A Case of Unresectable Pulmonary Artery Intimal Sarcoma with Prolonged Survival by Chemotherapy.

Pulmonary artery intimal sarcoma is a rare malignant tumor. Due to its low prevalence, little is known about efficacious systemic chemotherapies in cases where the tumors are unresectable or metastatic. In addition, the location of the disease can contribute to poor survival regardless of the response to therapy, as the tumor's position can cause pulmonary artery hypertension either rapidly or chronically. We encountered a case of unresectable pulmonary artery intimal sarcoma with lung metastases. Treatment with several cytotoxic agents resulted in prolonged survival of 14.2 months. Here, we report the clinical course of this case and present a review of the relevant literature.

Gastric cancer initially presenting as bone metastasis: Two case reports and a literature review.

Gastric cancer frequently spreads to the regional lymph nodes, liver and lungs following surgery or late in the clinical course. However, an initial clinical presentation of bone metastasis in gastric cancer patients is relatively rare. The current study presents two cases of gastric cancer diffusely metastasized to the spinal vertebrae and with a single metastasis to the trapezium, respectively. The initial presentations were an increased alkaline phosphatase level without any symptoms associated with bone metastasis in the first case and a swelling in the right carpometacarpal joint of the thumb in the second case. These clinical manifestations are also extremely rare in gastric cancer with bone metastasis. The study emphasizes that a diagnosis of gastric cancer should be considered in patients with increased alkaline phosphatase without clinical symptoms or with a single bone metastasis.

Successful Salvage Chemotherapy with Streptozocin in a Patient with Mediastinal Atypical Carcinoid Tumor Who Had Relapsed after Various Prior Therapies.

Pulmonary neuroendocrine tumors are rare, and there have been very few reports regarding optimal chemotherapeutic regimens. Two molecular targeted agents, everolimus and sunitinib, have recently been shown to provide an additional treatment benefit for pulmonary neuroendocrine tumors. However, little information is available regarding the usefulness of streptozocin chemotherapy. Here, we encountered a case of relapsed and refractory mediastinal atypical carcinoid tumor associated with multiple endocrine neoplasia type 1 for various cytotoxic and molecular targeted agents. The patient showed a good response to streptozocin monotherapy. We describe the case and review streptozocin chemotherapy in patients with pulmonary neuroendocrine tumors.

Signet Ring Cell Carcinoma of Unknown Primary Origin Detected Incidentally by Lymph Node Purification for Thyroid Carcinoma.

A 63-year-old woman underwent thyroidectomy for papillary thyroid adenocarcinoma and cervical lymph node resection. Pathological analyses revealed the presence of signet cell carcinoma in a resected lymph node, which were apparently different from the pathological findings of thyroid carcinoma. No evidence of a primary tumor could be found elsewhere despite detailed examinations, including esophagogastroduodenoscopy, colonoscopy, capsule endoscopy, CT scan, and fluorodeoxyglucose-positron emission tomography. Two and half years later, the patient developed multiple bone metastases and the pathological findings confirmed the presence of signet cell carcinoma. The primary origin remained undetermined. Metastatic signet ring cell carcinoma of unknown primary origin is extremely rare.

Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2-positive extramammary Paget's disease: A case report and review of the literature.

A 58-year-old woman with a histologically confirmed diagnosis of vulvar extramammary Paget's disease (EMPD) was referred to our hospital due to locally advanced and relapsed EMPD. The patient had undergone surgical resection three times for relapsed vulvar EMPD over a period of 12 years, but developed locally advanced and unresectable EMPD. As pathological examination indicated that the lesion was positive for human epidermal growth factor receptor 2 (HER2) on immunohistochemical staining, the patient was treated with trastuzumab plus paclitaxel. The primary tumor mass and lymph node metastasis regressed successfully with combined trastuzumab and paclitaxel therapy, and the disease has been stable for >2 years after the initiation of treatment. These observations suggest that HER2 status must be determined in patients with advanced and/or metastatic extramammary Paget's disease and therapy with HER2 inhibitors should be considered as an option for the treatment of HER2-positive EMPD.

Relapsed and unresectable inflammatory myofibroblastic tumor responded to chemotherapy: A case report and review of the literature.

A 63-year-old female patient who had undergone cholecystectomy for inflammatory myofibroblastic tumor (IMT) in the gallbladder was referred to our hospital. The patient's disease relapsed, involving the pancreas, and was diagnosed as inoperable IMT 13 months after the cholecystectomy. The patient failed to respond to steroid and non-steroidal anti-inflammatory drug therapy, but subsequently exhibited a good response to vinorelbine and methotrexate combination chemotherapy. Little information is currently available on the efficacy of chemotherapy for adult-onset IMT. The present case suggests that chemotherapy with vinorelbine and methotrexate is a viable therapeutic option for adult patients with unresectable IMT.

Plasma L-carnitine levels in terminally ill cancer patients receiving only palliative care.

BACKGROUND: Several studies indicated that plasma L-carnitine (LC) levels are significantly decreased during chemotherapy or chemoradiation and that LC supplementation can improve the fatigue score in some cancer patients. However, the LC levels in end-stage cancer patients treated only with palliative care remained unclear. The present study was performed to examine the plasma LC levels of terminally ill and hospitalized patients. METHODS: Twenty-one terminally ill cancer patients in our hospital, with expected survival of several months, were enrolled in the present study. Blood samples were taken for measurement of total, free, and acyl-LC. These values were compared with those in 22 chemo-naive cancer patients scheduled to receive cisplatin-containing chemotherapy as first-line therapy. We examined the relationships with body mass index, albumin and CRP levels, the presence of general fatigue, and body weight loss. RESULTS: Median survival in terminally ill cancer patients after enrollment was 38.5 days. Plasma concentrations of total, free, and acyl-LC in terminally ill cancer patients were 59.5±16.0, 46.1±14.2, and 13.4±5.9 µmol/L, respectively. These values were not significantly different from those in chemo-naive patients (58.3±18.1, 48.7±16.3, and 9.6±3.3 µmol/L, respectively). In addition, plasma LC levels in terminally ill patients showed no correlations with albumin or CRP values nor with other clinical parameters, such as fatigue or body weight loss. CONCLUSIONS: The present study suggested that plasma LC levels remain normal and its deficiency is not always common even in terminally ill and hospitalized palliative cancer patients.

Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer.

Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of each targeted lesion. SUVmax decreased in all lesions after therapy (mean SUVmax 8.3 ± 3.4 before to 3.7 ± 1.8 after therapy, p < 0.05). The % decrease in SUVmax of each lesion was significantly correlated with the % tumor size reduction (r = 0.44). In addition, the reduction rate of SUVmax in metastatic bone lesions after initiation of molecular targeted therapy was significantly lower than that in targeted organs (27.1 ± 27.5 vs. 51.2 ± 21.3%, respectively, p < 0.05). Early reduction in FDG-PET uptake after initiation of molecular targeted agents was able to predict subsequent tumor reduction in patients harboring EGFR-mutated or ALK-positive NSCLC. In addition, nontargeted bone metastasis may have different glucose metabolism after TKI treatment compared with other involved organs.

Successful treatment with doxorubicin and ifosfamide for mediastinal malignant peripheral nerve sheath tumor with loss of H3K27me3 expression.

Malignant peripheral nerve sheath tumor (MPNST) in the thorax is an extremely rare disease, and half of all cases of MPNST are associated with neurofibromatosis type I. Sporadic intrathoracic MPNST is difficult to diagnose and treat. Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. Herein, we present a case of inoperable mediastinal MPNST, in which the diagnosis was immunohistochemically made by the loss of H3K27me3 expression in a transbronchial needle biopsy specimen. The patient showed a good response to doxorubicin plus ifosfamide chemotherapy. The present case highlights that MPNST should be included in the differential diagnosis of non-posterior mediastinum thoracic lesions, and that appropriate diagnosis and treatment for intrathoracic MPNST should be considered in patients with a thoracic mass.

Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin Chemotherapy.

BACKGROUND AND AIMS: Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. METHODS: Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. RESULTS: Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. CONCLUSIONS: CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters.

Alectinib-Induced Alopecia in a Patient with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

Alectinib, a novel alternative anaplastic lymphoma kinase (ALK) inhibitor, is highly effective against ALK-positive non-small cell lung cancer (NSCLC) and is well tolerated. Molecular targeted agents generally have little contribution to alopecia. We encountered a case of alopecia that developed gradually over 2 months after initiation of alectinib administration for the treatment of ALK-positive NSCLC. The patient had no history of alopecia in previous treatments of cisplatin + pemetrexed and crizotinib. The present case indicates that alopecia should be taken into consideration as toxicity during alectinib treatment, which could adversely affect the psychological and emotional condition and quality of life even in patients treated with specific molecular targeted agents.

[Palliative Care with Regional Alliance by a University Hospital].

In this chapter, we described what the palliative care in the university hospital is doing; the role of the palliative care doctors in the university hospital, how should we consider the palliative care as a sub-speciality for anesthesiologists in the university hospital, how should we act to make the palliative care in the university hospital cooperating with community and what kind of task should anesthesiologists do cooperating with the community. In Japan, the aging of the society will be more ac- celerated in future, and our medical system for the home care and the out-of-hospital terminal care will be revised. Therefore it is necessary for the university hospitals to lead the preparation of the palliative care as a part of the community combined care system.

Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report.

Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin®) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome®) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered.

Comparison of the Pentax-AWS airway scope with the Macintosh laryngoscope for nasotracheal intubation: a randomized, prospective study.

STUDY OBJECTIVE: To evaluate the effectiveness of the Pentax-AWS Airway Scope (AWS) in comparison to the Macintosh laryngoscope during nasotracheal intubation. DESIGN: Prospective randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 90 ASA physical status 1 and 2 adults, aged 18 to 72 years, scheduled for orthodontia surgery requiring nasotracheal intubation. INTERVENTIONS: Patients were randomly assigned to three groups to undergo tracheal intubation with a Macintosh laryngoscope (Group Mac; n = 30), AWS with its tip inserted into the vallecula for indirect elevation of the epiglottis (Group AWS-I; n = 30), or AWS with its tip positioned posterior to the epiglottis for direct elevation of the epiglottis (Group AWS-D; n = 30). MEASUREMENTS: Percentage of glottic opening (POGO) score at the time of laryngeal exposure, time required for intubation, and intubation difficulty scale (IDS) were measured. The frequency of postoperative sore throat and hoarseness also were noted. MAIN RESULTS: Patient demographics did not differ among the groups. In Groups AWS-I and AWS-D, IDS scores were reduced significantly, and the percentages of glottic opening were significantly improved, compared with the Macintosh group. Time to place the endotracheal tube was significantly shortest in Group AWS-I. In one case from each group, intubation within two attempts failed and a different approach was required. CONCLUSION: The AWS offers better intubation conditions than the Macintosh laryngoscope during nasotracheal intubation. The AWS may be used to elevate the epiglottis both directly and indirectly for nasotracheal intubation.

[A case of neurotoxicity reduced with goshajinkigan in modified FOLFOX6 chemotherapy for advanced colon cancer].

In performing FOLFOX (infusional 5-FU/LV with oxaliplatin) for advanced colorectal cancer, neurotoxicity of oxaliplatin (L-OHP) is the serious dose limiting factor. On the other hand, goshajinkigan is recently considered as an effective agent for the neurotoxicity of taxanes in Japan. We have applied goshajinkigan (TJ 107) for a case of advanced colon cancer with mFOLFOX 6, and experienced a reduction in numbness, the adverse effect of LOHP. A 57-year-old woman with descending colon cancer (H 1, P 3, Stage IV) underwent hemicolectomy D 2, rt.colectomy, bilateral oophorectomy, cholecystectomy and transverse colonostomy. After operation, mFOLFOX 6 was applied. In order to reduce the neurotoxicity of L-OHP, TJ 107 was used together from the third course. The severities of neurotoxicity before and after administration of TJ 107 were grade 2 and 1,respectively. TJ 107 could reduce or prevent the neurotoxicity of L-OHP.

Induction of long-lasting depolarization in medioventral medulla neurons by cholinergic input from the pedunculopontine nucleus.

Stimulation of the pedunculopontine nucleus (PPN) is known to induce changes in arousal and postural/locomotor states by activation of such descending targets as the caudal pons and the medioventral medulla (MED). Previously, PPN stimulation was reported to induce prolonged responses (PRs) in intracellularly recorded caudal pontine neurons in vitro. The present study used intracellular recordings in semihorizontal slices from rat brain stem (postnatal days 12-21) to determine responses in MED neurons following PPN stimulation. One-half (40/81) of MED neurons showed PRs after PPN stimulation. MED neurons with PRs had shorter duration action potential, longer duration afterhyperpolarization, and higher amplitude afterhyperpolarization than non-PR MED neurons. PR MED neurons were significantly larger (568 +/- 44 microm2) than non-PR MED neurons (387 +/- 32 microm2). The longest mean duration PRs and maximal firing rates during PRs were induced by PPN stimulation at 60 Hz compared with 10, 30, or 90 Hz. The muscarinic cholinergic agonist carbachol induced depolarization in all PR neurons tested, and the muscarinic cholinergic antagonist scopolamine reduced or blocked carbachol- and PPN stimulation-induced PRs in all MED neurons tested. These findings suggest that PPN stimulation-induced PRs may be due to activation of muscarinic receptor-sensitive channels, allowing MED neurons to respond to a transient, frequency-dependent depolarization with long-lasting stable states. PPN stimulation appears to induce PRs in large MED neurons using parameters known best to induce locomotion.

Nifedipine potentiates the antinociceptive effect of endomorphin-1 microinjected into the periaqueductal gray in rats.

UNLABELLED: Endomorphin-1 is a novel endogenous mu-opioid ligand. We investigated the antinociceptive interaction between endomorphin-1 and nifedipine, an L-type calcium channel blocker, microinjected into the midbrain ventrolateral periaqueductal gray (vPAG), using the spinally-organized tail-flick test and the supraspinally-organized tail-pressure test in rats. Sprague-Dawley rats were stereotaxically implanted with a guide cannula lowered into the vPAG. Microinjection of endomorphin-1 into the vPAG led to dose-related increases in antinociceptive responses in the tail-flick test and tail-pressure test. Pretreatment with the mu-opioid receptor-selective antagonist beta-funaltrexamine blocked the antinociceptive effect of endomorphin-1. Pretreatment with beta-funaltrexamine alone had no effect on the tail-flick latency and tail-pressure threshold. Microinjection of nifedipine alone into the vPAG did not produce an antinociceptive response in the tail-flick test and tail-pressure test. However, injection of nifedipine into the vPAG potentiated the antinociceptive effect of endomorphin-1, producing a significant leftward shift in the dose-response curve of endomorphin-1 in both the tail-flick and tail-pressure tests. This result shows that the potent antinociceptive effect of endomorphin-1 microinjected into the vPAG is mediated through the mu-opioid receptor and is potentiated by concomitant administration of nifedipine. IMPLICATIONS: This study shows that the potent antinociceptive effect of endomorphin-1 microinjected into the ventrolateral periaqueductal gray is potentiated by concomitant administration of nifedipine. This suggests that calcium channel blockers may enhance the analgesia of opioids in patients with calcium channel blocker treatment.

Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like immunoreactivity in the rat spinal cord via activation of endogenous opioid systems.

We investigated the antagonism of sevoflurane antinociception by opioid antagonists in the rat formalin test. Formalin injection into the hindpaw of the rat induces the nocifensive flinching behavior and the expression of Fos-like immunoreactivity (Fos-LI) in the spinal cord. Sevoflurane significantly suppressed the flinching behavior and decreased the number of Fos-LI neurons in the dorsal horn of spinal cord compared with the control group. Moreover, pretreatment with intraperitoneal naloxone plus naltrexone antagonized the suppression of flinching behavior and the decrease of the number of Fos-LI neurons produced by 3% sevoflurane. Intraperitoneal opioid antagonists themselves had no effects on both the behavior response and the expression of Fos-LI induced by formalin injection. This study supports the hypothesis that sevoflurane suppresses the nociceptive response, at least in part, by activating endogenous opioid systems.