Relationship between the transcriptional expression of PIM1 and local control in patients with head and neck squamous cell carcinomas treated with radiotherapy.

PURPOSE: Proviral integration site for Moloney murine leukemia virus (PIMs) are proto-oncogenes encoding serine/threonine kinases that phosphorylate a variety of substrates involved in the regulation of cellular processes. Elevated expression of PIM-1 has been associated with poor prognosis in several types of cancer. There are no studies that have analyzed the response to radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC) according to the expression of PIM-1. The aim of our study was to analyze the relationship between the transcriptional expression of PIM-1 and local response to radiotherapy in HNSCC patients. METHODS: We determined the transcriptional expression of PIM-1 in 135 HNSCC patients treated with radiotherapy, including patients treated with chemoradiotherapy (n = 65) and bioradiotherapy (n = 15). RESULTS: During the follow-up, 48 patients (35.6%) had a local recurrence of the tumor. Patients with local recurrence had a higher level of PIM-1 expression than those who achieved local control of the disease (P = 0.017). Five-year local recurrence-free survival for patients with a high expression of PIM-1 (n = 43) was 44.6% (95% CI 29.2-60.0%), and for patients with low expression (n = 92) it was 71.9% (95% CI 62.5-81.3%) (P = 0.007). According to the results of multivariate analysis, patients with a high PIM-1 expression had a 2.2-fold increased risk of local recurrence (95% CI 1.22-4.10, P = 0.009). CONCLUSION: Patients with elevated transcriptional expression levels of PIM-1 had a significantly higher risk of local recurrence after radiotherapy.

Prognostic value of the nodal yield in elective neck dissections in patients with head and neck carcinomas.

PURPOSE: The objective of this study is to assess the prognostic capacity of the nodal yield in elective neck dissections performed in patients with head and neck squamous cell carcinomas (HNSCC) without clinical or radiological evidence of regional involvement (cN0) at the time of diagnosis. METHODS: Retrospective study including 647 patients with HNSCC treated with an elective neck dissection. RESULTS: Patients with < 15 dissected nodes (n = 172, 26.6%) had a 5-year disease-specific survival of 64.9% (95% CI: 57.3-72.5%), while for patients with ≥ 15 dissected nodes (n = 475, 73.4%), it was of 81.9% (95% CI: 78.4-85.4%) (P = 0.0001). The nodal yield category had prognostic capacity on the disease-specific survival in patients with tumors located in the oral cavity (P = 0.001), the oropharynx (P = 0.023) and the hypopharynx (P = 0.034), while for patients with tumors located in the larynx, no significant differences appeared (P = 0.779). Differences in regional recurrence-free survival were also observed based on the nodal yield category in patients with extra-laryngeal tumors (5-year regional recurrence-free survival of 81.0% in patients with < 15 dissected nodes vs 89.0% in patients with ≥ 15 dissected nodes; P = 0.046). CONCLUSION: The nodal yield in elective neck dissections in patients without evidence of lymph node disease (cN0) had prognostic capacity depending on the location of the primary tumor. For tumors located in the larynx, the number of dissected nodes did not significantly influence the prognosis. For tumors located in the oral cavity, oropharynx or hypopharynx, patients with < 15 dissected nodes had a disease-specific mortality 2.9 times higher than patients with ≥ 15 dissected nodes.

Low skeletal muscle mass assessed directly from the 3rd cervical vertebra can predict pharyngocutaneous fistula risk after total laryngectomy in the male population.

PURPOSE: Skeletal muscle mass (SMM) loss and sarcopenia have been identified as risk factors for postoperative complications. The aim of this study was to investigate the relationship between pharyngocutaneous fistula (PCF) formation after total laryngectomy (TL) and SMM assessed from a computed tomography image of the 3rd cervical vertebra (C3). METHODS: Retrospective study of 86 male patients who underwent TL between 2013 and 2019 in a single institution. We excluded women from the analysis due to our limited sample. SMM was determined from cross-sectional muscle area (CSMA) measurement at C3 using the ImageJ software. Results were compared with those for the skeletal muscle mass index (SMMI) calculated from the estimated measure at 3rd lumbar vertebra (L3). RESULTS: PCF formation occurred in 21/86 patients. According to the CSMA at a C3 cut-off of 35.5cm2, of 18 patients (20.9%) with low SMM, 9 developed PCFs (50.0%). Among patients with normal SMM (n = 68, 79.1%), 12 developed PCFs (17.6%). The CSMA at C3 was the only variable significantly associated with PCF risk, which was 4.7 times greater in patients with low SMM (p = 0.007). Sarcopenia was more frequent in underweight patients (p = 0.0001), patients undergoing extended surgeries (p = 0.003), or presenting preoperative anaemia (p = 0.009) or hypoalbuminemia (p = 0.027). CONCLUSION: Measuring the CSMA at C3 obtained results equivalent to those obtained by calculating the SMMI at L3, suggesting that direct SMM assessment from C3 is a useful approach to evaluating PCF formation risk after TL.

Causes of long-term mortality in patients with head and neck squamous cell carcinomas.

PURPOSE: After treatment of a head and neck squamous cell carcinoma (HNSCC), patients with an adequate control of the tumor have a decreased overall survival when compared to age- and gender-matched controls in the general population. The aim of our study was to analyze the causes of long-term mortality in patients with HNSCC. METHODS: We carried out a retrospective study of 5122 patients with an index HNSCC treated at our center between 1985 and 2018. We analyzed the survival considering three causes of death: mortality associated with the HNSCC index tumor, mortality associated with a second or successive neoplasm, and mortality associated with a non-cancer cause. RESULTS: After the diagnosis of an HNSCC the most frequent cause of death is the head and neck tumor itself during the first 3.5 years of follow-up. Thereafter, mortality is more frequently associated with competing causes of death, such as second malignancies and non-cancer causes. Mortality associated with second and successive neoplasms was 2.3% per year, a percentage that was maintained constant throughout the follow-up. Likewise, mortality attributable to non-cancer causes was 1.6% per year, which also remained constant. There were differences in the mortality patterns according to the characteristics of the patients. CONCLUSION: There are differences in the mortality patterns of patients with HNSCC depending on their characteristics. Knowledge of these patterns can help in the design of guidelines to improve the follow-up protocols of this group of patients to optimize the clinical cost-effectiveness.

BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice.

BACKGROUND/OBJECTIVES: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. METHODS: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. RESULTS: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. CONCLUSIONS: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity.

Prognostic capacity of the weighted lymph node ratio in head and neck squamous cell carcinoma patients treated with salvage neck dissection.

PURPOSE: The aim of the study was to assess the prognostic capacity of the recently described weighted lymph node ratio (WLNR) in patients with head and neck squamous cell carcinoma (HNSCC) who undergo salvage neck dissection for regional recurrence. MATERIAL AND METHODS: We retrospectively studied 197 adult patients with head and neck squamous cell carcinoma treated with salvage neck dissection from 1990 to 2017. RESULTS: The mean value for the WLNR for all patients was 26.2%. We established a classification based on the WLNR values taking 10.8% as the cut-off point. Five-year disease-specific survival for patients with WLNR ≤ 10.8% (n = 89, 45.2%) was 39.9% (IC 95% 29.4-50.4%), and for patients with WLNR ≥ 10.8% (n = 108, 54.8%) it was 20.5% (IC 95% 12.3-28.7%) (p = 0.007). The multivariate analysis showed the WLNR had a significant prognostic capacity. CONCLUSIONS: As a variable that integrates data related to the number of metastatic nodes with extracapsular spread to the LNR, the WLNR has a prognostic value in the pathological assessment of HNSCC patients with regional recurrence treated with salvage neck dissection.

Circulating microRNAs modulating glycolysis as non-invasive prognostic biomarkers of HNSCC.

BACKGROUND: The identification of prognostic non-invasive biomarkers is a priority for cancer patients' care. Circulating microRNA (miRNAs) have been described in numerous human malignancies as diagnostic, prognostic, and therapeutic cancer biomarkers. The aim of our study was to analyze the expression profile of a set of miRNAs, involved in the modulation of the glycolytic pathway, as prognostic factors in human head and neck squamous cell carcinomas (HNSCC). METHODS: Serum samples of 54 patients with untreated HNSCC were obtained at the time of diagnosis. The prognostic value of circulating miR-26b, miR-124, miR-155 and miR-375 was evaluated towards disease-free survival. RESULTS: We found that there were optimal miRNAs cut-off values for lower risk of recurrence in HNSCC patients. Kaplan-Meier curves showed that higher levels of miR-26b and lower levels of miR-155 were associated with better disease-free survival rates. In the multivariate analysis, patients with serum miR-26b > 0.062 and miR-155 < 0.159 presented more than 2.9 times lower risk of poor outcome. CONCLUSION: Our results suggest that two miRNAs that modulate the glycolytic pathway, miR-26b and miR-155, are independently associated with the risk of recurrence in patients with HNSCC. The overall results in this study supports the evidence that the glucose homeostasis may be a target to improve the outcomes for patients with HNSCC. LEVEL OF EVIDENCE: Individual retrospective cohort study (2b).

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer.

BACKGROUND: Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. METHODS: Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil-to-lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). RESULTS: All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109 /L as reference, patients with 4.8-9.1 × 109 /L neutrophils had 1.536 times higher risk of death (95% CI, 1.295-1.822), and patients with ≥9.1 × 109 /L had 3.076 times higher risk (95% CI: 2.170-4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. CONCLUSIONS: Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.

Does age influence disease-specific survival in patients with squamous cell carcinomas of the head and neck?

BACKGROUND AND OBJECTIVES: The number of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) at an advanced age has increased. The aim of this study is to evaluate the age at which disease-specific survival (DSS) significantly decreases in HNSCC. METHODS: We performed a retrospective study of 5469 patients with HNSCC treated at our center (1985-2016). External validation with 2082 oral squamous cell carcinomas from a collaborative institution from another continent was performed. RESULTS: We observed an orderly decrease in overall survival as age at diagnosis increased. There were no differences in DSS based on age for patients <80 years old (P = .623), while older patients had a significant decrease in DSS. These results were validated in the independent dataset. In a multivariable analysis performed in the test set, compared to patients <80 years old, patients between 80 to 85 had a 1.50 times higher risk of disease-specific death (95% confidence interval [CI]: 1.19-1.89; P = .001), and patients >85 had a 2.19 times higher risk (95% CI: 1.68-2.87; P < .001). CONCLUSIONS: DSS started to significantly decrease in HNSCC at 80 years old. These findings, validated in an independent cohort, indicate that chronological age on its own should not withhold curative treatment in the majority of patients with HNSCC.

Disease correction by AAV-mediated gene therapy in a new mouse model of mucopolysaccharidosis type IIID.

Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D. This autosomic recessive, heparan sulphate storage disease is caused by deficiency in N-acetylglucosamine 6-sulfatase (GNS). Mice deficient in GNS showed lysosomal storage pathology and loss of lysosomal homeostasis in the CNS and peripheral tissues, chronic widespread neuroinflammation, reduced locomotor and exploratory activity and shortened lifespan, a phenotype that closely resembled human MPSIIID. Moreover, treatment of the GNS-deficient animals with GNS-encoding adeno-associated viral (AAV) vectors of serotype 9 delivered to the cerebrospinal fluid completely corrected pathological storage, improved lysosomal functionality in the CNS and somatic tissues, resolved neuroinflammation, restored normal behaviour and extended lifespan of treated mice. Hence, this work represents the first step towards the development of a treatment for MPSIIID.

Indications and results of extended total laryngectomy with en-bloc resection of overlying cervical skin.

PURPOSE: Extended total laryngectomy with en-bloc resection of overlying cervical skin (ETL) is indicated in cases with infiltration of the pre-laryngeal soft tissues. The present study analyses the surgical indications and the results of ETL in our hospital. METHODS: Retrospective review of 38 patients treated with an ETL during the period 1988-2016. RESULTS: The indications for ETL were the initial treatment of tumors with extralaryngeal extension (n = 16), salvage treatment after failure of partial surgery or radiotherapy (n = 17), and total laryngectomy in patients with infection or fibrosis of the skin over the larynx (n = 5). The surgical defect was reconstructed with local flaps in 3 cases, with pectoralis major flaps in 34 cases, and with an internal mammary artery perforator flap in one case. The rate of pharyngocutaneous fistula in the postoperative period was 16%. 5-year cancer-specific survival for patients treated with an ETL was 67.1%. The patients with positive margins and those operated as a salvage treatment after failure of previous treatments showed worse survival. CONCLUSIONS: ETL offers acceptable oncological results for patients with tumors with extralaryngeal extension. Myocutaneous or myofascial pectoralis major flaps allow for adequate reconstruction of the surgical defect with a low rate of complications.

Pharyngocutaneous fistula after total laryngectomy: multivariate analysis of risk factors and a severity-based classification proposal.

PURPOSE: The aim of the study is to determine the predisposing factors for pharyngocutaneous fistula (PCF) in patients undergoing total laryngectomy (TL) or extended TL and, secondarily, to propose a new severity-based classification system. METHODS: This is a retrospective study of 400 patients who underwent TL or extended TL. Major fistula was defined as a fistula (1) persisting for ≥ 4 weeks, (2) requiring surgical treatment, or (3) associated with perioperative mortality. RESULTS: PCF formation occurred in 93 patients (23.3%) and major fistula in 72 (18.0%). Extended surgery with partial or total pharyngectomy, previous treatment with radiotherapy, and postoperative hemoglobin levels < 99 g/L were associated with a significantly higher risk of developing major fistula. CONCLUSIONS: We propose a new PCF classification system according to clinical severity. Predictors of major fistula were the type of surgery, previous radiotherapy, and low (< 99 g/L) postoperative hemoglobin levels. We consider the use of onlay flaps in irradiated patients who require partial pharyngectomy.

Prognostic value of CD45 transcriptional expression in head and neck cancer.

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) have a recognized antitumor activity in head and neck squamous cell carcinoma (HNSCC). CD45 is one of the most highly expressed proteins in lymphocytes. We carry out a study to assess the prognostic value of transcriptional expression of CD45 in HNSCC. MATERIAL AND METHODS: We determined the transcriptional expression of CD45 in 160 consecutive HNSCC patients and compared the TIL values according to the CD45 expression. RESULTS: Five-year disease-free survival for patients with a high transcriptional expression of CD45 (n = 107) was 62.4% and for patients with a low expression (n = 53) it was 36.2% (P = 0.003). Patients with a high expression of CD45 had a better local recurrence-free survival and disease-specific survival. The results of a multivariate analysis showed that patients with a low expression of CD45 had 2.0-fold high risk of recurrence (95% CI 1.2-3.2, P = 0.003). In oropharyngeal carcinomas, HPV-positive tumors showed a higher transcriptional CD45 expression than HPV-negative tumors. Tumors with high CD45 expression had immunohistochemical TIL scores significantly higher than those with low CD45 expression. CONCLUSION: According to our results, CD45 expression is a potential marker for tumor outcome in HNSCC patients.

Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy.

Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular for lysosomal storage diseases (LSD) caused by deficiencies in secretable lysosomal enzymes in which neither full restoration of normal enzymatic activity nor transduction of all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) are challenging because the disease's main target organ is the brain and enzymes do not efficiently cross the blood-brain barrier even if present at very high concentration in circulation. To overcome these limitations, we delivered AAV9 vectors encoding for α-N-acetylglucosaminidase (NAGLU) to the Cerebrospinal Fluid (CSF) of MPSIIIB mice with the disease already detectable at biochemical, histological and functional level. Restoration of enzymatic activity in Central Nervous System (CNS) resulted in normalization of glycosaminoglycan content and lysosomal physiology, resolved neuroinflammation and restored the pattern of gene expression in brain similar to that of healthy animals. Additionally, transduction of the liver due to passage of vectors to the circulation led to whole-body disease correction. Treated animals also showed reversal of behavioural deficits and extended lifespan. Importantly, when the levels of enzymatic activity were monitored in the CSF of dogs following administration of canine NAGLU-coding vectors to animals that were either naïve or had pre-existing immunity against AAV9, similar levels of activity were achieved, suggesting that CNS efficacy would not be compromised in patients seropositive for AAV9. Our studies provide a strong rationale for the clinical development of this novel therapeutic approach as the treatment for MPSIIIB.

Prognostic significance of extracapsular spread in isolated neck recurrences in head and neck squamous cell carcinoma patients.

Few studies have analyzed the appearance of extracapsular spread (ECS) in salvage neck dissections carried out after regional recurrence of the disease. The aim of our study was to evaluate the frequency of ECS in patients with an isolated regional recurrence treated with a salvage neck dissection, and to assess the influence of ECS on prognosis. We conducted a retrospective study of 123 patients treated with a salvage neck dissection. Eighty-two patients (66.7 %) had nodes with ECS. Five-year salvage-specific survival for patients without ECS was 77.2 %, whereas for patients with ECS it was 32.0 % (P = 0.0001). According to the results of a multivariate analysis, the presence of ECS in the salvage neck dissection was the only variable significantly related to the salvage-specific survival. Sixty-six percent of the patients with nodes with ECS had adjuvant treatment with radiotherapy or chemoradiotherapy. Five-year salvage-specific survival for patients with ECS who had not received adjuvant treatment (n = 26) was 15.2 %, whereas for patients treated with adjuvant radiotherapy (n = 39) or chemotherapy (n = 17), 5-year salvage-specific survival was 36.4 and 47.1 %, respectively. Patients with ECS could benefit from adjuvant treatment with radiotherapy or chemoradiotherapy.

Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.

Prostacyclin-synthase expression in head and neck carcinoma patients and its prognostic value in the response to radiotherapy.

Prostacyclin (PGI2 ) plays a role in cancer progression but the mechanism is currently poorly understood. Additionally, no data are available about the prognostic value of the PGI2 pathway in head and neck squamous cell carcinoma (HNSCC) therapy. We evaluated the expression of the PGI2 pathway in HNSCC patients. PGI2 production and PGI synthase (PGIS) expression, in terms of mRNA (RT-PCR) and protein (immunoblotting), were lower in tumour samples than in non-tumoural mucosa, whereas, as expected, COX-2 expression was increased in HNSCC tumour samples. Using local control of the tumour after radiotherapy or chemoradiotherapy as a dependent variable, patients were classified into two categories of PGIS transcript levels. The high-PGIS group had a significantly lower frequency of local and distant failure than the low-PGIS group, and the 5-year cancer-specific survival was higher [90.2% (95% CI 81.0-99.4%) versus 60.5% (95% CI 44.4-76.6%)]. None of the four HNSCC cell lines analysed expressed PGIS and therefore they did not produce PGI2 . However, HNSCC-conditioned media enhanced PGI2 production in endothelial cells (ECs). The stable analogue of PGI2 , carbaprostacyclin (cPGI2 ), exerted little effect on HNSCC cell line migration, and no effect on cell cycle distribution or proliferation rate after radiation injury was observed. Nevertheless, cPGI2 promoted EP-4-dependent in vitro angiogenesis. Von Willebrand factor expression (EC marker) and capillary density were significantly higher in the group of patients with high expression of PGIS. Our results indicate that PGIS expression was associated with radiotherapy efficiency. Although we do not provide direct evidence of a relationship between tumour vascularization and radiotherapy efficiency, our results suggest that the effect of PGI2 is related to its ability to promote vascularization. These results also support the concept that co-adjuvant therapy with PGIS enhancers, such as retinoids, could have therapeutic value for HNSCC treatment.

Management of recurrent head and neck cancer: variables related to salvage surgery.

After a local and/or regional recurrence of head and neck squamous cell carcinoma (HNSCC) not all patients are candidates to salvage treatment. The objective of this study was to identify the variables related to performance of salvage surgery with curative intent in these patients. We performed a retrospective study of 1088 HNSCC patients with a local and/or regional recurrence. According to a multivariate analysis, the variables related to performance of salvage surgery were the Karnofsky index, the location and extension of the primary tumor, the initial treatment, the disease-free interval between treatment of the initial tumor and diagnosis of the recurrence, and the year the recurrence was diagnosed. Considering salvage surgery as the dependent variable, the results of a recursive partitioning analysis defined four categories of patients in function of the category of local and regional extension of the initial tumor, the location of the primary tumor, the initial treatment and the disease-free interval between treatment of the initial tumor and diagnosis of the recurrence.

Expression of the CXCL12/CXCR4 chemokine axis predicts regional control in head and neck squamous cell carcinoma.

Expression of the CXCL12/CXCR4 chemokine axis has been related with the appearance of metastatic recurrence survival, including regional and distant recurrence, in patients with head and neck squamous cell carcinoma (HNSCC). RT-PCR was used to determine mRNA expression levels of CXCL12 and CXCR4 in biopsy tumor samples in 111 patients with HNSCC. Five-year regional recurrence-free survival for patients with low CXCR4 expression (n = 39, 31.5 %) was 97.4 %, for patients with high CXCR4/high CXCL12 expression (n = 22, 19.8 %) it was 94.7 %, and for patients with high CXCR4/low CXCL12 expression (n = 50, 45.0 %) it was 63.3 %. We found significant differences in the regional recurrence-free survival according to CXCR4/CXCL12 expression values (P = 0.001). HNSCC patients with high CXCR4 and low CXCL12 expression values had a significantly higher risk of regional recurrence and could benefit from a more intense treatment of lymph node areas in the neck.

Mini-laparoscopic live donor nephrectomy with the use of 3-mm instruments and laparoscope.

PURPOSE: To analyze our preliminary outcomes on the use of 3 mm instruments for laparoscopic live donor nephrectomy (LLDN). METHODS: Our series includes thirteen patients, who underwent LLDN using 3-mm instruments and laparoscope and 5-mm transumbilical trocar. The patients were followed at 7 and 14 days from discharge and were specifically asked about their cosmetic satisfaction. At follow-up, the recipient graft function was controlled, as well as the donor's cosmetic results. Eight months after surgery, all thirteen patients were asked to fill out the Patient Scar Assessment Questionnaire and Scoring System (PSAQ). RESULTS: All patients presented good recovery after surgery. Regarding cosmetic outcomes, the donors expressed their satisfaction toward the minimal incision size and optimal esthetic results at 7 and 14 days from discharge home. The low scores on each section of the PSAQ confirmed the favorable outcomes. Early graft function was satisfactory at 1 and 3 months after the kidney transplantation. Furthermore, there were no major complications in the recipients. CONCLUSIONS: Our persistent positive results with the use of 3-mm instruments during LLDN support this technique as a good alternative to the standard laparoscopic approach for minimizing the incision site, while maintaining safety and excellent clinical outcomes. The fact that the general laparoscopic standards are maintained could make this approach a very attractive alternative to the other minimally invasive approaches for live donor nephrectomy. The hope is in that the higher degree of satisfaction in the donor population demonstrated in this study may likely enhance living kidney donation.