Tumor size as a prognostic factor in patients with stage IIa colon cancer.

BACKGROUND: The aim of this study was to identify stage II colon cancer patients with a high risk of recurrence. METHODS: All patients who underwent surgery for stage II colon cancer (CC) were retrospectively enrolled and sub-grouped according to TNM staging (IIa-b-c) and stage IIa in high (IIaHR) and low risk (IIaLR) according to pathologic features. The primary outcomes measured were the 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 214 patients were reviewed. Only a maximum tumor diameter<4 cm in the IIaLR group was associated with a higher recurrence rate than a large tumor size (5-year DFS 71.7%vs.87.6%, p = 0.028). The DFS in the large IIaLR CC group was better than that in the IIaHR and IIb-c groups (5-year DFS: 92.7%vs.79.3%, p = 0.023). In contrast, the recurrence rate in the small IIaLR CC group was similar to that in the IIaHR, IIb-c stage CC group. CONCLUSIONS: In stage IIa CC evaluation of the tumor size as a prognostic factor may help identify patients who could benefit from additional postoperative therapy.

Liver surgery in the multidisciplinary management of gastrointestinal stromal tumour.

BACKGROUND: After the introduction of tyrosine kinase inhibitors (TKIs), the role of surgical resection in treating liver metastasis from gastrointestinal stromal tumour (GIST) is unclear. In this study, we evaluated the outcome of patients treated with TKIs followed by surgery for metastatic GIST. METHODS: Eleven patients who underwent liver resection after downsizing TKIs therapy for metastatic GIST from 2006 until 2010 were reviewed. RESULTS: One and 2-year overall survival (OS) rates were 80.8% and 70.7%. All patients with an initially resectable tumour were still alive without recurrence. Patients operated on clinical response had a better outcome (1-year and 2-year OS rate of 100%) than those operated on disease progression (1-year and 2-year OS rates of 60% and 40%; P = 0.043). No deaths were observed among patients who achieved an R0 resection (R0 versus R1/R2, P = 0.001). CONCLUSION: R0 resection and clinical response to TKI are predictors of survival. Surgical resection should be performed as soon as feasible in responder patients. In poor responders, surgery may not add any survival benefit, except in localized progressive disease. In resectable metastatic liver disease, preoperative TKIs or upfront surgery followed by adjuvant therapy could be considered. Larger studies are needed to determine the optimum approach in patients with metastatic GIST.

Prognostic factors for primary gastrointestinal stromal tumours: are they the same in the multidisciplinary treatment era?

PURPOSE: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The introduction of tyrosine kinase inhibitors (TKIs) has lead to increasing use of combination of medical and surgical therapy. The aim of this study was to look at outcomes from a series of surgically treated GISTs and determine prognostic factors in the context of multimodal therapy. METHODS: We analysed 104 single surgeon's patients with GIST. End points of the study were disease-specific survival (DSS), disease-free survival (DFS) and post-operative complications. RESULTS: Three- and 5-year DSS rates were 96.7 and 94.6 %. On univariate analysis, clear resection margins were predictive of DSS. Patients with R2 resection had a worse prognosis (3-year DSS rate of 83.3 %; 5-year DSS rate of 62.5 %) compared to patients with R0 (3-year DSS rate of 98 %; 5-year DSS rate of 98 %) or R1 resection (3-year DSS rate of 100 %; 5-year DSS rate of 100 %) (R0 vs R1 vs. R2 p = 0.001). Pre-operative factors associated with R2 resection were clinical metastatic disease (p < 0.001), non-gastric tumour site (p = 0.002) and large tumour diameter (p = 0.031). Three- and 5-year DFS rates were 65.5 and 59.8 %. Serosal perforation (p = 0.013) and mitotic rate (p = 0.05) were found to be independently predictive of increased DFS. The presence of serosal perforation was associated with tumour site (p = 0.018), mitotic rate (p = 0.035), tumour diameter (p < 0.001), growth pattern (p = 0.007) and age (p = 0.040). CONCLUSIONS: In the multidisciplinary management of GIST, serosal perforation may represent an additional predictor of recurrence along with mitotic rate. Complete macroscopic surgical resection is the most reliable prognostic factor, and an aggressive surgical approach should be advocated.

Liver surgery in the multidisciplinary management of gastrointestinal stromal tumour.

INTRODUCTION: After the introduction of tyrosine kinase inhibitors (TKIs), the role of surgical resection in treating liver metastasis from gastrointestinal stromal tumour (GIST) is unclear. In this study, we evaluated the outcome of patients treated with TKIs followed by surgery for metastatic GIST. METHODS: Eleven patients underwent liver resection after downsizing TKIs therapy for metastatic GIST from 2006 until 2010 were reviewed. RESULTS: One and two-year overall survival rates were 80.8 and 70.7%. All patients with an initially resectable tumour were still alive without recurrence. Patients operated on clinical response had a better outcome (1- and 2-year overall survival (OS) rate 100%) than those operated on disease progression (1- and 2-year OS rates 60 and 40%; P = 0.043). No deaths were observed among patients who achieved an R0 resection (R0 versus R1/R2, P = 0.001). DISCUSSION: R0 resection and clinical response to TKI are predictor of survival. Surgical resection should be performed as soon as feasible in responding patients. In poor responders, surgery may not add any survival benefit, except in localized progressive disease. In resectable metastatic liver disease, preoperative TKIs or upfront surgery followed by adjuvant therapy could be considered. Larger studies are needed to determine the optimum approach in patients with metastatic GIST.

Surgical management of intraabdominal metastases from melanoma: role of the neutrophil to lymphocyte ratio as a potential prognostic factor.

BACKGROUND: The aims of this study were to evaluate the role of surgery in the management of patients with intraabdominal metastases from melanoma and to investigate the neutrophil to lymphocyte ratio (NLR) as prognostic factor in this group of patients. METHODS: Altogether, 44 patients who underwent surgery for Intraabdominal metastases from melanoma with curative, cytoreductive, or palliative intent were analyzed. RESULTS: There were 77 intraabdominal organ resections performed during the 44 operations. R0 resection was achieved in 19 (43 %) cases. Factors associated with R0 resection were an absence of extra-abdominal metastases, low serum lactate dehydrogenase, involvement of fewer than three sites, and the presence of fewer than three metastatic lesions. The 1-, 3-, and 5-year overall survival rates were, respectively, 79, 66, and 44 % in the curative intent group; 36, 18, and 9 % in the cytoreduction group; and 21, 0 and 0 % in the palliation group (curative intent vs. cytoreduction vs. palliation p < 0.001). By Cox's multivariate analysis, the independent prognostic factors were time from excision of primary melanoma to the diagnosis of intraabdominal metastases, NLR, and residual disease after surgery. CONCLUSIONS: Our results confirm the usefulness of major surgical interventions as reported in previous studies. We reviewed recent evidence that immunologic phenomena may explain the unexpectedly good response rate in patients with advanced disease. The simple estimation of the NLR has been advocated as a prognostic marker for several cancers. We show that it is likewise useful in metastatic melanoma. We stress the need for developing additional immunologic markers.

"Chronic" metastatic pancreatic acinar cell carcinoma.

Acinar cell carcinoma (ACC) of the pancreas is a rare exocrine tumour for which there is very limited information about chemotherapy regimens and prognosis. Even though there are clinical guidelines for management of ductal cell carcinoma, a definitive and specific regime has not yet been agreed for this type of pancreatic cancer. We report a case of metastatic ACC of pancreas who has been treated with a multimodal approach, including novel combinations of different targeted drugs with conventional chemotherapy, surgery and radiofrequency ablation since the last 11 years. This degree of long term survival has not been reported so far in such a case of metastatic ACC of the pancreas. This case highlights the importance of a personalised multidisciplinary therapeutic strategy, employing locoregional therapies along with combinations of established and novel systemic therapies to control the disease, and the importance of flexibility when instigating new treatment paradigms for progressive cancer. Also, this case demonstrates that complete tumour eradication may not be the sole purpose of surgical oncology.

Long-term survival and outcome of patients originally given Mycobacterium vaccae for metastatic malignant melanoma.

BACKGROUND: The long-term prognosis of patients with stage IV AJCC melanoma is extremely poor. We have previously published short-term clinical outcome and immunological responses to a heat killed Mycobacterium vaccae-based vaccine. RESULTS: In this study we report on a better than expected long-term survival (3-y DSS 29·6%, 5-y, and 7-y DSS both 23·9%) relative to historical controls in the patients who received the vaccine in these trials, published in 1999 and 2003. Although the complete or partial response was only 10%, it was the remarkable response to other interventions upon relapse, such as surgery and radiotherapy followed by stable disease that was previously unexpected. METHODS: We reviewed the outcome of 72 patients who were treated with M. vaccae for metastatic melanoma between January 1996 and July 2004. CONCLUSION: Given this remarkable outcome in stage IV metastatic melanoma and its lack of toxicity we propose that this would make a promising candidate for randomized trials for stage III fully resected melanoma.

The road to curative surgery in gastric cancer treatment: a different path in the elderly?

BACKGROUND: The aim of this study was to evaluate the possibility of a different path to achieve curative surgery in patients older than age 70 years and affected by resectable gastric cancer. STUDY DESIGN: This is a multicentric retrospective study based on an analysis of 1,465 patients with gastric adenocarcinoma who underwent surgery with curative intent. Patients were divided into 2 age groups (younger than 70 years vs older than 70 years) and were evaluated with respect to postoperative morbidity and mortality and survival. RESULTS: Postoperative morbidity and mortality in elderly and nonelderly groups were 24.8% vs 20.6% and 2.6% vs 3.7%, respectively (p = NS). In the elderly group, multivisceral resection was independently associated with surgical complications (hazard ratio [HR] = 1.988; 95% CI, 1.124-3.516; p = 0.018), total gastrectomy with medical complications (HR = 2.007; 95% CI, 1.165-3.459; p = 0.012), and higher postoperative mortality (HR = 4.319; 95% CI, 1.571-11.873; p = 0.005); D1 lymph node dissection was predictive of a lower postoperative mortality rate (HR = 0.219; 95% CI, 0.080-0.603; p = 0.003). Five-year overall survival rates differed significantly in young and elderly patients (58.9% vs 38.9%; p < 0.001), and 5-year cancer-specific survival did not show any significant difference. CONCLUSIONS: Age should not be considered as a factor in the selection of treatment for gastric cancer patients. Curative surgery can be performed as safely in elderly patients as in younger patients, with comparable postoperative results and long-term survival rates, although the life expectancy of elderly patients is shorter.

Log odds of positive lymph nodes in colon cancer: a meaningful ratio-based lymph node classification system.

BACKGROUND: The log odds of positive lymph nodes (LODDS), defined as the log of the ratio between the numbers of positive and negative lymph nodes, has recently been proposed as a new prognostic index in surgical oncology. The aim of the present study was to investigate whether the LODDS system of lymph node classification was a more accurate prognostic tool than the tumor node metastasis (TNM) and lymph node ratio (LNR) classifications in colon cancer patients. MATERIALS AND METHODS: Clinicopathologic data from 258 colon cancer patients who had undergone surgical resection were reviewed. Lymph node parameters were categorized according to the Internation Union Against Cancer/American Joint Cancer Commission (UICC/AJCC) TNM staging system, the LNR (LNR0 with ratio ≤ 0.05, LNR1 with 0.05 < ratio ≤ 0.20, LNR2 with ratio > 0.20), and the log odds ratio (LODDS0 ≤ -1.36, -1.36 < LODDS1 ≤ -0.53, and LODDS2 > -0.53). RESULTS: The LODDS was able to identify patients who would have been included in different prognostic categories, according to both the TNM and LNR. In addition, LODDS was significantly related to the number of positive and negative lymph nodes, as well as the number of examined lymph nodes. In multivariate analysis, LODDS classification (LODDS0: HR 1; LODDS1: HR 3.687, p = 0.003; LODDS2: HR 9.440, p < 0.001) was identified as an independent prognostic factor. DISCUSSION: The LODDS system is a highly reliable staging system with strong predictive ability for patient outcome. Compared with other nodal staging systems, the prognostic power of LODDS is less influenced by the number of lymph nodes dissected and examined.

7-Year survival results of perioperative chemotherapy with epidoxorubicin, etoposide, and cisplatin (EEP) in locally advanced resectable gastric cancer: up-to-date analysis of a phase-II study.

BACKGROUND: Perioperative chemotherapy is considered an effective treatment option for patients with gastric carcinoma. We report the results after a 7-year follow-up of a study aimed at evaluating a perioperative chemotherapy protocol in a group of patients with locally advanced gastric cancer (LAGC). METHODS: Between February 1996 and May 2000, 24 patients with LAGC underwent D2-gastrectomy after three preoperative cycles of chemotherapy (Epidoxorubicin, Etoposide, Cisplatinum). Three further cycles were planned after surgery. Differences among groups were evaluated using the chi-square test. Survival rate was calculated after a 7-year follow-up, and differences were assessed using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model. RESULTS: A total of 24 patients received preoperative chemotherapy and underwent surgical resection. Of these, 17 (71%) received postoperative treatment. The main toxicity was grade 3-4 neutropenia. Curative resection (R0) was achieved in 83.3% of patients. No pathologic complete responses were documented, but tumor downstaging was obtained in 10 of 24 patients (41.7%). Overall median survival was 40 months, and 7-year survival rate was 46%. At univariate and multivariate analysis, R0 resection and tumor diameter were the most important prognostic factors. CONCLUSION: Long-term results in our series show a survival benefit for LAGC patients treated by perioperative chemotherapy and D2-gastrectomy when compared with previously studied controls who had surgery with postoperative chemotherapy alone. The high rate and prognostic impact of R0 resection in this study stressed the role of the therapy during the preoperative phase.

[Surgical anatomy of the anterior mediastinum]. / Anatomia chirurgica del mediastino anteriore.

The mediastinum is located from the thoracic inlet to the diaphragm between the left and right pleural cavities and contains vital structures of the circulatory, respiratory, digestive, and nervous system. Over the years, since there are no fascial or anatomic planes, anatomists and radiologists have suggested various schemes for subdividing the mediastinum and several anatomical and radiological classifications of the mediastinum are reported in the literature. The most popular of these scheme divides medistinum, for purposes of description, into two parts: an upper portion, above the upper level of the pericardium, which is named the superior mediastinum; and a lower portion, below the upper level of the pericardium. For clinical purposes, the mediastinum may be subdivided into three major areas, i.e. anterior, middle, and posterior compartments. The anterior mediastinum is defined as the region posterior to the sternum and anterior to the heart and brachiocephalic vessels. It extends from the thoracic inlet to the diaphragm and contains the thymus gland, fat, and lymph nodes. This article will review surgical anatomy of the anterior mediastinum and will focus on the surgical approch to anterior mediastinum and thymic diseases.