Wide cross-species RNA-Seq comparison reveals convergent molecular mechanisms involved in nickel hyperaccumulation across dicotyledons.

The Anthropocene epoch is associated with the spreading of metals in the environment increasing oxidative and genotoxic stress on organisms. Interestingly, c. 520 plant species growing on metalliferous soils acquired the capacity to accumulate and tolerate a tremendous amount of nickel in their shoots. The wide phylogenetic distribution of these species suggests that nickel hyperaccumulation evolved multiple times independently. However, the exact nature of these mechanisms and whether they have been recruited convergently in distant species is not known. To address these questions, we have developed a cross-species RNA-Seq approach combining differential gene expression analysis and cluster of orthologous group annotation to identify genes linked to nickel hyperaccumulation in distant plant families. Our analysis reveals candidate orthologous genes encoding convergent function involved in nickel hyperaccumulation, including the biosynthesis of specialized metabolites and cell wall organization. Our data also point out that the high expression of IREG/Ferroportin transporters recurrently emerged as a mechanism involved in nickel hyperaccumulation in plants. We further provide genetic evidence in the hyperaccumulator Noccaea caerulescens for the role of the NcIREG2 transporter in nickel sequestration in vacuoles. Our results provide molecular tools to better understand the mechanisms of nickel hyperaccumulation and study their evolution in plants.

Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

Effectiveness of a multidisciplinary patient care bundle for reducing surgical-site infections.

BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.

Incisional hernias after laparoscopic and robotic right colectomy.

PURPOSE: Incisional hernia (IH) is a common complication after colectomy, with impacts on both health care utilization and quality of life. The true incidence of IH after minimally invasive colectomy is not well described. The purpose of this study was to examine IH incidence after minimally invasive right colectomies (RC) and to compare the IH rates after laparoscopic (L-RC) and robotic (R-RC) colectomies. METHODS: This is a retrospective review of patients undergoing minimally invasive RC at a single institution from 2009 to 2014. Only patients undergoing RC for colonic neoplasia were included. Patients with previous colectomy or intraperitoneal chemotherapy were excluded. Three L-RC patients were included for each R-RC patient. The primary outcome was IH rate based on clinical examination or computed tomography (CT). Univariate and multivariate time-to-event analyses were used to assess predictors of IH. RESULTS: 276 patients where included, of which 69 had undergone R-RC and 207 L-RC. Patient and tumor characteristics were similar between the groups, except for higher tumor stage in L-RC patients. Both the median time to diagnosis (9.2 months) and the overall IH rate were similar between the groups (17.4 % for R-RC and 22.2 % for L-RC), as were all other postoperative complications. In multivariable analyses, the only significant predictor of IH was former or current tobacco use (hazard raio 3.0, p = 0.03). CONCLUSIONS: This study suggests that the incidence of IH is high after minimally invasive colectomy and that this rate is equivalent after R-RC and L-RC. Reducing the IH rate represents an important opportunity for improving quality of life and reducing health care utilization after minimally invasive colectomy.

Prognostic aspects of DCE-MRI in recurrent rectal cancer.

OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI findings correlate with clinical outcome in patients who undergo surgical treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE-MRI in patients with recurrent rectal cancer was performed after obtaining an IRB waiver. We queried our PACS from 1998 to 2012 for examinations performed for recurrent disease. Two radiologists in consensus outlined tumour regions of interest on perfusion images. We explored the correlation between K(trans), Kep, Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and resection margin status. Univariate Cox PH models were used for survival, while univariate logistic regression was used for margin status. RESULTS: Among 58 patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P = 0.04) were inversely correlated with positive margins. No significant correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were significantly associated with clear resection margins; however overall survival and time to re-recurrence were not predicted. Such information might be helpful for treatment individualisation and deserves further investigation.

Goblet cell carcinoid neoplasm of the appendix: clinical and CT features.

PURPOSE: To describe the clinical and CT imaging features of goblet cell carcinoid (GCC) neoplasm of the appendix. METHODS AND MATERIALS: A computer search of pathology and radiology records over a 19-year period at our two institutions was performed using the search string "goblet". In the patients with appendiceal GCC neoplasms who had abdominopelvic CT, imaging findings were categorized, blinded to gross and surgical description, as: "Appendicitis", "Prominent appendix without peri-appendiceal infiltration", "Mass" or "Normal appendix". The CT appearance was correlated with an accepted pathological classification of: low grade GCC, signet ring cell adenocarcinoma ex, and poorly differentiated adenocarcinoma ex GCC group. RESULTS: Twenty-seven patients (age range, 28-80 years; mean age, 52 years; 15 female, 12 male) with pathology-proven appendiceal GCC neoplasm had CT scans that were reviewed. Patients presented with acute appendicitis (n=12), abdominal pain not typical for appendicitis (n=14) and incidental finding (n=1). CT imaging showed 9 Appendicitis, 9 Prominent appendices without peri-appendiceal infiltration, 7 Masses and 2 Normal appendices. Appendicitis (8/9) usually correlated with typical low grade GCC on pathology. In contrast, the majority of Masses and Prominent Appendices without peri-appendiceal infiltration were pathologically confirmed to be signet ring cell adenocarcinoma ex GCC. Poorly differentiated adenocarcinoma ex GCC was seen in only a small minority of patients. Hyperattenuation of the appendiceal neoplasm was seen in a majority of cases. CONCLUSIONS: GCC neoplasm of the appendix should be considered in the differential diagnosis in patients with primary appendiceal malignancy. Our cases demonstrated close correlation between our predefined CT pattern and the pathological classification.

A regression model for estimating DNA copy number applied to capture sequencing data.

MOTIVATION: Target enrichment, also referred to as DNA capture, provides an effective way to focus sequencing efforts on a genomic region of interest. Capture data are typically used to detect single-nucleotide variants. It can also be used to detect copy number alterations, which is particularly useful in the context of cancer, where such changes occur frequently. In copy number analysis, it is a common practice to determine log-ratios between test and control samples, but this approach results in a loss of information as it disregards the total coverage or intensity at a locus. RESULTS: We modeled the coverage or intensity of the test sample as a linear function of the control sample. This regression approach is able to deal with regions that are completely deleted, which are problematic for methods that use log-ratios. To demonstrate the utility of our approach, we used capture data to determine copy number for a set of 600 genes in a panel of nine breast cancer cell lines. We found high concordance between our results and those generated using a single-nucleotide polymorphsim genotyping platform. When we compared our results with other log-ratio-based methods, including ExomeCNV, we found that our approach produced better overall correlation with SNP data. AVAILABILITY: The algorithm is implemented in C and R and the code can be downloaded from http://bioinformatics.nki.nl/ocs/ CONTACT: l.wessels@nki.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multivisceral resections for rectal cancer.

BACKGROUND: En bloc resection of adjacent pelvic organ(s) may be needed to achieve clear surgical margins in rectal cancer surgery. An institutional experience is reported with perioperative morbidity and oncological outcomes. METHODS: Patients were identified retrospectively from a prospectively collected institutional database (1992-2010). Outcomes, and clinical and pathological factors were determined from medical records. Estimated overall survival, overall recurrence and local recurrence were compared using the log rank method and Cox regression analysis. RESULTS: Among 1831 patients with rectal cancer, 124 (6·8 per cent) underwent en bloc resection of part or all of an adjacent organ (vagina/uterus/ovary 90, prostate/seminal vesicle 23, bladder/ureter 15, small bowel/appendix 7). Five-year overall survival and local recurrence rates were 53·3 and 18·8 per cent respectively. There was one postoperative death, from multiple organ failure in a patient with liver cirrhosis. Fifty-two patients underwent sphincter-preserving surgery and three (6 per cent) developed an anastomotic leak. On univariable analysis, the only factor associated with local recurrence was completeness of resection (local recurrence rate 15 per cent versus 69 per cent for R0 versus R1 resection; P < 0·001). On multivariable analysis, factors associated with overall survival were sphincter-preserving surgery, absence of metastatic disease and R0 resection. CONCLUSION: Multiple organ resection for locally advanced primary rectal cancer had good oncological outcomes when clear resection margins were achieved.

Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer.

OBJECTIVE: To determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer. METHODS: In a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, K(trans), k(ep), v(e), AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman's Rank correlation was used. For categorical variable comparison, the Kruskal-Wallis test was used. P ≤ 0.05 was considered significant. RESULTS: Percentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy K(trans) (mean 0.5 min(-1) vs. 0.2 min(-1), P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone. CONCLUSION: After neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR. KEY POINTS: Dynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours. These objective quantitative measures may be more helpful than subjective imaging alone Some parameters differed markedly between completely responding and incompletely responding rectal cancers. Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.

Risk-reducing surgery in FAP: role for surgeons beyond the incision.

BACKGROUND: Although primary therapy in familial adenomatous polyposis (FAP) is surgical, little is known about patients' surgical decision-making experience. The objective was to explore the decision-making process surrounding risk-reducing surgery in FAP using qualitative methodology. METHODS: In-depth, semi-structured interviews with 14 FAP patients and 11 healthcare providers with experience caring for FAP patients were conducted. Using grounded theory, line-by-line content analysis identified categories from which themes describing patients' experiences emerged; analysis continued until data saturation. RESULTS: Median age at surgery was 23 (7-37) years; at interview 41 (19-74) years. Two patients underwent surgery secondary to cancer, the remainder for risk-reduction. Content experts included colorectal surgeons (3), geneticists (2), gastroenterologists (3), nurses (3).Three themes emerged: Information: Family was the primary information source, and patients' level of information varied. The importance of up-front information was emphasized. Influences on decision-making: Influential factors included family experiences, youth, emotional state, support, and decision-making role. Although patients often sought opinions, most (12/14) wanted an active/shared role in decision-making. Life after surgery: Patients described surgery as the "easy part," emphasizing the need for long-term relationships with care providers. CONCLUSIONS: Decisions surrounding risk-reducing surgery in FAP are unique. A decision support tool may facilitate decision-making, better preparing patients for life after surgery.

[Traumatic rupture of the diaphragm]. / Rotura diafragmática traumática.

OBJECTIVE: Traumatic rupture of the diaphragm (TRD) is a rare occurrence, with variable morbidity and mortality. The aim of this study was to analyze cases of TRD in a tertiary hospital and assess prognostic factors associated with mortality. PATIENTS AND METHODS: A retrospective study was performed of patients diagnosed with TRD in Hospital Universitario La Fe, Valencia, Spain, between 1969 and 2006. The following variables were analyzed: sex, age, cause, diagnosis, associated lesions, surgical procedure, side and size of the lesion, visceral herniation, and postoperative morbidity and mortality. RESULTS: The study group comprised 132 patients (105 men, 79.5%) with a mean (SD) age of 39.64 (17.04) years. Traffic accidents were the most common cause of TRD. Rupture involved the left hemidiaphragm in 96 cases (72.7%), and 113 patients (85.6%) had associated lesions, most often affecting the abdomen. Thoracotomy was performed in 83 cases (62.9%) and laparotomy in 41 (31.1%). Visceral herniation was reported in 90 patients (68.3%), most often involving the stomach. The rates of perioperative morbidity and mortality were 62.8% and 20.5%, respectively. Diagnostic delay and the presence of morbidity and serious associated lesions all had a statistically significant impact on mortality (P< .05). In the case of serious associated lesions, the odds ratio was 2.898 (95% confidence interval, 1.018-8.250) and for perioperative morbidity it was 1.488 (95% confidence interval, 1.231-1.798). CONCLUSIONS: TRD is an infrequent occurrence in young men, is generally caused by traffic accidents, and is more common on the left side. Associated lesions are present in most cases and represent the main prognostic factor affecting morbidity and mortality. TRD can be considered a relative surgical emergency when not accompanied by other lesions that in themselves constitute surgical emergencies.

Rotura diafragmática traumática / Traumatic rupture of the diaphragm

Objetivo: La rotura diafragmática traumática (RDT) es una lesión infrecuente, con tasas variables de morbimortalidad. El objetivo del estudio ha sido analizar la experiencia en RDT de un hospital terciario y los factores pronósticos de mortalidad. Pacientes y métodos: Se ha realizado un estudio analítico y retrospectivo de los pacientes diagnosticados de RDT entre 1969 y 2006 en el Hospital La Fe. Se analizaron: sexo, edad, causa, diagnóstico, lesiones asociadas, procedimiento quirúrgico, lado y tamaño, herniación visceral y morbimortalidad postoperatoria. Resultados: Se incluyó en el estudio a 132 pacientes (105 varones; 79,5%) con una edad media ± desviación estándar de 39,64 ± 17,04 años. Los accidentes de tráfico fueron la causa más frecuente de RDT. En 96 casos (72,7%) se afectó el hemidiafragma izquierdo y 113 pacientes (85,6%) asociaron lesiones, de las cuales las abdominales fueron las más frecuentes. Se abordaron por toracotomía 83 casos (62,9%) y por laparotomía 41 (31,1%). En 90 pacientes (68,3%) se evidenció herniación visceral, siendo el estómago la más frecuente. Las tasas de morbilidad y mortalidad perioperatorias fueron del 62,8 y el 20,5%, respectivamente. La presencia de morbilidad y de lesiones asociadas graves, y el retraso diagnóstico tuvieron un impacto significativo en la mortalidad (p < 0,05. Lesiones graves: odds ratio = 2,898; intervalo de confianza del 95%, 1,018-8,250. Morbilidad perioperatoria: odds ratio = 1,488; intervalo de confianza del 95%, 1,231-1,798). Conclusiones: La RDT es una entidad infrecuente que se da en varones jóvenes, generalmente por accidentes de tráfico, y es más frecuente en el lado izquierdo. Las lesiones asociadas están presentes en la mayoría de los casos y son el principal factor pronóstico que condiciona la morbimortalidad. La RDT puede considerarse una urgencia quirúrgica diferida, en ausencia de otras lesiones que constituyan una urgencia quirúrgica en sí mismas

Objective: Traumatic rupture of the diaphragm (TRD) is a rare occurrence, with variable morbidity and mortality. The aim of this study was to analyze cases of TRD in a tertiary hospital and assess prognostic factors associated with mortality. Patients and methods: A retrospective study was performed of patients diagnosed with TRD in Hospital Universitario La Fe, Valencia, Spain, between 1969 and 2006. The following variables were analyzed: sex, age, cause, diagnosis, associated lesions, surgical procedure, side and size of the lesion, visceral herniation, and postoperative morbidity and mortality. Results: The study group comprised 132 patients (105 men, 79.5%) with a mean (SD) age of 39.64 (17.04) years. Traffic accidents were the most common cause of TRD. Rupture involved the left hemidiaphragm in 96 cases (72.7%), and 113 patients (85.6%) had associated lesions, most often affecting the abdomen. Thoracotomy was performed in 83 cases (62.9%) and laparotomy in 41 (31.1%). Visceral herniation was reported in 90 patients (68.3%), most often involving the stomach. The rates of perioperative morbidity and mortality were 62.8% and 20.5%, respectively. Diagnostic delay and the presence of morbidity and serious associated lesions all had a statistically significant impact on mortality (P<.05). In the case of serious associated lesions, the odds ratio was 2.898 (95% confidence interval, 1.018-8.250) and for perioperative morbidity it was 1.488 (95% confidence interval, 1.231-1.798). Conclusions: TRD is an infrequent occurrence in young men, is generally caused by traffic accidents, and is more common on the left side. Associated lesions are present in most cases and represent the main prognostic factor affecting morbidity and mortality. TRD can be considered a relative surgical emergency when not accompanied by other lesions that in themselves constitute surgical emergencies

Young age influences treatment but not outcome of colon cancer.

BACKGROUND: Early age at onset is often considered a poor prognostic factor for colon cancer. The aim of this study was to determine the association between age, clinicopathologic features, adjuvant therapy, and outcomes following colon cancer resection. METHODS: A prospective database of 1,327 surgical stage I-III colon cancer patients operated on from 1990-2001 was evaluated, and patients grouped by age. RESULTS: Sixty-eight patients (5%) were diagnosed at age 40 (older). Younger patients were more likely to have left-sided tumors (66% vs 51%, P = .02), but no more likely to present with symptomatic lesions, more advanced tumors, or have worse pathologic features. Younger patients were noted to have more nodes retrieved in their surgical specimens than older patients (median 18 vs 14, P = .001), although the numbers of total colectomies were similar in both groups. Younger patients were also more likely to receive adjuvant chemotherapy, and this was most pronounced in the stage II cohort: 39% vs 14%, P = .003. With a median follow-up of 55 months, 5-year disease-specific survival (DSS) was similar in both study groups: 86% vs 87%, but 5-year overall survival (OS) was significantly higher in the younger patient cohort (84% vs 73%, P = .001). CONCLUSION: Younger patients undergoing complete resection of stage I-III colon cancer had DSS similar to older patients. However, younger patients had more nodes retrieved from their specimens and were more likely to receive adjuvant therapy, especially for node-negative disease. These factors may have contributed to their overall favorable outcome.

Neuroendocrine carcinomas of the colon and rectum.

PURPOSE: This study was designed to review experience with neuroendocrine carcinomas of the colon and rectum at a single institution, with emphasis on the pathology and clinical characteristics of this uncommon malignancy. METHODS: A study group of patients was identified from a prospective colorectal service database. Pathology was reviewed and neuroendocrine tumors were classified by a single pathologist. Medical records were retrospectively reviewed. RESULTS: From March 1975 to September 1998, 38 patients with neuroendocrine carcinomas were identified from the colorectal service database comprising 6495 patients (0.6 percent). These neuroendocrine carcinomas did not include carcinoid tumors. Average patient age was 57 years (range, 29-86 years). There were 17 males (44.7 percent) and 21 females (55.3 percent). Tumors were located as follows: 17 colon, 14 rectum, 6 anal canal, and 1 appendix. The diagnosis of neuroendocrine carcinoma was suggested preoperatively from tissue biopsy in 59.3 percent (16/27) of patients evaluable. Pathology was reviewed and tumors were categorized as small cell carcinoma (n = 22) or large cell neuroendocrine carcinoma (n = 16). Most tumors (20/25 evaluable, 80 percent) stained positive by means of immunohistochemistry for neuroendocrine markers, including chromogranin (18/19), synaptophysin (10/15), and/or neuron-specific enolase (14/15). Metastatic disease was detected at the time of diagnosis in 69.4 percent of the patients (25/36). Tumors were advanced at the time of diagnosis, with American Joint Committee on Cancer (AJCC) Stage I (n = 6), Stage III (n = 7), and Stage IV (n = 25) tumors. As a group, these tumors had a poor prognosis, with a median survival of 10.4 months. One-year, two-year, and three-year survival was 46 percent, 26 percent, and 13 percent, respectively. There was no significant difference in survival based on pathologic subtypes. Median follow-up time was 9.4 months (range, 0.6-263.7 months). CONCLUSIONS: Neuroendocrine carcinomas of the colon and rectum are uncommon, comprising less than 1 percent of colon and rectal cancers. Pathologically, these tumors are poorly differentiated carcinomas with distinctive cytoarchitectural features and are often immunoreactive for markers of neuroendocrine differentiation. The prognosis for high-grade neuroendocrine carcinomas is poor, as most patients have metastatic disease at the time of diagnosis.

Surgical resection and high dose rate intraoperative radiation therapy for locally recurrent rectal cancer.

For intra-pelvic recurrence of rectal cancer, surgical resection is technically difficult and must be aggressive to achieve a high rate of negative resection margins. Resection with clear margins can be curative, particularly for those patients with true anastomotic recurrence. HDR-IORT is a safe, feasible, versatile, logistically sound modality that is highly reliable in delivering radiation to at-risk surgical margins in the pelvis. Despite surgery and IORT, overall local failure rates in this population are 33 to 50 percent. The most important prognostic variable is the state of surgical resection margins. At our institution, in patients with negative and positive resection margins the 2-year actuarial local recurrence rates are 33 percent versus 73 percent and 5-year survival rates are 51 percent versus 16 percent, respectively. On subset analysis, the most favorable outcome was seen in patients with true anastomotic recurrences (78 percent 5-year survival).

Carcinoma broncogénico e infección por virus de la inmunodeficiencia humana / Bronchogenic carcinoma and virus infection in human immunodeficiency

Propósito: Mostrar nuestra experiencia en pacientes con carcinoma broncogénico (CB) e infección por el virus de la inmunodeficiencia humana (HIV).- Pacientes y método: Se presentan cuatro pacientes con CB y VIH tratados mediante cirugía. - Resultados: La edad media fue de 43 años y tres pacientes tenían antecedentes tuberculosos. La tasa media de CD4 fue de 211/mm3. Se realizaron tres lobectomías y una neumonectomía. El diagnóstico histológico más frecuente fue el de carcinoma epidermoide. Sólo un enfermo vive en la actualidad tras cinco años de la intervención. - Conclusión: La aparición de un CB en pacientes HIV, población con una alta incidencia de patología pulmonar por infecciones oportunistas, es cada día más frecuente por lo que hay que tener en cuenta la posible asociación de ambos procesos (AU)

Results after rectal cancer resection with in-continuity partial vaginectomy and total mesorectal excision.

BACKGROUND: Although sharp mesorectal excision reduces circumferential margin involvement and local recurrence, a concomitant partial vaginectomy may be required in women with locally advanced rectal cancer. METHODS: Sixty-four patients requiring a partial vaginectomy during resection of primary rectal cancer were identified. Survival was determined by the Kaplan-Meier method, and distributions were compared by the log-rank test. RESULTS: Locally advanced disease was reflected by presentation with malignant rectovaginal fistulae (n = 6) or cancers described as bulky or adherent/tethered to the rectovaginal septum (n = 32). Thirty-five patients received adjuvant radiation with or without chemotherapy. At a median follow-up of 22 months, 27 (42%) patients developed recurrent disease, with most of these occurring at distant sites. The 5-year overall survival was 46%, with a median survival of 44 months. The 2-year local recurrence-free survival was 84%. The crude local failure rate was 16% (10 of 64), and local recurrence was more common in patients with a positive as opposed to a negative microscopic margin (2 [50%] of 4 vs. 8 [13%] of 60, respectively). Positive nodal status had a significant effect on overall survival (P <.001). CONCLUSIONS: Partial vaginectomy is indicated for locally advanced rectal cancers involving the vagina. The results are most favorable in patients with negative surgical margins and node-negative disease.

Resection of locally recurrent colorectal cancer in the presence of distant metastases: can it be justified?

BACKGROUND: We aimed to determine the outcome of resections for local recurrence of colorectal carcinoma in the presence of distant (M1) disease. METHODS: Patients who underwent resection of local recurrence in the presence of potentially resectable M1 disease were identified from the colorectal database. Outcome was determined by chart review. RESULTS: Forty-two patients (23 men) of mean age 60 years (range, 34-88 years) underwent complete gross resection of their local recurrence in the presence of M1 disease. Thirteen of the 42 underwent synchronous M1 resections to render them free of gross disease (R0). Nine of the 29 patients who left with residual disease (R1) subsequently underwent staged M1 resection, so that 22 of 42 were rendered R0 by surgery. The median survival of all patients was 14.5 months (interquartile range, 6-30 months), and that of patients rendered R0 was 23 months (interquartile range, 10-37 months), in comparison with 7 months (interquartile range, 3-25 months) for those of R1 status (P =.006; log-rank method). Ability to achieve R0 status by synchronous or staged resection was the only factor predictive of survival. CONCLUSIONS: The presence of M1 disease per se should not preclude resection of local recurrence, although case selection is problematic.

Preoperative radiation with or without chemotherapy and full-thickness transanal excision for selected T2 and T3 distal rectal cancers.

BACKGROUND AND AIMS: To evaluate the clinical outcome of selected patients with distal rectal cancer treated by preoperative radiation with or without chemotherapy and full-thickness local excision (FTLE). PATIENTS AND METHODS: Ten patients with invasive distal rectal cancer (six T2, four T3) were treated with preoperative radiotherapy (3600-5040 cGy) with or without 5-fluorouracil based chemotherapy. FTLE was performed 4-6 weeks after completion of radiotherapy, primarily because of comorbid diseases or patient refusal of a permanent colostomy. Median follow-up was 28.5 months. RESULTS: There were no prolonged wound complications, and only one positive microscopic margin was detected. Among three cases of complete pathological response, two remain without evidence of disease. All patients retained sphincter function and avoided creation of a stoma. Two patients developed recurrence, one with widespread disease including pelvic recurrence 26 months after surgery and the other with distant disease only at 23 months. There were four deaths: two unrelated to cancer, one of undetermined cause after 7 years, and one after widespread recurrence at 26 months, with death 4 months later. Two-year actuarial survival was 78%. CONCLUSIONS: This pilot study demonstrates that preoperative radiotherapy and FTLE avoids major abdominal surgery yet facilitates sphincter preservation, excision with negative margins, and short-term local control in selected patients with distal rectal cancer.

Tissue inhibitor of metalloproteinase-3 is a basement membrane-associated protein that is significantly decreased in human colorectal cancer.

PURPOSE: The balance between local levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases is believed to play a key role in tumor invasion and metastases. Because tissue inhibitor of metalloproteinase-3 suppresses tumorigenicity and tumor invasion in vitro, the aim of this study was to determine its expression in human colorectal cancer. METHODS: Thirty-nine human colorectal cancer specimens, three adenomas, and matched normal adjacent mucosa from 39 colorectal cancer patients were analyzed. Tissue inhibitor of metalloproteinase-3 ribonucleic acid and protein expression were analyzed by Northern blot hybridization and Western blot analysis, respectively. The cellular localizations of tissue inhibitor of metalloproteinase-3 ribonucleic acid and protein were determined by in situ hybridization and immunolocalization. RESULTS: Tissue inhibitor of metalloproteinase-3 ribonucleic acid expression was increased in colorectal cancer compared with paired normal mucosa. In contrast, tissue inhibitor of metalloproteinase-3 protein level was higher in normal mucosa than in the corresponding colorectal cancer. In addition, tissue inhibitor of metalloproteinase-3 protein levels progressively decreased with advancing colorectal cancer stages. Tissue inhibitor of metalloproteinase-3 protein tumor to normal mucosa ratio was 0.74 +/- 0.12, 0.51 +/- 0.18, 0.48 +/- 0.12, and 0.45 +/- 0.2 for Dukes A (n = 8), B (n = 9), C (n = 9), and D (n = 13) stages, respectively. Both tissue inhibitor of metalloproteinase-3 messenger ribonucleic acid and protein were located predominantly within spindle-shaped and round stromal cells. Furthermore, in colonic epithelium, tissue inhibitor of metalloproteinase-3 and type IV collagen protein were similarly concentrated in the basal region. CONCLUSIONS: These data provide the first detailed description of the cellular expression of tissue inhibitor of metalloproteinase-3 in colorectal cancer and identify it as a basement membrane-associated protein. This is an important observation, because the presence of tissue inhibitor of metalloproteinase-3 protein near the basement membrane supports its role in preventing proteolytic degradation, angiogenesis, and apoptosis.