| 1. |
- Kauppila, Joonas H, et al.
(author)
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Gastrectomy compared to oesophagectomy for Siewert II and III gastro-oesophageal junctional cancer in relation to resection margins, lymphadenectomy and survival
- 2017
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In: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 2045-2322.
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Journal article (peer-reviewed)abstract
- It is unclear whether gastrectomy or oesophagectomy offer better outcomes for gastro-oesophageal junction (GOJ) cancer. A total of 240 patients undergoing total gastrectomy (n = 85) or oesophagectomy (n = 155) for Siewert II-III GOJ adenocarcinoma were identified from a Swedish prospective population-based nationwide cohort. The surgical approaches were compared in relation to non-radical resection margins (main outcome) using multivariable logistic regression, providing odds ratios (ORs) and 95% confidence intervals (CIs), mean number of removed lymph nodes with standard deviation (SD) using ANCOVA, assessing mean differences and 95% CIs, and 5-year mortality using Cox regression estimating hazard ratios (HRs) and 95% CIs. The models were adjusted for age, sex, comorbidity, tumour stage, and surgeon volume. The non-radical resection rate was 15% for gastrectomy and 14% for oesophagectomy, and the adjusted OR was 1.61 (95% CI 0.68-3.83). The mean number of lymph nodes removed was 14.2 (SD +/- 9.6) for gastrectomy and 14.2 (SD +/- 10.4) for oesophagectomy, with adjusted mean difference of 2.4 (95% CI-0.2-5.0). The 5-year mortality was 76% following gastrectomy and 75% following oesophagectomy, with adjusted HR = 1.07 (95% CI 0.78-1.47). Gastrectomy and oesophagectomy for Siewert II or III GOJ cancer seem comparable regarding tumour-free resection margins, lymph nodes removal, and 5-year survival.
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| 2. |
- Kauppila, Joonas H, et al.
(author)
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Intratumoral lactate metabolism in Barrett’s esophagus and adenocarcinoma
- 2017
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In: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Journal article (peer-reviewed)abstract
- Background: Monocarboxylate transporters (MCTs) are cell membrane proteins which transport pyruvate, lactate and ketone bodies across the plasma membrane. MCTs are activated in various cancers, but their expression in esophageal adenocarcinoma is not known. The present study was conducted to elucidate the expression of MCTs in esophageal adenocarcinoma and its precursor lesions. Results: Cytoplasmic MCT1, MCT4 and MTCO1 expression linearly increased from normal epithelium to Barrett's mucosa to dysplasia and cancer. Low cytoplasmic MCT1 expression associated with high T-class (P < 0.01), positive lymph node metastases (P < 0.05), positive distant metastases (P < 0.01) and high tumor stage (P < 0.01). High cytoplasmic MCT4 expression correlated significantly with positive distant metastases (P < 0.05). Both low MCT1 and high MCT4 histoscore predicted survival in univariate analysis (P < 0.01). MCT4 histoscore predicted survival in multivariate analysis (P = 0.043; HR 1.8 95%CI 1.0–3.1). MTCO1 expression was not correlated to clinicopathological variables or survival. Materials and Methods: MCT1, MCT4 and mitochondrial cytochrome c oxidase (MTCO1) expression were determined with immunohistochemistry in esophageal specimens from 129 patients with columnar dysplasia or adenocarcinoma. Specimens including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51), low-grade (n = 42), high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were evaluated. Conclusions: Major increase in markers of tumor metabolism occurs during carcinogenesis and progression of esophageal adenocarcinoma. MCT1 and MCT4 are prognostic factors in esophageal adenocarcinoma.
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| 3. |
- Kauppila, Joonas H, et al.
(author)
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Meta-analysis of health-related quality of life after minimally invasive versus open oesophagectomy for oesophageal cancer
- 2017
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In: British Journal of Surgery. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 0007-1323 .- 1365-2168.
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this systematic review and meta-analysis was to compare health-related quality of life (HRQoL) outcomes between minimally invasive and open oesophagectomy for cancer at different postoperative time points. METHODS: A search of PubMed (MEDLINE), Web of Science, Embase, Scopus, CINAHL and the Cochrane Library was performed for studies that compared open with minimally invasive oesophagectomy. A random-effects meta-analysis was conducted for studies that measured HRQoL scores using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OES18 questionnaires. Mean differences (MDs) greater than 10 in scores were considered clinically relevant. Pooled effects of MDs with 95 per cent confidence intervals were estimated to assess statistical significance. RESULTS: Nine studies were included in the qualitative analysis, involving 1157 patients who had minimally invasive surgery and 907 patients who underwent open surgery. Minimally invasive surgery resulted in better scores for global quality of life (MD 11.61, 95 per cent c.i. 3.84 to 19.39), physical function (MD 11.88, 3.92 to 19.84), fatigue (MD -13.18, -17.59 to -8.76) and pain (MD -15.85, -20.45 to -11.24) compared with open surgery at 3 months after surgery. At 6 and 12 months, no significant differences remained. CONCLUSION: Patients report better global quality of life, physical function, fatigue and pain 3 months after minimally invasive surgery compared with open surgery. No such differences remain at longer follow-up of 6 and 12 months.
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| 4. |
- Kauppila, Joonas H, et al.
(author)
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Tenascin-C and fibronectin in normal esophageal mucosa, Barrett's esophagus, dysplasia and adenocarcinoma
- 2017
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In: Oncotarget. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1949-2553.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tenascin-C and fibronectin are adhesive glycoproteins modulating the structure of the extracellular matrix and cellular functions. Their expression and function in esophageal adenocarcinoma is poorly known. The aim of this study was to evaluate the expression of tenascin-C and fibronectin in esophageal adenocarcinoma and its precursor stages. RESULTS: Stromal tenascin-C and fibronectin expression were found in all evaluated lesion types. Expression of both molecules increased from gastric metaplasia towards adenocarcinoma (p<0.05). In carcinomas, tenascin-C expression in the bulk was associated with T-stage (p=0.006), presence of lymph node (p=0.004) and distant organ metastases (p=0.007). Abundant tenascin-C expression associated with poor survival (p=0.034) in univariate analysis. Fibronectin expression associated to T-stage (p=0.030). Expression of tenascin-C or fibronectin in the tumor invasive front was not associated to clinicopathological variables or survival. No significant correlation with tumor/stroma percentage, cancer-associated fibroblasts or mean vascular density was observed with either tenascin-C or fibronectin. METHODS: Tenascin-C and fibronectin were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal adenocarcinoma (n=90) or dysplasia (n=30). Structures and lesion were evaluated including normal esophagus (n=77), gastric (n=61) or intestinal (n=51) metaplasia without dysplasia, and low-grade (n=42) or high-grade (n=34) dysplasia, and esophageal adenocarcinoma (n=90). In carcinomas, both bulk and invasive front were separately evaluated. In addition, tumor/stroma percentage, cancer-associated fibroblasts and mean vascular density were evaluated. CONCLUSIONS: Tenascin-C and fibronectin are upregulated in esophageal adenocarcinoma when compared to Barrett's esophagus and dysplasia. Increased tenascin-C expression is associated with metastasis and poor prognosis in esophageal adenocarcinoma.
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| 5. |
- Ringborg, Cecilia, et al.
(author)
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Health‑related quality of life after gastrectomy, esophagectomy, and combined esophagogastrectomy for gastroesophageal junction adenocarcinoma
- 2017
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In: Gastric Cancer. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1436-3291 .- 1436-3305.
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Journal article (peer-reviewed)abstract
- BACKGROUND: The postoperative health-related quality of life (HRQOL) outcomes in patients with gastroesophageal junction (GEJ) adenocarcinoma after gastrectomy and esophagectomy are unclear. The aim was to evaluate HRQOL outcomes 6 months after extended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy. METHODS: Patients who underwent surgery for GEJ adenocarcinoma of Siewert type 2 or 3 in 2001-2005 were identified from a nationwide Swedish prospective and population-based cohort. Three surgical strategies, i.e., gastrectomy, esophagectomy, or esophagogastrectomy, were analyzed in relationship to HRQOL measured at 6 months after surgery (main outcome). HRQOL was assessed using well-validated questionnaires for general (EORTC QLQ-C30) and esophageal cancer-specific (EORTC QLQ-OES18) symptoms. Mean score differences (MSD) and 95% confidence intervals (CI) were analyzed using ANCOVA and adjusted for age, sex, tumor stage, comorbidity, education level, hospital volume, and postoperative complications. MSDs > 10 were regarded as clinically relevant. RESULTS: Among 176 patients with complete information on HRQOL and covariates, none of the MSDs for HRQOL among the three surgery groups were clinically and statistically significant. MSDs comparing esophagectomy and gastrectomy showed no major differences in global quality of life (MSD, +8, 95% CI, 0 to +16), physical function (MSD, +2, 95% CI, -5 to +9), pain (MSD, -3, 95% CI, -12 to +7), or reflux (MSD, +5, 95% CI, -4 to +14). Also, complication rates and 5-year survival rates were similar comparing esophagectomy and gastrectomy. CONCLUSIONS: Extended total gastrectomy, subtotal esophagectomy, and combined esophagogastrectomy seemed to yield similar 6-month postoperative HRQOL outcomes for patients with GEJ adenocarcinoma.
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