Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.     

Should rituximab be the rescue therapy for refractory mixed cryoglobulinemia associated with hepatitis C?

BACKGROUND: Mixed cryoglobulinemia (CG) is a systemic immune complex-mediated disease that involves small-to-medium vessel vasculitis, provoked by the CG containing immune complexes that precipitate in cold. It is associated with hepatitis C virus (HCV) infection in 80% of patients. Mixed CG-mediated vasculitis can affect vital organs such as kidney, liver and heart. Laboratory parameters show presence of cryoglobulin, and in most cases of mixed CG, rheumatoid factor IgM kappa. The current treatment strategy of HCV-associated CG includes targeting the viral trigger HCV with a combination of antiviral medication, interferon-alpha (IFN-alpha) and ribavirin, or the downstream pathogenic events by means of plasmapheresis, steroids or immunosuppression. With multiorgan involvement, the antiviral therapy may be limited due to severity of renal disease, treatment failure, side effects or contraindications. On the other hand, immunosuppressive therapy may be poorly tolerated or ineffective. Therefore, new treatment options such as rituximab (RIT), a chimeric monoclonal anti-CD20 antibody, have been proposed as a rescue therapy. METHODS: We reviewed the literature to evaluate the current evidence in treating HCV-related refractory mixed CG. RESULTS: The use of RIT in treatment of HCV-related CG was first described by Zaja et al. Since then there have been numerous published case series and case reports. So far there has been no randomized controlled trial. In the literature, there have been 60 patients with CG treated with RIT. The male to female ratio was 14:46. Fifty-three patients were HCV-positive. Forty-six patients had mixed type II CG, 7 had type III CG and for 7 the type was not specified. Twenty-five patients had renal involvement ranging from proteinuria, to nephrotic syndrome, to nephritic syndrome to chronic kidney disease. Eight patients had had a renal transplant and were on immunosuppression. Most patients responded to RIT, with only 17 of 60 patients relapsing, and 8 of 17 of those were rechallenged with RIT with a good response. Total follow-up period varied between 3 and 31 months. CONCLUSION: RIT is a suitable rescue therapy in recalcitrant CG associated with HCV. There is evidence supporting the use of RIT as first-line therapy, as opposed to the proposals of others who would strongly recommend antiviral therapy. However, a prospective randomized controlled trial is required to evaluate the efficacy and safety of RIT compared with current standard therapy, which includes antiviral therapy, immunosuppression and plasmapheresis.     

Outcomes after identical and compatible orthotopic liver transplantation for fulminant hepatic failure: a single center experience in UK

To analyze the outcomes between identical and compatible liver transplantation (OLT) for fulminant hepatic failure (FHF) from September 1984 to November 2005. The patients were divided in three groups; group 1 (identical), group 2 (compatible) and group 3 (incompatible), according to the donor-recipient blood type matching. We analyzed several outcomes regarding mortality, patient and graft survival, incidence of acute graft rejection during the first postoperative month (30 days), incidence of biliary complications and indications of re-transplantation. We also analyzed the relationship of Coomb's positive test with postoperative hemolysis to all the above mentioned factors. During the study period, 168 males and 112 females underwent their first OLT for FHF, with 37.1% overall mortality and 42.1% overall graft failure rate. The results between group 1 (203 patients) and group 2 (73 patients) were comparable. A statistically significant difference was recorded in 1 year and overall graft survival between group 1 and group 2 (P = 0.049 and log-rank = 0.035 respectively). Coomb's positive test did not influence the outcomes. OLT in FHF can be safely carried out whether the donor organs are identical or compatible. Hemolysis (Coomb's positive test) after identical or compatible OLT does not influence the outcomes.     

Outcomes of Laparoscopic Sleeve Gastrectomy in Patients Older than 60 Years

Background

Morbidity and mortality following laparoscopic sleeve gastrectomy (LSG) occur at acceptable rates, but its safety and efficacy in the elderly are unknown.

Methods

A retrospective review was performed of all patients aged >60 years who underwent LSG from 2008 to 2012. These patients were 1:2 matched, by gender and body mass index (BMI) to young patients, 18?<?age?<?50. Data analyzed included demographics, preoperative and postoperative BMI, postoperative complications, and improvement or resolution of obesity-related comorbidities.

Results

Fifty-two morbid obese patients older than 60 years underwent LSG (mean age, 62.9?±?0.3 years). These were matched to 104 young patients, age 18–50 years (mean age, 35.7?±?0.8 years). Groups did not differ in male gender (44 vs. 43 %, p?=?0.9), preoperative BMI (42.6?±?0.7 vs. 42.6?±?0.6, p?=?0.97), and length of follow-up (17?±?2 vs. 22?±?1.4 months, p?=?0.06). Obesity-related comorbidities were significantly higher in the older group (96 vs. 65 %, p?<?0.001). Excess weight loss (EWL) was higher in the younger group (75?±?2.4 vs. 62?±?3 %, p?=?0.001). Older patients had a significantly higher rate of a concurrent hiatal hernia repair (23 vs. 1.9 %, p?<?0.001). Overall postoperative minor complication rate was higher in the older group (25 vs. 4.8 %, p?<?0.001). This included atrial fibrillation (9.5 %), urinary tract infection (7 %), trocar site hernia (4 %), dysphagia, surgical site infection, bleeding, bowel obstruction, colitis, and nutritional deficiency (2 %, each). No perioperative mortality occurred. Comorbidity resolution or improvement was comparable between groups (88 vs. 80 %, p?=?0.13).

Conclusions

LSG is safe and very efficient in patients aged >60, despite higher rates of perioperative comorbidities.     

Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice

The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of these wounds are sufficient to activate the inflammasome, as wound-conditioned medium activates caspase-1 and induces release of interleukin (IL)-1β and IL-18 in cultured Mp via a reactive oxygen species–mediated pathway. Importantly, inhibiting inflammasome activity in wounds of db/db mice using topical application of pharmacological inhibitors improved healing of these wounds, induced a switch from proinflammatory to healing-associated Mp phenotypes, and increased levels of prohealing growth factors. Furthermore, data generated from bone marrow–transfer experiments from NLRP-3 or caspase-1 knockout to db/db mice indicated that blocking inflammasome activity in bone marrow cells is sufficient to improve healing. Our findings indicate that sustained inflammasome activity in wound Mp contributes to impaired early healing responses of diabetic wounds and that the inflammasome may represent a new therapeutic target for improving healing in diabetic individuals.     

Gynaecomastia correction: A review of our experience

Introduction:

Gynaecomastia is a common problem in the male population with a reported prevalence of up to 36%. Various treatment techniques have been described but none have gained universal acceptance. We reviewed all gynaecomastia patients operated on by one consultant over a 7-year period to assess the morbidity and complication rates associated with the procedure.

Materials and Methods:

Clinical notes and outpatient records of all patients who underwent gynaecomastia correction at University Hospital North Staffordshire between 01/10/2001 to 01/10/2009 were retrospectively reviewed. A modified version of the Breast Evaluation Questionnaire was used to assess patients satisfaction with the procedure.

Results:

Twenty-nine patients and a total of 53 breasts were operated on during the study period. Patients underwent either liposuction alone (6 breasts - 11.3%), excision alone (37 breasts - 69.8%) or both excision and liposuction (10 breasts - 18.9%). Twelve operated breasts (22.6%) experienced some form of complication. Minor complications included seroma (2 patients), superficial wound dehiscence (2 patients) and minor bleeding not requiring theatre (3 patients). Two patients developed haematomas requiring evacuation in theatre. No cases of wound infection, major wound dehiscence or revision surgery were encountered. Twenty-six patients (89.7%) returned the patient satisfaction questionnaire. Patients scored an average 4.12 with regards comfort of their chest in different settings, 3.98 with regards chest appearance in different settings, and 4.22 with regards satisfaction levels for themselves and their partner/family. Overall complication rate was 22.6%. Grade III patients experienced the highest complication rate (35.7%), followed by grade II (22.7%) and grade I (17.6%). Overall complication rates among the excision only group was the highest (29.8%) followed by the liposuction only group (16.7%) and the liposuction and excision group (10.0%). There were high satisfaction rates amongst both patients and surgeon. Eleven patients (37.9%) had their outcome classified as ‘excellent’ by the operating surgeon, 16 patients (55.2%) as ‘good’, 1 (3.4%) as ‘satisfactory’ and 1(3.4%) as ‘poor’.

Conclusion:

Gynaecomastia is a complex condition which poses a significant challenge to the plastic surgeon. Despite the possible complications our case series demonstrates that outcomes of operative correction can be favourable and yield high levels of satisfaction from both patient and surgeon.KEY WORDS: Plastic Surgery, University Hospital North Staffordshire, Correction, gynaecomastia, surgery     

Mangiferin Stimulates Carbohydrate Oxidation and Protects Against Metabolic Disorders Induced by High-Fat Diets

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.     

Enhanced Recovery Pathway for Urgent Colectomy

Background

Enhanced recovery protocols have been proven to decrease complications and hospital stay following elective colorectal surgery. However, these principles have not yet been reported for urgent surgery procedures. We aimed to assess our initial experience with urgent colectomies performed within an established enhanced recovery pathway.

Methods

In a prospective cohort study, all patients undergoing colonic resection between April 2012 and March 2013 were treated according to a standardized enhanced recovery protocol. Urgent surgeries were compared with the elective procedures with regards to baseline characteristics, compliance with enhanced recovery items, and clinical outcome.

Results

Patients (N = 28) requiring urgent colonic resection were included and compared with patients undergoing elective colectomy (N = 63). Overall compliance with the protocol was 57 % for the urgent compared with 77 % for the elective procedures (p = 0.006). The pre-operative compliance was 64 versus 96 % (p < 0.001), the intra-operative compliance was 77 versus 86 % (p = 0.145), and the post-operative compliance was 49 versus 67 % (p = 0.015), for the urgent and elective resections, respectively. Overall, 18 urgent patients (64 %) and 32 elective patients (51 %) developed postoperative complications (p = 0.261). Median postoperative length of stay was 8 days in the urgent setting compared with 5 days in the elective setting (p = 0.006).

Conclusions

Many of the intra-operative and post-operative enhanced recovery items can also be applied to urgent colectomy, entailing outcomes that approach the results achieved in the elective setting.     

Genomic Profiling of Intrahepatic Cholangiocarcinoma: Refining Prognosis and Identifying Therapeutic Targets

Background

The molecular alterations that drive tumorigenesis in intrahepatic cholangiocarcinoma (ICC) remain poorly defined. We sought to determine the incidence and prognostic significance of mutations associated with ICC among patients undergoing surgical resection.

Methods

Multiplexed mutational profiling was performed using nucleic acids that were extracted from 200 resected ICC tumor specimens from 7 centers. The frequency of mutations was ascertained and the effect on outcome was determined.

Results

The majority of patients (61.5 %) had no genetic mutation identified. Among the 77 patients (38.5 %) with a genetic mutation, only a small number of gene mutations were identified with a frequency of >5 %: IDH1 (15.5 %) and KRAS (8.6 %). Other genetic mutations were identified in very low frequency: BRAF (4.9 %), IDH2 (4.5 %), PIK3CA (4.3 %), NRAS (3.1 %), TP53 (2.5 %), MAP2K1 (1.9 %), CTNNB1 (0.6 %), and PTEN (0.6 %). Among patients with an IDH1-mutant tumor, approximately 7 % were associated with a concurrent PIK3CA gene mutation or a mutation in MAP2K1 (4 %). No concurrent mutations in IDH1 and KRAS were noted. Compared with ICC tumors that had no identified mutation, IDH1-mutant tumors were more often bilateral (odds ratio 2.75), while KRAS-mutant tumors were more likely to be associated with R1 margin (odds ratio 6.51) (both P < 0.05). Although clinicopathological features such as tumor number and nodal status were associated with survival, no specific mutation was associated with prognosis.

Conclusions

Most somatic mutations in resected ICC tissue are found at low frequency, supporting a need for broad-based mutational profiling in these patients. IDH1 and KRAS were the most common mutations noted. Although certain mutations were associated with ICC clinicopathological features, mutational status did not seemingly affect long-term prognosis.