Outcomes of extended radical resections for locally advanced and recurrent pelvic malignancy involving the aortoiliac axis.

AIM: Currently, there is no clear consensus on the role of extended pelvic resections for locally advanced or recurrent disease involving major vascular structures. The aims of this study were to report the outcomes of consecutive patients undergoing extended resections for pelvic malignancy involving the aortoiliac axis. METHODS: Prospective data were collected on patients having extended radical resections for locally advanced or recurrent pelvic malignancies, with aortoiliac axis involvement, requiring en bloc vascular resection and reconstruction, at a single institution between 2014 and 2018. RESULTS: Eleven patients were included (median age 60 years; range 31-69 years; seven women). The majority required resection of both arterial and venous systems (n = 8), and the technique for vascular reconstruction was either interposition grafts or femoral-femoral crossover grafts. The median operative time was 510 min (range 330-960 min). Clear resection margins (R0) were achieved in nine patients. The median length of stay was 25 days (range 7-83 days). Seven patients did not suffer an early complication. There was one serious complication (Clavien-Dindo ≥ 3), an arterial graft occlusion secondary to thrombus in the immediate postoperative period, requiring a return to theatre and thrombectomy. The median length of follow-up in this study was 22 months (range 4-58 months). CONCLUSION: This series demonstrates that en bloc major vascular resection and reconstruction can be performed safely and can achieve clear resection margins in selected patients with locally advanced or recurrent pelvic malignancy at specialist surgery centres.

Successful patient-oriented surgical outcomes in robotic vs laparoscopic right hemicolectomy for cancer - a systematic review.

AIM: Minimally invasive surgical approaches for cancer of the right colon have been well described with significant patient and equivalent oncological benefits. Robotic surgery has advanced in its ability to provide multi-quadrant abdominal access, leading the surgical community to widen its application outside of the pelvis to other abdominal compartments. Globally it is being realized that a patient's surgical episode of care is becoming the epicentre of cancer treatment. In order to establish the role of robotic surgery in a patient's episode of care, 'successful patient-oriented surgical' parameters in right hemicolectomy for malignancy were measured. The objective was to examine the rates of successful patient-oriented surgical outcomes in robotic right hemicolectomy (RRH) compared to laparoscopic right hemicolectomy (LRH) for cancer. METHODS: A systematic search of MEDLINE (Ovid: 1946-present), PubMed (NCBI), Embase (Ovid: 1966-present) and Cochrane Library was conducted using PRISMA for parameters of successful patient-oriented surgical outcomes in RRH and LRH for malignancy alone. The parameters measured included postoperative ileus, anastomotic complication, surgical wound infection, length of stay (LOS), incisional hernia rate, conversion to open, margin status, lymph node harvest and overall morbidity and mortality. RESULTS: There were 15 studies which included 831 RRH patients and 3241 LRH patients, with a median age of 62-74 years. No study analysed the concept of successful patient-oriented surgical outcomes. There was no significant difference in the incidence of postoperative ileus, with less time to first flatus in RRH (2.0-2.7 days, compared with 2.5-4.0 days, P < 0.05). Anastomotic leak rate in one study reported a significant increase in LRH compared to RRH (P < 0.05, 0% vs 8.3%). Significantly decreased LOS following RRH was outlined in six studies. One study reported a significantly higher rate of incisional hernias following LRH with extracorporeal anastomoses compared to RRH with intracorporeal anastomoses. Overall rates of conversion to open surgery were less with RRH (0%-3.9% vs 0%-18%, P < 0.001, 0.05). One study outlined significantly higher rates of incomplete resection with an open right hemicolectomy compared with minimally invasive laparoscopic and robotic resections, with positive margin rates of 2.3%, 0.9% and 0% respectively (P < 0.001). Two studies reported significantly higher lymph node harvest in RRH (P < 0.05). Overall morbidity and 30-day mortality were comparable in both approaches. CONCLUSION: Thirty-day morbidity and mortality were comparable between the two approaches, with patients undergoing RRH having lower anastomotic complications, increased lymph node harvest, and reduced LOS, conversion to open and incisional hernia rates in a number of studies. There are limited data on surgical approach and impact on quality of life and what patients deem successful surgical outcomes. There is a further need for a randomized controlled trial examining successful patient-oriented outcomes in right hemicolectomy for malignancy.

Video-assisted anal fistula treatment: a high volume unit initial experience.

Introduction Perianal fistulas are a common problem. Video-assisted anal fistula treatment is a new technique for the management of this difficult condition. We describe our initial experience with the technique to facilitate the treatment of established perianal fistulas. Methods We reviewed a prospectively maintained database relating to consecutive patients undergoing video-assisted anal fistula treatment in a single unit. Results Seventy-eight consecutive patients had their perianal fistulas treated with video-assistance from November 2014 to June 2016. Complete follow-up data were available in 74 patients, with median follow-up of 14 months (interquartile range 7-19 months). There were no complications and all patients were treated as day cases. Most patients had recurrent disease, with 57 (77%) having had previous fistula surgery. At follow-up, 60 (81%) patients reported themselves 'cured' (asymptomatic) including 5 patients with Crohn's disease and one who had undergone 10 previous surgical procedures. Logistical stepwise regression did not demonstrate any statistically significant factors that may have been considered to affect outcome (age, gender, diabetes, previous I&D, Crohn's disease, smoking, type of fistula). Conclusions Our data have shown that video-assisted anal fistula treatment is safe and effective in the management of perianal fistulas in our patients and this suggests it may be applied to all patients regardless of comorbidity, underlying pathology or type of fistula.

Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC.

BACKGROUND: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. PATIENTS AND METHODS: Patients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored. RESULTS: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months (95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences. CONCLUSIONS: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals. CLINICAL TRIALS NUMBER: ClinicalTrials.gov identifier, NCT00903175.

Peritoneal implantation of ureter in cadaveric renal transplant.

We report here a case of complication of peritoneal implantation of ureter in cadaveric renal transplant. The patient presented with anuria and delayed graft function. The diagnosis was suspected upon physical examination and radiological investigation. The complication was managed with reimplantation of the ureter into the bladder and the patient recovered with good graft function. We discuss this case, review the literature on this rare complication, and share our suggestions on how it can be prevented.

Should all nasopharyngeal carcinoma with masticator space involvement be staged as T4?

INTRODUCTION: The prognostic significance of the involvement of anatomical masticator space (MS) in nasopharyngeal carcinoma (NPC) was retrospectively reviewed. MATERIAL AND METHODS: 1104 Patients with non-metastatic NPC treated with radical radiotherapy between 1998 and 2010 were re-staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system; tumors with medial pterygoid muscle (MP) and/or lateral pterygoid muscle (LP) involvement but did not fulfill the criteria for T3 or T4 were staged as TX. The tumor volume data, dosimetric data and survival endpoints of different T stage diseases were analyzed and compared to study the significance of MS involvement. RESULTS: The overall MS involvement rate was 61.0%. The median volumes of the primary gross tumor volume were 9.6ml, 15.2ml, 19.9ml, 32.6ml and 77.3ml for T1, T2, TX, T3 and T4, respectively (p<0.001). T1, T2 and TX tumors received higher minimum dose to the gross tumor volume and planning target volume than T3 and T4. Multivariate analysis showed that age, gender, T-/N-classification and the use of chemotherapy were significant prognostic factors for various survival end-points. Patients with TX disease had similar survival rates as with T1-T2; and had a significantly better 5-year overall survival rate (86.6% vs. 76.6%; p=0.013) and a trend of higher 5-year distant failure-free survival rate (91.5% vs. 81.3%; p=0.09) than patients with T3 disease. CONCLUSION: NPC with the involvement of MP and/or LP alone should be classified as T2 disease.

Docetaxel chemotherapy for Chinese patients with castrate-resistant prostate cancer.

OBJECTIVE. To determine the effectiveness and toxicity of docetaxel for Chinese patients with castrate-resistant prostate cancer in a local Hong Kong hospital. DESIGN. Case series. SETTING. A tertiary cancer centre in Hong Kong. PATIENTS. In all, 39 castrate-resistant prostate cancer patients were treated with 3-weekly docetaxel at 75 mg/m(2) and prednisolone 10 mg daily between January 2006 and December 2011 in Queen Elizabeth Hospital. MAIN OUTCOME MEASURES. Prostate-specific antigen control rate, pain control rate, progression-free survival, overall survival, and complication rates. RESULTS. The prostate-specific antigen response rate was 36%, and 27 (69%) of the patients had improved pain control after chemotherapy. The median progression-free survival, cancer-specific survival, and overall survival was 7.8 (95% confidence interval, 4.9-10.8) months, 13.0 (95% confidence interval, 9.6-16.3) months, and 12.2 (95% confidence interval, 9.3-15.1) months, respectively. The grade 3 anaemia and thrombocytopenia rates were 5%, and the neutropenic fever rate was 8%. CONCLUSIONS. Chemotherapy with docetaxel at a dose of 75 mg/m(2) given once every 3 weeks together with daily prednisolone is well tolerated in Chinese and can offer good symptom palliation in suitable patients with castrate-resistant prostate cancer.

Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties.

Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of ß-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and ß-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB α-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and ß-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the ß-catenin function.

Phos-tag-based analysis of myosin regulatory light chain phosphorylation in human uterine myocytes.

BACKGROUND: The 'phosphate-binding tag' (phos-tag) reagent enables separation of phospho-proteins during SDS-PAGE by impeding migration proportional to their phosphorylation stoichiometry. Western blotting can then be used to detect and quantify the bands corresponding to the phospho-states of a target protein. We present a method for quantification of data regarding phospho-states derived from phos-tag SDS-PAGE. The method incorporates corrections for lane-to-lane loading variability and for the effects of drug vehicles thus enabling the comparison of multiple treatments by using the untreated cellular set-point as a reference. This method is exemplified by quantifying the phosphorylation of myosin regulatory light chain (RLC) in cultured human uterine myocytes. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated and validated the concept that, when using an antibody (Ab) against the total-protein, the sum of all phosphorylation states in a single lane represents a 'closed system' since all possible phospho-states and phosphoisotypes are detected. Using this approach, we demonstrate that oxytocin (OT) and calpeptin (Calp) induce RLC kinase (MLCK)- and rho-kinase (ROK)-dependent enhancements in phosphorylation of RLC at T18 and S19. Treatment of myocytes with a phorbol ester (PMA) induced phosphorylation of S1-RLC, which caused a mobility shift in the phos-tag matrices distinct from phosphorylation at S19. CONCLUSION/SIGNIFICANCE: We have presented a method for analysis of phospho-state data that facilitates quantitative comparison to a reference control without the use of a traditional 'loading' or 'reference' standard. This analysis is useful for assessing effects of putative agonists and antagonists where all phospho-states are represented in control and experimental samples. We also demonstrated that phosphorylation of RLC at S1 is inducible in intact uterine myocytes, though the signal in the resting samples was not sufficiently abundant to allow quantification by the approach used here.

A population-based analysis of incidence, mortality, and stage-specific survival of cervical cancer patients in Hong Kong: 1997-2006.

OBJECTIVES: To determine the trends in incidence and mortality of cervical cancer patients diagnosed during 1997 to 2006, and to describe stage-specific survival using population-based cancer registry data. DESIGN: Retrospective, population-based study. SETTING: Hong Kong. PATIENTS: All patients diagnosed with cervical cancer between 1997 and 2006. Patients eligible for survival analysis were followed up till 31 December 2007. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates and average annual percent changes in these parameters were calculated using the Poisson regression model. Survival was expressed as relative survival rate using a period approach. Hazard ratios of mortality including 95% confidence intervals for certain variables were estimated using the Cox proportional hazards model. RESULTS: During the 10-year period of the study, overall annual incidence and mortality rates decreased by 4.2% and 6.0%, respectively. Significant rates of reduction were observed in all age-groups except those younger than 45 years. The reduction in incidence of squamous cell carcinoma (3.6% annually) was less than that of adenocarcinoma (5.2%) and other histological types (6.8%). In all, 3807 (86.4%) of the patients were included in survival analysis. The overall 5-year relative survival rate was 71.3% (95% confidence interval, 69.5-73.1%), while the values for stages I, II, III, and IV were 90.9%, 71.0%, 41.7%, and 7.8%, respectively. Age, stage, and histology were independent prognostic factors. Survival of stage IA patients was as good as that of the general population. CONCLUSIONS: As in other industrialised countries, the incidence and mortality rate of cervical cancer were decreasing. Stage-specific population-based cancer survival was available for the first time, and was useful as an indicator of cancer control. Collaboration between public and private sectors to further improve the follow-up data could provide more comprehensive surveillance information.

The first 5 years since trauma center designation in the Hong Kong Special Administrative Region, People's Republic of China.

BACKGROUND: In 1994, the Hong Kong Special Administrative Region (HKSAR) introduced plans to implement a trauma system based on the recommendations outlined by Professor Donald Trunkey in his report to the local Hospital Authority. Five government-subsidized public hospitals were subsequently designated as trauma centers in 2003. This article reviews the initial experience in these five centers. METHODS: Prospective trauma registries from January 2004 to December 2008 were reviewed. Primary clinical outcome measures were hospital mortality. The Trauma and Injury Severity Score methodology was used for benchmarking with the Major Trauma Outcome Study (MTOS) database. RESULTS: The majority (83.3%) of the 10,462 patients suffered from blunt trauma. Severe injury, defined as Injury Severity Score>15, occurred in 29.7% of patients. The leading causes of trauma were motor vehicle collisions and falls, with crude hospital mortality rates of 6.9% and 10.7%, respectively. The M-statistic was 0.95, indicating comparable case-mix with the MTOS. The worst outcome occurred in the first year. Significant improvement was seen in patients with penetrating injuries. By 2008, these patients had significantly higher survival rates than expected (Z-statistic=0.85). Although the overall mortality rates for blunt trauma were higher than expected, the difference was no longer statistically significant from the second year onward. CONCLUSIONS: The case-mix of trauma patients in the HKSAR is comparable with that of the MTOS. A young trauma system relatively unburdened by dissimilar reimbursement and patient access issues may achieve significant improvement and satisfactory patient outcomes. Our findings may serve as a useful benchmark for HK and other Southeast Asian cities and trauma systems to establish local coefficients for future evaluations.

Sodium 5,6-benzylidene-L-ascorbate induces oxidative stress, autophagy, and growth arrest in human colon cancer HT-29 cells.

Our previous studies have demonstrated the oxidative stress properties of sodium ascorbate (SAA) and its benzaldehyde derivative (SBA) on cancer cell lines, but the molecular mechanisms mediating their cytotoxicity remain unclear. In this study, we treated human colon cancer HT-29 cells with SAA and SBA, and found a significant exposure time-dependent increase of cytotoxicity in both treatments, with a higher cytotoxicity for 24 h with SAA (IC(50) = 5 mM) than SBA (IC(50) = 10 mM). A short-term treatment of cells with 10 mM SAA for 2 h revealed a destabilization of the lysosomes and subsequent induction of cell death, whereas 10 mM SBA triggered a remarkable production of reactive oxidative species, phosphorylation of survival kinase AKT, expression of cyclin kinase-dependent inhibitor p21, and induction of transient growth arrest. The crucial role of p21 mediating this cytotoxicity was confirmed by isogenic derivatives of the human colon carcinoma HCT116 cell lines (p21(+/+) and p21(-/-)), and immunoprecipitation studies with p21 antibody. The SAA cytotoxicity was blocked by co-incubation with catalase, whereas the SBA cytotoxicity and its subsequent growth arrest were abolished by N-acetyl-L-cysteine (NAC), but was not affected by PI3K phosphorylation inhibitor LY294002, or catalase, suggesting two separated oxidative stress pathways were mediated by these two ascorbates. In addition, neither active caspase 3 nor apoptotic bodies but autophagic vacuoles associated with increased LC3-II were found in SBA-treated HT-29 cells; implicating that SBA induced AKT phosphorylation-autophagy and p21-growth arrest in colon cancer HT-29 cells through an NAC-inhibitable oxidative stress pathway.

Magnetoencephalography and its role in evaluation for epilepsy surgery.

Magnetoencephalography is a newly developed technology used for diagnostic and brain mapping imaging during the presurgical evaluation of patients with medically intractable epilepsy. It provides comprehensive localisation of an epileptogenic focus using simultaneous recordings from the entire brain surface. Magnetoencephalography and electroencephalography are considered complementary and confirmatory to one another. We present a patient with magnetic resonance imaging-negative, non-lesional, neocortical epilepsy. Magnetoencephalography was used for re-evaluation of the epileptogenic zone and this enabled subsequent surgical removal of the epileptic focus. The role of magnetoencephalography in epilepsy surgery is discussed in this report.