Lateral lymph node dissection in rectal cancer: State of the art review.

Half of the local regional recurrences from rectal cancer are nowadays located in the lateral compartments, most likely due to lateral lymph node (LLN) metastases. There is evidence that a lateral lymph node dissection (LLND) can lower the lateral local recurrence rate. An LLND without neoadjuvant (chemo)radiotherapy in patients with or without suspected LLN metastases has been the standard of care in the East, while Western surgeons believed LLN metastases to be cured by neoadjuvant treatment and total mesorectal excision (TME) only. An LLND in patients without enlarged LLNs might result in overtreatment with low rates of pathological LLNs, but in patients with enlarged LLNs who are treated with (C)RT and TME only, the risk of a lateral local recurrence significantly increases to 20%. Certain Eastern and Western centers are increasingly performing a selective LLND after neoadjuvant treatment in the presence of suspicious LLNs due to new scientific insights, but (inter)national consensus on the indication and surgical approach of LLND is lacking. An LLND is an anatomically challenging procedure with intraoperative risks such as bleeding and postoperative morbidity. It is therefore essential to carefully select the patients who will benefit from this procedure and where possible to perform the LLND in a minimally invasive manner to limit these risks. This review gives an overview of the current evidence of the assessment of LLNs, the indications for LLND, the surgical technique, pitfalls in performing this procedure and the future studies are discussed, aiming to contribute to more (inter)national consensus.

Breast cancer surgery in patients with schizophrenia: short-term outcomes from a nationwide cohort.

BACKGROUND: Although patients with schizophrenia have a higher risk of developing breast cancer than the general population, studies that have investigated postoperative complications after breast cancer surgery in patients with schizophrenia are scarce. This study examined associations between schizophrenia and short-term outcomes following breast cancer surgery. METHODS: Patients who underwent surgery for stage 0-III breast cancer between July 2010 and March 2017 were identified from a Japanese nationwide inpatient database. Multivariable analyses were conducted to compare postoperative complications and hospitalization costs between patients with schizophrenia and those without any psychiatric disorder. Three sensitivity analyses were performed: a 1 : 4 matched-pair cohort analysis with matching for age, institution, and fiscal year at admission; analyses excluding patients with schizophrenia who were not taking antipsychotic medication; and analyses excluding patients with schizophrenia who were admitted to hospital involuntarily. RESULTS: The study included 3660 patients with schizophrenia and 350 860 without any psychiatric disorder. Patients with schizophrenia had a higher in-hospital morbidity (odds ratio (OR) 1.37, 95 per cent c.i. 1.21 to 1.55), with more postoperative bleeding (OR 1.34, 1.05 to 1.71) surgical-site infections (OR 1.22, 1.04 to 1.43), and sepsis (OR 1.20, 1.03 to 1.41). The total cost of hospitalization (coefficient €743, 95 per cent c.i. 680 to 806) was higher than that for patients without any psychiatric disorder. All sensitivity analyses showed similar results to the main analyses. CONCLUSION: Although causal inferences remain premature, multivariable regression analyses showed that schizophrenia was associated with greater in-hospital morbidity and higher total cost of hospitalization after breast cancer surgery than in the general population.

Rectal cancer lateral lymph nodes: multicentre study of the impact of obturator and internal iliac nodes on oncological outcomes.

BACKGROUND: In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. METHODS: Patients with low cT3-4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. RESULTS: More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P < 0.001). Obturator LLNs with a SA larger than 6 mm after (C)RT were associated with a higher 5-year distant metastasis rate and lowered CSS in patients who did not undergo LLND. The survival difference was not present after LLND. Multivariable analyses found that only cT category (HR 2.22, 1.07 to 4.64; P = 0.033) and margin involvement (HR 2.95, 1.18 to 7.37; P = 0.021) independently predicted the development of metastatic disease. CONCLUSION: Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes.Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.

Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer.

Background: There is a lack of large studies focusing on the prognostic significance of lateral lymph node (LLN) metastasis following LLN dissection (LLND) in rectal cancer. The aim of this study was to evaluate the prognostic impact of LLN metastases on survival of patients with advanced low rectal cancer. Methods: Consecutive patients with locally advanced, but not metastatic, extraperitoneal rectal cancer treated with neoadjuvant (chemo)radiotherapy plus total mesorectal excision between 2004 and 2015 were included in the study. LLND was performed when pretreatment imaging documented enlarged LLNs (7 mm or greater in size). Localization of nodal metastases and long-term outcomes were analysed. Kaplan-Meier analysis was used to compare the survival of patients with ypN0 disease with that of patients with mesorectal ypN+/LLN- status and patients with positive LLNs. The Cox proportional hazards model was used to evaluate predictors of disease-free survival (DFS) and local recurrence. Results: A total of 613 patients were included in the study; LLND was performed in 212 patients (34·6 per cent) and 57 (9·3 per cent) had LLN metastasis. Patients with LLN metastasis had improved DFS and local recurrence cumulative incidence rates compared with patients with mesorectal ypN2+/LLN- disease (DFS: P = 0·014; local recurrence: P = 0·006). Although the DFS rate of patients with LLN metastasis was worse than that of patients with ypN0 disease (P < 0·001), the cumulative incidence of local recurrence was similar (P = 0·491). In multivariable analysis, residual LLN metastasis was not an independent predictor of worse DFS or local recurrence. Conclusion: LLN metastasis is not an independent predictor of local recurrence or survival. Survival of patients presenting with LLN metastasis after (chemo)radiotherapy was intermediate between that of patients with ypN0 status and those with mesorectal ypN2 positivity.

Antecedentes: No existen en la literatura grandes estudios dirigidos a investigar la importancia pronóstica de las metástasis en los ganglios linfáticos laterales (lateral lymph nodes, LLN) después de la disección de los mismos (LLN dissection, LLND) en pacientes con cáncer de recto. El objetivo de este estudio fue evaluar el impacto pronóstico de las metástasis en los LLN sobre la supervivencia de los pacientes con cáncer de recto. Métodos: Se analizaron 613 pacientes consecutivos con cáncer de recto localmente avanzado extraperitoneal y no metastásico tratados con (quimio)radioterapia neoadyuvante seguida de resección total del mesorrecto (total mesorectal excision, TME) entre 2004 y 2015. Se realizó una LLND cuando el estudio mediante pruebas de imagen previo el tratamiento mostró LLN aumentados de tamaño ≥ 7 mm. Se analizó la localización de las metástasis ganglionares y los resultados a largo plazo. El análisis de supervivencia se realizó mediante el método de Kaplan­Meier para comparar las supervivencias de los pacientes ypN0 frente a los pacientes ypN con positividad mesorrectal/LLN negativos y frente a los pacientes LLN positivos. Se utilizó el modelo de riesgo proporcional de Cox para evaluar los factores predictivos de supervivencia libre de enfermedad y de recidiva local. Resultados: Se realizó una LLND en 212 (34,6%) pacientes, y 57 (9,3%) pacientes presentaban metástasis en los LLN. Los pacientes con metástasis en los LLN presentaron mejores curvas de incidencia acumulada de recidiva local y de supervivencia libre de enfermedad en comparación con los pacientes con ganglios mesorrectales ypN2 positivos/LLN negativos (respectivamente, P = 0,0135 y P = 0,0060). Aunque la curva de la supervivencia libre de enfermedad de los pacientes con metástasis en los LLN fue peor que la de los pacientes ypN0 (P < 0,0001), la incidencia acumulada de recidiva local fue similar (P = 0,4905). En el análisis multivariable, la metástasis residual en los LLN no fue un factor predictivo independiente de peor supervivencia libre de enfermedad ni de recidiva local. Conclusión: Las metástasis en los LLN no es un factor predictivo independiente de recidiva local o supervivencia. Los pacientes que presentaron metástasis en los LLN después de (quimio)radioterapia mostraron características de supervivencia intermedias entre ypN0 y pacientes con ganglios mesorrectales ypN2 positivos.

BYSTANDER WI-38 CELLS MODULATE DNA DOUBLE-STRAND BREAK REPAIR IN MICROBEAM-TARGETED A549 CELLS THROUGH GAP JUNCTION INTERCELLULAR COMMUNICATION.

Bi-directional signaling involved in radiation-induced bystander effect (RIBE) between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to radiation cancer therapy. Using the SPICE-NIRS microbeam, we delivered 500 protons to A549-GFP lung carcinoma cells, stably expressing H2B-GFP, which were co-cultured with normal WI-38 cells. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured up to 24-h post-irradiation in both targeted and bystander cells. As a result, inhibition of gap junction intercellular communication (GJIC) attenuated DSB repair in targeted A549-GFP cells, and suppressed RIBE in bystander WI-38 cells but not in distant A549-GFP cells. This suggests that GJIC plays a two-way role through propagating DNA damage effect between carcinoma to normal cells and reversing the bystander signaling, also called 'rescue effect' from bystander cells to irradiated cells, to enhance the DSB repair in targeted cells.

Randomized clinical trial of 24 versus 72 h antimicrobial prophylaxis in patients undergoing open total gastrectomy for gastric cancer.

BACKGROUND: Open total gastrectomy carries a high risk of surgical-site infection (SSI). This study evaluated the non-inferiority of antimicrobial prophylaxis for 24 compared with 72 h after open total gastrectomy. METHODS: An open-label, randomized, non-inferiority study was conducted at 57 institutions in Japan. Eligible patients were those who underwent open total gastrectomy for gastric cancer. Patients were assigned randomly to continued use of ß-lactamase inhibitor for either 24 or 72 h after surgery. The primary endpoint was the incidence of SSI, with non-inferiority based on a margin of 9 percentage points and a 90 per cent c.i. The secondary endpoint was the incidence of remote infection. RESULTS: A total of 464 patients (24 h prophylaxis, 228; 72 h prophylaxis, 236) were analysed. SSI occurred in 20 patients (8·8 per cent) in the 24-h prophylaxis group and 26 (11·0 per cent) in the 72-h group (absolute difference -2·2 (90 per cent c.i. -6·8 to 2·4) per cent; P < 0·001 for non-inferiority). However, the incidence of remote infection was significantly higher in the 24-h prophylaxis group. CONCLUSION: Antimicrobial prophylaxis for 24 h after total gastrectomy is not inferior to 72 h prophylaxis for prevention of SSI. Shortened antimicrobial prophylaxis might increase the incidence of remote infection. Registration number: UMIN000001062 ( http://www.umin.ac.jp).

Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection.

BACKGROUND: The use of oral prophylactic antibiotics for the prevention of surgical-site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer is controversial. The aim of this RCT was to evaluate whether intravenous perioperative antibiotics are inferior to combined preoperative oral and perioperative intravenous antibiotics in this setting. METHODS: Patients undergoing elective laparoscopic colorectal resection in a single cancer centre were assigned randomly to combined preoperative oral antibiotics (metronidazole and kanamycin) and perioperative intravenous antibiotics (cefmetazole) (oral/IV group) or to perioperative intravenous antibiotics (cefmetazole) alone (IV-only group). Patients were stratified for the analyses based on type of operation (colonic surgery, anterior resection or abdominoperineal resection), preoperative use of mechanical bowel preparation, preoperative chemoradiotherapy and the presence of diabetes mellitus. The primary endpoint was the overall rate of SSI. Secondary endpoints were the rates of incisional site infection, organ/space infection, anastomotic leakage, intra-abdominal abscess, adverse events and postoperative complications. RESULTS: Of 540 patients offered participation in the trial in 2013-2014, 515 agreed to take part and were randomized. Some 256 patients in the IV-only group and 255 in the oral/IV group completed the treatment per protocol. The overall rate of SSI was 7·8 per cent (20 of 256) in the IV-only group and 7·8 per cent (20 of 255) in the oral/IV group, confirming that perioperative administration of intravenous antibiotics alone was not inferior to the combined regimen (P = 0·017). There were no differences in rates of incisional site infection (5·5 versus 5·9 per cent respectively), organ/space infection (2·3 versus 2·0 per cent) or other secondary endpoints between the two groups. CONCLUSION: Intravenous perioperative antimicrobial prophylaxis alone is not inferior to combined preoperative oral and intravenous perioperative prophylaxis with regard to SSI in patients with colorectal cancer undergoing elective laparoscopic resection. Registration number: UMIN000019339 ( http://www.umin.ac.jp/ctr/).

Laparoscopic salvage lateral pelvic lymph node dissection for locally recurrent rectal cancer.

AIM: The lateral pelvic lymph nodes are one of the major sites and sources of local recurrence (LR) after surgery for rectal cancer. Salvage lateral pelvic lymph node dissection (LPLD) is potentially curative, but the value of laparoscopic surgery in such cases is unknown. Our aim was to report the technical details of laparoscopic salvage LPLD for LR at these nodes after rectal cancer surgery. METHOD: The study was based on nine patients who underwent laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes after surgery for rectal cancer. The safety and feasibility of this procedure were determined. RESULTS: The median operation time was 381 min and the median estimated blood loss was 130 ml. There were no conversions. Adjacent structures removed en bloc were the pelvic plexus in four patients, the internal iliac artery in seven patients and the seminal vesicle in one patient. The median number of metastatic lymph nodes was 1 (range 1-11). CONCLUSION: Our novel technique of laparoscopic salvage LPLD for LR at the lateral pelvic lymph nodes is safe and feasible.

Zinc-substituted hydroxyapatite: a biomaterial with enhanced bioactivity and antibacterial properties.

Hydroxyapatite (HA) is a synthetic biomaterial and has been found to promote new bone formation when implanted in a bone defect site. However, its use is often limited due to its slow osteointegration rate and low antibacterial activity, particularly where HA has to be used for long term biomedical applications. This work will describe the synthesis and detailed characterization of zinc-substituted HA (ZnHA) as an alternative biomaterial to HA. ZnHA containing 1.6 wt% Zn was synthesized via a co-precipitation reaction between calcium hydroxide, orthophosphoric acid and zinc nitrate hexahydrate. Single-phase ZnHA particles with a rod-like morphology measuring ~50 nm in length and ~15 nm in width, were obtained and characterized using transmission electron microscopy and X-ray diffraction. The substitution of Zn into HA resulted in a decrease in both the a- and c-axes of the unit cell parameters, thereby causing the HA crystal structure to alter. In vitro cell culture work showed that ZnHA possessed enhanced bioactivity since an increase in the growth of human adipose-derived mesenchymal stem cells along with the bone cell differentiation markers, were observed. In addition, antibacterial work demonstrated that ZnHA exhibited antimicrobial capability since there was a significant decrease in the number of viable Staphylococcus aureus bacteria after in contact with ZnHA.

[Pericardiocentesis and drainage].

Diagnosis and treatment of pericardial effusion need to be performed frequently by pericardiocentesis or surgical pericardiotomy. Large retention of the effusion is treated conventionally by percutaneous blind puncture, while possible injuries to the myocardium are avoided feasibly by ultrasonically-guided puncture even in case that the effusion remains moderately or unevenly inside the pericardial space. Along with the puncture, drainage tube introduced into the pericardial sac using coaxial method contributes to relieving coexistent pericardial or chronic exudation. The pericardium is also surgically approached traditionally via parasternal, subxiphoid, or lateral-thoracic route. Specimen of the pericardium is optionally sampled to promote analyzing the pathogenesis, and drainage tubes of larger diameter facilitate evacuating the purulent substance in the settings of infectious origins. The lateral thoracotomy is occasionally applied to the effusion around the posterior aspect of the heart, which is preferably replaced by less-invasive video-assisted procedure. Those several measures would facilitate the treatment for pericardial effusion.

Localization of N-myc downstream-regulated gene 1 in gastric cancer tissue.

BACKGROUND AND AIM: N-myc downstream-regulated gene 1 is detected in normal tissue but is down-regulated in cancer tissue. Furthermore, research has suggested that co-expression with p53 is necessary for induction of p53-mediated apoptosis. This study sought to investigate the clinicopathological significance of N-myc downstream-regulated gene 1 and p53 expression in gastric cancer tissue. PATIENTS AND METHODS: Immunohistochemical detection of N-myc downstream-regulated gene 1 and p53 was performed with tissue samples from 96 cases of gastric cancer, and the relationship between expression profiles of proteins and clinicopathological characteristics was statistically analysed. RESULTS: Positive staining of N-myc downstream-regulated gene 1 was observed in the cytoplasm (22 of 96 cases, 22.9%) and/or nucleus (29 of 96 cases, 30.2%) of cancer cells. In 15 cases (15.6%), both cytoplasm-positive cells and nucleus-positive cells were observed in the cancerous region. The nuclear localization of N-myc downstream-regulated gene 1 was frequently observed in the region of cancerous invasion and was significantly related to lymph node metastasis. In addition, accumulation of p53 protein in the nucleus of cancer cells significantly coincided with the nuclear localization of N-myc downstream-regulated gene 1. CONCLUSIONS: Localization of N-myc downstream-regulated gene 1 and its significant correlation with p53 expression may play an important role in cancer progression.

[A new technique of aortic occlusion in patient with severe aortic calcification].

A 63-year-old woman with severe aortic valve insufficiency and bilateral subclavian artery occlusion underwent ascending aorta-to-biaxillary artery bypass and aortic valve replacement, simultaneously. Because of severe aortic calcification, a hand-made aortic occluder was utilized to prevent embolic stroke. We believe that the new technique of aortic occllusion might be very useful for patients with severe aortic calcification.

Unusual pressure-induced rupture of colonic volvulus in a patient with long-term corticosteroid therapy.

Perforation due to colonic volvulus is typically considered to occur following ischemic necrosis of the intestinal wall. In this report, we report a rare case of sigmoid colon volvulus rupture caused by increasing intraluminal pressure without any sign of ischemia. The patient was an 88-year old Japanese male, who had been treated with 5 mg of oral prednisolone daily for 8 years. He consulted for severe abdominal pain that had lasted for three days. X-ray and computed tomography showed free peritoneal air, suggesting peritonitis. He was diagnosed with sigmoid colon volvulus perforation and underwent emergency surgery. Pathological examination showed no ischemic necrosis around the perforations in the resected intestine. As a result, we came to believe that the fragility of the colonic wall, caused by the patient's long-term use of corticosteroid, had lowered the threshold for pressure-induced colonic rupture.

Induction of detoxifying enzyme by sesquiterpenes present in Inula helenium.

Our previous study showed that the methanolic extract of Inula helenium (elecampane) had the potential to induce detoxifying enzymes such as quinine reductase (QR) and glutathione S-transferase. In this study we further fractionated the methanolic extract into hexane-, dichloromethane-, butanol-, and water-soluble fractions according to polarity. The hexane fraction showed the highest QR-inducing activity and also induced glutathione S-transferase in a dose-dependent manner. Its potential to induce the reporter activity suggested an antioxidant response element-mediated mechanism of action in the induction of phase II detoxifying enzymes. Intraperitoneal injection of the hexane fraction of I. helenium into ICR mice caused a significant increase of QR activity in liver, kidney, small intestine, and stomach. Sesquiterpenes, isolated from the hexane fraction, appeared to be major components responsible for QR induction. Among the seven compounds tested in this study, alantolactone, isoalantolactone, and 5alpha-epoxyalantolactone significantly induced QR activity in both Hepa1c1c7 and BPRc1 cells. In conclusion, sesquiterpenes, including alantolactone, isoalantolactone and 5-epoxyalantolactone, present in I. helenium merit further evaluation as chemopreventive agents.

Clinical and experimental features of MuSK antibody positive MG in Japan.

We investigated the presence of antibodies (Abs) against muscle-specific tyrosine kinase (MuSK) in Japanese myasthenia gravis (MG) patients. MuSK Abs were found in 23 (27%) of 85 generalized seronegative MG (SNMG) patients but not in any of the ocular MG patients. MuSK Ab-positive patients were characterized as having female dominance (M:F, 5:18), age range at onset 18 to 72 (median 45) years old, and prominent oculobulbar symptoms (100%) with neck (57%) or respiratory (35%) muscle weakness. Limb muscle weakness was comparatively less severe (52%), thymoma absent. Most patients had good responses to simple plasma exchange and steroid therapy. MuSK IgG from all 18 patients was exclusively the IgG 4 subclass and bound mainly with the MuSK Ig 1-2 domain. Serial studies of 12 individuals showed a close correlation between the variation in MuSK Ab titers and MG clinical severity (P = 0.01 by Kruskal-Wallis). MuSK Ab titers were sharply decreased in patients who had a good response to early steroid therapy or simple plasma exchange, but there was no change, or a rapid increase on exacerbation after thymectomy. Measurement of MuSK Ab titers aids in the diagnosis of MG and the monitoring of clinical courses after treatment.