Transanal total mesorectal excision for locally advanced middle-low rectal cancers.

BACKGROUND: This study investigated the results of transanal total mesorectal excision (TaTME) combined with laparoscopy for locally advanced mid-low rectal cancer. METHODS: Patients with mid-low locally advanced rectal cancer (T3 category or above and/or N+) who underwent rectal resection with TaTME technique were enrolled prospectively. Patients who had distant metastasis, multiple malignancies, intestinal obstruction or perforation, or a clinical complete response to chemoradiotherapy were excluded. Postoperative results, including morbidity, circumferential resection margin (CRM) assessment, short-term survival and functional outcomes, were analysed. RESULTS: Thirty-eight patients, with 25 mid and 13 low rectal tumours, who had elective resection by TaTME from March 2015 to September 2018 were included. There were 25 men and 13 women. Mean(s.d.) age was 58·2(16·4) years and mean(s.d.) BMI was 24·2(2·5) kg/m2 . Tumours were 3-9 cm from the anal verge. Mean(s.d.) duration of surgery was 210(42) min. All patients had hand-sewn anastomoses and protective ileostomies. There were no conversions, abdominal perineal resections or postoperative deaths. Four patients had a complication, including three presacral abscesses, all managed by transanastomotic drainage. At 3 months after ileostomy closure, all patients had perfect continence. Apart from a greater tumour diameter in patients with low rectal cancers (6·0 cm versus 4·6 cm in those with mid rectal tumours; P = 0·035), clinical features were similar in the two groups. CRM positivity was greater for low than for mid rectal tumours (3 of 13 versus 0 of 25 respectively; P = 0·034), and more patients with a low tumour had TME grade 2 (4 of 13 versus 1 of 25; P = 0·038). There was no difference in oncological outcomes at 17 months. CONCLUSION: Although this study cohort was small, special attention should be paid to bulky low rectal tumours to reduce the rate of CRM positivity.

ANTECEDENTES: La escisión total del mesorrecto transanal (transanal total mesorectal excision, TaTME) combinada con la laparoscopia convencional se ha descrito como un procedimiento prometedor para el tratamiento del cáncer de recto medio-inferior localmente avanzado. El objetivo de este estudio fue investigar los resultados de TaTME combinados con la laparoscopia para el cáncer de recto medio-inferior localmente avanzado. MÉTODOS: Se incluyeron de forma prospectiva los pacientes con cáncer de recto medio-inferior localmente avanzado (≥ T3 y/o N+) a los que se realizó una resección anterior de recto con la técnica TaTME. Se excluyeron aquellos pacientes con metástasis a distancia, neoplasias múltiples, obstrucción intestinal o perforación y aquellos que presentaron una respuesta clínica completa después de la quimiorradioterapia. Los pacientes recibieron tratamiento neoadyuvante de acuerdo con las guías de práctica clínica internacionales. Se analizaron los resultados postoperatorios entre los que se incluyen la morbilidad, la evaluación del margen de resección circunferencial (circumferential resection margin, CRM) y la supervivencia a corto plazo junto con los resultados funcionales. RESULTADOS: Se seleccionaron 38 pacientes, 25 con el tumor en el recto medio y 13 con el tumor en el recto inferior que se sometieron a una resección anterior de recto electiva por TaTME desde marzo de 2015 hasta septiembre de 2018. Las localizaciones de los tumores oscilaron entre 3 y 9 cm desde el margen anal. La relación varón/mujer fue de 1,93, la edad media fue de 58,2 ± 16,4 años y el IMC medio de 24,2 ± 2,5 kg/m2 . El tiempo medio operatorio fue de 210 ± 42 minutos. En la todos los pacientes se realizó una anastomosis manual y una ileostomía de protección. No se registró ninguna conversión, ninguna amputación abdomino-perineal y ninguna muerte postoperatoria en toda la cohorte. Cuatro pacientes (10,5%) presentaron alguna complicación, incluidos tres abscesos presacros (7,9%), todos tratados mediante drenaje a través de la anastomosis. La continencia a los 3 meses del cierre de la ileostomía fue grado I según la clasificación de Horgan en todos los pacientes. Las características clínicas fueron similares en los cánceres de recto medio e inferior, sin embargo, este último grupo presentó un diámetro tumoral medio mayor en la estadificación clínica (4,8 en el cáncer de recto medio versus 6,0 cm en el cáncer de recto inferior; P = 0,03). En comparación con los tumores del recto medio, aunque en una cohorte muy pequeña, los tumores del recto inferior presentaron una tasa de afectación del CRM significativamente mayor (3 casos de afectación del CRM versus ninguno, P = 0,02) y así como un mayor número con escisión completa del mesorrecto grado 2 (4 pacientes versus 1 paciente; P = 0,02). No se encontraron diferencias significativas en los resultados oncológicos después de una mediana de seguimiento de 17 meses. CONCLUSIÓN: Aunque este estudio es el resultado de una pequeña cohorte, se debe prestar especial atención a los tumores de recto inferior voluminosos para reducir la tasa de positividad de CRM.

Interaction of Functionalized Naphthalenophanes with Abasic Sites in DNA: DNA Cleavage, DNA Cleavage Inhibition, and Formation of Ligand-DNA Adducts.

Ligands interacting with abasic (AP) sites in DNA may generate roadblocks in base-excision DNA repair (BER) due to indirect inhibition of DNA repair enzymes (e.g., APE1) and/or formation of toxic byproducts, resulting from ligand-induced strand cleavage or covalent cross-links. Herein, a series of 12 putative AP-site ligands, sharing the common naphthalenophane scaffold, but endowed with a variety of substituents, have been prepared and systematically studied. The results demonstrate that most naphthalenophanes bind to AP sites in DNA and inhibit the APE1-induced hydrolysis of the latter in vitro. Remarkably, their APE1 inhibitory activity, as characterized by IC50 and KI values, can be directly related to their affinity and selectivity to AP sites, as assessed by means of fluorescence melting experiments. On the other hand, the molecular design of naphthalenophanes has a crucial influence on their intrinsic AP-site cleavage activity (i.e., ligand-catalyzed ß- and ß,δ-elimination reactions at the AP site), as illustrated by the compounds either having an exceptionally high AP-site cleavage activity (e.g., 2,7-BisNP-S, 125-fold more efficacious than spermine) or being totally devoid of this activity (four compounds). Finally, the unprecedented formation of a stable covalent DNA adduct upon reaction of one ligand (2,7-BisNP-NH) with its own product of the AP-site cleavage is revealed.

Auxiliary-directed etherification of sp2 C-H bonds under heterogeneous metal-organic framework catalysis: synthesis of ethenzamide.

An efficient protocol for 8-aminoquinoline assisted alkoxylation and phenoxylation of sp2 C-H bonds under heterogeneous catalysis was developed. The optimal conditions employed Cu-MOF-74 (20%), K2CO3 base, pyridine ligand or dimethyl formamide solvent, and O2 oxidant at 80 °C or 100 °C for 24 hours. Cu-MOF-74 revealed remarkably higher activity when compared with other previously commonly used Cu-MOFs in cross coupling reactions, supported copper catalysts, and homogeneous copper salts. The reaction scope with respect to coupling partners included a wide range of various substrates. Interestingly, the developed conditions are applicable for the synthesis of high-profile relevant biological agents from easily accessible starting materials. Furthermore, a leaching test confirmed the reaction heterogeneity and the catalyst was reused and recycled at least 8 times with trivial degradation in activity.

Natural orifice transluminal endoscopic surgery for colorectal cancer.

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has theoretical advantages over other approaches. METHODS: This was a prospective cohort study of colorectal cancers operated on by NOTES (transanally for rectal tumours, transvaginally for sigmoid tumours) between December 2013 and December 2015, with a minimum follow-up of 1 year. Eligibility criteria included ASA fitness grade I-III, BMI below 25 kg/m2 and TNM stage T3 N0 M0. Exclusion criteria included pregnancy or distant metastasis. The anastomosis was either handsewn or performed mechanically. RESULTS: Sixteen patients were operated on by a transanal and four by a transvaginal approach. There were ten men and ten women, with a mean(s.d.) age of 55·6(12·1) years. Mean BMI was 22·4(2·6) kg/m2. Four anterior, 11 low anterior and five intersphincteric resections were performed for 16 rectal and four low sigmoid tumours. The mean duration of surgery was 258(11) min. No conversion to laparotomy was needed, and there were no deaths. Five patients required additional ports, for intraoperative bleeding (1), suture of an intraoperative urethral injury with covering ileostomy (1) and difficulty in dissection (3). One patient had an anastomotic leak requiring transanal closure and ileostomy on day 7. Both ileostomies were closed after 2 months. The mean hospital stay was 6·4(1·8) days. All resections were R0. CONCLUSION: In carefully selected patients NOTES for colorectal cancer resection was feasible and effective.

Neurosurgery in Vietnam.

BACKGROUND: The development and current state of Vietnamese neurosurgery is presented, in order to highlight the difficulties faced by neurosurgeons in Vietnam and other developing countries. METHODS: Information has been collected personally by the authors in Vietnam. RESULTS: The conditions of neurosurgery endured by our neurosurgical colleagues in Vietnam are far inferior to those in the developed world, particularly in terms of training, educational aids, investigative and operating room equipment, and postoperative and rehabilitative care. CONCLUSIONS: The recent formation of the Neurosurgical Society of Vietnam will help to improve these conditions, but help and encouragement from neurosurgeons in the developed world will also be of much value. The instigation of preventive strategies will likely make a significant impact on the health costs of neurotrauma in Vietnam.

[The effects of Ara-A on viral markers in duck hepatitis B virus carrier ducks].

Duck hepatitis B virus (DHBV) carrier ducks of one week old were injected with Ara-A (adenine arabinoside) of different dose including 2.5 (11 ducks), 5.0 (11), 10.0 (10) and 20.0 (10) mg/kg for 14 days. This antiviral effect showed dose-dependence up to 5.0 mg/kg and this dose seemed effective to obtain significant antiviral effect. Viral DNA and DNA polymerase activity were reduced significantly from the 1st week after starting the administration of Ara-A. This antiviral effect was maintained even at the 1st week after discontinuation of the drug. These findings were quite similar to those observed in HBV carriers. With the increasing necessity of Ara-A treatment in patients who will not respond to interferon therapy, DHBV seemed a suitable model for the investigation of the dose and antiviral effect of Ara-A treatment in humans.

Inflammation of the liver causes mutations in duck hepatitis B virus genome.

To investigate whether hepatitis causes mutation in the viral genome, DNA sequences in the pre-core region of duck hepatitis B virus (DHBV) DNA were analyzed in both ducks with hepatitis and without hepatitis. Five DHBV carrier ducks were injected with DHBV particle proteins purified from duck serum with Freund's complete adjuvant (FCA) intrahepatically from 14 day posthatch for 9 weeks (immunized group). Serum was drawn at the end of the 1st and 4th week after the 1st injection of DHBV particle protein and ducks were killed at the end of the 9th week to obtain the liver. Another five ducks without treatment were used as controls. All ducks of the immunized group showed moderate to severe hepatitis at the 9th week. All ducks in the immunized group showed one mutation except one duck that showed two mutations only at the 9th week. Mutations were observed in the 5th, 13th, 21st, 22nd, and 28th codon of the pre-core region. All of them were point mutation at the 3rd base in the triplets. The frequency of mutation was different in each duck from 20% to 60% but not 100%. There was no mutations in ducks in control group. These results suggest that hepatitis causes mutation in the pre-core lesion genome of duck hepatitis B virus.

[Clinical basis of acupuncture analgesia (author's transl)]. / Bases cliniques de l'analgésie acupuncturale.

Based on 249 observations acupuncture analgesia has been studied in its clinical picture and its abilities in surgery. Clinically, whatever may be the acupuncture sites, the first appearance of analgesia is noticed on the hands, the feet, the vertex, the auricles of the ears. Then, from these areas the propagation of analgesia extends towards the trunk where analgesia zones are to meet. A generalized analgesia may be obtained on the whole body with non specific, even arbitary acupuncture sites. It is incomplete, not so efficient as analgesia with novocaine. It involves only superficial layers of the skin, the buccal muquous membrane and that of the pharynx, the cornea, the teeth... Deep layers of tissues, muscles, nerves, deep viscera... are not affected by analgesia. Sixty four operations of all kinds have been performed with the view to test acupuncture analgesia. Progressive and late appearance of analgesia seems to favour the hypothesis of a humoral way in the mechanism of acupuncture analgesia.