Standardization of oncoplastic breast conserving surgery.

The emphasis on esthetic outcomes and quality of life after breast cancer surgery has motivated surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still rare in most countries, and there is little standardization, which challenges the scientific evaluation of the techniques. The present article attempts to standardize OPS nomenclature, indications, and reconstruction choice selection embedded in a thorough review of the literature. We propose four breast conserving surgery (BCS) categories: Conventional tumorectomy, oncoplastic mastopexy, oncoplastic tumorectomy and oncoplastic reduction mammoplasty. The main volume displacement techniques are glandular re-approximation, use of tailored glandular or dermoglandular flaps and nipple-areola complex pedicles. We developed an indication algorithm based on the size and shape of the breast as well as the size and location of the tumor. A reconstruction algorithm suggests a selection of suitable tailored flaps and pedicles based on tumor location and vascular supply of the breast. The application of these algorithms results in known and novel OPS techniques, which are presented here with long-term results. We designed the algorithms to help tailor every operation to the individual patient in a standardized manner, since OPS is now on the rise, more than two decades after the publication of the first techniques. A rapidly increasing body of observational evidence suggests comparable rates of local recurrence between OPS and conventional BCS. Importantly, the rates of clear resection margins are in favor of OPS despite extended indications to larger tumors. Finally, OPS optimizes patient satisfaction by improving esthetic outcomes after BCS.

Dual role of tumour-infiltrating T helper 17 cells in human colorectal cancer.

BACKGROUND: The immune contexture predicts prognosis in human colorectal cancer (CRC). Whereas tumour-infiltrating CD8+ T cells and myeloid CD16+ myeloperoxidase (MPO)+ cells are associated with favourable clinical outcome, interleukin (IL)-17-producing cells have been reported to correlate with severe prognosis. However, their phenotypes and functions continue to be debated. OBJECTIVE: To investigate clinical relevance, phenotypes and functional features of CRC-infiltrating, IL-17-producing cells. METHODS: IL-17 staining was performed by immunohistochemistry on a tissue microarray including 1148 CRCs. Phenotypes of IL-17-producing cells were evaluated by flow cytometry on cell suspensions obtained by enzymatic digestion of clinical specimens. Functions of CRC-isolated, IL-17-producing cells were assessed by in vitro and in vivo experiments. RESULTS: IL-17+ infiltrates were not themselves predictive of an unfavourable clinical outcome, but correlated with infiltration by CD8+ T cells and CD16+ MPO+ neutrophils. Ex vivo analysis showed that tumour-infiltrating IL-17+ cells mostly consist of CD4+ T helper 17 (Th17) cells with multifaceted properties. Indeed, owing to IL-17 secretion, CRC-derived Th17 triggered the release of protumorigenic factors by tumour and tumour-associated stroma. However, on the other hand, they favoured recruitment of beneficial neutrophils through IL-8 secretion and, most importantly, they drove highly cytotoxic CCR5+CCR6+CD8+ T cells into tumour tissue, through CCL5 and CCL20 release. Consistent with these findings, the presence of intraepithelial, but not of stromal Th17 cells, positively correlated with improved survival. CONCLUSIONS: Our study shows the dual role played by tumour-infiltrating Th17 in CRC, thus advising caution when developing new IL-17/Th17 targeted treatments.

Reversal after Hartmann's procedure in patients with complicated sigmoid diverticulitis.

AIM: Hartmann's procedure (HP) is commonly used for the emergency treatment of complicated sigmoid diverticulitis (CSD). It is intended to restore intestinal continuity; however, in practice, reversal is not carried out in all patients. It is important to know the frequency of reversal and the impact of patient-related factors on the decision for reversal. METHOD: A retrospective study was conducted on all patients who underwent HP for CSD at a tertiary referral hospital between 1 May 2005 and 31 December 2010. We assessed the frequency of reversal over time and the prognostic factors affecting the decision for reversal. RESULTS: Of 67 patients [median age 76 (interquartile range: 68-81) years] who had HP for CSD, 28 (42%) underwent reversal. The cumulative incidence of reversal after 48 weeks was 48% (95% CI: 36-62%). Reversal was less likely in elderly patients [hazard ratio (HR) per decade increase = 0.43; 95% CI: 0.26-0.71], with cardiac insufficiency or coronary heart disease (HR = 0.60; 95% CI: 0.26-1.40) and with preoperative immunosuppression or chemotherapy (HR = 0.31; 95% CI: 0.07-1.33). There was no apparent effect of these factors on mortality. CONCLUSION: Approximately half of the patients having HP for CSD undergo reversal within 48 weeks of the initial operation. The finding that age, cardiac or coronary heart disease and preoperative immunosuppression or chemotherapy have an impact on the decision for reversal is relevant to healthcare professionals and patients.

A new stomaplasty ring (Koring™) to prevent parastomal hernia: an observational multicenter Swiss study.

BACKGROUND: Parastomal hernias (PSH) are one of the most frequent complications of enterostomies with a non-negligible complication rate and a significant socioeconomic effect. Therefore, preventing PSH by placing a mesh at the time of primary surgery has been advocated. The aim of our study was to evaluate the safety and feasibility of the new stomaplasty ring [Koring™, (Koring GmbH, Basel, Switzerland)] and investigate the reason why surgeons are reluctant to take preventive measures. METHODS: A multicenter observational study was conducted on 30 patients between December 2013 and January 2015. In permanent end colostomies and end ileostomies, the Koring™ was implanted. The primary outcome was the 30-day morbidity (infection and other stoma-related complications). Secondary endpoints were the technical feasibility and the time needed to fix the ring. In addition, an online survey of 107 surgeons was performed. RESULTS: Twenty-seven patients received permanent end colostomies, and three received end ileostomies. No stoma-related complication was detected within the first 30 days post-operatively. The Koring™ ring was evaluated by the surgeons as easy and very easy to implant in more than half of the patients. Average additional operating time for ring implantation was 19 min. CONCLUSIONS: Koring™ implantation at the time of creating the stoma is safe, easy and only adds minimally operating time. A long-term follow-up as well as a randomized controlled study is needed to evaluate the impact of the Koring™ on PSH prevention. The ease and rapidity with which Koring™ can be implanted may help surgeons to overcome their apprehension of using a preventative device.

Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes.

Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2(+)/MAM-A(+) breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer.

Nuclear expression of snail is an independent negative prognostic factor in human breast cancer.

BACKGROUND: Snail is a key regulator of epithelial-mesenchymal transition of tumor cells. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. OBJECTIVES AND METHODS: To further explore the role of Snail expression in breast cancer, we conducted a study on a tissue microarray, encompassing 1043 breast cancer cases. RESULTS: A total of 265 (25.4%) breast cancers were positive for Snail. Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype. In multivariate analysis, Snail proved to be an independent negative prognostic factor for OS. In the intrinsic subtypes, Snail expression was a negative prognostic factor for OS in the luminal B HER2(-), the luminal B HER2(+), and the basal-like subtype. CONCLUSIONS: This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, thus suggesting that it may represent a potential therapeutic target.

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer.

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1(+) TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1(+) TIL were present in 104 (15.8 %) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1(+) TIL was associated with a significantly worse overall survival (HR = 2.736, p < 0.001). In subset analyses, the presence of PD-1(+) TIL was associated with significantly worse overall survival in the luminal B HER2(-) subtype (HR = 2.678, p < 0.001), the luminal B HER2(+) subtype (HR = 3.689, p < 0.001), and the basal-like subtype (HR = 3.140, p < 0.001). This is the first study to demonstrate that the presence of PD-1(+) TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease.

EpCAM expression varies significantly and is differentially associated with prognosis in the luminal B HER2(+), basal-like, and HER2 intrinsic subtypes of breast cancer.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) is frequently expressed in breast cancer, and its expression has been associated with poor prognosis. Breast cancer can be subdivided into intrinsic subtypes, differing in prognosis and response to therapy. METHODS: To investigate the association between EpCAM expression and prognosis in the intrinsic subtypes of breast cancer, we performed immunohistochemical studies on a tissue microarray encompassing a total of 1365 breast cancers with detailed clinicopathological annotation and outcomes data. RESULTS: We observed EpCAM expression in 660 out of 1365 (48%) cases. EpCAM expression varied significantly in the different intrinsic subtypes. In univariate analyses of all cases, EpCAM expression was associated with a significantly worse overall survival. In the intrinsic subtypes, EpCAM expression was associated with an unfavourable prognosis in the basal-like and luminal B HER2(+) subtypes but associated with a favourable prognosis in the HER2 subtype. Consistently, specific ablation of EpCAM resulted in increased cell viability in the breast cancer cell line SKBR3 (ER(-), PR(-), and HER2(+)) but decreased viability in the breast cancer cell line MDA-MB-231 (ER(-), PR(-), and HER2(-) ). CONCLUSION: The differential association of EpCAM expression with prognosis in intrinsic subtypes has important implications for the development of EpCAM-targeted therapies in breast cancer.

Influence of additional resection of the gastric fundus on excessive weight loss in laparoscopic very very long limb Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is the gold standard in bariatric surgery. The effect of the procedure is based on restriction, malabsorption and changes in hormonal axis. Ghrelin is an important appetite hormone which is produced mainly in the gastric fundus. By adding a resection of the gastric fundus, we hypothesized that excessive weight loss will be more prominent and the satiety feelings less pronounced compared to standard RYGB. A total of 73 patients with standard very very long limb (VVLL) RYGB (group A) were compared with 44 patients with VVLL RYGB with resection of the fundus (group B). Outcome measures were excessive weight loss (EWL), body mass index (BMI), early postoperative morbidity, change of co-morbidities, and appetite reduction as assessed by an appetite questionnaire over a postoperative period of 24 months. Groups were comparable in basic preoperative descriptions. Additional fundus resection did not influence EWL (group A 66.1 % vs. group B 70.6 %, p = 0.383) or BMI (group A 29 kg/m(2) vs. group B 27 kg/m(2), p = 0.199). No significant difference in morbidity or change of co-morbidities occurred. The appetite and satiety questionnaire showed no difference between group A and group B, respectively. Adding a resection of the gastric fundus in RYGB did not alter the clinical results, i.e., increased excessive weight loss, decrease of appetite, or increase of satiety. The value of removing a part of the ghrelin-producing cells might be overestimated.

PTP1B expression is an independent positive prognostic factor in human breast cancer.

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has come into focus as a critical regulator of multiple signaling pathways. The role of PTP1B in breast cancer remains unclear with evidence suggesting that PTP1B can exert both tumor-suppressing and tumor-promoting effects. To better define the role of PTP1B in human breast cancer, and its relationship with HER2, we performed immunohistochemical studies on a large cohort of functionally annotated primary breast cancer specimens. 683 of 1,402 (49 %) evaluable primary breast cancers are positive for PTP1B. There is no statistically significant association between PTP1B expression and age, tumor size, T stage, histologic grade, lymph node status, or histological subtype. Of note, there is no significant association between PTP1B expression and HER2 expression (PTP1B expression 53.1 % in HER2(+) cancers vs. 47.5 % in HER2(-) cancers, p = 0.0985). However, PTP1B expression is significantly associated with estrogen receptor expression (PTP1B expression 50.7 % in ER(+) cancers vs. 43.1 % in ER(-) cancers, p = 0.0137) and intrinsic molecular subtype (PTP1B expression 53.9 % in the luminal B HER2(+) subtype and 37.9 % in the basal-like subtype). Of note, multivariate analyses demonstrate that PTP1B is an independent predictor of improved survival in breast cancer (HR 0.779, p = 0.006). Taken together, we demonstrate in the largest study to date that (1) PTP1B is commonly expressed in breast cancer, (2) there is no association or functional impact of PTP1B expression in HER2(+) breast cancer, and (3) PTP1B expression in breast cancer is associated with significantly improved clinical outcome. Until additional studies are performed, caution should be exercised in using PTP1B inhibitors in human breast cancer.

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.

[Futility: a concept in routine surgery?]. / Futility: ein Begriff im chirurgischen Alltag?

In surgical practice we are often confronted with ethically challenging situations when treating patients not capable of expressing their own wishes. Issues of futile treatment by indicating operations arise particularly with regard to severe dementia. The concept of futility describes forms of therapy which are not appropriate to improve the patient's condition, but for application in clinical practice the concept is insufficiently defined.In ethically challenging situations, e.g. in the treatment of severely demented patients, we need to balance the medical condition and prognosis with the documented or assumed wishes of the patients. Involving the relatives competently is essential. The indication for surgery in patients with severe dementia, for example, needs to be individualized striving for optimal care, a clear communication about treatment goals with the relatives and preventing distress and burnout for staff. Co-operation with specialists in medical ethics is recommended.

Surveillance of surgical site infections by surgeons: biased underreporting or useful epidemiological data?

Surgical site infections (SSIs) significantly increase post-operative morbidity and mortality. SSI surveillance is an established monitoring tool and reduces SSI rates. The purpose of this study was to compare prospective in-hospital SSI surveillance (I) by the surgical staff and (II) additionally by an infection control team (ICT). The reference method (III) was defined by data generated by the surgical team, supplemented by the ICT and completed by post-discharge surveillance with a post-operative follow-up of one year representing the sum of all available resources. During 24 months, all consecutive inpatient procedures (N=6283) were prospectively recorded by the surgical staff until patients' discharge (I). SSI rates were compared with the surveillance performed by the ICT (II) and with the reference method (III). The overall SSI rate (reference method) was 4.7% (N=293), of which 187 (63.8%) were detected in-hospital and 106 (36.2%) after discharge. (I) The surgical staff detected 91/187 (48.7%) of in-hospital SSIs [91/293 (31.0%) of the reference], (II) the ICT an additional 96/187 (51.3%) during hospitalisation [96/293 (32.8%) of the reference]. Further cross-checking as performed in the visceral surgery department increased the surgeons' detection rate (I) to 59/105 (56.2%) of in-hospital SSIs [59/147 (40.1%) of the reference]. SSI surveillance by the surgical staff detects almost half of all in-hospital SSIs and has the potential to increase the detection rate by simple interventions such as cross-checking. Such a relatively inexpensive surveillance system is an option for hospitals without an ICT or for low risk surgical procedures. Moreover, trends in SSI rates can easily be detected, allowing early intervention.

Laparoscopic treatment of a rare right diaphragmatic rupture with small bowel herniation after blunt thoracic trauma.

Blunt traumatic diaphragmatic rupture (BTDR) is a life-threatening condition with an incidence from 0,8%-1,6% in blunt trauma, mostly located on the left side. The main prognostic factors are severe side injuries and the delay of diagnosis. We present a rare case of a 68-year-old female, with an isolated right diaphragm rupture. The diagnosis was done with a delay of 4 days by thoracic radiographs, which showed a herniation of small bowel into the right thoracic cavity. A reposition of the small bowel and a closure of the diaphragmatic defect by running suture were carried out laparoscopicly. Although large prospective studies concerning the outcome of laparoscopic approach to right BTDR are still missing, we could show, that laparoscopy can be performed safely in right traumatic diaphragm rupture.

Primary anastomosis vs Hartmann's procedure in patients undergoing emergency left colectomy for perforated diverticulitis.

OBJECTIVE: Comparison of primary anastomosis (PA) and Hartmann's procedure (HP) in perforated diverticulitis is biased as the patient groups are different in age, comorbidity and severity of disease. Still, PA has been advocated as the procedure of choice. The aim of this study was to compare the two surgical procedures after eliminating this selection bias using a propensity score model. METHOD: Sixty-five HP and 46 PA patients who underwent emergency laparotomy for perforated diverticulitis were analysed. Multivariate logistic regression using the Mannheim peritonitis index, Colorectal Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity, Charlson comorbidity index and Hinchey score was performed to determine the propensity score. RESULTS: Patients with HP had significantly higher scores, median age and were more often on immunosuppressive medication. Unadjusted logistic regression for outcome showed a significant risk of HP vs PA for nonsurgical morbidity (odds ratio 3.25, 95% CI: 1.26-8.43; P = 0.015), but not for mortality and surgical morbidity. After adjusting for the propensity score, outcome was not significantly different. Patients with PA had a clinical leak rate of 28% and none of the patients with leakage had a protective ileostomy. Patients with PA and leak had higher Charlson scores whereas all other scores were similar to nonleak patients. CONCLUSION: The theory that PA is generally superior to HP cannot be supported. HP remains a safe technique for emergency colectomy in perforated diverticulitis, especially in elderly patients with multiple comorbidities. If PA is performed, a protective ileostomy must be considered.

[Course system of the Working Group for Gastro-intestinal Surgery Davos]. / Kurssystem der Arbeitsgemeinschaft für Gastrointestinale Chirurgie Davos.

Training in technical skills is essential for advanced surgical education. Training is moving more and more from the operating room to surgical training laboratories. A crucial impulse for this development came from Davos, where the first skills course was organized in 1984 after the formation of the Working Group for Gastro-intestinal (GI) Surgery (AGC Davos). Since this first course more than 5,000 residents have successfully completed the GI skills training course in Davos and many of the alumni are themselves teaching surgery today. The level and quality of this course has remained stable for 27 years on a high quality level although teaching has continuously been adjusted to modern techniques. The language of this international workshop is English. The number of applications exceeds the course capacity every year, which is an indication for the need of such training courses and should be principally included into the skills curriculum for surgeons.

Juxtapapillary duodenal diverticula: MDCT findings in 1010 patients and proposal for a new classification.

The aim of this study is to analyze the MDCT findings of juxtapapillary duodenal diverticula (JPDD) and to propose a new radiological classification. CT-examinations of 1010 consecutive patients, all examined by 16-row MDCT of the abdomen over a time period of 20 months were retrospectively analyzed. All study patients were examined by triple phase CT (native, arterial and portal venous CT scan) of the abdomen and all recieved positive oral contrast prior to the examination. Thirty-three patients showed a juxtapapillary duodenal diverticulum, which could be seen on all CT scans, but jusually was depicted most clearly on the thin collimated arterial phase CT images. Size of diverticula range from 4 mm to 4.5 cm (mean 1.7 cm). In 17 cases the diverticulum was located ventrally to the vaterian sphincter complex, extending less or more into the pancreas at the site where the dorsal and the ventral anlage of the pancreas have fused (type I). 12 diverticula were located dorsally to the sphincter complex (type II). Three patients presented with a bilobated juxtapapillary diverticulum extending to both sides, ventrally and dorsally (type III) and one patient showed a little diverticulum ventrally to the minor papilla (type IV).Three patients presented with food impaction in the diverticulum but only one of these patients with a large IPDD showed a Lemmel-syndrome, whereas the other three patients with non-calculous extrahepatic cholostasis showed larger diverticula without food impaction. MDCT allows to identify four different types of juxtapapillary duodenal diverticula and using the proposed classification may be helpful for a more exact, anatomy based radiological description of this CT finding.

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.

Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism.

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.

Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.

BACKGROUND AND STUDY AIMS: To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer (CRC), and report appropriateness criteria developed by an expert panel, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy, EPAGE II. METHODS: A systematic search of guidelines, systematic reviews and primary studies regarding the evaluation and management of surveillance colonoscopy after polypectomy and after resection of CRC was performed. The RAND/UCLA Appropriateness Method was applied to develop appropriateness criteria for colonoscopy for these conditions. RESULTS: Most CRCs arise from adenomatous polyps. The characteristics of removed polyps, especially the distinction between low-risk adenomas (1 or 2, small [< 1 cm], tubular, no high-grade dysplasia) vs. high-risk adenomas (large [> or = 1 cm], multiple [> 3], high-grade dysplasia or villous features), have an impact on advanced adenoma recurrence. Most guidelines recommend a 3-year follow-up colonoscopy for high-risk adenomas and a 5-year colonoscopy for low-risk adenomas. Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection, surveillance colonoscopy is recommended by most guidelines. The timing of the first surveillance colonoscopy differs. The expert panel considered that 56 % of the clinical indications for colonoscopy for surveillance after polypectomy were appropriate. For surveillance after CRC resection, it considered colonoscopy appropriate 1 year after resection. CONCLUSIONS: Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria. Despite the limitations of the published studies, colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection.