Tumour-infiltrating lymphocytes and survival in patients with adenocarcinoma of the oesophagus.

INTRODUCTION: Tumor-infiltrating lymphocytes (TILs) and forkhead box transcription factor positive (FoxP3(+)) regulatory T-lymphocytes (TREGs) have been analyzed in a variety of tumors but not in oesophageal adenocarcinoma. PATIENTS AND METHODS: Tissue from 130 adenocarcinomas of the oesophagus was re-evaluated in the centre and periphery of tumour, respectively, using immunohistochemical staining with anti-CD3, anti-CD4, anti-CD8, anti-CD25 and anti-FoxP3 antibodies. Patients were stratified according neoadjuvant treatment. 106 patients proceeded directly to surgery and 24 underwent pre-operative radio-chemotherapy (RCT). RESULTS: In patients without RCT, TILs were found significantly more frequently in the periphery with the exception of CD25(+) cells. Patients with centrally low counts of FoxP3(+) TREGs had higher tumour stages than patients with high counts (p < 0.011). The number of FoxP3(+) TREGs was significantly associated with the number of CD8(+) cells (centre: p < 0.001, periphery: p = 0.002). The multivariate regression analysis identified UICC stage (IIB/III vs. I/IIA, hazard ratio 2.6, p = 0.011) and completeness of resection (no vs. yes, hazard ratio 2.3, p = 0.015) as independent predictors of survival. RCT significantly reduced the number of TREGs in the centre (p = 0.016) but not the number of the other TILs. CONCLUSION: UICC stage and completeness of resection but none of the TILs were prognostic markers for long-term survival. We found no morphologic evidence that TREGs suppress immunological response, represented by the infiltration of CD8(+) cells. Preoperative RCT affected the centre of tumours more than the periphery, which may indicate that it does not inhibit the host-to-tumour reaction. RCT affects TREGs more than the other TILs.

Metformin induces glucose uptake in human preadipocyte-derived adipocytes from various fat depots.

To evaluate the effect of metformin on basal and insulin-induced glucose uptake in subcutaneous and visceral preadipocyte-derived adipocytes from obese and non-obese patients, preadipocytes were obtained from subcutaneous and visceral fat depots during abdominal surgery. Differentiation efficiency was evaluated by measurement of intracellular triglyceride accumulation. Preadipocyte-derived adipocytes were treated with metformin (1 mM) for 24 h with or without the addition of insulin (100 nM) for 20 min and glucose uptake was measured. In cells from each donor, intracellular triglyceride accumulation was more abundant in subcutaneous preadipocyte-derived adipocytes than in visceral preadipocyte-derived adipocytes (p < 0.001). Insulin stimulated glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. basal). In visceral preadipocyte-derived adipocytes, insulin did not increase basal glucose uptake. In subcutaneous preadipocyte-derived adipocytes from non-obese and obese patients, metformin alone increased glucose uptake to 2.7 +/- 0.2 (p < 0.001) and 2.1 +/- 0.1 fold (p < 0.001) respectively. Metformin increased glucose uptake in visceral preadipocyte-derived adipocytes from non-obese (1.7 +/- 0.1 fold vs. basal, p < 0.001) and obese (2.0 +/- 0.2 fold vs. basal, p < 0.001) patients. Combined treatment with metformin and insulin increased glucose uptake in subcutaneous preadipocyte-derived adipocytes from both non-obese and obese patients (p < 0.001 vs. insulin alone). In preadipocyte-derived adipocytes glucose uptake is induced by metformin independent of the fat depot origin of the preadipocytes (subcutaneous or visceral) and the obesity state of the patients (non-obese or obese). In adipocytes, metformin seems to induce glucose uptake independent of insulin suggesting an alternative mechanism of action of this drug.

Influence of neoadjuvant radio-chemotherapy on tumor-infiltrating lymphocytes in squamous esophageal cancer.

INTRODUCTION: Data on influence of radio-chemotherapy (RCT) on tumor-infiltrating lymphocytes (TILs) is scarce and no study addressed this issue in esophageal squamous cell cancer (SCC) so far. METHODS: Tumor specimens of 49 patients with SCC were re-evaluated with immunohistochemical staining with anti-CD3, anti-CD4, anti-CD8, anti-CD25 and anti-FOXP3 antibodies. Lymphocytes were counted in one high power field (0.189 mm(2)) at the periphery and in the centre of tumors. RESULTS: 21 patients received preoperative RCT, 28 proceeded directly to surgery. There was no significant difference in survival between the two groups (median survival 23.2 months vs. 22.1 months, log rank test p=n.s.). Cox regression analysis showed that no variable had a significant effect on survival. The infiltrating pattern of TILs revealed higher numbers peripherally independent of the administration of RCT. There was a significant decrease in all cell numbers except CD4(+) cells in the centre of the tumors after RCT (CD3(+)p=0.005; CD8(+)p=0.02; CD25(+)p=0.01; FoxP3(+)p=0.01). There were fewer TILs in the periphery after RCT; however, this difference only reached significance in FoxP3(+) cells (p=0.01). CONCLUSION: Neoadjuvant RCT reduced the number of TILs in esophageal SCC. This was primarily seen in the centre of tumors and suggests that the effect of RCT on immunological response is located in the centre of tumors.

Volume-controlled vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery: a meta-analysis.

It is unknown whether there are any clinically relevant differences between volume-controlled (<30-50 ml/24h across trials) vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery on outcomes such as seroma formation, wound infection or length of hospital stay. Randomised controlled trials comparing volume-controlled drainage vs no or short-term drainage after axillary lymph node dissection in breast cancer surgery were identified systematically using Pubmed, EMBASE and The Cochrane library. Trial data were reviewed and extracted independently by two reviewers in a standardised unblinded manner. Six randomised controlled trials which included a total of 561 patients fulfilled our inclusion criteria. Patients randomised to volume-controlled drainage were less likely to develop clinically relevant seromas compared to patients randomised to no/short-term drainage. There was, however, no difference in wound infections between patients treated with volume-controlled drainage and patients with no or short-term drainage. Patients randomised to volume-controlled drainage stayed significantly longer in hospital than patients randomised to no/short-term drainage. Based on available evidence, clinically relevant seromas occur more frequently in patients treated with no/short-term drainage. However, no/short-term drainage after axillary lymph node dissection does not lead to an increase in wound infections and is associated with shorter hospital stay.

Randomized clinical trial of Lichtenstein's operation versus mesh plug for inguinal hernia repair.

BACKGROUND: Two of the most commonly used open prosthetic tension-free techniques for inguinal hernia repair are Lichtenstein's operation and the mesh plug repair. The technique of choice remains a subject of ongoing debate. The objective of the present investigation was to compare the two surgical procedures with respect to associated morbidity and recurrence rates. METHODS: Five hundred and ninety-five patients with 700 primary or recurrent inguinal hernias were randomized to undergo either Lichtenstein's operation or mesh plug repair. The primary endpoint of the investigation was the recurrence rate 1 year after surgery. Secondary endpoints were perioperative complications and reoperation rates. RESULTS: At 12-month follow-up, 597 hernia repairs (85.3 per cent) were evaluated. There were no significant differences regarding recurrence rates and perioperative complications. However, there was a significant difference in the overall reoperation rate between the two treatment groups, with 13 reoperations (4.2 per cent) in the Lichtenstein group and four (1.4 per cent) in the mesh plug group (P = 0.047). CONCLUSION: Lichtenstein's operation and the mesh plug repair are comparable with respect to perioperative complications and recurrence rates.

Dissection along the optic nerve axis by a BB.

A 13-year-old Hispanic boy suffered a perforating injury to his right eye from a BB. The clinical examination and computed tomographic scan revealed questionable light perception and a dense foreign body, consistent with a BB, situated behind the globe. A vitrectomy was performed that was unsuccessful. Six months later the eye was enucleated, and the BB was found to be within the optic nerve sheath. Foreign bodies within the optic nerve are uncommon. The foreign body in this case, a BB, entered the optic nerve through the nerve head after traversing the globe. The histopathologic findings in this unusual case are presented herein.

Changes in bovine mammary insulin binding during pregnancy and lactation.

1. Binding of insulin to microsomes from mammary glands of pregnant and lactating dairy cows was characterized. 2. Binding affinities of the insulin receptor did not change from pregnancy to lactation. 3. Maximal specific binding occurred in microsomes from cows in mid-pregnancy and declined in microsomes from cows in late pregnancy. 4. Insulin binding continued to decrease from early to mid-lactation and increased during late lactation. 5. Results indicate that decreased sensitivity in mammary tissue from lactating dairy cows is at least in part a result of a reduction in insulin receptor number. 6. Results demonstrate further physiological differences between the ruminant and non-ruminant mammary gland.