Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii.

BACKGROUND AND PURPOSE: L-DOPA is generally considered to alleviate the symptoms of Parkinson's disease by its conversion to dopamine. We have proposed that DOPA is itself a neurotransmitter in the CNS. However, specific receptors for DOPA have not been identified. Recently, the gene product of ocular albinism 1 (OA1) was found to exhibit DOPA-binding activity. Here, we have investigated whether OA1 is a functional receptor of DOPA in the nucleus tractus solitarii (NTS). EXPERIMENTAL APPROACH: We examined immunohistochemical expression of OA1 in the NTS, and the effects of DOPA microinjected into the depressor sites of NTS on blood pressure and heart rate in anaesthetized rats, with or without prior knock-down of OA1 in the NTS, using shRNA against OA1. KEY RESULTS: Using a specific OA1 antibody, OA1-positive cells and nerve fibres were found in the depressor sites of the NTS. OA1 expression in the NTS was markedly suppressed by microinjection into the NTS of adenovirus vectors carrying the relevant shRNA sequences against OA1. In animals treated with OA1 shRNA, depressor and bradycardic responses to DOPA, but not those to glutamate, microinjected into the NTS were blocked. Bilateral injections into the NTS of DOPA cyclohexyl ester, a competitive antagonist against OA1, suppressed phenylephrine-induced bradycardic responses without affecting blood pressure responses. CONCLUSION AND IMPLICATIONS: OA1 acted as a functional receptor for DOPA in the NTS, mediating depressor and bradycardic responses. Our results add to the evidence for a central neurotransmitter role for DOPA, without conversion to dopamine.

Eldecalcitol for the treatment of osteoporosis.

Eldecalcitol [1α,25-dihydroxy-2ß-(3-hydroxypropyloxy)-vitamin D3] is an analogue of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], bearing a hydroxypropyloxy residue at the 2ß position. Eldecalcitol shows stronger effects than alfacalcidol to increase bone mineral density and reduce bone resorption markers in osteoporotic patients, and oral once-daily 0.75 µg eldecalcitol reduced vertebral fracture incidence by 26% compared to 1.0 µg alfacalcidol in a 3-year randomized, double-blind, active-comparator clinical trial. The effect of eldecalcitol on vertebral fracture incidence was sustained throughout the 3-year study period, and the annual incidence of vertebral fracture during the third year was significantly lower with eldecalcitol rather than with alfacalcidol treatment (3.9% vs 7.0%, respectively). Eldecalcitol also reduced the incidence of wrist fractures by 71% compared to alfacalcidol. Eldecalcitol is well tolerated and is not associated with serious side effects including sustained hypercalcemia. Eldecalcitol was approved for the treatment of osteoporosis in Japan in 2011.

R1 resection for aggressive or advanced colorectal liver metastases is justified in combination with effective prehepatectomy chemotherapy.

AIMS: Here we reassess anticipated inability to obtain a microscopically clear surgical margin as an absolute contraindication to surgery for colorectal liver metastases in view of improvements in treatment modalities adjunctive to surgery. METHODS: We retrospectively analysed 310 patients treated at our institution to estimate the survival benefit from R1 hepatectomy performed to remove liver metastases from colorectal cancer. RESULTS: Considering all 310 patients evaluated, the R1 resection group (positive margin; n = 55) showed a lower disease-free rate (P < 0.01) and worse overall survival (P < 0.01) than the R0 resection group (negative margin; n = 255). When patients were divided according to initial resectability, similar differences in disease-free rate and overall survival (P = 0.03) between R1 (n = 19) and R0 (n = 182) were observed in patients whose metastases were resectable. However, superior impact of R0 resection (n = 73) compared to R1 resection (n = 36) on disease-free rate (P = 0.44) and overall survival (P = 0.50) was not confirmed in patients with initially unresectable or marginally resectable metastases, especially those with a favourable response to prehepatectomy chemotherapy. CONCLUSIONS: A predicted positive surgical margin after resection no longer should be an absolute contraindication to surgery for aggressive or advanced liver metastases.

Adjuvant therapies using biliary stenting for malignant biliary obstruction.

The aim of this study was to analyze the patency of expandable metallic stents in malignant biliary obstruction and to evaluate the efficacy of adjuvant therapy accompanied by biliary stenting. We analyzed 29 patients in whom bile duct stenting was performed for malignant biliary obstruction. Their types of disease were: hilar ductal carcinoma (n = 8), gallbladder carcinoma (n = 11), and pancreatic carcinoma (n = 10). Initially, 46 expandable metallic stents were placed in 29 patients. In 23 of the 29 patients, adjuvant therapy was administered. Seventeen patients underwent radiotherapy, and 16 patients received various systemic chemotherapies. In principle, hyperthermia was performed twice a week, simultaneously with radiotherapy. Patient survival and the probability of stent patency were calculated using actuarial life table analysis. There was no significant difference in stent patency among the patients according to type of disease. Hyperthermia did not influence the stent patency rate. The median stent patency time was significantly greater in the chemo-radiation group than in the no-adjuvant therapy group: 182 days versus 68 days, respectively (P = 0.017). Moreover, a significant increase was seen in the median survival time in the chemo-radiation group: 261 days versus 109 days (P = 0.0337). Complications occurred in 9 patients (31.0%). Stent occlusion occurred in 6 patients (20.7%), with all of these patients managed successfully using a transhepatically placed new expandable metallic stent, employing the stent-in-stent method. Stent migration occurred in 2 patients after radiotherapy. Adjuvant therapies such as radiotherapy and systemic chemotherapy, in combination with stent insertion, resulted in an increase in the patency period of expandable metallic stents and in increased patient survival time.

Cobalt-substituted Fe-type nitrile hydratase of Rhodococcus sp. N-771.

When the genes encoding alpha and beta subunits of Fe-type nitrile hydratase (NHase) from Rhodococcus sp. N-771 were expressed in Escherichia coli in Co-supplemented medium without co-expression of the NHase activator, the NHase specifically incorporated not Fe but Co ion into the catalytic center. The produced Co-substituted enzyme exhibited rather weak NHase activity, initially. However, the activity gradually increased by the incubation with an oxidizing agent, potassium hexacyanoferrate. The oxidizing agent is likely to activate the Co-substituent by oxidizing the Co atom to a low-spin Co(3+) state and/or modification of alphaCys-112 to a cysteine-sulfinic acid. It is suggested that the NHase activator not only supports the insertion of an Fe ion into the NHase protein but also activates the enzyme via the oxidation of its iron center.

Use of transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection.

BACKGROUND/AIMS: Hepatectomy has been accepted as a reliable cure for primary hepatocellular carcinoma (HCC). However, the residual liver recurrence rate after hepatectomy remains high. To improve the prognosis after hepatectomy for HCC, repeated post-operative transcatheter arterial infusions of anticancer drugs and lipiodol (TAI) was given. This study evaluates the efficacy of this treatment for preventing residual liver recurrence after hepatectomy. METHODOLOGY: TAI after hepatectomy was performed in 24 (TAI group) of 65 cases showing tumor invasion such as infiltration to the capsule, intraportal spread, and intrahepatic metastasis. In TAI, a mixture of Mitomycin C (MMC) and Adriamycin (ADM) is administered with lipiodol via the hepatic artery. The recurrence and survival rates of the TAI (n = 24) and non-TAI (n = 41) groups were compared to evaluate the efficacy of TAI after hepatectomy. RESULTS: The TAI group had a lower cumulative residual liver recurrence rate than the non-TAI group (p < 0.01). Division of residual liver recurrence cases into two groups according to the duration of recurrence showed that the rate of recurrence within 1 year after hepatectomy was lower in the TAI group (10.0%) (1/10) than in the non-TAI group (48.4%) (15/31) (p = 0.07). Also, the cumulative survival rate in the TAI group was significantly higher (p < 0.05). The morbidity rate was 16.6%. Bilomas occurred without infection in 2 cases, and liver abscess in one. CONCLUSIONS: TAI may be an effective surgical adjuvant against residual liver recurrence, and we suggest that its effectiveness results from suppression of intrahepatic micrometastases rather than multicentric carcinogenesis.