Neoadjuvant therapy or upfront surgery? A systematic review and meta-analysis of T2N0 esophageal cancer treatment options.

BACKGROUND: Esophageal carcinoma usually shows poor long-term survival rates, even when esophagectomy, the standard curative treatment is performed. As a result, there has been increasing interest in the neoadjuvant therapy, which could potentially downstage cancer, eliminate micrometastasis and ergo increase resectability and curative (R0) resection. Currently, for the earliest stage esophageal cancers, most guidelines point out to the role of endoscopic treatment, and for T1bN0 upfront surgery. For locally advanced cases, several studies have demonstrated the benefits of neoadjuvant therapy to increase resectability. For clinical stage T2N0 esophageal cancer, there is no consensus as to the optimal treatment strategy. METHODS: A systematic review and meta-analysis was performed to compare neoadjuvant therapy with surgery alone on clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence, post-operative mortality, anastomotic leak, and R0 resection rate. RESULTS: For overall survival at the mean follow-up point, the neoadjuvant therapy was not associated to a higher probability of survival than upfront surgery in cT2N0 patients (risk difference: 0.00; 95% CI: -0.09, 0.09). There was no difference between neoadjuvant therapy and primary surgery concerning recurrence (risk difference: 0.21; 95% CI: -0.03, 0.45); perioperative mortality (risk difference: 0.00; 95% CI: -0.02, 0.01); and risk for anastomotic leak (risk difference: -0.08; 95% CI: -0.21, 0.05). Pooled data showed that neoadjuvant therapy was associated to a higher risk for positive margins after resection (risk difference: 0.04; 95% CI: 0.02, 0.06). CONCLUSIONS: This review showed that neoadjuvant therapy is not associated to better results than surgery alone, for the management of clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence rate, perioperative mortality, anastomotic leak, and seems to be associated to a higher risk for resection with positive margins.

Gastric secretory and hormonal patterns in end-stage chagasic achalasia.

Achalasia surgical treatment alters the esophagogastric junction anatomy (cardiomyotomy plus fundoplication or esophagectomy and gastric pull-up), thus favoring a certain degree of gastroesophageal reflux. Gastric secretory and hormonal functioning is not completely known in chagasic patients. The aim of this study was to evaluate the gastric secretory and hormonal response in patients with end-stage chagasic achalasia compared with normal subjects. Gastric secretion and hormonal response were assessed by estimation of gastric acid secretion (GAS) in basal condition and after pentagastrin stimulation, basal serum gastrin, and serum pepsinogen (SP) in basal condition and after betazole hydrochloride (Histalog; Eli Lilly and Company, Indianapolis, IN, USA) stimulation in 27 patients with chagasic achalasia. The results were then compared with those of 24 normal subjects. In the chagasic group, the mean basal and stimulated GAS were significantly lower than in the control group (basal: 1.277 vs. 3.13, P = 0.002; stimulated: 15.9 vs. 35.8, P = 0.0001). Chagasic patients' SG levels showed a significantly higher basal value than the control group (83.3 vs. 36.8, P = 0.0001). There was a significant increase of SP after stimulation compared with the basal levels in both chagasic and control groups. Although the chagasic patients' SP values were higher than the controls, this difference was not statistically significant, either in basal and stimulated conditions (basal: 122.0 vs. 108.9, stimulated 120 min: 177.1 vs. 158.9). In patients with chronic Chagas' disease (ChD), although autonomic denervation does not suppress the strength of the gastric mucosal cells' secretory response to stimulation, it reduces GAS (parietal cell) without, however, affecting SP production (chief cells). On the other hand, the gastrin-producing cells have continuously been stimulated by low GAS.

[Multiple recurrent cardiac myxomas].

A 49-year-old male had undergone resection of biatrial multiple myxomas 4 years previously in another hospital. Echocardiography revealed new masses in the left atrium and the right ventricle. Both tumors were removed surgically and subsequently treated with adjuvant chemotherapy. There was no further recurrence during the following 4 years. It was considered that the multiple recurrences in our case were due to multicentricity of the tumor.

[Removal of methicillin-resistant staphylococcus aureus infected pacemaker leads under cardiopulmonary bypass: report of a case].

A 71-year-old man, who underwent an intravenous pacemaker implantation previously, suffered from fever and local infection of the generator pocket. A blood culture showed positive for methicillin-resistant staphylococcus aureus (MRSA). He underwent removal of total pacemaker system under cardiopulmonary bypass support successfully. Two leads were tightly adhered to the right atrial free wall, tricuspid valve and right ventricular trabeculation. Postoperative course was uneventful with administration of antibiotics for 5 weeks. Removal under cardiopulmonary bypass is considered to be an effective procedure for treatment of patients with infected pacemaker lead.

[Prosthetic valve endocarditis complicated with cardiogenic shock and disseminated intravascular coagulation; report of a case].

A 67-year-old man, who had been performed aortic and mitral valve replacement 3 years before, was admitted because of appetite loss, general fatigue and anemia. Although transthoracic echocadiogram showed no evidence of prosthetic valves failure, the patient fell in profound shock. He needed endotracheal intubation and inotropic support. Transesophageal echocadiogram revealed vegetation formation on the prosthetic mitral valve and massive periprosthetic valve leakage. The diagnosis of prosthetic valve endocarditis was established. Blood examination showed severe disseminated intravascular coagulation (DIC). The patient underwent re-mitral valve replacement and recovered well from shock and DIC.

[Mid-term outcome of aortic arch operation for true aneurysms; using an axillary artery perfusion].

To prevent cerebral infarction during perioperative period, we have used an axillary artery for systemic perfusion and selective cerebral perfusion for aortic arch operation. Since 1996, 34 aortic arch operations were performed in our institution. Simultaneous 5 CABGs, 4 AVRs, 2 aortic root replacements and 1 MVR were performed. There were 2 hospital deaths (5.9%, sepsis and acute heart failure) and only 1 (2.9%) cerebral infarction. There were no deaths in patients over 75 years of age and in patients with extensive aneurysm which were replaced by 2-staged operation. Overall 3 years survival was 94.1% with no further death. We conclude that aortic arch operation through an axillary artery perfusion and with hypothermic selective cerebral perfusion can be performed with very low mortality and morbidity.

Molecular Identification and Classification of Strawberry Phylloid Fruit Phytoplasma in Group 16SrI, New Subgroup.

Plants of commercial strawberry (Fragaria × ananassa Duch., cv. Camarosa) exhibiting extensive fruit phyllody (development of leafy structures from achenes) were observed in a winter greenhouse production facility in West Virginia. In July 2001, 95 dormant, cold-stored plants were purchased from a California strawberry nursery, potted and grown in this West Virginia facility. Five of the plants developed fruits with phylloid growths. These fruits were assessed for phytoplasma infection using nested polymerase chain reactions (PCRs) in which initial ribosomal (r) DNA amplification was primed by phytoplasma-universal primer pair P1/P7 (2), and rDNA reamplification was primed by primer pair R16F2n/R16R2 (1). Amplification of phytoplasma-characteristic 1.2-kbp 16S rDNA in the nested reactions primed by R16F2n/R16R2 confirmed that the symptomatic plants were infected by a phytoplasma, termed strawberry phylloid fruit (StrawbPhF) phytoplasma. No phytoplasma DNAs were amplified from healthy plants. Restriction fragment length polymorphism (RFLP) patterns of 16S rDNA digested with AluI, KpnI, HhaI, HaeIII, HpaII, MseI, RsaI, and Sau3A1 restriction endonucleases indicated that StrawbPhF phytoplasma belonged to group 16SrI (group I, aster yellows phytoplasma group) according to the phytoplasma classification system of Lee et al. (4). However, the collective patterns distinguished StrawbPhF from its closest known relative, clover phyllody (CPh) phytoplasma, and from all other phytoplasmas classified in group 16SrI. On the basis of the RFLP patterns of 16S rDNA, the StrawbPhF was classified in group 16SrI, new subgroup R. The StrawbPhF phytoplasma 1.2-kbp 16S rDNA PCR product was cloned in Escherichia coli using TOPO TA Cloning Kit (Invitrogen, Carlsbad, CA), sequenced, and the sequence deposited in GenBank under Accession No. AY102275. The StrawbPhF 16S rDNA sequence shared 99.9 and 99.8% similarity with the two sequence heterogeneous operons, rrnA and rrnB, respectively, of CPh phytoplasma, and shared 99.9% similarity with 16S rDNA of the unclassified cirsium yellows (CirY) phytoplasma (GenBank Accession No. AF200431) reported in Cirsium arvense L. in Lithuania (3). The restriction sites in 16S rDNA of StrawbPhF were identical to those in 16S rDNA of CPh rrnA and CirY. Three restriction sites (AluI, HaeIII, and MseI) and three base substitutions distinguished StrawbPhF 16S rDNA from rrnB of CPh phytoplasma. No evidence was obtained for the presence of a second (sequence heterogeneous) rRNA operon in StrawbPhF phytoplasma, as reported in CPh phytoplasma (4), which clearly distinguishes this phytoplasma from CPh phytoplasma. Future studies on StrawbPhF phytoplasma may provide important information on the evolution of phytoplasmas. References: (1) D. E. Gundersen and I.-M. Lee. Phytopathol. Mediterr. 35:144, 1996. (2) R. Jomantiene et al. Int. J. Syst. Bacteriol. 48:269, 1998. (3) R. Jomantiene et al. Phytopathology 90:S39, 2000. (4) I.-M. Lee et al. Int J. Syst. Bacteriol. 48:1153, 1998.

[Current status of implementation in Japan of the WHO guidelines for cancer pain relief and future perspectives].

The WHO guidelines have much improved cancer pain management in Japan. In 1987, the Ministry of Health established new policy on palliative care, revised narcotics control measures, and edited guidelines on palliative care. Thus, national cancer pain relief program has been implemented and relieved many cancer patients of their severe persistent pain. Annual consumption of morphine for medical purposes gradually rose to 973 kg in 1999, but the annual morphine consumption per capita is still less than one-sixth of that in the US. In order to further achieve program implementation, educational approach should be much more strengthened. It is also emphasized that each health care professional should recognize the ethics in pain relief and each hospital should urgently has its policy to achieve freedom from cancer pain for all throughout Japan.

Patterns of basal cell keratin 14 expression in Bowen's disease: a possible marker for tumour progression.

BACKGROUND: Bowen's disease is a well-established in situ malignancy of the epidermis. The keratin expression in Bowen's disease has been studied in many reports. However, the patterns of keratin (K) 14 expression in each case have not been closely examined. OBJECTIVES: To investigate if the pattern of expression of K14 has a relationship with tumour progression, we analysed the expression patterns of K14 in relation to the nature of tumour cells, comparing tumour cells in direct contact with the dermis, tumour cells separated from the dermis, and tumour cells invading into the dermis. METHODS: Twenty-seven tissue sections from 22 patients were stained with anti-K14 antibody, as well as with antilaminin and periodic acid-Schiff (PAS) staining to evaluate the conditions of the basement membrane. Staining patterns of K10 and integrin beta1, and their relationships with proliferating cell nuclear antigen (PCNA) and Ki-67 staining patterns, were also examined. RESULTS: Tumour cells with no, or with obscured, basement membranes always showed positive staining for K14, while those with continuous (intact) basement membranes usually did not. Of 10 sections showing dermal involvement of Bowen's disease, five were K14 positive and five were K14 negative. All of these K14-positive sections with dermal involvement showed negative or obscured laminin and PAS staining. Most of the sections having K14-negative tumour cells with dermal involvement showed K14-positive lining cells with continuous staining with laminin and PAS-positive basement membranes. K10 was reciprocally expressed with K14 in most of the sections. Integrin beta1 was expressed in the basal layers of non-tumour epidermal cells, but not in tumour cells. Ki-67 and PCNA were expressed at high frequencies in tumour cells, clearly demarcating tumour cells from non-tumour cells. CONCLUSIONS: Tumour cells separated from the dermis by lining cells were K14 negative with PAS- and laminin-positive basement membranes around them; tumour cells without lining cells were K14 positive with or without continuous basement membranes. K14 expression may be a marker of tumour progression in Bowen's disease.

Simultaneous mitral valve replacement and bypass grafting for mycotic aneurysm of the femoral artery during the active phase of infective endocarditis: a case report.

A 52-year-old woman with a 3-week history of fever and cough was diagnosed as having bacterial endocarditis with vegetation and severe mitral valve insufficiency by echocardiography. Blood culture revealed Streptococcus mitis. After antibiotic treatment for 3 weeks, the patient noticed swelling with pain in her left groin. Computed tomography revealed an occluded aneurysm in the left common femoral artery. Simultaneous surgical treatments of mitral valve replacement and bypass grafting using a saphenous vein following resection of the mycotic femoral arterial aneurysm were performed. Pathohistological examination of surgical specimens revealed acute inflammatory findings, but no microorganisms were found, probably because of the preoperative antibiotic therapy. Her postoperative course was uneventful, and there was no recurrence of mycotic aneurysms in a period of 10 months after the operation. Prompt recognition and urgent simultaneous surgical treatments for mycotic aneurysms complicated with infective endocarditis were effective.

The development of use of oral morphine within the last 10 years in Japan.

Japan's national cancer relief programme was initiated with a field-test of the WHO guidelines for cancer pain management in 1982. It revealed in an excellent result that 87% of 156 cancer patients could be completely relieved of their persistent pain, but this result were ignored by most Japanese health professionals, because of their lack of interest in cancer pain relief. The WHO guidelines were published in 1986 and made quite an impact on those health professionals in Japan. In 1987, a special research team appointed by the Ministry of Health and Welfare of Japan (MOHW) initiated discussion on the philosophy of palliative care in Japan. According to the recommendations made by this research team, the MOHW established a new policy on palliative care, edited manuals on palliative care for terminally ill cancer patients which included guidelines on cancer pain management, and revised narcotics control measures by 1992 in order to much improve the accessibility of opioid analgesics to cancer patients who need them for effective pain relief. The annual consumption of morphine for medical purposes was only 65 kg in 1986 in Japan, but it rose to 973 kg in 1999. Currently, morphine is mostly given by mouth and two-thirds of morphine preparations consumed are MS Contin Tablets. However, the current morphine consumption per capita in Japan is still less than one-sixth of the consumption in the United States. In order to achieve further improvement, educational effort should be much emphasized. In the 1990s, approximately 70% of medical and nursing schools in Japan have initiated their educational curriculum for cancer pain relief and palliative care. There have been government-sponsored, medical, nursing and pharmaceutical societies-sponsored seminar courses on appropriate morphine use in cancer pain management, palliative care and opioid availability, all of which have increasingly strengthened postgraduate education.

Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants.

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.

Identification of the novel developmentally regulated gene, Bdm2, which is highly expressed in fetal rat brain.

Most of the neurogenesis take place during the embryonic stage; the genes expressed predominantly in this stage may play important roles in the control of development of the central nervous system. Using a differential display method, we identified the novel rat gene, brain development-related molecule 2 (Bdm2), that is expressed more abundantly in the embryonic brain than in the adult brain. Full-length Bdm2 cDNA consists of 1842 base pairs (bp) and contains an open reading frame of 1260 bp. Northern blot analysis demonstrated that Bdm2 was strongly expressed in the late embryonic brain and was still detected at lower levels in an early postnatal period; in adults, Bdm2 mRNA was decreased to an undetectable level in brain, though the expression of this mRNA was revealed in other tissues. Level of Bdm2 mRNA was maintained during neuronal differentiation of mouse embryonal carcinoma cell P19, but decreased during the differentiation to glial and unidentified non-neuronal cells. In situ hybridization study demonstrated the wide distribution of Bdm2 mRNA in the embryonic brain; in the adult brain, the hybridization signals became more restricted to the hippocampus, olfactory bulb, cerebellum, and neocortex, almost coinciding with the regions where nascent and immature neurons are present. Thus, it appears likely that Bdm2 encodes a protein that is involved in both the regulation of growth of undifferentiated neural cells and the terminal differentiation of neuronal cells.

[A case of lung cancer (small cell carcinoma) occurring esophago-pericardial fistula and purulent pericarditis].

A 72-year-old woman who had had an endoscopic sclerotherapy for esophageal varices presented with high fever and severe cough. Chest X-ray and CT demonstrated a pneumopericardium and pericardial effusion. Esophagoscopy and esophagography revealed an esophageal perforation into the pericardial cavity and into the lung. Consequently, drainage and irrigation of the pericardial cavity and mediastinum were done for MRSA infection. However, these procedures failed to reduce the inflammation, and she expired because of liver failure soon after placing a covered stent in the esophagus. Postmortem examination revealed small cell carcinoma in the left lung invading into the esophagus and pericardium.

A comparative study of the removal of smear layer by three endodontic irrigants and two types of laser.

AIM: The effects of three endodontic irrigants and two types of laser on a smear layer created by hand instrumentation were evaluated in vitro in the middle and apical thirds of root canals. METHODOLOGY: Sixty human mature extracted mandibular premolar teeth with a single root canal and a closed apex were distributed randomly into five groups of 12 teeth each. Whilst cleaning and shaping up to a size 60 master apical file with a step-back technique, the root canals were irrigated with 3 mL of 5.25% NaOCL and 3% H2O2, alternately, between each file size. Group 1 (G1) were control specimens that were irrigated with a final flush of 17% EDTA. The teeth in group 2 (G2) were irrigated with a final flush of 6% phosphoric acid, and group 3 (G3) with 6% citric acid. In the specimens of group 4 (G4) the root canals were irradiated with a carbon dioxide (CO2) laser, and specimens of group 5 (G5) were irradiated using an Er:YAG laser. The teeth were split longitudinally and prepared for examination by scanning electron microscopy. RESULTS: Control specimens (G1) showed clean root-canal walls with open dentinal tubules in the middle one-third, but in some specimens thick smear layer was observed in the apical one-third. Specimens irrigated with a final flush of 6% phosphoric acid (G2) or 6% citric acid (G3) were cleaner than with 17% EDTA, showing very clean root canal surfaces in the middle one-third but in the apical one-third the smear layer was not completely removed, especially at the openings of the dentinal tubules. The specimens irradiated with the CO2 laser (G4) showed clean root-canal walls with the smear layer absent, charred, melted, recrystallized and glazed in both middle and apical thirds. The root-canal walls of the specimens irradiated with the Er:YAG laser (G5) revealed an absent smear layer with open dentinal tubules in the middle and apical thirds. Statistical analysis showed no significant difference in the cleanliness of root-canal wall between G1 and G2, and G1 and G3. However, there were statistically significant differences (P < 0.01) between G1 and G4, and G1 and G5 in the cleanliness of the middle and apical one-thirds of the root canals. CONCLUSIONS: Irrigation with 17% EDTA, 6% phosphoric acid and 6% citric acid did not remove all the smear layer from the root-canal system. In addition, these acidic solutions demineralized the interbular dentine around tabular openings, which became enlarged. The CO2 laser was useful in removing and melting the smear layer on the instrumented root-canal walls and the Er:YAG laser was the most effective in removing the smear layer from the root-canal wall.

Molecular cloning and characterization of a novel developmentally regulated gene, Bdm1, showing predominant expression in postnatal rat brain.

Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.

Morphological and atomic analytical changes of root canal wall dentin after treatment with thirty-eight percent Ag(NH3)2F solution and CO2 laser.

OBJECTIVE: The morphological and atomic analytical changes of the root canal wall dentin, treated with 38% diamine silver fluoride [Ag(NH3)2F] solution and irradiated by carbon dioxide (CO2) laser at the continuous wave mode were evaluated in vitro. SUMMARY BACKGROUND DATA: There has been no report on the morphological or atomic analytical changes of the effect of Ag(NH3)2F solution and CO2 laser on root canal walls. METHODS: Eighty extracted human single-rooted teeth were instrumented using a conventional technique and randomly divided into 8 groups of 10 teeth each. The teeth in group 1 were neither treated with Ag(NH3)2F solution nor lased. Groups 2, 3, and 4 were irradiated by laser at the parameters of 1, 2, and 3 W for 10 seconds, respectively. Group 5 was treated with Ag(NH3)2F solution only. The other 3 groups were treated with Ag(NH3)2F solution and then lased by the same method as groups 2, 3, and 4. After this treatment, 4 specimens each from group 1, 5, and 6 were analyzed by scanning electron microscope-energy dispersive x-ray spectroscopy (SEM-EDX) and other specimens in all groups were examined by scanning electron microscopy (SEM). RESULTS: The smear layer and debris of the control and lased specimens were not completely removed, but the areas of carbonization of evaporation of smear layer and open dentinal tubules were observed on the specimens treated with Ag(NH3)2F and lased at 1 W (group 6). After laser irradiation, the amount of silver on the root canal surfaces was significantly reduced to approximately one-third level on the measurement of SEM-EDX (p < 0.01). CONCLUSION: These results suggest that CO2 laser is an effective method to remove or melt smear layer of root canal walls after treatment with 38% Ag(NH3)2F solution if an appropriate parameter is selected.

Role of the kappa-opioid system in the attenuation of the morphine-induced place preference under chronic pain.

We previously reported that the morphine-induced place preference was attenuated under inflammation produced by the unilateral injection of 2.5 % formalin (50 microl) into the hind paw of rats. In the present study, to elucidate the mechanism of this attenuation, the effects of pretreatment with delta- and kappa-opioid receptor antagonists, naltrindole (NTI) and nor-binaltorphimine (nor-BNI), on the development of the morphine-induced place preference under inflammation were examined in rats. Nor-BNI, but not NTI, eliminated the suppression of the morphine-induced place preference in inflamed groups. These results suggest that endogenous kappa-opioid systems may be activated in the presence of chronic inflammatory nociception; as a result, the development of morphine's rewarding effect may be suppressed under inflammation.