Long-term results of a phase 2 study of neoadjuvant chemotherapy with molecularly targeted agents for locally advanced rectal cancer.

BACKGROUND: We previously reported the feasibility and efficacy of neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Here, we report the results of a long-term follow-up study. METHODS: This was a multi-institutional, prospective phase 2 study of patients with locally advanced rectal cancer. Patients received neoadjuvant chemotherapy with molecularly targeted agents before undergoing total mesorectal excision. Six cycles of modified FOLFOX (mFOLFOX6) with bevacizumab were administered to KRAS-mutant patients, and mFOLFOX6 with cetuximab was administered to KRAS-wild-type patients. Here, we report the secondary end points of overall survival, relapse-free survival, and local recurrence rate. RESULTS: Sixty patients were enrolled in this study. R0 resection was achieved in 98.3% (59/60) patients, and pathological complete response was achieved in 16.7% (10/60) patients. After a median follow-up of 5.4 years, the 5 year overall survival was 81.6%, the 5 year relapse-free survival was 71.7%, and the 5 year local recurrence rate was 12.6%. None of the patients who achieved pathological complete response developed recurrence within 5 years. CONCLUSIONS: The use of molecularly targeted agents in the neoadjuvant setting for locally advanced rectal cancer has an acceptable prognosis.

Identification of patient subgroups with low risk of postoperative local recurrence for whom total mesorectal excision surgery alone is sufficient: a multicenter retrospective analysis.

PURPOSE: For rectal cancer, a multimodality approach is mandatory including neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and lateral pelvic lymph node (LPLN) dissection, in addition to the total mesorectal excision (TME). However, these treatments are associated with adverse events. It is important to select patients who do or do not need these treatments. METHODS: We retrospectively analyzed patients with cStage II and III rectal cancer who underwent curative resection at three hospitals. Recurrence patterns were classified into three types; pelvic cavity, LPLN, and distant recurrences, and the risk factors for each pattern of recurrence were compared. We then analyzed the risk of recurrence in the patients who underwent TME alone. RESULTS: In total, 506 patients were enrolled in this study. Pelvic cavity recurrence was significantly associated with clinical assumption of circumferential resection margin involvement (cCRM) (p < 0.001), distant recurrence was associated with cN positivity (p < 0.001), and LPLN recurrence was associated with pretreatment LPLN swelling ≥ 5 mm (p < 0.001), lower tumor location (p = 0.016), and serum CEA level > 5 ng/mL (p = 0.008). In patients without cCRM and swollen LPLN, the local recurrence rate was extremely low even if they underwent TME alone; the 5-year recurrence rates of pelvic cavity and LPLN were 2.2% and 1.9%, respectively. CONCLUSION: Additional treatments to TME for rectal cancer need to be performed based on the risk factors for each recurrence pattern.

[Locally Advanced Gastric Cancer Showing Marked Tumor Shrinkage after the First Dose of Nivolumab for Fourth-Line Chemotherapy].

We report a case of locally advanced gastric cancer, which showed marked tumor shrinkage after the first dose of nivolumab. A 75-year-old woman was diagnosed with locally advanced gastric cancer with pancreatic invasion and pyloric stenosis. We performed gastrojejunostomy before chemotherapy. The first-line, second-line, and third-line chemotherapies were not effective, resulting in tumor progression and necrosis with abdominal wall penetration. Her performance status was good, so we started nivolumab therapy as the fourth-line chemotherapy. Nine days after the first dose of nivolumab, she had a severe abdominal pain and a sense of fatigue. CT imaging showed a remarkable degree of tumor necrosis just beneath the skin. We diagnosed progressive disease and discontinued the chemotherapy. However, her general condition gradually improved and CT imaging 4 months after the first dose of nivolumab showed marked tumor shrinkage. We restarted nivolumab therapy and she has been alive for 2 years 10 months since the introduction of chemotherapy. It was suggested that a single dose of nivolumab only could lead to marked tumor shrinkage in chemotherapy for advanced gastric cancer.

Trans-perineal minimally invasive surgery during laparoscopic abdominoperineal resection for low rectal cancer.

BACKGROUND: Laparoscopic abdominoperineal resection (APR) for low rectal cancer (LRC) is performed worldwide. However, APR involves technical difficulties and often causes intractable perineal complications. Therefore, a novel and secure technique during APR is required to overcome these critical issues. Although the usefulness of the endoscopic trans-anal approach has been documented, no series of the endoscopic trans-perineal approach during laparoscopic APR for LRC has been reported. METHODS: Trans-perineal minimally invasive surgery (TpMIS) has been used during laparoscopic APR in our institution since April 2014. TpMIS is defined as an endoscopic trans-perineal approach using a single-port device and laparoscopic instruments. In this study, we retrospectively evaluated 50 consecutive patients with LRC who underwent laparoscopic APR at our institution from February 2011 to June 2017 and compared the outcomes of the patients who underwent TpMIS [trans-perineal APR (TpAPR) group, n = 21] versus the conventional trans-perineal approach (conventional group, n = 29). We investigated our experiences with TpMIS in detail and evaluated the safety and utility of TpMIS for patients with LRC. Moreover, major features and difficulties of TpMIS were examined from a surgical viewpoint. RESULTS: Intraoperative blood loss (median (range) 55 (10-600) vs. 120 (20-1650) ml) and severe perineal wound infection (Clavien-Dindo grade 3, 0 vs. 5 cases) were significantly lower in the TpAPR than conventional group. TpMIS led to a shortened hospital stay (median (range), 14 (10-74) vs. 23 (10-84) days), and neither mortality nor conversion to open surgery occurred in the TpAPR group. CONCLUSIONS: Magnified visualization via endoscopy provided more accurate dissection and less blood loss during surgery. Minimal skin incisions enabled a reduction in postoperative perineal complications, and consequently shortened the hospital stay. TpMIS during laparoscopic APR is safe and beneficial for patients with LRC.

Feasibility of Extended Dissection of Lateral Pelvic Lymph Nodes During Laparoscopic Total Mesorectal Excision in Patients with Locally Advanced Lower Rectal Cancer: A Single-Center Pilot Study After Neoadjuvant Chemotherapy.

BACKGROUND The feasibility of additional dissection of the lateral pelvic lymph nodes (LPLNs) in patients undergoing total mesorectal excision (TME) combined with neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC) is controversial. The use of laparoscopic surgery is also debated. In the present study, we evaluated the utility of laparoscopic dissection of LPLNs during TME for patients with LARC and metastatic LPLNs after NAC, based on our experience with 19 cases. MATERIAL AND METHODS Twenty-five patients with LARC with swollen LPLNs who underwent laparoscopic TME and LPLN dissection were enrolled in this pilot study. The patients were divided into 2 groups: those patients with NAC (n=19) and without NAC (n=6). Our NAC regimen involved 4 to 6 courses of FOLFOX plus panitumumab, cetuximab, or bevacizumab. RESULTS The operative duration was significantly longer in the NAC group than in the non-NAC group (648 vs. 558 minutes, respectively; P=0.022). The rate of major complications, defined as grade ≥3 according to the Clavien-Dindo classification, was similar between the 2 groups (15.8% vs. 33.3%, respectively; P=0.4016). No conversion to conventional laparotomy occurred in either group. In the NAC group, a histopathological complete response was obtained in 2 patients (10.5%), and a nearly complete response (Tis N0 M0) was observed in one patient (5.3%). Although the operation time was prolonged in the NAC group, the other perioperative factors showed no differences between the 2 groups. CONCLUSIONS Laparoscopic LPLN dissection is feasible in patients with LARC and clinically swollen LPLNs, even after NAC.

A Multicenter Phase 2 Study on the Feasibility and Efficacy of Neoadjuvant Chemotherapy Without Radiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: This prospective multicenter phase 2 study aimed to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) without radiotherapy for locally advanced rectal cancer (LARC). METHODS: Patients with LARC (cStage II and III) were included in the study. Those with cT4b tumor were excluded. Six cycles of modified FOLFOX6 (mFOLFOX6) plus either bevacizumab or cetuximab, depending on KRAS status, were administered before surgery. The primary end point of the study was the R0 resection rate. The secondary end points were adverse effect, rate of NAC completion, postoperative complications, and pathologic complete response (pCR) rate. RESULTS: The study enrolled 60 patients from eight institutions. For the study, mFOLFOX6 was administered with cetuximab to 40 patients who had wild-type KRAS and with bevacizumab to 20 patients who had KRAS mutations. The completion rate for NAC was 88.4%. Sphincter-preserving surgery was performed for 43 patients and abdominoperineal resection for 17 patients. The median operation time was 335 min, and the median blood loss was 40 g. The R0 resection rate was 98.3%, and the pCR rate was 16.7%. The overall postoperative complication rate (≥grade 2) was 21.7%. The complications included anastomotic leakage (11.6%), surgical-site infection (6.7%), and urinary dysfunction (3.3%). The patients with wild-type KRAS did not differ significantly from those with KRAS mutations in terms of response rate, postoperative complication rate, and pCR rate. CONCLUSION: The findings show that NAC is a feasible and promising treatment option for LARC (This study is registered with UMIN-CTR, UMIN000005654).

Clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy following pancreatoduodenectomy.

BACKGROUND AND PURPOSE: Pancreatic fistula after pancreatoduodenectomy (PD) is not uncommon, but few reports describe a stricture after pancreatogastrointestinalstomy. We investigated the clinical influence of anastomotic stricture caused by pancreatogastrointestinalstomy after PD. METHODS: The subjects of this prospective cohort study were 132 patients who underwent PD or pylorus-preserving PD. We reviewed the relationships between pancreatic duct dilatation of the remnant pancreas and several risk factors. We also compared pancreatic duct dilatation with pancreatic atrophy and analyzed nutrient parameters in the first postoperative year. RESULTS: Patients with a preoperative pancreatic duct diameter less than 3 mm had a significantly dilated postoperative pancreatic duct diameter (p = 0.0001). The average atrophy rate of the remnant pancreas was 26.3 %, with the lowest atrophy rate (7.3 %) seen in patients without pre- or postoperative pancreatic duct dilation. A normal pancreas in which pancreatic duct dilatation developed postoperatively had a high atrophy rate (34.9 %). Moreover, only patients without pre- or postoperative pancreatic dilatation gained body weight (3.9 %). CONCLUSION: This study shows a significant correlation between pancreatic atrophy rate and weight loss. Atrophy of the remnant pancreas caused by anastomotic stricture influences the exocrine function of patients after PD. The anastomotic method must be improved to prevent pancreatic duct dilatation and allow for early diagnosis and management of stenotic lesions.

Therapy with immunoglobulin in patients with acute myocarditis and cardiomyopathy: analysis of leukocyte balance.

Intravenous immunoglobulin (IVIG) therapy has been used to treat several autoimmune or inflammatory diseases. We conducted a clinical trial of immunoglobulin therapy for acute myocarditis. The study consisted of two projects: (1) a comparison of prognosis between patients treated with and those not treated with IVIG in a multi-center study; (2) analyses of inflammatory cytokines and blood cell profiles in a substudy. In (1), 15 patients were treated with IVIG (1-2 g/kg, over 2 days), whereas 26 were untreated. There was a statistically significant difference between the survival curves of the patients treated with IVIG and the survival curves of those not treated with IVIG. There was no significant difference between the IVIG-treated and untreated groups in terms of clinical parameters of the acute and chronic phases. In (2), 10 patients were treated with IVIG and 6 were untreated. In both groups, all of the data except for changes in the fraction of lymphocytes and the fraction of monocytes decreased due to the treatment or during the course. In patients in the IVIG group, the percentage of peripheral eosinophils was decreased and the percentage of peripheral monocytes was increased by this treatment when they were compared with the pretreatment data. Therefore, therapy with IVIG seems to be a promising treatment for acute myocarditis given that it improves the clinical course, which may be due to modulation of inflammatory cytokines and the peripheral leukocyte balance.

Characteristics of plaque progression detected by serial coronary computed tomography angiography.

We previously reported that serial coronary computed tomography angiography (CTA) had a potential to evaluate the interval change of plaque morphology of coronary arteries. The aim of this study was to evaluate variables associated with the plaque progression by serial CTA. We included 148 patients (age 66.3 ± 9.8 years, male 81.1 %, median scan interval 12 months) with coronary artery disease undergoing serial CTA. Each coronary artery was compared visually between baseline and follow-up CTA to detect plaque progression. Baseline characteristics between progression and nonprogression patients did not demonstrate any significant differences. Logistic analysis revealed that only low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dl at follow-up was associated with plaque progression (odds ratio 2.59, 95 % confidence interval 1.12-6.34, P = 0.0263). Cutoff value of LDL-C for plaque progression at follow-up was 103.0 mg/dl based on receiver-operator characteristic curves analyses. Of the 36 progressive lesions in 32 patients, plaque composition at baseline included 13 lesions (36.1 %) of noncalcified plaque, 1 lesion (2.8 %) of calcified plaque, 12 lesions (33.3 %) of partially calcified plaque, and the remaining 10 lesions (27.8 %) had no plaque at baseline and revealed de novo plaques at follow-up. There were 9 lesions (25 %) with high-risk plaque (HRP) characteristics at baseline and 18 lesions (50 %) with HRP at follow-up. Plaque progression of coronary arteries by serial CTA was associated with LDL-C ≥100 mg/dl at follow-up regardless of baseline LDL-C level. There was no specific finding to predict plaque progression on the baseline plaque characteristics.

[Curative resection for Stage IV advanced gastric cancer that responded to combination chemotherapy with docetaxel, cisplatin, and S-1].

A 50-year-old man was diagnosed with advanced gastric cancer(Borrmann type 3)accompanied with N3.Staging laparoscopy revealed invasion to the transverse mesocolon and positive cytology from peritoneal washing (CY1). After the patient underwent gastrojejunostomy, we administered DCS combination chemotherapy consisting of docetaxel (40 mg/m² intravenously on day 1), cisplatin(60 mg/m² intravenously on day 1), and S-1 (orally 80 mg/m² on days 1 to 14).Four courses of this treatment were provided every 4 weeks, and it resulted in a partial response (PR).We performed curative distal gastrectomy with transverse mesocolon resection and D2 plus 14v lymph node dissection. Cytological analysis of the samples obtained after peritoneal washing showed negative results.Histopathologically, no variable cancer cells remained in the primary lesion, but a few degenerated cancer cells remained in one of the lymph nodes.Pathological features were classified as Grade 3 for the primary lesion and Grade 2 for the lymph node lesions.S -1 and S-1/cisplatin were administered as adjuvant chemotherapy.One year and 6 months after surgery, the patient is alive and free of disease.

[A case of resection for a huge pancreatic acinar cell carcinoma with tumor thrombus in the portal vein].

A 6 3-year-old man with a huge pancreatic tumor was referred to our hospital. Abdominal computed tomography revealed a heterogeneously enhanced encapsulated mass, 14 cm in diameter, in the pancreas head. The tumor thrombus extended to the bifurcation of the portal vein. The tumor, which had invaded the descending duodenum, was diagnosed as a probable case of acinar cell carcinoma, based on the biopsy results. Prior to resection, we prepared an ileocecal vein-umbilical vein bypass. Initially, we planned to perform a pancreatoduodenectomy, however, a total pancreatectomy had to be performed due to the atrophy of the residual pancreas tail. Since the tumor thrombus was visible, floating up from the portal vein wall at the upper level of pancreas, we dissected the portal vein at this level. The thrombus was extracted after securing the main tract and both (right and left) branches of the portal vein with vessel tape. About 5 cm of portal vein was resected and reconstructed. Since patients who undergo resection of acinar cell carcinoma have a better prognosis and long-term survival is often reported for cases of resected tumor thrombus of the portal vein, it is advisable to resect acinar cell carcinomas even in cases as advanced as reported here.

[A case of advanced gastric cancer successfully treated with trastuzumab, capecitabine, and Cisplatin therapy followed by curative resection].

We report a case of human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer successfully treated with combination therapy of trastuzumab, capecitabine, and cisplatin, followed by a curative resection. A 23-year-old woman was diagnosed with advanced type 3 gastric cancer, and the clinical findings were T3N0M0, StageIIA. A laparoscopic exploration revealed that it was a CY1 unresectable StageIV cancer. Initially, docetaxel, cisplatin, and S-1 therapy was chosen. However, the patient's HER2 status proved to be positive (IHC 3+), and so trastuzumab, capecitabine and cisplatin therapy was administered. After four cycles, the tumor significantly decreased in size, suggesting a partial response(PR). A further laparoscopic exam showed no apparent dissemination or metastatic cancer cells. We performed a curative resection consisting of a laparoscopic distal gastrectomy and D2 lymphadenectomy. The patient's postoperative course has been uneventful. She has been alive for 4 months and is receiving adjuvant chemotherapy comprising trastuzumab and S-1.

[Analysis of the eligibility of elderly colorectal cancer patients for adjuvant chemotherapy combined with polysaccharide K].

We enrolled 62 elderly patients( ≥70 years of age) with colorectal cancer who had undergone surgery and postoperative adjuvant chemotherapy at our department and analyzed the overall surviva(l OS) and disease-free surviva(l DFS) to identify the patients who responded to treatment. Postoperative adjuvant chemotherapy was performed with oral anticancer agents, including doxifluridine( 5'-DFUR), uracil/tegafur( UFT), and UFT/Leucovorin( LV); all patients also received polysaccharide K( PSK), an immunomodulator, in combination with chemotherapy. The 3-year OS and DFS rates for all patients were 83.4% and 78.6%, respectively, with no significant differences in these rates based on the chemotherapeutic agents used. The patients were assigned to low and high groups on the basis of the median cut-off values of each clinical laboratory parameter and the data obtained were subjected to univariate analysis. The results of the univariate analysis suggested that carcinoembryonic antigen (CEA) and cancer antigen 125 (CA125) levels were significant prognostic factors. Further multivariate analysis using Cox regression analysis identified the preoperative CEA level alone as an independent factor. When stratification analysis was performed using a preoperative CEA level of 4.0 ng/mL as the cut-off value, the results indicated that the outcome of patients with a high preoperative CEA level may be 8-fold worse than that of patients with a low preoperative CEA level. For these patients, the use of chemotherapeutic drugs that elicit a more potent antitumor effect should be considered.

Anesthetic induction and endotracheal intubation in the sitting position due to the fixed forearm caught by a meat grinder.

A male patient was scheduled for urgent amputation of his right forearm. His right forearm was stuck inside the insertion slot of a meat grinder, resulting in severe pain to his injured arm. His upper body could not move to sit in a semi-upright position. An endotracheal tube was successfully placed after rapid sequence intubation using a video laryngoscope from behind the patient on the first attempt. This case report is the first documentation of successful anesthetic induction with subsequent endotracheal intubation using a video laryngoscope from behind an injured patient whose upper body was upright with limited positioning.

Fluorescence diagnosis of metastatic lymph nodes using 5-aminolevulinic acid (5-ALA) in a mouse model of colon cancer.

BACKGROUND: Lymph node metastasis is one of the most critical prognostic factors in patients with colorectal cancer. Although regional lymph nodes should be surgically resected and pathologically examined, techniques for the intraoperative diagnosis of lymph node metastasis remain to be well established. Fluorescence diagnosis using 5-aminolevulinic acid (5-ALA) is a promising technique for evaluating various malignancies. After exogenous administration of 5-ALA, protoporphyrin IX (PPIX) accumulates in malignant cells and can be detected as red fluorescence. In this study, we investigated the usefulness of fluorescence diagnosis using 5-ALA for the detection of lymph node metastasis in a mouse model of colon cancer. MATERIALS AND METHODS: An orthotopic colon cancer model was prepared by inoculating the cecal wall of nude mice with HCA7, a human colon adenocarcinoma cell line. After 3 wk, 40 mg/kg of 5-ALA was administered intraperitoneally (IP) or orally (PO). Fluorescence diagnosis with a D-Light System (Karl Storz) was then performed after 3 or 6 h. RESULTS: In the IP group, PPIX fluorescence was detected in metastatic lymph nodes as well as in other malignant lesions, including primary tumors and abdominal implantations, while non-metastatic nodes were fluorescence-negative. In contrast, no obvious fluorescence was detected in cancerous tissues in the PO group. CONCLUSIONS: PPIX fluorescence induced by intraperitoneal injection of 5-ALA allows metastatic lymph nodes to be accurately diagnosed in this mouse model. This technique may facilitate the intraoperative diagnosis of lymph node metastases from colon cancer in a clinical setting.

Transcriptional factor Prox1 plays an essential role in the antiproliferative action of interferon-γ in esophageal cancer cells.

BACKGROUND: We previously reported interferon-γ (IFN-γ)-induced apoptosis in 10 (32%) of 31 esophageal squamous cell carcinoma (ESCC) cell lines. However, the molecular basis of antiproliferative action by IFN-γ remains elusive. Here we demonstrate that IFN-γ induces transcriptional factor Prox1, and we explore the link between Prox1 and the IFN-γ system in ESCC cells. METHODS: By using ESCC cell lines, we investigated the relationship between p53 mutations and the responsibility to IFN-γ, and studied the role of Prox1 in the antiproliferative effect of IFN-γ by knockdown and overexpression methods. RESULTS: p53 mutations were found in seven of nine ESCC cell lines responsible for IFN-γ. The frequency was not different from that of p53 mutations in total ESCC cell lines (21 of 28 cell lines). Treatment of ESCC cells with IFN-ß but not IFN-γ resulted in increase of p53 messenger RNA (mRNA) expression, whereas IFN-γ but not IFN-ß induced cell growth inhibition of ESCCs harboring p53 mutations. IFN-γ induced Prox1 expression in ESCC cells but not in those transfected with dominant-negative STAT1. Cell growth inhibition by IFN-γ was significantly suppressed in ESCC cells transfected with Prox1 short interfering RNA (siRNA). In addition, overexpression of Prox1 induced antiproliferative effect in ESCC cells. We also demonstrate that Prox1 is expressed in primary esophageal cancer tissues (five of nine samples treated with neoadjuvant chemotherapy before surgery). CONCLUSIONS: Prox1 mediates the antiproliferative effect by IFN-γ in ESCC cells. Prox1 may be a candidate target for novel therapeutic strategies of ESCCs.

The importance of precompression time for secure stapling with a linear stapler.

BACKGROUND: One prerequisite for the safe stapling of anastomoses is the formation of perfectly aligned B-shaped staples. Using an animal model, this study investigated whether precompression enhances secure staple formation. METHODS: A 45-mm linear stapler with a blue cartridge (staple leg length, 3.5 mm) was used on three portions each of six porcine stomachs (cardia, center, and pylorus). Staple shape and height were examined according to the precompression time (0, 1, or 5 min) before firing. The shape was classified as optimal or suboptimal, and the heights of the staples were measured individually. The completeness of the proximal staple lines also was compared with the distal lines. RESULTS: The optimal staple rate in the 5-min group (52.7%) was significantly higher than in the 1-min group (28.7%; p<0.001) or the 0-min group (17.1%; p=0.002). The optimal staple rate in the 5-min group for the cardiac portion (mean wall thickness, 2.7 mm) reached 98.9%. However, this rate was less than 50% in the center (5.3 mm) and pylorus (4.2 mm) portions regardless of the precompression time. Compared with the root side, the top side of the cartridge had a lower optimal rate (45.3 vs. 18.7%; p<0.001). A high correlation of completeness was observed between the distal and proximal sides of the stump. CONCLUSIONS: When a linear stapling device is used, proper staple formation is correlated with intestinal wall thickness, and a sufficient amount of precompression time is effective for gaining the secure staple formation.

Cardio-renal interaction: impact of renal function and anemia on the outcome of chronic heart failure.

The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

Chromene and prenylated xanthones from the roots of Cratoxylum formosum ssp. pruniflorum.

Two new xanthones, namely pruniflorone K (1) and L (2), have been isolated from the roots of Cratoxylum formosum ssp. pruniflorum, along with thirteen known xanthones (3-15). Their structures were mainly established using the spectroscopic methods. Only isolated compounds with sufficient amount were evaluated for antibacterial and antifungal activities.

New cytotoxic steroids from the fruits of Syzygium siamense.

A new sterol, stigmast-5-ene-3beta,17alpha-diol (1), together with six known compounds, stigmast-5-ene-3beta-yl formate (2), stigmast-5-ene-3beta,7alpha-diol (3), stigmast-5-ene-7alpha-methoxy-3beta-ol (4), stigmast-5-ene-3-one (5), 3beta-sitostanol (6), and 3beta-sitosterol (7), was isolated from the fruits of Syzygium siamense, of which compound 2 is reported for the first time from a natural source. Their structures were elucidated by spectroscopic methods. The isolated compounds (1-7) were evaluated for their cytotoxic activities against human oral epidermoid carcinoma cancer (KB), human breast cancer (BC), and human small cell lung cancer (NCI-H187) cell lines.