José Luis Hernández-Lizoain

Fasting plasma Ghrelin concentrations 6 months after gastric bypass are not determined by weight loss or changes in insulinemia

Background: Ghrelin is a gastric peptide with potent orexigenic effects. Circulating ghrelin concentrations are increased in obese subjects, but increase after weight loss. However, in patients undergoing Roux-en-Y gastric bypass (RYGBP), a decrease in ghrelin levels has been reported. The effect of comparable weight loss induced by either adjustable gastric banding (AGB), RYGBP or conventional dietary treatment (Conv) on ghrelinemia was studied. Methods: 24 matched obese male patients in whom similar weight loss had been achieved by either AGB (n=8), RYGBP (n=8) or Conv (n=8) were studied before and 6 months after treatment start. The independence of ghrelin concentrations from body mass index (BMI) and weight loss was further analyzed in a group of patients with total gastrectomy (TtGx, n=6). Results: Comparable weight loss after 6 months exerted significantly different effects on plasma ghrelin concentrations, depending on the procedure applied (AGB: 424.6 ± 32.8 pg/ml; RYGBP: 131.4 ± 13.5; Conv: 457.3 ± 18.7; P<0.001). Without significant differences in body weight and BMI, patients who had undergone the RYGBP exhibited a statistically significant decrease in fasting ghrelin concentrations, while the other two procedures (AGB and Conv) showed a weight loss-induced increase in ghrelin levels. Despite significant differences in BMI between RYGBP and TtGx patients after 6 months (31.9 ± 2.2 vs 22.0 ± 0.7 kg/m2, respectively; P<0.05), both groups showed similar ghrelin concentrations. Conclusion: The reduction in circulating ghrelin concentrations in RYGBP patients after 6 months of surgery are not determined by an active weight loss or an improved insulin-sensitivity but rather depend on the surgically-induced bypass of the ghrelin-producing cell population of the fundus.

Analysis of Early Postoperative Morbidity Among Patients with Rectal Cancer Treated with and without Neoadjuvant Chemoradiotherapy

BackgroundThe impact of neoadjuvant treatment and their subsequent early complications in the treatment of rectal cancer has not been adequately assessed. The aim of this prospective study was to evaluate early postoperative morbidity and mortality among patients with rectal cancer treated with adjuvant radiotherapy and chemotherapy followed by surgery, compared with patients treated with surgery alone. We also identified independent risk factors associated with early major complications.MethodsBetween 1995 and 2004, 273 consecutive patients underwent treatment for rectal cancer. A total of 170 patients (group A) received preoperative radiotherapy with a total of 45–50.4 Gy (180 cGy per day) and 5-fluorouracil-based chemotherapy, followed by surgery; 103 patients (group B) were treated with surgery alone. Dependent variables related to patients, treatment, radiotherapy, and tumor were analyzed.ResultsBoth groups were similar with regard to age, sex, body mass index, American Society of Anesthesiologists (ASA) score, and tumor location but not for ileostomy (27% in group A vs. 6.8% in group B). The number of complications was similar in both groups (43.1% in group A vs. 44.6% in group B). No differences in wound infection (8.2% vs. 7.8%), intra-abdominal abscess (4.7% vs. 4.9%), anastomotic dehiscence (4.2% vs. 3.8%), postoperative hemorrhage (3.5% vs. 3.9%), urinary complications (6.5% vs. 4.9%), paralytic ileus (8.9% vs. 9.7%), or general complications (7.1% vs. 9.6%) were found. The global mortality in the first 30 days after surgery was .7%. An ASA score of III–IV and surgery duration longer than 3 hours were identified as independent prognostic factors for early complications.ConclusionsPreoperative chemoradiation in patients with rectal cancer treated with surgery is not associated with a higher incidence of early postoperative complications. The patient’s preoperative clinical condition and lengthy surgery time are prognostic factors for early complications.

Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy

Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer.

Patterns of Response After Preoperative Treatment in Gastric Cancer

PURPOSE To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. METHODS AND MATERIALS From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. RESULTS Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. CONCLUSIONS The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.

Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer

Preoperative chemotherapy followed by radical surgery is an attractive treatment for locally advanced colon cancer (LACC) given the promising results of this approach in other locally advanced tumours. The study evaluates the outcome and treatment‐related complications of perioperative oxaliplatin‐ and capecitabine‐based chemotherapy and surgery for clinical Stage III colon cancer.

Low colorectal anastomosis after pelvic exenteration for gynecologic malignancies: risk factors analysis for leakage.

Objective: To study risk factors for low colorectal anastomotic leak after pelvic exenteration for gynecologic malignancies. Methods: Data from 60 patients, 32 with ovarian cancer and 28 with nonovarian cancer who underwent pelvic exenteration with colorectal anastomosis (CRA) were retrospectively analyzed. Results: Overall rate of CRA leak was 20%. The CRA leak was associated with type of tumor (3% for the ovarian cancer and 40.8% for the nonovarian cancer, P = 0.004), CRA height (<5 cm vs ≥5 cm, 75% vs 6.3%; P = 0.001), and previous radiotherapy (RT; 53.3% vs 8.9%; P = 0.001). Multivariate analysis showed that only previous RT and CRA height were associated with the CRA leak. Rectosigmoid wall involvement (81.8% vs 27%; P = 0.001) and mesorectum infiltration (69.2% vs 21.7%; P = 0.001) were more frequent among patients with ovarian cancer patients. Conclusion: Previous RT and CRA at or less than 5 cm from the anal verge pose a high risk for CRA leak. In these cases, a definitive colostomy should be recommended.

Analysis of POSSUM score and postoperative morbidity in patients with rectal cancer undergoing surgery

BackgroundThe Physiological and Operative Severity Score for the enUmeration of Mortality andmorbidity (POSSUM) and later modifications (P-POSSUM y CR-POSSUM) have been used to predictmorbidity and mortality rates among patients with rectal cancer undergoing surgery. These calculations needsome adjustment, however. The aim of this study was to assess the applicability of POSSUM to a group ofpatients with rectal cancer undergoing surgery, analysing surgical morbidity by means of several variables.Methods between January 1995 and December 2004, 273 consecutive patients underwent surgery forrectal cancer. Information was gathered about the patients, tumour and therapy. To assess the predictioncapacity of POSSUM, subgroups for analysis were created according to variables related to operativemorbidity and mortality.ResultsThe global morbidity rate was 23.6% (31.2% predicted by POSSUM). The mortality rate was 0.7%(6.64, 1.95 and 2.08 predicted by POSSUM, P-POSSUM and CR-POSSUM respectively). POSSUMpredictions may be more accurate for patients younger than 51 years, older than 70 years, with low anaesthetic risk (ASA I/II), DUKES stage C and D, surgery duration of less than 180 minutes and for thosereceiving neoadjuvant therapy.ConclusionPOSSUM is a good instrument to make results between different institutions and publicationcomparable. We found prediction errors for some variables related to morbidity. Modifications of surgicalvariables and specifications for neoadjuvant therapy as well as physiological variables including life stylemay improve future prediction of surgical risk. More research is needed to identify further potential riskfactors for surgical complications.

Impact of Perineural and Lymphovascular Invasion on Oncological Outcomes in Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy and Surgery

The prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery. A total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied. At a median follow-up of 79.0 months (range 3–250 months), a total of 80 patients (24.7 %) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4 %, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7 % for grade 1, 63.8 % for grade 2, 75.0 % for grade 3, 90.4 % for grade 3+, and 96.0 %,for grade 4. The 10-year DFS was 31.8 % for grade 1, 58.6 % for grade 2, 70.4 % for grade 3, 88.4 % for grade 3+, and 97.1 % for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS. The presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.BackgroundThe prognostic significance of perineural and/or lymphovascular invasion (PLVI) and its relationship with tumor regression grade (TRG) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT) and surgery.MethodsA total of 324 patients with LARC were treated with CRT and operated on between January 1992 and June 2007. Tumors were graded using a quantitative 5-grade TRG classification and the presence of PLVI was histologically studied.ResultsAt a median follow-up of 79.0 months (range 3–250 months), a total of 80 patients (24.7 %) relapsed. The observed 5- and 10-year overall survival (OS) was 83.2 and 74.9 %, respectively. The 5- and 10-year disease-free survival (DFS) was 75.1 and 71.4 %, respectively. A significant correlation was found between the TRG and survival (log rank, p < 0.001). The 10-year OS was 32.7 % for grade 1, 63.8 % for grade 2, 75.0 % for grade 3, 90.4 % for grade 3+, and 96.0 %,for grade 4. The 10-year DFS was 31.8 % for grade 1, 58.6 % for grade 2, 70.4 % for grade 3, 88.4 % for grade 3+, and 97.1 % for grade 4. In patients with PLVI, the TRG had no impact on survival. When excluding patients with PLVI, the TRG was an independent prognostic factor for OS and DFS.ConclusionsThe presence of PLVI is a more powerful prognostic factor than TRG in LARC patients treated with neoadjuvant CRT followed by surgery. PLVI denotes an aggressive phenotype, suggesting that these patients may benefit from adjuvant systemic therapy.

Transthoracic oesophagectomy with lymphadenectomy in 100 oesophageal cancer patients.: Multidisciplinary approach

ObjetivesAnalysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists.MethodsBetween January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality.ResultsThe average patient age was 55 years (range 31–83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classification according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0–28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10–40 days)ConclusionsThe results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges reported in the literature for teams with high prevalence of the disease.

Patterns of Response After Preoperative Intensity-Modulated Radiation Therapy and Capecitabine/Oxaliplatin in Rectal Cancer: Is There Still a Place for Ecoendoscopic Ultrasound?

PURPOSE The main goals of preoperative chemoradiotherapy (CHRT) in rectal cancer are to achieve pathological response and to ensure tumor control with functional surgery when possible. Assessment of the concordance between clinical and pathological responses is necessary to make decisions regarding alternative conservative procedures. The present study evaluates the patterns of response after a preoperative CHRT regimen, and the value of endoscopic ultrasound (EUS) in assessing response. METHODS AND MATERIALS A total of 51 EUS-staged T3 to T4 and/or N0 to N+ rectal cancer patients received preoperative CHRT (intensity-modulated radiation therapy and capecitabine/oxaliplatin (XELOX) followed by radical resection. Clinical response was assesed by EUS. Rates of pathological tumor regression grade (TRG) and lymph node (LN) involvement were determined in the surgical specimen. Clinical and pathological responses were compared, and the accuracy of EUS in assessing response was calculated. RESULTS Twenty-four patients (45%) achieved a major pathological response (complete or >95% pathological response (TRG 3+/4)). Sensitivity, specificity, negative predictive value, and positive predictive value of EUS in predicting pathological T response after preoperative CHRT were 77.8%, 37.5%, 60%, and 58%, respectively. The EUS sensitivity, specificity, negative predictive value, and positive predictive value for nodal staging were 44%, 88%, 88%, and 44%, respectively. Furthermore, EUS after CHRT accurately predicted the absence of LN involvement in 7 of 7 patients (100%) with major pathological response of the primary tumor. CONCLUSION Preoperative IMRT with concomitant XELOX induces favorable rates of major pathological response. EUS has a limited ability to predict primary tumor response after preoperative CHRT, but it is useful for accurately determining LN status. EUS may have a potential value in identifying patients with a very low risk of LN involvement in association with a good pathological response as potential candidates for conservative local surgical protocols.