Incidence and management of patients with colorectal cancer and synchronous and metachronous colorectal metastases: a population-based study.

BACKGROUND: This population-based study aimed to examine the incidence, patterns and results of multimodal management of metastatic colorectal cancer. METHODS: A retrospective population-based study was conducted on patients with metastatic colorectal cancer in Central Finland in 2000-2015. Clinical and histopathological data were retrieved and descriptive analysis was conducted to determine the pattern of metastatic disease, defined as synchronous, early metachronous (within 12 months of diagnosis of primary disease) and late metachronous (more than 12 months after diagnosis). Subgroups were compared for resection and overall survival (OS) rates. RESULTS: Of 1671 patients, 296 (17·7 per cent) had synchronous metastases, and 255 (19·6 per cent) of 1302 patients with resected stage I-III tumours developed metachronous metastases (94 early and 161 late metastases). Liver, pulmonary and intraperitoneal metastases were the most common sites. The commonest metastatic patterns were a combination of liver and lung metastases. The overall metastasectomy rate for patients with synchronous metastases was 16·2 per cent; in this subgroup, 3- and 5-year OS rates after any resection were 63 and 44 per cent respectively, compared with 7·1 and 3·3 per cent following no resection (P < 0·001). The resection rate was higher for late than for early metachronous disease (28·0 versus 17 per cent respectively; P = 0·048). Three- and 5-year OS rates after any resection of metachronous metastases were 78 and 62 per cent respectively versus 42·1 and 18·2 per cent with no metastasectomy (P < 0·001). Similarly, 3- and 5-year OS rates after any metastasectomy for early metachronous metastases were 57 and 50 per cent versus 84 and 66 per cent for late metachronous metastases (P = 0·293). CONCLUSION: The proportion of patients with metastatic colorectal cancer was consistent with that in earlier population-based studies, as were resection rates for liver and lung metastases and survival after resection. Differentiation between synchronous, early and late metachronous metastases can improve assessment of resectability and survival.

ANTECEDENTES: El objetivo de este estudio de base poblacional fue analizar la incidencia, la forma de presentación y los resultados del tratamiento multimodal del cáncer colorrectal metastásico (metastatic colorectal cancer, mCRC). MÉTODOS: Se realizó un estudio retrospectivo de base poblacional en pacientes con mCRC en la región central de Finlandia entre 2000 a 2015. Se recuperaron los datos clínicos e histopatológicos y se realizó un análisis descriptivo con el objetivo de analizar la forma de presentación de la enfermedad metastásica. La enfermedad metastásica se definió como sincrónica, metacrónica precoz (< 12 meses) y metacrónica tardía (> 12 meses después del diagnóstico de la enfermedad primaria) y se compararon las tasas de resección y de supervivencia global (overall survival, OS) en estos subgrupos. RESULTADOS: De los 1.671 pacientes revisados, 296 (17,7%) presentaron metástasis sincrónicas, mientras que de los 1.302 pacientes resecados en estadios I-III, 255 (19,6%) tuvieron metástasis metacrónicas: 94 precoces y 161 tardías. La localización metastásica más frecuente fue el hígado, los pulmones y el peritoneo. La combinación más frecuente fue la de metástasis hepáticas y pulmonares. La tasa de resección para pacientes con metástasis sincrónicas fue del 16,2%; en este subgrupo, la OS a 3 y 5 años después de cualquier tipo de resección fue del 62,6% y 44,2% versus 7,1% y 3,3% en los pacientes sin resección, respectivamente (P < 0,001). La tasa de resección fue mayor en la enfermedad metacrónica tardía que en la enfermedad metacrónica precoz (28% versus 17%, P = 0,048). Las tasas de OS a 3 y 5 años después de cualquier resección en los casos de metástasis metacrónicas fueron del 77,8% y 61,9% versus 42,1% y 18,2% en los pacientes sin metastasectomía, P < 0,001. Las tasas de OS a 3 y 5 años después de cualquier metastasectomía en los casos de metástasis metacrónicas precoces fueron del 57,4% y 50,3%, versus 84,3% y 65,6% en las tardías (P = 0,29) CONCLUSIÓN: La proporción de pacientes con mCRC fue similar a la de estudios anteriores de base poblacional, así como las tasas de resección para metástasis hepáticas y pulmonares y la supervivencia después de la resección. Diferenciar entre metástasis sincrónicas, metacrónicas precoces y tardías puede mejorar la posibilidad de resecabilidad y la supervivencia.

Population-based study of anastomotic stricture rates after minimally invasive and open oesophagectomy for cancer.

Background: The population-based incidence of anastomotic stricture after minimally invasive oesophagectomy (MIO) and open oesophagectomy (OO) is not known. The aim of this study was to compare rates of anastomotic stricture requiring dilatation after the two approaches in an unselected cohort using nationwide data from Finland and Sweden. Methods: All patients who had MIO or OO for oesophageal cancer between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. Outcomes were the overall rate of anastomotic stricture and need for single or repeated (3 or more) dilatations for stricture within the first year after surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95 per cent confidence intervals, adjusted for age, sex, co-morbidity, histology, stage, year, country, hospital volume, length of hospital stay and readmissions. Results: Some 239 patients underwent MIO and 1430 had an open procedure. The incidence of strictures requiring one dilatation was 16·7 per cent, and that for strictures requiring three or more dilatations was 6·6 per cent. The HR for strictures requiring one dilatation was not increased after MIO compared with that after OO (HR 1·19, 95 per cent c.i. 0·66 to 2·12), but was threefold higher for repeated dilatations (HR 3·25, 1·43 to 7·36). Of 18 strictures following MIO, 14 (78 per cent) occurred during the first 2 years after initiating this approach. Conclusion: The need for endoscopic anastomotic dilatation after oesophagectomy was common, and the need for repeated dilatation was higher after MIO than following OO. The increased risk after MIO may reflect a learning curve.

Antecedentes: Se desconoce la incidencia poblacional de estenosis anastomóticas tras esofaguectomía mínimamente invasiva (minimally invasive oesophagectomy, MIO) y esofaguectomía abierta (open oesophagectomy, OO). El objetivo de este estudio fue comparar las tasas de estenosis anastomótica que precisan dilataciones después de los dos abordajes de esofaguectomía en una cohorte no seleccionada utilizando los datos poblacionales de Finlandia y Suecia. Métodos: Todos los pacientes sometidos a MIO (n = 239) o OO (n = 1430) por cáncer de esófago entre 2007 y 2014 fueron identificados a partir de los registros nacionales en Finlandia y Suecia. Las variables de resultados fueron la incidencia global de estenosis anastomótica y la necesidad de una sola dilatación o dilataciones repetidas (≥ 3) para la estenosis durante el primer año de la cirugía. La regresión multivariable de Cox proporcionó los cocientes de riesgos instantáneos (hazard ratios, HRs) con los i.c. del 95% ajustados por edad, sexo, comorbilidad, histología, estadio, año, país, volumen del hospital, duración de la estancia hospitalaria y reingresos. Resultados: La incidencia de estenosis que precisaron una dilatación fue del 16,7%, y del 6,6% para estenosis que precisaron ≥ 3 dilataciones. El HR de estenosis que requirieron una dilatación no se incrementó tras MIO en comparación con OO (HR 1,19, i.c. del 95% 0,66­2,12), pero fue 3 veces más para dilataciones repetidas (≥ 3) (HR 3,25, i.c. del 95% 1,43­7,36). De las 18 estenosis tras MIO, 14 (78%) ocurrieron durante los primeros dos años en los que se inició este abordaje. Conclusión: La necesidad de dilatación endoscópica de la anastomosis tras esofaguectomía fue frecuente y la necesidad de dilataciones repetidas fue más alta tras MIO en comparación con OO. El riesgo aumentado tras MIO puede deberse a la curva de aprendizaje.

Boerhaave's syndrome: lessons learned from 83 cases over three decades.

The authors describe their experience in the treatment of 83 Boerhaave patients. During the last few years the mortality of the disease has decreased. A successful treatment requires good treatment resources and experienced team work. The tailored open primary repair technique with fundic reinforcement, developed by the authors, is described in detail. This technique has decreased the amount of postoperative fistulation and esophageal resection. The mortality after stenting was 20%.

A novel peptide (Thx) homing to non-small cell lung cancer identified by ex vivo phage display.

AIM: To identify linear peptide homing to non-small cell lung cancer (NSCLC) tumor cells using ex vivo phage display method. MATERIALS AND METHODS: Twenty-six clinical patient samples were used to identify linear homing peptide, which was exposed to NSCLC cell cultures and control cell lines to determine cell binding affinity and cell localization. Also, ex vivo biodistribution was analyzed using tumor-bearing mice. RESULTS: The panning yielded peptide enrichment with a core motif (A)/SRXPXXX. Based on this, an amino acid sequence, ARRPKLD, was selected for characterization and named Thx-peptide. The in vitro binding properties of Thx-peptide demonstrated selectivity toward NSCLC. Internalization assays showed that Thx-Alexa and fluorescein conjugates were located in a subset of perinuclearly located lysosomes of tumor cells. Thx-peptide appeared with fluorescein-labeled peptide and peptide-DTPA-chelator complex in adenocarcinoma xenografts in mice. CONCLUSION: Thx shows promise for targeted imaging and drug delivery.

Impact of perceptual ability and mental imagery training on simulated laparoscopic knot-tying in surgical novices using a Nissen fundoplication model.

BACKGROUND: Performing minimally invasive surgery requires training and visual-spatial intelligence. The aim of our study was to examine the impact of visual-spatial perception and additional mental training on the simulated laparoscopic knot-tying task performed by surgical novices. METHODS: A total of 40 medical students randomly assigned to two groups underwent two sessions of laparoscopic basic training on a VR simulator (SimSurgery®, Oslo, Norway). The variables time and tip trajectory (total path length of the instrument tip trajectory) were used to assess the performance of the intracorporeal knot-tying task using a laparoscopic Nissen fundoplication model. The experimental group completed additional mental practice during the interval between the two training sessions. All performed a cube subtest of a standard intelligence test (I-S-T 2000 R) to evaluate visual-spatial ability. RESULTS: All participants achieved an improvement in time (t = 9.861; p < 0.001) and tip trajectory (t = 6.833; p < 0.001) in the second training session. High scores on the visual-spatial test correlated with a faster performance (r = -0.557; p < 0.001) and more precise movements (r = -0.377; p = 0.016). Comparison of the two groups did not show any statistical significant differences in the parameters time and tip trajectory. CONCLUSIONS: Visual-spatial intelligence tested by a cube test correlated with simulated laparoscopic knot-tying skills in surgical novices. Additional mental practice did not improve the overall knot-tying performance. Further studies are therefore required to determine whether mental practice might be beneficial for experienced laparoscopic surgeons or for more complex tasks.

Proliferative and anti-apoptotic activity of esophageal mucosa in gastroesophageal reflux disease is not affected by fundoplication: a 4-year follow-up study.

BACKGROUND: The role of fundoplication in the prevention of esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist regarding their response to fundoplication. METHODS: Ki-67 and Bcl-2 expression was assessed in the esophagogastric junction (EGJ) and the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication and in 7 controls. Endoscopy was performed preoperatively and 6 (20 patients) and 48 months (16 patients) postoperatively. RESULTS: There were positive correlations between Ki-67 and Bcl-2 levels in the EGJ (p > 0.001) and in the distal (p = 0.001) and proximal esophagus (p = 0.013). Compared to the preoperative level, Ki-67 expression was elevated in the distal (p = 0.012) and proximal (p = 0.007) esophagus at 48 months. In addition, compared to control values, Ki-67 expression was lower at the 6-month follow-up in the EGJ (p = 0.037) and the proximal esophagus (p = 0.003), and higher at the 48-month follow-up in the distal esophagus (p = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (p = 0.038). CONCLUSIONS: Proliferative activity after fundoplication increased in the long term in the distal esophagus despite a normal fundic wrap and healing of GERD.

Impact of early angiographic evaluation on the frequency of emergency reoperations after coronary bypass surgery.

BACKGROUND AND AIMS: early graft failure following coronary bypass surgery results in elevated morbidity and mortality. This study focused on the impact of angiographic graft evaluation. MATERIAL AND METHODS: of 5251 coronary artery bypass grafting (CABG) patients, 36 with postoperative persistent ischaemia underwent early angiography (23) or emergency resternotomy (13) 2000-2007 (Angiography era). Of the 23 patients, who underwent angiography, five were subsequently reoperated. Of 8807 CABG patients, 76 underwent postoperative emergency resternotomy 1988-1999 (Pre-angiography era) and served as controls. RESULTS: the angiography era patients were older (64.0 years vs. 58.2 years, P = 0.002) and the proportion of female patients (22% vs. 43%, P = 0.029) was smaller. The rate of emergency reoperations decreased (0.86% vs 0.34%, P < 0.001) during the Angiography era and graft repairs (P = 0.013) or additional grafts (P = 0.006) were less frequent, although occluded anastomoses were observed more often (P = 0.043). In 5 Angiography era patients graft complications were corrected with percutaneous coronary intervention. ICU stay (5.72 + 0.98 days vs. 5.53 + 0.68 days) and hospital stay (12.2 + 1.54 days vs. 13.1 + 1.63 days) did not differ between the groups, but the rate of myocardial infarction (63.8% vs. 92.1%, P < 0.001) and in-hospital death (22.2% vs. 46.1%, P = 0.015) decreased. CONCLUSION: after the introduction of early postoperative angiographic evaluation of CABG patients the rate of emergency reoperations and related morbidity and mortality decreased.

Long-term indwelling pleural catheter (PleurX) for malignant pleural effusion unsuitable for talc pleurodesis.

AIMS: Talc pleurodesis using talc slurry via chest tube is a primary option in malignant pleural effusion, since life expectancy is short and surgical decortication is hazardous. Incomplete lung expansion after fluid evacuation, and/or excessive fluid secretion predicts failure of pleurodesis. A mini-invasive alternative was investigated. METHODS: Between March 2004 and September 2005, 51 consecutive patients with malignant pleural effusion, and clinically considered unsuitable for talc pleurodesis, received an indwelling pleural catheter (Denver PleurX). In 47, implantation was done bedside using local anaesthesia. There were 24 men and 27 women, median age 63 (range 36-85) years, receiving 39 right side, 10 left side, and 2 bilateral catheters. There were 19 non-small cell lung cancer cases, 7 mesothelioma, and 25 with other malignancy. Chemotherapy was being given to 18 patients and was not interrupted. RESULTS: Discharge to home was possible in 71% (36 of 71 patients) on the following day. At 2 years follow-up in September 2007, one patient was alive. Mean survival was 3 months (range 5 days to 37+months) for all patients, with best median survivals of 5.5-6 months in breast and ovarian cancer. Catheter was removed or replaced in 15% (8 of 51 patients) due to infection, air leak, or blockage. One patient requested decortication for excessive fluid secretion. None required surgery or died due to catheter-related complications. Pleural fusion with subsequent catheter removal was achieved in 21% (11 of 51 patients). CONCLUSIONS: An indwelling pleural catheter is a safe alternative for patients with malignant pleural effusion unsuitable for talc pleurodesis. In some, pleural fusion may be achieved.

The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours.

PURPOSE: The most common marker of oxidative DNA damage is 8-hydroxydeoxyguanosine (8-OHdG), which is linked with several malignancies. In the present study we investigated whether DNA damage linked to oxidative stress (as 8-OHdG) is present in Barrett's mucosa with or without associated adenocarcinoma or high-grade dysplasia and in normal controls' squamous mucosa. EXPERIMENTAL DESIGN: We measured 8-OHdG in 51 patients (13 Barrett's metaplasia, six Barrett's oesophagus with high-grade dysplasia, 18 adenocarcinoma of the distal oesophagus/oesophagogastric junction and 14 normal controls). The amount of DNA damage was determined by high-performance liquid chromatography in oesophagus samples obtained either from endoscopy or as samples from surgery. The median 8-OHdG concentration was expressed as the ratio of 8-OHdG per 10(5) deoxyguanosine. RESULTS: Analysis revealed that 8-OHdG was present in both Barrett's metaplasia with and without dysplasia as well as in adenocarcinoma of the oesophagus/oesophagogastric junction. Although the study group was small the amount of 8-OHdG was significantly increased in the distal oesophagus both in Barrett's epithelium 1.26 (0.08-29.47) and in high-grade dysplasia 1.35 (1.04-1.65) as well as in adenocarcinoma of oesophagus/oesophagogastric junction 1.08 (0.59-1.94) compared to controls 0.06 (0-4.08) (p=0.002, p=0.012, p=0.001, respectively). Barrett's patients had no significant difference in 8-OHdG levels between their distal and proximal oesophageal samples. CONCLUSIONS: Our results show the presence of oxidative DNA damage in the distal oesophagus of patients with Barrett's oesophagus and adenocarcinoma of the oesophagus/oesophagogastric junction. This may have a connection to carcinogenesis in Barrett's oesophagus.

Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.

BACKGROUND: HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma. PATIENTS AND METHODS: The frequency of HER-2/neu and Topoisomerase IIalpha gene amplification was studied in adenocarcinomas of the stomach (n=131) and the gastroesophageal junction (n=100) by chromogenic in situ hybridization (CISH). Sensitivity of a gastric cancer cell line N87 with HER-2/neu amplification to trastuzumab was studied by a cell viability assay and compared with that of a HER-2 amplified breast cancer cell line SKBR-3. Growth inhibition of N87 cells was also verified in vivo in N87 xenograft tumors. RESULTS: HER-2/neu amplification was present in 16 (12.2%) of the 131 gastric and in 24 (24.0%) of the 100 gastroesophageal adenocarcinomas. Co-amplification of Topoisomerase IIalpha was present in the majority of gastric (63%) and esophagogastric junction cancers (68%) with HER-2/neu amplification. HER-2/neu amplification was more common in the intestinal histologic type of gastric cancer (21.5%) than in the diffuse (2%) or the mixed/anaplastic type (5%, P=0.0051), but it was not associated with gender, age at diagnosis or clinical stage. Presence of HER-2/neu amplification was associated with poor carcinoma-specific survival (P=0.0089). HER-2/neu targeting antibody trastuzumab inhibited the growth of a p185(HER-2/neu) overexpressing gastric and breast carcinoma cell lines (N87 and SKBR-3) with equal efficacy. CONCLUSIONS: HER-2/neu amplification is common in the intestinal type of gastric carcinoma, and it is associated with a poor outcome. HER-2 might be a useful target in this disease, and this hypothesis deserves to be investigated in clinical trials.

Inoperable adenocarcinoma of the oesophagogastric junction: a comparative clinical study of laser coagulation versus self-expanding metallic stents with special reference to cost analysis.

AIMS: Neither clinical nor financial comparisons yet exist between self-expanding metallic stents (SEMS) and laser therapy, concentrating on the treatment of obstructive adenocarcinomas of the oesophagogastric junction. The aim of our study was to compare the relative lifetime costs and clinical results of the Nd:YAG laser to those of SEMS as alternative forms of primary palliation of dysphagia for adenocarcinoma near the oesophagogastric junction. METHODS: Fifty-two patients with distal oesophageal or oesophagogastric adenocarcinomas underwent palliative treatment for dysphagia: 32 treated with laser therapy and 20 with SEMS in this retrospective study. The clinical outcome and real cumulative costs as physical units and in financial terms were analysed for these study groups. RESULTS: Although patients palliated with SEMS underwent fewer procedures (1.9+/-1.6 vs 3.4+/-4.0, P=0.0048) and spent less time in endoscopic theatre (38+/-25min vs 118+/-152min, P=0.0048), they spent as many days in hospital (12.9 vs 15.1, P=0.370) and required as high overall costs for therapy (5360 EUR vs 5450 EUR, P=0.679) as those treated with laser therapy. In addition, they had higher morbidity rates (30 vs 6.3%, P=0.043), hospital mortality (20 vs 3.1%, P=0.066), and 30-day mortality (40 vs 3.1%, P=0.0011) than did patients with laser therapy, with no evidence of SEMS being the more effective treatment modality. CONCLUSIONS: In patients with adenocarcinoma at the distal oesophagus or at the oesophagogastric junction, laser therapy palliates dysphagia effectively with lower morbidity and mortality rates and without increased costs or hospital stays than does use of self-expanding metallic stents.

The epidemiology of oesophageal adenocarcinoma: has the cancer of gastric cardia an influence on the rising incidence of oesophageal adenocarcinoma?

BACKGROUND: Owing to overgrowth and definitional problems in classification, the cancer of gastric cardia may affect significantly the epidemiological analysis of oesophageal adenocarcinoma. The purpose of the present study was to evaluate the changes in the incidence of all the adenocarcinomas near the gastrooesophageal junction. METHODS: Trends in the incidence rates of adenocarcinoma of the oesophagus and the gastric cardia were described through the Finnish Cancer Registry. The annual age-standardized incidence rates during 1976-95 were analysed by a linear regression technique. RESULTS: The total incidence of oesophageal carcinoma remained around 3.5/100,000 in men, and decreased from 2.8 to 1.3/100,000 in women. The incidence of oesophageal adenocarcinoma increased from 0.28 to 0.77/100,000 (nearly 300%) in males, and from 0.08 to 0.11 per 100,000 in females. There were no significant changes with time in the incidence rate of gastric cardia cancer in either sex. Combined gastric cardia and oesophageal adenocarcinoma incidence rates remained stable in women, and increased slightly, but significantly, from 2.4 to 2.9/100,000 in men. CONCLUSION: Oesophageal adenocarcinoma has increased significantly in men in Finland, but the combined incidence of cancers of the gastro-oesophageal junction has increased only slightly. To overcome the difficulties in classification of oesophageal adenocarcinoma and the cancer of gastric cardia in the epidemiological studies, the focus should be on all adenocarcinomas at or near the oesophagogastric junction.

Subacute primary Candida lung abscess.

A case of primary subacute Candida lung abscess is described. The most reliable way to diagnose a rare pulmonary disease is to perform an open lung biopsy. A review of the literature suggests that the diagnosis of a primary subacute abscess due to Candida albicans in vivo is unique.