Downstaging of lymph node metastasis after neoadjuvant intraperitoneal and systemic chemotherapy in gastric carcinoma with peritoneal metastasis.

PURPOSE: The aim of the present study was to evaluate the clinical features and prognosis of lymph node metastasis (LNM) in gastric cancer patients with peritoneal metastasis (PM) after neoadjuvant intraperitoneal and systemic chemotherapy. METHODS: A total of 69 gastric cancer patients with PM and LNM who received neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) of intraperitoneal docetaxel (DXT) and cisplatin (CDDP); intravenous chemotherapy of DXT and CDDP and oral S-1in Kishiwada Tokushukai Hospital between January 2008 and February 2017. After surgical resection, the response of LNMs was studied to confirm the effect of NIPS on LNMs. RESULTS: After NIPS, 197 lymph nodes (LNs) (42.5%) were graded as G3, the progression in LNMs were significantly better than in the primary tumors. Until the last follow-up, 1-year overall survival rate was 82.6%, and the median survival period was 22.0 ±â€¯3.7 months. In the group of patients who had achieved a more than 50% G3 grade of the response of LNMs, the median survival period is 38 months; in the less than 50% G3 grade group, it is 14 months, that is a significantly different result. Multivariate analyses showed that the factors PCI, Post-therapeutic N status and response of the LNMs were found to be as independent prognostic factors. CONCLUSION: Downstaging of LNMs were achieved in patients of gastric cancer with PM who received NIPS. Downstaging of LNMs after NIPS is related with the prognosis of gastric cancer and should be valued in subsequent surgery for gastric cancer with peritoneal and lymph nodes metastasis.

The performance of a novel ball-tipped Flush knife for endoscopic submucosal dissection: a case-control study.

BACKGROUND: Endoscopic submucosal dissection (ESD) using short needle knives is safe and effective, but bleeding is a problem due to low haemostatic capability. AIM: To assess the performance of a novel ball-tipped needle knife (Flush knife-BT) for ESD with particular emphasis on haemostasis. METHODS: A case-control study to compare the performance for ESD of 30 pairs of consecutive early gastrointestinal lesions (oesophagus: 12, stomach: 32, colorectum: 16) with standard Flush knife (F) vs. Flush knife-BT (BT). Primary outcome was efficacy of intraprocedure haemostasis. Secondary outcomes included procedure time, procedure speed (dividing procedure time into the area of resected specimen), en bloc resection rate and recurrence rate. RESULTS: Median intraoperative bleeding points and bleeding points requiring haemostatic forceps were smaller in the BT group than in the F group (4 vs. 8, P < 0.0001, 0 vs. 3, P < 0.0001). There was no difference between groups for procedure time; however, procedure speed was shorter in the BT group (P = 0.0078). En bloc and en bloc R0 resection rates were 100%, with no perforation or post-operative bleeding. No recurrence was observed in either group at follow-up 1 year postprocedure. CONCLUSIONS: Ball-tipped Flush knife (Flush knife-BT) appears to improve haemostatic efficacy and dissection speed compared with standard Flush knife.

Retrospective study of technical aspects and complications of endoscopic submucosal dissection for laterally spreading tumors of the colorectum.

BACKGROUND AND STUDY AIMS: Laterally spreading tumors - non granular type (LST-NG) are more often considered candidates for endoscopic submucosal dissection (ESD) than laterally spreading tumors - granular type (LST-G), because of their higher potential for submucosal invasion. However, ESD for LST-NG can be technically difficult. The aim of our study was to compare our ESD results for LST-NG and for LST-G. PATIENTS AND METHODS: Ninety-nine LST-NG and 169 LST-G measuring 20 mm in size or more were removed by ESD. We retrospectively evaluated the clinicopathological features of the tumors and treatment results (en bloc resection rate, procedure time and speed, rate of use of ancillary devices, and complication and recurrence rates). RESULTS: Histopathology revealed that there were more submucosally invasive lesions in the LST-NG than in the LST-G group (28 % vs. 9 %; P < 0.0001). The en bloc resection rate, en bloc R0 resection rate, and en bloc curative resection rate of LST-NG were similar to those of LST-G (LST-NG: 99 %, 98 %, and 88 %; LST-G: 99 %, 98 %, and 91 %). In LST-NG, the median procedure time tended to be longer (LST-NG: 69 min; LST-G: 60 min) and the median procedure speed was slower (LST-NG: 0.15 cm (2)/min; LST-G: 0.25 cm (2)/min; P < 0.0001). Use of ancillary devices was higher for LST-NG (38 % vs. 15 % for LST-G; P < 0.0001), as was the perforation rate (5.1 % vs. 0.6 % for LST-G; P = 0.027). No recurrence was seen in either group. CONCLUSIONS: ESD was an effective treatment method for both LST-NG and LST-G. However, the degree of technical difficulty appears higher for LST-NG than for LST-G lesions, as shown by the lower dissection speed and higher perforation rate. ESD for LST-NG should probably be performed by those with significant experience of colorectal ESD.

Complete response of highly advanced gastric cancer with peritoneal dissemination after new combined chemotherapy of S-1 and low-dose cisplatin: report of a case.

TS-1(S-1) has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose cisplatin. Remarkable tumor reduction was observed after two cycles of this therapy in the primary tumor and metastatic lymph nodes, and the ascites disappeared. This was concluded to be a partial response. The only adverse effect was skin pigmentation of the fingers (grade 1), leading to early timing of operation after chemotherapy. The gastric tumor showed evident invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also recognized in the omentum and mesocolon. Total gastrectomy with regional lymph node dissection was performed. Disseminated tumors were all resected. Histological examination showed that no tumor cells were detected in the gastric primary lesion, metastatic lymph nodes or disseminated peritoneal tumors, suggesting pathological complete remission. It was suggested that this regimen could be a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma, and it could be useful as neoadjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.

Effect of aquatic weeds on methane emission from submerged paddy soil.

Paddy fields are one of the dominant anthropogenic sources of methane emission to the atmosphere, and the main passageway of methane from paddy soil is through the rice plant. However, the effect of aquatic weeds on methane emission from rice paddies has not been properly evaluated yet. Methane emission from weeded pots and unweeded ones with anaerobic paddy soil was measured throughout the period of rice growth. More than double the amount of methane was emitted from weeded pots compared with unweeded ones. Peroxidase activity of rice root was not different between weeded and unweeded pots. However, methanogenic bacteria populations were higher in weeded pots than in unweeded ones, while methane oxidation activity, measured by the propylene oxidation technique, was higher in unweeded pots than in weeded ones. Methane oxidation activity of roots from three typical aquatic weeds in paddy fields, Lipocarpha sp., Rotala indica, and Ludwigia epilobioides, was higher than that of rice plants, while lower stems of these aquatic plants showed similar or lower activity compared with the same areas of rice plants. These results indicate that the role of aquatic weeds in paddy soil in methane emission should not be overlooked in evaluating mitigation options for reducing methane emission from paddy fields.

Renal collecting duct carcinoma. Report of a case with cytologic findings on fine needle aspiration.

BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is a rare type of renal cell carcinoma (RCC) of collecting duct origin. Cytologic differentiation of CDC from conventional RCC is important because CDC has a poorer prognosis than the latter. CASE: A 60-year-old male incidentally demonstrated a left renal mass that was hypovascular by angiography. Fine needle aspiration (FNA) revealed numerous clusters of cells arranged in a tubular structure. The cells consisted of highly atypical cells having large nuclei with coarse or vesicular chromatin, prominent nucleoli and lacy or granular cytoplasm. Based on these findings, which were indicative of high grade RCC, he underwent left radical nephrectomy and lymphadenectomy. Histologic and immunohistochemical findings, including anti-high-molecular-weight cytokeratin (HMCK) antibody, confirmed the diagnosis of CDC. CONCLUSION: CDC should be added to the differential diagnosis when the result of cytologic examination of a renal mass is suggestive of high grade RCC. These features of FNA smears, together with HMCK immunohistochemistry, can be useful for the cytologic differential diagnosis of renal tumors.

Isolation of embryo sacs from Dianthus ovules by enzymatic treatments and microdissection.

Mature ovules of Dianthus (Caryophyllaceae) were histologically observed by clearing and serial sectioning to characterize the cells of the embryo sac. The results show that the mature embryo sac was located deep inside the hemitropous ovule due to thick nucellar tissue at the micropylar region. For the isolation of the embryo sacs, ovules were collected from ovaries of flowers 1 day after anthesis, and treated with an enzyme solution for digesting cell walls on a gyratory shaker. After 12 h of enzyme treatment, these ovules were dissected using a glass needle under an inverted microscope to release the embryo sacs. The embryo sacs, characterized by their specific size, were successfully released by these successive treatments. The viability of the embryo sacs was more than 80% as assessed with fluorescein diacetate staining. Fluorescent staining with 4,6-diamidino-2-phenylindole revealed the nuclei of the egg apparatus in the isolated embryo sacs. The procedure for isolating embryo sacs established in this study will offer a new approach to further in vitro studies on fertilization in Dianthus.

Three groups of species in Petunia sensu Jussieu (Solanaceae) inferred from the intact seed.

The intact seed surface morphology in 45 taxa of Petunia sensu Jussieu native to South America (Petunia sensu Wijsman plus Calibrachoa) was compared under scanning electron microscopy. The existence of three groups of species, differentiated in terms of seed morphology, was revealed as follows: (1) all species of Petunia sensu Wijsman, having coarse wavy middle lamellae and anticlinal walls; (2) Calibrachoa parviflora and C. pygmaea, having fine wavy middle lamellae embedded in straight anticlinal walls; and (3) the other species of Calibrachoa, having straight middle lamellae and anticlinal walls. Close relationships between seed morphology and the other characteristics observable in the groups of species are discussed.

Bassiatin, a new platelet aggregation inhibitor produced by Beauveria bassiana K-717.

A new platelet aggregation inhibitor, bassiatin, was isolated from the cultured broth of Beauveria bassiana which had been isolated from a soil sample collected in Yunnan province, China. The structure of bassiatin was determined to be (3S, 6R)-4-methyl-6-(1-methylethyl)-3-phenylmethyl-1, 4-perhydrooxazine-2,5-dione by NMR analysis, X-ray crystallographic analysis and chemical synthesis. Bassiatin inhibited ADP-induced aggregation of rabbit platelets with the IC50 being 1.9 x 10(-4) M.

Malignant schwannoma of the intrathoracic vagus nerve: report of a case.

We report herein the case of a 48-year-old man with malignant schwannoma of the intrathoracic vagus nerve associated with von Recklinghausen's disease. Malignant intrathoracic vagal tumors are extremely rare and to our knowledge, only four other cases have been documented in the literature, none of which were associated with von Recklinghausen's disease.

A combined small cell and spindle cell carcinoma of the lung. Report of a unique case with immunohistochemical and ultrastructural studies.

A unique bronchial tumor is reported. The tumor grew as an endobronchial polyp and obstructed the right main bronchus. Histologically the lesion consisted of two different types of neoplastic cells; epithelial small cell nests and atypical spindle-shaped cells. Immunohistochemical studies with a panel of antibodies showed that the small cell nests were immunoreactive for epithelial and neuroendocrine markers. The spindle-shaped cells showed positive staining for smooth muscle actin. Epithelial markers were also positive focally in the spindle cells. Electron microscopy confirmed that the spindle-shaped cells had both epithelial and mesenchymal features. Based on these results, the tumor was considered to be a unique combination of small cell and spindle cell carcinoma.

Trophoblast-derived interleukin-1 (IL-1) stimulates the release of human chorionic gonadotropin by activating IL-6 and IL-6-receptor system in first trimester human trophoblasts.

Interleukin-1 (IL-1) has a unique activity to stimulate the release of multiple hormones in a number of human and murine endocrine systems. IL-6 also expresses such activities by activating IL-6-receptor (R)-mediated signal transduction pathways. Since the placenta produces both of these cytokines and endocrine hormones such as hCG, we investigated how these cytokines regulate hCG release by normal trophoblasts. Trophoblasts purified by Percoll density gradient released hCG from 120 min after stimulation with recombinant (r) IL-1 alpha, and its release was dependent on the rIL-1 alpha concentration used. The rIL-1 alpha-stimulated trophoblasts released a molecule with IL-6 activity antecedently, as determined by an IL-6-dependent cell line, MH60.BSF2 cells. The IL-6 identity of the released molecule was confirmed by goat anti-IL-6 antiserum. rIL-1-mediated hCG release from trophoblasts was completely abrogated to the basal level by pretreatment of the trophoblasts with PM1, an anti-IL-6-R monoclonal antibody. Identical results were observed with rIL-1 beta. These results showed that rIL-1-induced hCG release was totally dependent on IL-6- and IL-6-R-mediated signal transduction in human trophoblasts. The presence of peripheral monocytes in the purified trophoblast fraction, however, induced a rapid decrease in IL-6 and hCG release after their maximal release, suggesting some regulatory interaction between trophoblasts and the monocytes. In contrast, rIL-1-mediated enhancement of IL-6 and hCG secretion by purified trophoblasts was no longer observed at 24 h compared with that of the unstimulated trophoblasts, while spontaneous hCG secretion was significantly inhibited by pretreatment of trophoblasts with PM1. The results showed that IL-6 and hCG secretion might also be regulated by a number of agents besides IL-1, and that hCG secretion as well as its release is dependent on IL-6 and IL-6-R system in trophoblasts.

[Effect of low-dose aspirin therapy on utero-placental blood flow and malondialdehyde (MDA) as an indicator of its therapeutic effect].

Pregnancy-induced hypertension (PIH) and preeclampsia develop when an imbalance occurs between prostacyclin (PGI2) and thromboxane A2 (TXA2) production. PGI2 promotes vasodilation and decreases platelet adhesiveness, while TXA2 acts as a vasoconstrictor and enhances platelet aggregation and adhesion to vascular walls. The PGI2/TXA2 ratio appears to be important in pregnancy and the development of the functioning uteroplacental unit. Recently, antiplatelet treatment such as low-dose aspirin therapy has been effective in preventing the development of PIH and preeclampsia. TXA2 breaks down spontaneously into a stable substance, TXB2, which is inactive. Another stable, inactive metabolite, malondialdehyde (MDA), is formed via the same pathway. TXB2 and MDA are produced in approximately equimolar quantities. We studied the effects of a low-dose aspirin prescription. Production of MDA was remarkably suppressed during the low-dose aspirin therapy. Furthermore, pulsed doppler ultrasound assessment of blood flow was performed in the fetal descending aorta, umbilical artery and uterine artery of the low-dose aspirin therapy patients. Doppler abnormalities were improved during the therapy. It is concluded that low-dose aspirin improves the uteroplacental blood flow assessed by pulse doppler waveform and that determination of MDA is useful as an indicator of platelet thromboxane synthesis.

Trophoblast-derived interleukin-6 (IL-6) regulates human chorionic gonadotropin release through IL-6 receptor on human trophoblasts.

We examined the capacity of trophoblast-derived interleukin-6 (IL-6) to stimulate secretion of placental hormones, including hCG. IL-6 stimulated hCG secretion by trophoblasts to a level similar to that stimulated by a GnRH analog. The analog, however, released hCG by an IL-6-independent mechanism because PM-1, a monoclonal antibody specific for IL-6 receptors (R), failed to block GnRH-mediated responses, but completely blocked IL-6-mediated hCG secretion, suggesting the existence of two distinct regulatory pathways for hCG release. Immunohistochemical analysis with another IL-6-R-specific antibody, MT-18, showed that IL-6-R was located only on the trophoblast layer of the placenta. Our data revealed the existence of a local regulatory network by which trophoblast-derived IL-6 interacts with IL-6-R on the trophoblasts, resulting in hCG release. Thus, two different regulatory networks, an IL-6 and IL-6-R system and a GnRH and GnRH-R system, regulate hCG release by human trophoblasts independently.

Clinical evaluation of a direct colorimetic method for determination of amniotic phospholipids.

Evaluation of amniotic phospholipids, which are a parameter of fetal lung maturation, is important in the management of premature infants. The method available for measuring the lecithin/sphingomyelin (L/S) ratio, which appears to provide an index to fetal lung maturity, is laborious, involving determinations of phospholipids, and so is unsuitable for rapid quantitative measurement of phospholipids in the amniotic fluid in the perinatal period. We developed a simple, sensitive colorimetric assay for phospholipids without their extraction. This assay is based on the fact that phospholipids form stable hydrophobic complexes with Co(SCN)4, Fe(SCN)2- and Fe(SCN)3 within about 1 hr. Amniotic fluid samples (n = 115) were collected from women with normal and abnormal pregnancies in week 16-41 of pregnancy, and these samples were examined both by thin layer chromatography (TLC) and by our method of phospholipid determination. Good correlations were observed between the L/S ratio determined by TLC and the values obtained by this method. Moreover the distributions of the dipalmitoylphosphatidylcholine (DPPC) content and DPPC/sphingomyelin (SM) ratio were similar to those of the PC content and L/S ratio. This method was proved to be more accurate than other methods such as TLC and the shake test for predicting neonatal RDS.

Immunoreactive corticotropin-releasing hormone, adrenocorticotropin and cortisol in human plasma during pregnancy and delivery and postpartum.

The activity of the hypothalamo-pituitary adrenal axis was examined, by measuring the levels of immunoreactive (IR) corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and cortisol (F) in human plasma during normal pregnancy and after delivery with or without complications and during normal postpartum using a specific RIA. The level of IR-CRH in maternal plasma increased progressively during pregnancy, increased further at delivery and declined rapidly to the non-pregnant level on the 1st day postpartum. The level of IR-F in maternal plasma also increased progressively during pregnancy, increased further at delivery, but decreased slowly postpartum, not returning to the non-pregnant level within 5 days. Significant correlations were found between the level of IR-CRH and IR-ACTH, IR-CRH and IR-F, and IR-ACTH and IRF in maternal plasma both during pregnancy and after delivery. It is noteworthy that the concentration of IR-CRH in the maternal plasma at delivery was higher in multiple pregnancy than in normal pregnancy, and that the level of IR-CRH in the umbilical cord in uncomplicated cases was much lower than that in the maternal plasma, and was significantly lower than those in the umbilical cord plasma in cases of asphyxia, IUGR or premature delivery. The level of IR-F, not IR-CRH and IR-ACTH, at normal vaginal delivery was significantly higher than that at elective cesarean section. On these results, we investigated the feto-maternal-hypothalamo-pituitary adrenal axis during pregnancy and delivery, in which CRH plays an important role.

Plasma concentrations of human atrial natriuretic peptide at vaginal delivery and elective cesarean section.

The change in plasma concentration of atrial natriuretic peptide (hANP) at delivery was examined by measuring the concentrations of hANP in plasma samples from 21 subjects after 36 weeks of normal pregnancy, 22 subjects after normal spontaneous delivery and 20 subjects after elective cesarean section. The maternal plasma concentration of hANP after normal delivery (38.0 +/- 8.2 fmol/ml, mean +/- S.E.M.) was significantly higher than that after 36 weeks of normal pregnancy (16.8 +/- 2.3 fmol/ml), but its concentration after cesarean section was not different from that after 36 weeks of pregnancy. After normal delivery, the plasma concentration of hANP in the umbilical artery (66.9 +/- 11.8 fmol/ml) was also significantly higher than that in the umbilical vein (35.1 +/- 7.3 fmol/ml). In contrast, after elective cesarean section, the hANP levels in the umbilical artery and vein were not significantly different. These results suggest that hANP secretion into the maternal and fetal circulation may be stimulated by the dynamic movement of the mother in labour and the stress of the fetus at delivery, respectively.

Non-Hodgkin's lymphoma involving the brain. Diagnostic usefulness of stereotactic needle biopsy in combination with paraffin-section immunohistochemistry.

A stereotactic needle biopsy was examined for applicability in diagnosing brain non-Hodgkin's lymphoma (NHL), because the procedure is far less aggressive than biopsy by open surgery. Formalin-fixed materials including four stereotactic specimens were available from nine patients with brain NHL. In addition to routine histopathology and histochemistry, paraffin-section immunohistochemistry was performed using a panel of monoclonal antibodies suited to such sections. Although several histopathological features characteristic of brain NHL could not be evaluated in three of the four stereotactic specimens owing to the small size of the specimens and partial invasion by lymphoma cells, the lesions in all cases could be characterised by immunohistochemistry. Examination for cytoplasmic immunoglobulin (cIg) was also performed, but specific identification of cIg was difficult in five cases because of diffuse background staining and passive diffusion of plasma protein into the cells during tissue processing. A review of the literature indicates the technical difficulty in cIg staining, since the incidence of cIg-positive cases in an individual study varied considerably, and lymphoma cells in 15 of 128 cIg-positive brain NHL cases have been reported to possess both light chains. From these findings, together with the relative difficulty in obtaining fresh tissues for study, it is concluded that, when the specimens are to be examined by paraffin-section immunohistochemistry using the above monoclonal antibodies, stereotactic needle biopsy is a useful, less aggressive method for diagnosing brain NHL.

Lymph node involvement in chronic neutrophilic leukemia. An immunohistochemical study.

An immunohistochemical study was performed on autopsy material from a patient with chronic neutrophilic leukaemia (CNL) using antibodies against various cell lineage-related antigens. Proliferation of immature neutrophils with occasional clusters of erythroblasts and megakaryocytes were noted in the retroperitoneal lymph nodes, spleen, and kidneys as well as in the bone marrow. Predominance of immature neutrophils in the lymph nodes suggested the emergence of a blast crisis, although there was no increase of blasts in the peripheral blood. Since immature myeloid cells are difficult to distinguish from malignant lymphoid cells on tissue sections, we suggest that immunohistochemical identification of cell lineage-related molecules on these cells is necessary for the more accurate interpretation of lymph node lesions in myeloid neoplasms.

Autopsy findings in a Japanese patient with acquired immunodeficiency syndrome.

A 37-year-old Japanese man was diagnosed as having acquired immunodeficiency syndrome (AIDS) on the basis of a homosexual history, generalized lymphadenopathy, marked decrease of helper/inducer T cells in the peripheral blood, and positive serum antibody (antibodies) against human immunodeficiency virus (human T-lymphotropic virus type III/lymphadenopathy-associated virus). Autopsy showed severe depletion of lymphocytes in the lymphoid organs including the systemic lymph nodes, spleen, and gut-associated lymphoid tissue. Pneumocystis carinii pneumonia and adrenal cytomegalovirus infection ('necrotizing adrenalitis') were identified, but there was no neoplasm. Postmortem findings in AIDS were reviewed in the literature.