Prognostic factors of survival in patients treated with nab-paclitaxel plus gemcitabine regimen for advanced or metastatic pancreatic cancer: A single institutional experience.

The objectives of this study were to evaluate the effectiveness of nab-paclitaxel plus gemcitabine (NAB-P/GEM) regimen in an unselected population of patients with advanced inoperable or metastatic pancreatic cancer (PC), and to identify the prognostic factors influencing overall survival (OS). EXPERIMENTAL DESIGN: Patients with age < 85 years, ECOG-performance status (PS) < 3, and adequate renal, hepatic and hematologic function were eligible. NAB-P (125 mg/m2) and GEM (1000 mg/m2) day 1,8,15 every 4 weeks were employed for 3-6 cycles or until highest response. RESULTS: Overall, 147 cycles (median 4, range 1-11 cycles) were administered on thirty-seven consecutive patients (median 66 years old, range 40-82) treated. The median overall progression-free survival and OS were 6.2 and 9.2 months, respectively. The G 3-4 dose-limiting toxicity were neutropenia (20.7%), severe anemia (17.2%), and cardiovascular toxicity (10.3%). PS, number of cycles, baseline CA 19-9 and LDH serum levels, were found to be significantly related to OS. The multivariate analysis showed that both number of cycles (HR = 9.14, 95% CI 1.84-45.50, p = 0.001) and PS (HR = 13.18, 95% CI 2.73-63.71, p = 0.001) were independently associated with OS. CONCLUSION: NAB-P/GEM regimen should be used in all patients with advanced or metastatic PC, with the exception of those with serious contraindications to chemotherapy, such as severe renal or hepatic impairment or major cardiovascular diseases

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. Methods We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5–14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4–8·6]; rate ratio 1·37 [95% CI 1·17–1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92–1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95–1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94–1·15]; p=0·45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered—eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy

Parathyroid cancer: etiology, clinical presentation and treatment.

Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of patients with primary hyperparathyroidism (HPT), but a relatively higher incidence has been reported in Italy and Japan. The etiology of the tumour remains unclear, but molecular analysis studies have hypothesised the involvement of mutations of several genes in the pathogenesis of PC, including the oncogene cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53 tumour suppressor gene. The clinical presentation of patients with PC is mainly related to the increased secretion of PTH rather than to the tumour burden. The pre-operative diagnosis of malignancy is very difficult to obtain, and, thus, intra-operative recognition of PC is mandatory. However, reliable signs of malignancy are rarely detectable. Probably, only vascular invasion, that correlates with tumour recurrence and metastases, should be considered useful in confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used to aid in the definitive diagnosis. The en bloc resection of the tumour, together with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding any capsular rupture of the mass, represents the gold standard of surgical treatment of patients. Although the PC has traditionally been considered as a radioresistant tumour, there are some retrospective data holding a possible benefit from post-operative irradiation. No cytotoxic regimen with proven efficacy is currently available for patients with PC, but since hypercalcemia is ultimately the most frequent cause of death, several studies have suggested the usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate), calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey reports an overall five- and ten-year survival rate of 85% and 49%, respectively. However, it is very difficult to predict the clinical behaviour of patients with PC and probably the ultimate prognosis depends on successful resection of the tumour at the initial surgery

Apoptosis: life through planned cellular death. Regulating mechanism, control systems, and relations with thyroid diseases

Apoptosis is an active biologic process that represents a form of programmed cellular suicide, activated either by genetic factors or by cellular lesions caused by various extracellular traumatic agents. The alterations of its functional mechanisms control cellular homeostasis are involved in the genesis of many illnesses. There are different control systems that can both stimulate and inhibit apoptosis, such as the p53 and Bcl-2 proteins. Different injuries may cause a rapid increase in the levels of p53 and the activation of the complex mechanism which leads either to damage repair or cellular apoptosis. The concept of tumor growth as a dynamic balance between cellular development and death is well applicable to differentiated thyroid carcinomas, which are generally not highly invasive and present excellent prognosis. On the contrary, in aggressive anaplastic thyroid carcinoma there is an increase in p53, whereas in normal thyroid cells there is a high expression of Bcl-2, so as to interfere with apoptosis when physiologic hormone levels are normal. However, only some of the biomolecular mechanisms behind the genesis of thyroid tumors have been explained, and the role of apoptosis in thyroid diseases has not been well defined. T his review provides information about relationship between apoptosis and thyroid diseases

Serum tumor markers in breast cancer

Several serum tumor markers have been investigated in patients with breast cancer for assessing outcome, predicting recurrence and monitoring the therapeutic response. There is general consensus concerning their limited application in diagnosing malignancy. However, serum tumor markers can be considered in the early detection of recurrences. Moreover, a number of new markers are under observation, although their long-term efficacy in predicting relapse of malignancy has not been confirmed. The most effective markers for this indication were shown to be CA 15-3, CA 27.29 and c-erbB-2, although their efficacy in establishing disease progression has not been determined to date. In terms of evaluating prognosis and predicting response to therapies, only the expression of c-erbB-2 has clinical evidence. In conclusion, at present, no tumor marker is cost-effective, and no one can be used with confidence in the decision-making regarding breast cancer patients

Breast cancer recurrence: role of serum tumor markers CEA and CA 15-3

Breast cancer is a heterogeneous, most frequent disease in women. All patients with breast cancer may develop progression or recurrence of the disease, and thus they need an effective lifelong follow-up. Breast cancer recurrence is a significant problem for clinicians. Even patients with early stage of the disease (stage I\u2013II) have a recurrence rate of 30%, and local recurrences after conserving therapy have been reported from 6% to 12% at 5 and 10 years, respectively. In spite of advances in the diagnosis and therapy achieved over the past decade, a share of patients with breast cancer still develop relapse and metastases, from which they will ultimately die. An early detection and treatment of recurrence may improve the quality of life of patients who have undergone curative surgery and adjunctive therapy, although it does not seem to have a significant impact on long-term survival. In patients with breast cancer, the axillary node status still remains the main prognostic factor, especially in those with early-stage disease, but different factors, enclosing tumor markers serum levels, are available and potentially useful

Serum Tumor Markers in Breast Cancer

Tumor markers are molecules occurring in blood or tissue that are associated with cancer, and whose measurement or identification is useful in patient diagnosis or clinical management. This book analyses potential signals of cancerous tumors, otherwise known as markers or indicators. This includes, direct and rapid determination of cancer antigen, potential tumor markers for cholangiocarcinoma, melanoma inhibitory activity, metastatic uveal melanoma, measurement of tumor oxygenation, bladder cancer markers, epithelial cell adhesion and progresion markers in prostate tumors. This book provides leading edge research in this field from around the globe

Surgical Treatment of Hypercalcemia

In patients with hypercalcemia the surgical treatment is likely limited to those with primary hyperparathyroidism (HPT), which represents the most frequent cause of this biochemical alteration. Hypercalcemia may also occur in up to 30% of patients with cancer, but unfortunately they are usually unsuitable for surgery. Surgery of parathyroid glands is particularly challenging, because PT anatomy is one of the variables of our organism. The treatment of choice for patients with symptomatic primary HPT is removal of the affected parathyroid(s), that can be achieved both by surgical and non-surgical techniques. The latter is used only in selected patients, when surgery is contraindicated. In asymptomatic patients, surgical parathyroidectomy is usually suggested to prevent complications, but its role is controversial. Bilateral cervical exploration has been the procedure of choice for decades, and it is still mandatory in case of suspicion of multiglandular disease or malignancy, and multiple endocrine neoplasia or familial syndromes. Recent advances in preoperative localization studies, and intraoperative adjuncts, such as quick parathyroid hormone assay, encouraged as a less invasive surgery. Currently, minimally invasive arathyroidectomy is widely performed, both videoassisted and radioguided. Considering the significant improvements of clinical features of the disease after surgery, and the effectiveness and safety of minimally invasive surgical techniques, parathyroidectomy should be suggested both in symptomatic patients and in those with minimally symptomatic primary HPT. However, each patient should be referred to an experienced parathyroid surgeon or endocrinologist, with the aim of having a better definition of the disease, and the best recommendation for treatment

Leading article. Sentinel lymph node biopsy in breast cancer

Since the first radical mastectomy proposed by William S Halsted in the 1890s, axillary lymph node dissection (ALND) has been considered the standard procedure for surgical treatment of breast cancer. Although the extent of surgery decreased, ALND was extensively performed for a century. ALN status is the most important prognostic factor for patients with breast cancer. However, although ALND is accurate in determining nodal status, this is at the expense of significant morbidity, both physical (pain, lymphedema, loss of strength) and psychological (worsening of body image). The concept of the \u201csentinel lymph node\u201d (SLN) in breast cancer was introduced in the 1990s, following research on penile cancer and melanoma [4]. The objective was to perform less invasive surgery in a targeted population, given the risk of postoperative complications and discomfort experienced after ALND