mesylate.

The glucagon provocative test for the diagnosis and treatment of Zollinger-Ellison syndrome.

OBJECTIVE: Our aim was to determine whether the glucagon provocative test could be used in place of secretin test in patients with gastrinoma. METHODS: Three patients with gastrinoma underwent the following examinations: (1) preoperative intravenous glucagon test to enable a definitive diagnosis, (2) intra-arterial glucagon injection test to localize the tumor, and (3) intraoperative and postoperative intravenous glucagon test to confirm the completeness of the resection. RESULTS: Serum gastrin levels increased in response to intravenous glucagon in all three patients preoperatively. Computed tomography scans revealed a tumor in the lesser omentum, pancreatic head, and the pancreatic uncinate in cases 1, 2, and 3, respectively. Intra-arterial glucagon test revealed that the feeding artery for the tumor was the left gastric artery in case 1 and the superior mesenteric artery in case 3. Resection of the remnant stomach with tumor, pancreaticoduodenectomy with portal vein resection, and enucleation of the tumor were performed in cases 1, 2, and 3, respectively. Serum gastrin levels did not increase in response to intravenous glucagon intraoperatively and postoperatively in cases 1 and 3. Although intravenous glucagon caused a slight increase in serum gastrin in case 2, no recurrent tumors were evident. CONCLUSION: These results indicate that the glucagon provocative test is a suitable alternative to testing with secretin, which is not commercially available in Japan.

Inosine alleviates rat caerulein pancreatitis and pancreatitis-associated lung injury.

BACKGROUND: Recent studies have shown that inosine, a purine nucleoside produced during the breakdown of adenosine, has immunomodulatory and anti-inflammatory properties. The aim of this study was to examine the effects of inosine on the course of acute pancreatitis. METHODS: Edematous pancreatitis was induced by the intraperitoneal injection of caerulein (50 micro g/kg), seven times, at 1-h intervals, in male Wistar rats (caerulein pancreatitis). Inosine (100 mg/kg) was administered 30 min before or 1 h after the first injection of caerulein. The effects of inosine on the severity of pancreatitis were assessed by serum amylase, pancreatic edema (wet/dry ratio), myeloperoxidase activity, cytokine-induced neutrophil chemoattractant-1 concentrations, and histological changes. RESULTS: Prophylactic administration of inosine significantly decreased the elevation of serum amylase, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant-1 concentrations in the pancreas and the lung. Inosine did not significantly affect edema formation. Histologically, vacuole formation in pancreatic acinar cells, infiltration of inflammatory cells in the pancreas and the lung, and alveolar wall thickening in the lung were reduced. Inosine improved the histological findings and reduced myeloperoxidase activity even if it was administered 1 h after the first injection of caerulein. CONCLUSIONS: Inosine reduced the severity of acute pancreatitis, suggesting a possible application of this compound in the treatment of acute pancreatitis.

Nuclear factor kappa B expression in peripheral blood mononuclear cells of patients with acute pancreatitis.

INTRODUCTION: Although many experimental studies have implicated the activation of nuclear factor kappa B (NF-kappaB) as a pivotal step in the pathobiology of acute pancreatitis, no clinical investigations have been reported. AIMTo investigate the expression of NF-kappaB and its characteristics in peripheral blood mononuclear cells (PBMCs) of patient with acute pancreatitis. METHODOLOGY: Forty-five patients were prospectively enrolled. The expression of NF-kappaB in PBMCs was measured in the patients by electrophoretic mobility shift assay at admission and 14 days after the onset of acute pancreatitis. Twelve healthy individuals were also included as control subjects. RESULTS: At admission, the PBMCs from patients with acute pancreatitis showed higher levels of NF-kappaB activities than did those from control subjects. In vitro, the lipopolysaccharide (LPS) treatment of the PBMCs from the control subjects and patients with mild pancreatitis induced further activation of the NF-kappaB. The response was significantly reduced in patients with severe pancreatitis. Patients who had persistently high NF-kappaB activities, a reduced response of NF-kappaB to LPS, and a low p50p65:p50p50 ratio after LPS stimulation at 14 days developed serious systemic complications in the later clinical course. CONCLUSIONS: An alteration of the characteristics of PBMCs occurs in the early phase of acute pancreatitis and may predispose patients to a higher risk of serious systemic complications.

Macrophage migration inhibitory factor is a critical mediator of severe acute pancreatitis.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF), originally described as an inhibitor of the random migration of macrophages, has been shown recently to be involved in the pathogenesis of several inflammatory diseases such as sepsis. The aim of this study was to clarify the role of MIF in acute pancreatitis (AP). METHODS: Hemorrhagic necrotizing pancreatitis and edematous pancreatitis were induced by the injection of taurocholic acid (TCA pancreatitis) and cerulein (cerulein pancreatitis), respectively, on male Wistar rats. MIF levels in ascitic fluids, serum, and the organs were determined. The effects of anti-MIF antibody were examined on the prognosis of rats with TCA pancreatitis and of female CD-1 mice with choline-deficient, ethionine-supplemented, diet-induced model of severe AP. In addition, serum MIF levels in AP patients and in healthy controls were measured. RESULTS: Serum and ascitic MIF levels in TCA pancreatitis were increased rapidly and decreased gradually thereafter. Ascitic MIF levels were also increased in cerulein pancreatitis, but to a lesser degree. MIF level was increased in the lung in TCA pancreatitis, but not in the pancreas and the liver. Prophylactic (1 hour before and immediately after induction) administration of anti-MIF antibody significantly improved the survival rate of rats with TCA pancreatitis. The survival rate of mice with severe AP was also improved significantly by the antibody treatment. Serum MIF levels were higher in severe AP patients than mild AP patients and healthy controls. CONCLUSIONS: These results suggest a role of MIF in the pathogenesis of severe AP.

Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis.

INTRODUCTION: The mortality associated with severe acute pancreatitis is still high, and death in the later stage of the disease is chiefly due to bacterial infection and sepsis. However, objective parameters for the risk of sepsis in acute pancreatitis have not been established. AIM: To investigate the value of human leukocyte antigen-DR (HLA-DR) on peripheral monocytes for predicting the development of sepsis during acute pancreatitis. METHODOLOGY: The expression of HLA-DR on peripheral monocytes was measured in 64 patients by flow cytometry at admission and 7 and 14 days after the onset of acute pancreatitis. Twenty-eight patients with severe acute pancreatitis and 36 with mild acute pancreatitis, as determined by the Atlanta classification, were enrolled. RESULTS: Six patients had sepsis, and two of them died during the hospital stay. At admission, the percentage of HLA-DR-expressing cells in the monocyte population was significantly lower in the patients who had sepsis in the later course than in the patients who did not have sepsis. A percentage lower than 80% at admission was observed in 17 patients, and the patients who had persistently low percentages of HLA-DR-expressing monocytes throughout the observation period had sepsis in the later clinical course, whereas the patients in whom expression recovered to the normal range were spared the development of sepsis. CONCLUSION: In acute pancreatitis, the low percentage of HLA-DR-expressing cells in the monocyte population is a reliable predictor of the development of sepsis. Monitoring of monocyte HLA-DR expression may be a useful marker for identifying the patients who are at high risk of sepsis in acute pancreatitis.

Activation of adenosine A2a receptor pathway reduces leukocyte infiltration but enhances edema formation in rat caerulein pancreatitis.

INTRODUCTION: Adenosine plays important roles in a variety of pathophysiologic conditions through receptor-mediated mechanisms. Recent studies have shown that adenosine exerts potent anti-inflammatory properties that are chiefly brought about through the occupancy of the A2a receptor. AIM: To examine the effect of A2a receptor stimulation or inhibition on the pathologic findings during acute pancreatitis. METHODOLOGY: Rats were randomized into three groups and received a selective A2a receptor agonist CGS-21680 (CGS), a selective A2a antagonist 3,7-dimethyl-1-[2-propynyl]-xanthine (DMPX), or saline. Thirty minutes after the injection, acute pancreatitis was produced in the rats by seven intraperitoneal injections of caerulein. The severity of acute pancreatitis was evaluated by serum amylase activity, pancreas myeloperoxidase (MPO) activity, Evans blue extravasation, and pathologic changes of the pancreas. In addition, we investigated the effects of CGS on the pathologic findings of caerulein pancreatitis induced in neutrophil-depleted rats. RESULTS: Administration of caerulein produced hyperamylasemia and morphologic changes of the pancreas including interstitial edema, acinar cell vacuolization, and infiltration of inflammatory cells. In CGS-treated rats, the pancreatic edema and the Evans blue extravasation were aggravated significantly compared with those of saline-treated rats, whereas leukocyte infiltration and MPO activity of the pancreas were decreased. In contrast to CGS, administration of DMPX ameliorated the pancreatic edema and Evans blue extravasation. Treatment with CGS accelerated the pancreatic edema in pancreatitis even after the depletion of neutrophils. CONCLUSION: The activation of adenosine A2a receptors modulates the pathology of acute pancreatitis through at least two diverse properties. One is an anti-inflammatory effect involving neutrophils, and the other is a propagating effect for pancreatic edema formation. The actions of the A2a receptor pathways are unique, and they may have an important role in the progression of acute pancreatitis.