Pretreatment Primary Tumor Stage is a Risk Factor for Recurrence in Patients with Esophageal Squamous Cell Carcinoma Who Achieve Pathological Complete Response After Neoadjuvant Chemoradiotherapy

Annals of Surgical Oncology - Although pathological complete response (pCR) after multimodal treatment for esophageal cancer is associated to the best prognosis, recurrence may occur in...     

ASO Author Reflections: Recurrence After Pathological Complete Response in Esophageal Cancer: Analysis of Risk Factors for this Unexpected Event

Annals of Surgical Oncology -     

Gastric Stump Cancer After Distal Gastrectomy for Benign Disease: Clinicopathological Features and Surgical Outcomes

Purpose

The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease.

Methods

We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6–207) months.

Results

One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2–T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002).

Conclusions

Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC.     

Serotonin transporter gene polymorphisms and treatment-resistant depression

Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.     

Indexes of Surgical Quality in Gastric Cancer Surgery: Experience of an Italian Network

Background  Short-term results of gastric cancer surgery vary remarkably worldwide, and international surgical quality criteria are urgently needed. To contribute to defining these criteria, we reviewed short-term results of gastrectomy for gastric cancer in three centers of the Italian Research Group for Gastric Cancer, with an average of 24.7, 29.5, and 18 gastrectomies per year. Methods  Between 1988 and 2002, 1,032 patients underwent gastrectomy for gastric cancer in Verona, Siena, and Padua. D1, D2, and D3 lymphadenectomy were performed, respectively, in 228, 584, and 220 cases. Results  The median number of retrieved lymph nodes was 14 (interquartile range 9–18.75) after D1, 29 (21–38) after D2, and 46.5 (37–57) after D3. Fewer than 15 nodes were retrieved in 54.5%, 6.2%, and 1.4% of cases undergoing, respectively, D1, D2, and D3. Adjacent organ removal was rare during D1 (splenectomy: 6.1%, splenopancreasectomy: 1.8%), and quite common during D3 (11.4%, 11.4%). Forty patients (3.9%) died postoperatively. Neither postoperative morbidity nor mortality was significantly associated with extension of lymphadenectomy. Conclusion  We conclude that at least D2 lymphadenectomy is necessary to achieve adequate disease staging (≥15 nodes retrieved). Spleen and pancreas tail are more frequently removed during D3, but this removal is not associated with higher postoperative morbidity or mortality.     

Chemoradiotherapy followed by surgery for squamous cell carcinoma of the thoracic esophagus with clinical evidence of adjacent organ invasion

BACKGROUND: The role of surgery for esophageal squamous cell carcinoma (SCC) with clinical evidence of adjacent organ invasion (cT4) is a debated issue. This study was aimed at analyzing our experience with chemoradiotherapy (CRT) followed by surgery as treatment for non-metastatic cT4 SCC of the thoracic esophagus. METHODS: The results of 51 patients consecutively treated at the First Department of General Surgery, University of Verona, from January 1987 to December 2004 were analyzed. RESULTS: The most frequently clinically involved structures were the trachea (43.1%), the main left bronchus (17.6%), and the thoracic aorta (15.7%). CRT was completed in all but one of the patients (98.0%) without toxicity-related deaths. After completion of induction treatment 49 patients underwent surgery (96.1%), and resection was possible in 40 patients (78.4%) but R0 surgery was rarely obtained (39.2%). Pathologic downstaging was achieved in 18 cases (35.3%) while a major response (responders) was observed in 10 patients (19.6%) and a complete response (pT0N0) in 7 (13.7%). The overall median survival time was 11.1 months with a 3-year survival rate of 8.8%. A significantly better survival (P < 0.001) was observed after a R0 resection (median: 22.3 months; 3-year survival: 25.4%; P < 0.001) and for responders (median: 33.1 months; 3-year survival: 25.7%; P = 0.019). CONCLUSIONS: Aggressive multi-modal therapy with CRT followed by surgery in cT4 SCC of the thoracic esophagus is feasible. Surgery should be limited to patients with significant response to induction treatment and a high probability of R0 resection.     

TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

Background:

About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma.

Methods:

TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma.

Results:

In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard''s tumour regression grade classifications, respectively).

Conclusions:

The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy.     

Tumor site and perigastric nodal status are the most important predictors of para-aortic nodal involvement in advanced gastric cancer

Background  

This study was designed to identify pathological predictors of para-aortic nodal invasion in advanced gastric cancer.