Bridging the gap between gastric pouch and jejunum: a bariatric nightmare.

BACKGROUND: Even in a large volume bariatric centre, bariatric surgeons are sometimes confronted with intraoperative anatomical challenges which force even the most experienced surgeon into a pioneering position. In this video we present how a large gap of approximately 8 cm is bridged by applying several techniques that are not part of our standardized surgical procedure. CASE PRESENTATION: After creation of a 20 mL gastric pouch we discovered that the alimentary limb could not be advanced further cranially due to a very short a thick jejunal mesentery in a 49 year old male patient during laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. By dissecting the gastro-oesophageal junction form the crus, stretching the gastric pouch, transecting the jejunal mesentery, using a retrocolic/retrogastric route, and creating a fully hand-sewn gastrojejunostomy we were able to safely complete the LRYGB. Drains were left near the gastrojejunostomy and the patient was kept nil by mouth for 5 days. On the 5th postoperative day radiographic swallow series were obtained which revealed no sign of leakage. The patient was discharged in good clinical condition on the 6th postoperative day. To date, no complications have occurred. Weight loss results are -31.5 % of the preoperative total body weight. CONCLUSIONS: When confronted with a large distance between the gastric pouch and the alimentary limb, several techniques presented in this video may be of aid to the bariatric surgeon. We stress that only experienced bariatric surgeon should embark on these techniques. Inspecting the alimentary limb before the creation of the gastric pouch may prevent the need for such complex techniques.

Complete pathological response is predictive for clinical outcome after tri-modality therapy for carcinomas of the superior pulmonary sulcus.

The objective was to define the relationship between histopathological changes after pre-operative chemo-radiotherapy (CRT) and clinical outcome following tri-modality therapy in patients with superior sulcus tumours. A retrospective analysis of tumour material was performed in a series of 46 patients who received tri-modality therapy between 1997 and 2007. Median follow-up was 34 months (5-154). Pathological complete response (pCR) was present in 20/46 tumours (43 %). The most common RECIST score after CRT in patients with pCR was a partial response (PR; 10/17, three unknown), whereas in patients without a pCR, stable disease was the most common (22/26) (p = 0.002). In 26 specimens with residual tumour, this was mainly located in the periphery of the lesion rather than the centre (Spearman's correlation = 0.67, p < 0.001). Prognosis was significantly better after a pCR compared to residual tumour (70 % 5-year overall survival vs. 20 %; p = 0.001) and in patients with fewer than 10 % vital tumour cells as compared to those with >10 % (65 % 5-year overall survival vs. 18 %; p < 0.001). A low mitotic count was associated with a longer disease-free survival (p = 0.02). Complete pathological response and the presence of fewer than 10 % vital tumour cells after pre-operative CRT are both associated with a more favourable prognosis. A modification of the pathological staging system after radiotherapy, incorporating the percentage of vital tumour cells, is proposed.

Tumor response and toxicity of neoadjuvant erlotinib in patients with early-stage non-small-cell lung cancer.

PURPOSE: The development of targeted therapy has introduced new options to improve treatment outcome in selected patients. The objective of this prospective study was to investigate the safety of preoperative erlotinib treatment and the (in vivo) response in patients with early-stage resectable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This study was designed as an open-label phase II trial, performed in four hospitals in the Netherlands, according to a Simon's minimax two-stage procedure. Initially, operable patients with early-stage NSCLC (n = 15) were entered from an enriched population (never-smoker, female sex, nonsquamous histology, or Asian ethnicity); thereafter, unselected patients were included to a total of N = 60. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. Response to treatment was evaluated using [18F] fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) scans during treatment and histologic examination of the resection specimen. Primary end points were toxicity and pathologic response. RESULTS: Sixty patients were included. Seven patients stopped treatment prematurely (12%). Skin toxicity was present in 37 patients (62%), and diarrhea was present in 21 patients (35%). PET evaluation revealed metabolic response (> 25% standardized uptake value decrease) in 16 patients (27%); CT evaluation using Response Evaluation Criteria in Solid Tumors (RECIST) showed response in three patients (5%). At surgery, no unexpected complications occurred. Pathologic examination showed more than 50% necrosis in 14 patients (23%), of whom three (5%) had more than 95% tumor necrosis. The response rate in the enriched population was 34% (10 of 29 patients). CONCLUSION: According to predefined criteria, neoadjuvant erlotinib has low toxicity and sufficient activity to deserve further testing in future studies in an enriched population.

Concurrent high-dose radiotherapy with low-dose chemotherapy in patients with non-small cell lung cancer of the superior sulcus.

BACKGROUND AND PURPOSE: In the treatment of patients with tumours of the sulcus superior (SST), achieving local control is essential because residual or recurrent disease is associated with severe locoregional problems. This study evaluates the efficacy of concurrent daily low-dose cisplatin (6 mg/m(2)) and high-dose radiotherapy (66 Gy) followed by surgical resection in selected patients. MATERIAL AND METHODS: Clinical charts, imaging and pathology reports were retrospectively reviewed. Survival was analysed using the Kaplan-Meier method. RESULTS: Forty-nine patients with stage II/III SST were treated with concurrent high-dose radiotherapy and low-dose chemotherapy (CRT). Mean follow-up was 49 months (range 2-152). Nineteen patients underwent additional resection after CRT. In 53% a pathological complete response (pCR) was observed (10/19 pts). Acute severe toxicity occurred in 49% (9/19 pts). Late severe toxicity occurred in 3 patients. The 2- and 5-year overall survival was 74% and 33%, respectively. Local tumour control was 100%. Thirty patients received CRT only. Acute severe toxicity occurred in 23% (7/30 pts). Treatment-related mortality was 2%. The 2- and 5-year overall survival was 31% and 18%, respectively. Locoregional disease-free survival was 48% at 5 years. CONCLUSIONS: Concurrent high-dose (66 Gy) radiotherapy and daily low-dose cisplatin was associated with a high pCR rate. Excellent local control was achieved after additional resection in selected patients. However, the occurrence of severe toxicity in long-term survivors after concurrent chemoradiation followed by surgery must be considered.

Ligands of epidermal growth factor receptor and the insulin-like growth factor family as serum biomarkers for response to epidermal growth factor receptor inhibitors in patients with advanced non-small cell lung cancer.

INTRODUCTION: The selection of patients with non-small cell lung cancer (NSCLC) for epidermal growth factor receptor (EGFR) inhibitor (EGFR-tyrosine kinase inhibitors [TKIs]) therapy is suboptimal as tumor tissue is often unavailable. Ligands of EGFR, transforming growth factor-alpha (TGFa) and amphiregulin (ARG), and the insulin-like growth factor (IGF) family have been associated with resistance to EGFR-TKIs. The aim of our study was to explore whether concentrations of these factors measured in serum were predictive of response to EGFR-TKIs. METHODS: We assessed serum levels of marker candidates using enzyme-linked immunosorbent (TGFa and ARG) and chemiluminescent (IGF1 and IGF-binding protein-3) assays in 61 patients with advanced NSCLC treated with EGFR-TKIs and 63 matched advanced NSCLC control patients without EGFR-TKIs treatment. We dichotomized marker levels at the 20th, 50th, or 80th percentile and evaluated whether the effect of EGFR-TKIs treatment on disease-specific survival (DSS) differed by marker level based on multivariate proportional hazards regression with an interaction term. RESULTS: The effect of EGFR-TKIs treatment on DSS showed a significant difference by TGFa and ARG (interaction p = 0.046 and p = 0.004, respectively). Low concentrations of TGFa and high concentrations of ARG were associated with a better DSS in EGFR-TKIs patients compared with control patients. Patients with high concentrations of IGF-binding protein-3 had significantly longer DSS, independent of treatment (hazard ratio: 0.60 per 1 mg/liter, 95% confidence interval: 0.46-0.79). CONCLUSION: Our results suggest that concentrations of TGFa and ARG measured in serum are predictive of EGFR-TKI response. The combination of these two biomarkers could be of value in the process of selecting patients for treatment with EGFR-TKIs.

Is 18F-FDG PET/CT useful for the early prediction of histopathologic response to neoadjuvant erlotinib in patients with non-small cell lung cancer?

UNLABELLED: Early prediction of treatment response is of value in avoiding the unnecessary toxicity of ineffective treatment. The objective of this study was to prospectively evaluate the role of integrated (18)F-FDG PET/CT for the early identification of response to neoadjuvant erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor. METHODS: From October 2006 to March 2009, 23 patients with non-small cell lung cancer eligible for surgical resection were evaluated for this study. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. (18)F-FDG PET/CT was performed before and at 1 wk after the administration of erlotinib. Changes in tumor (18)F-FDG uptake during treatment were measured by standardized uptake values and assessed prospectively according to the criteria of the European Organization for Research and Treatment of Cancer. Patients with a decrease in standardized uptake values of 25% or more after 1 wk were classified as "metabolic responders." The metabolic response was compared with the pathologic response, obtained by histopathologic examination of the resected specimen. RESULTS: Following the (18)F-FDG PET/CT criteria of the European Organization for Research and Treatment of Cancer, 6 patients (26%) had a partial response within 1 wk, 16 patients (70%) had stable disease, and 1 patient (4%) had progressive disease. The median percentage of necrosis in the early metabolic responder group was 70% (interquartile range, 30%-91%), and the median percentage of necrosis in the nonresponder group was 40% (interquartile range, 20%-50%; P = 0.09). The kappa-agreement between the metabolic and pathologic responders was 0.55 (P = 0.008). CONCLUSION: The results of this study suggest that early during the course of epidermal growth factor receptor tyrosine kinase inhibitor therapy, (18)F-FDG PET/CT can predict response to erlotinib treatment in patients with non-small cell lung cancer.

Surgery after induction chemotherapy in stage IIIA-N2 non-small cell lung cancer: why pneumonectomy should be avoided.

BACKGROUND: The role of surgery in the treatment of patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) is a hot topic. Since variable results of surgery versus radiotherapy after induction chemotherapy are being reported, this study aimed to analyze results of surgery after induction chemotherapy and to identify relevant factors influencing outcome in patients with stage IIIA NSCLC. METHODS: Patients with stage IIIA (N2) NSCLC, treated with platinum-based induction chemotherapy between 1994 and 2006, were identified. By a retrospective review of hospital records, response to induction treatment, short-term outcome, recurrence of disease and survival were evaluated. RESULTS: Ninety-nine patients, 66 men and 33 women, were identified. Median follow-up was 54 months (range 13-129). Median age at treatment was 62 (range 36-77). Mediastinal downstaging was seen in 32 patients. Forty-three patients received radical radiotherapy and 39 patients underwent surgery: 19 pneumonectomies, 19 lobectomies and one exploratory thoracotomy. Microscopic complete resection (R0) was reached in 30 patients. Pathological response to induction therapy was CR in 5%, PR in 59% and SD in 36%. Postoperative mortality was 3%. The 1-year mortality was 26% after pneumonectomy and 11% after lobectomy. Five-year survival after surgery was 28%, and was better after lobectomy than after pneumonectomy (43% versus 16%; p=0.03). Other factors as age, weight loss, clinical mediastinal downstaging, radicality, and histology did not substantially contribute to this difference. CONCLUSION: Type of surgical resection was the major factor influencing outcome in patients with stage IIIA (N2) NSCLC after induction chemotherapy. These results suggest that patients with stage IIIA (N2) NSCLC may benefit from surgical resection, as long as a lobectomy can be performed.

Results of combined modality treatment in patients with non-small-cell lung cancer of the superior sulcus and the rationale for surgical resection.

OBJECTIVE: Superior sulcus tumours (SSTs) or Pancoast tumours are preferably treated with chemoradiotherapy (CRT) followed by surgical resection. However, when followed by surgery, it is associated with an increased complication rate. This study aims to evaluate the efficacy and safety of a concurrent induction protocol of 66Gy radiotherapy with cisplatinum and evaluate the rationale for subsequent surgery. METHODS: Patients with SST treated in our institute from 1994 to 2006 were identified. The preferred induction treatment consisted of accelerated radiation (66 Gy in fractions of 2.75 Gy) with concurrent daily cisplatinum 6 mgm(-2). Surgical resection was planned 4-6 weeks thereafter. Performance status, co-morbidity, clinical and pathological tumour stage, (response to) treatment and survival were reviewed. Survival analysis was performed using the Kaplan-Meier method. RESULTS: Over these 12 years, 85 patients with Pancoast tumours, 57 men and 28 women, were referred. Mean follow-up was 42 months (range: 2-120 months). Twenty-five patients had stage IIB (29%), seven had stage IIIA (8%), 32 had stage IIIB (38%) and 21 had stage IV (25%). Of the 64 patients presenting with stage II or III disease, 38 medically operable patients with potentially resectable tumours received induction therapy. After restaging, 22 patients underwent resection. All resections were complete and local recurrences were not observed. In 13 patients (62%) a pathologic complete response was found. In most cases, pathologic response was not evident from radiological imaging. The morbidity of surgery after induction treatment was acceptable. There was no fatal toxicity or treatment-related mortality. The 2- and 5-year overall survival of this selected group was 70% and 37%, respectively. CONCLUSION: This schedule of induction therapy with high-dose radiation and concurrent cisplatinum was safe and highly effective in fit patients. At this time, pathologic complete response cannot be reliably recognised preoperatively, and better tools for response assessment are critical for more tailored treatment of patients with SST.