Preoperative versus postoperative docetaxel-cisplatin-fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial.

BACKGROUND: Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data. PATIENTS AND METHODS: Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy. RESULTS: This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A. CONCLUSION: Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.

Endoscopic mucosal resection in high- and low-volume centers: a prospective multicentric study.

BACKGROUND: Endoscopic mucosal resection (EMR) is an effective therapeutic technique well-standardized worldwide for the treatment of gastrointestinal neoplasm limited to the mucosal layer. To date, no study has compared technical and clinical differences based on the number of EMRs performed per year. This study aimed to compare EMR technical success, complications, and clinical outcome between low-volume centers (LVCs) and high-volume centers (HVCs). A total of nine endoscopic centers were included in the study. METHODS: This prospective study investigated consecutive patients with sessile polyps or flat colorectal lesions 1 cm or larger referred for EMR. RESULTS: A total of 427 lesions were resected in 384 patients at nine endoscopic centers. Males accounted for 60.4% and females for 39.6% of the patients. Most of the EMRs (84.8%) were performed in HVCs and only 15.2% in LVCs. All the lesions were resected in only one session. Argon plasma coagulation was performed on the margins of piecemeal resection in 15.7% of the patients in HVCs only. Complete excision was achieved for 98.6% of the lesions in HVCs and 98.8% of the lesions in LVCs. The complication rate was 4.4% in HVCs and 4.6% in LVCs (p = 0.94). Delayed bleeding occurred in 2.5% of the HVC cases and 3.1% of the LVC cases. Perforation occurred in 1.9% of the HVC cases and 1.5% of the LVC cases (p = 1.00). Recurrences were experienced with 15% of the lesions: 15.5% in HVCs and 14% in LVCs (p = 0.79). CONCLUSIONS: The study showed that EMR can be performed also in LVC.

Meta-analysis: the relative efficacy of oral bowel preparations for colonoscopy 1985-2010.

BACKGROUND: Previous reviews of bowel preparation for colonoscopy have given contradictory answers. AIM: To provide a definitive insight, using PRISMA-compliant methodology. METHODS: A comprehensive literature review identified randomised controlled trials comparing bowel preparation regimens. Data for quality of bowel preparation were pooled in multiple meta-analyses exploring a range of inclusion criteria. RESULTS: A total of 104 qualifying studies were identified, the majority of which involved comparisons of sodium phosphate (NaP) or polyethylene glycol (PEG). There was no significant difference demonstrated between NaP and PEG overall (OR = 0.82; 95% CI = 0.56-1.21; P = 0.36). Cumulative meta-analysis demonstrated that this conclusion has been qualitatively similar since the mid 1990s, with little quantitative change for the past 10 years. Amongst studies with previous day dosing in both study arms there was a significant advantage in favour of PEG (OR = 1.78; 95% CI = 1.13-2.81; P = 0.006). Studies focussing on results in the proximal colon also favoured PEG (OR = 2.36; 95% CI = 1.16-4.77; P = 0.012). PEG was also significantly more effective than non-NaP bowel preparation regimens (OR = 2.02; 95% CI = 1.08-3.78; P = 0.03). Other comparisons showed no significant difference between regimens. CONCLUSIONS: Although there is no compelling evidence favouring either of the two most commonly used bowel preparation regimens, this may reflect shortcomings in study design. Where studies have ensured comparable dosage, or the clinically relevant outcome of proximal bowel clearance is considered, PEG-based regimens offer the most effective option.

[Robotic rectal resection in rectal cancer: short term results in a monocentric prospective study]. / Trattamento chirurgico del cancro del retto con tecnica robotica: risultati a breve termine di uno studio prospettico monocentrico.

AIM: The aim of this study was to evaluate technical feasibility, oncological safety and short-term clinical results of robotic rectal resection for cancer. METHODS: From January 2008 to July 2010, 46 patients (27 males and 19 females, median age 69 years, median BMI 24.6 kg/m2) with histologically-proven adenocarcinoma of medium and distal rectum were enrolled in a prospective database. Preoperative assessment was performed with colonoscopy with biopsies, thoraco-abdominal CT scan, pelvic MRI and endorectal-ultrasound (ERUS). In the case of locally advanced non metastatic disease (T3/4 or N1/2), patients received preoperative radiotherapy (45 Grays in 5 weeks) and chemotherapy (oral Capecitabine). The robotic system was a four-arms Da Vinci® (Intuitive Surgical, Sunnyvale, CA, USA); arms position is not modified during the entire surgical procedure. RESULTS: Twenty-five patients received a preoperative radio-chemotherapy. Surgical procedure was an abdomino-perineal amputation in nine patients and an anterior resection in the remaining 37, with temporary ileostomy in 16 cases and a laparoscopic mobilization of splenic flexure in 25. Median operative time was 251 minutes, median time of first bowel movements 1.7 days and median hospital stay 6.7 days. Major complications requiring reoperation verified in 2 patients, while overall complication rate is 15.2%. Median number of harvested lymph nodes per patient was 18; median distance of the tumour from distal resection margin was 2 cm; distance of the tumour from circumferential margin was superior to 1 mm in all of the patients. At a median follow up of 11 months, all patients are alive and disease-free. CONCLUSION: Robotic rectal resection is a feasible technique which can provide good oncological and short-term clinical results.

Robotic versus laparoscopic total mesorectal excision for rectal cancer: a comparative analysis of oncological safety and short-term outcomes.

BACKGROUND: We assessed feasibility, short-term oncologic safety, and short-term outcomes in robotic total mesorectal excision (R-TME) for rectal cancer compared with laparoscopic TME. METHODS: From March 2008 to June 2009, 50 patients with proven middle/lower rectal adenocarcinoma underwent minimally invasive TME; 25 received R-TME. The groups were balanced (R-TME versus L-TME) in terms of age (median 69 versus 62 years; p = 0.8), disease stage, and body mass index (median 23 versus 26.5 kg/m(2); p = 0.06). There were 37 (74%) anterior resections and 13 (26%) abdominoperineal resections. Twenty-three (46%) patients received preoperative radiochemotherapy. The robot was a four-arm Da Vinci S (Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: Median operating time (R-TME versus L-TME) was 240 versus 237 min (p = 0.2); first bowel movement was 2 versus 3 days (p = 0.5); median hospital stay was 6.5 versus 6 days (p = 0.4). Major complications with reoperation were two in R-TME (one anastomotic leakage, one small bowel perforation) and three in L-TME (one colonic ischemia, two anastomotic leakage). Postoperative complications were 16% versus 24% (p = 0.5). A median of 18 versus 17 (p = 0.7) lymph nodes were retrieved; distal resection margins were disease free in both groups; circumferential margin was involved (<1.0 mm) in one (4%) of L-TME. There were 0 versus 1 (5%) conversions to laparotomy. CONCLUSIONS: R-TME in rectal cancer is feasible, with short-term oncologic and other outcomes similar to those of L-TME. The greater maneuverability and visibility afforded by the robotic approach are attractive. Future studies should more systematically address advantages and costs of R-TME.

Bowel preparation before colonoscopy in the era of mass screening for colo-rectal cancer: a practical approach.

Colonoscopy constitutes the principal investigation for colo-rectal neoplasms due to its ability to detect and remove most of precancerous lesions; due to the ongoing or planned colon cancer screening programs in many European countries we should expect an enormous increase in colonoscopic demand over the next few years. Diagnostic accuracy and therapeutic safety of colonoscopy strictly depends upon the quality of bowel cleansing which is often perceived as the most unpleasant part of the procedure in individuals undergoing this examination. The ideal preparation for colonoscopy should reliably empty the colon from all faecal material allowing the optimal visualization of the entire colonic mucosa without causing great patient's discomfort nor significant shifts in fluids or electrolytes. Standard PEG solutions and sodium phosphate (NaP) compounds are the most frequently used preparations; both are accepted and relatively well tolerated by the majority of patients undergoing colonoscopy; however, NaP compounds should be avoided in elderly subjects as well as in those with congestive heart failure, renal and hepatic insufficiency or taking diuretics, ACE inhibitors or angiotensin receptor blockers, since they can induce severe electrolyte and/or fluid disturbances. Standard PEG solutions are often taken incompletely due to the low palatability and the high volume of liquids required which induce nausea and vomiting with negative consequences in terms of colon cleansing. Reduced volume and better palatability of PEG solutions, such as those obtained with the newest PEG formulations, as well as improved patient education concerning the importance of bowel cleansing could undoubtedly increase compliance with oral bowel preparations and promote adherence to colo-rectal cancer screening programs.

Confocal laser endomicroscopy diagnosis of gastric adenocarcinoma in a patient treated for gastric diffuse large-B-cell lymphoma.

The association between gastric carcinoma and lymphoma is rare. Confocal laser endomicroscopy is a new diagnostic tool that allows the identification of cellular and vascular architecture during endoscopy. This is the first report of an in vivo early gastric carcinoma diagnosis by confocal laser endomicroscopy in a patient successfully treated for a primary gastric diffuse large-B-cell lymphoma.

Confocal laser endomicroscopy for the detection of mucosal changes in ileal pouch after restorative proctocolectomy.

BACKGROUND: Pouchitis and dysplasia may affect the reservoir after restorative proctocolectomy. AIMS: To assess the suitability of confocal laser endomicroscopy for the in vivo diagnosis of mucosal changes in ileal pouch for ulcerative colitis and familial adenomatous polyposis. METHODS: Standard endoscopy and endomicroscopy were performed in 18 pouches. Confocal images were scored for the presence of villous atrophy, inflammation, ulceration, colonic metaplasia and dysplasia. Targeted biopsies were taken. Endomicroscopic and histological findings were compared. RESULTS: At standard endoscopy, the signs of pouchitis were recorded in 7/18 (38.9%) patients. At endomicroscopy, pathological features were found in 16/18 (88.9%), villous atrophy in 15/18 (83.3%), inflammation in 13/18 (72.2%), ulceration in 3/18 (16.7%), and colonic metaplasia in 12/18 (67.7%). No dysplasia was observed. At histology, abnormalities were present in 17/18 (94.4%): villous atrophy in 15/18 (83.3%), inflammation in 17/18 (94.4%), ulceration in 6/18 (33.3%), colonic metaplasia in 15/18 (83.3%). Morphological changes of the ileal pouch could be predicted with an accuracy of 94.4% (95% CI: 74.2-99.0). The k-value for intra- and interobserver agreement was 0.93 and 0.78, respectively. CONCLUSIONS: Endomicroscopy may be helpful in the evaluation of morphologic changes in ileal pouch. The small size of the population sample requires further studies for the results to be confirmed.

Efficacy of 90Y ibritumomab-tiuxetan treatment in a case of resistant gastric MALT non-Hodgkin's lymphoma.

Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin's lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results.Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin ((90)Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches.

Long-term endoscopic and clinical follow-up of untreated type 1 gastric neuroendocrine tumours.

BACKGROUND AND AIMS: Type 1 gastric neuroendocrine tumour surveillance and treatment are a matter of debate. Endoscopic, or surgical, resection and chronic somatostatin analog therapy have been proposed. Based on the favourable behaviour of this neoplasm, we performed an endoscopic and clinical follow-up in 11 patients affected by type 1 gastric neuroendocrine tumours, avoiding any specific treatment. METHODS: Between 1994 and 2006, we prospectively recorded the data of 11 untreated patients with type 1 gastric neuroendocrine tumours who underwent an endoscopic and clinical follow-up. All the patients were also evaluated by means of an abdominal computed tomography scan, somatostatin receptor scintigraphy and blood tests. RESULTS: During the follow-up (median 54 months, range 9-136), the endoscopic picture of 4 (36%) out of 11 patients changed in terms of increased number of lesions. In none of the cases were detected any lesions that exceeded 10mm in diameter, and none of the patients demonstrated any evidence of local or distant metastases. CONCLUSIONS: Our data confirm the literature data of the indolent behaviour of type 1 gastric neuroendocrine tumours and suggest that a careful endoscopic follow-up, without any treatment, might represent a reasonable and safe option in selected patients.

Metal stent placement in acute malignant colorectal obstruction.

BACKGROUND: Obstruction is a common complication of advanced colorectal cancer. Stent insertion can reduce the need for emergency surgery and allows chemotherapy to begin immediately. AIMS: To evaluate the technical and clinical success and long-term outcome of stent placement in the management of acute malignant colorectal obstruction. METHODS: From July 2002 to April 2005, 29 self-expanding metal stents were placed in 24 patients (13 men, mean age 67 years, range 36-83). Stents were inserted under endoscopic and fluoroscopic control. Patients were clinically and endoscopically followed up. RESULTS: Twenty-eight out of 29 stents were successfully placed (96.5%) in 23 out of 24 patients with 25 strictures. The clinical success rate was 95.8% (23/24). Two early stent migrations were observed in two patients (8.3%). Late complications developed in eight patients (33.3%) after a median of 3.8 months (range <1-8.6): two migrations and six occlusions. The median survival was 9.8 months (range <1-27). Eleven patients (45.8%) died from progressive disease without any clinical evidence of recurrent obstruction. CONCLUSION: Stent placement is safe and effective. Stent complications are frequent but not life-threatening, and are easy to manage. An improvement in stent design and well-scheduled follow-up are needed in order to prevent such complications.

Endoscopic ultrasound and Computed Tomography in the diagnosis, locoregional staging and assessment of vascular infiltration of pancreatic carcinoma.

PURPOSE: The aim of this study was to evaluate the diagnostic accuracy of colour-Doppler Endoscopic Ultrasonography (EUS), in the detection, loco-regional staging and assessment of vascular infiltration in pancreatic carcinoma, and to compare the results with those obtained by Computed Tomography (CT). MATERIALS AND METHODS: A series of 57 patients with diagnosed or suspected pancreatic carcinoma was retrospectively analysed. All patients underwent EUS and thin-slice (< 5 mm) spiral dynamic CT. The final diagnosis (carcinoma in 37 patients and benign lesion in 20) was obtained by laparotomy in 21 patients, fine-needle aspiration cytology (FNAC) in 17, and follow-up in 19. RESULTS: The specificity and sensitivity for the diagnosis of malignancy were respectively 45% and 92% for EUS and 45% and 89% for CT, with an accuracy of 75% for EUS (p <0.05) and 74% for CT (p = 0.07). The specificity and sensitivity for the diagnosis of loco-regional nodal metastases were both 100% for EUS. The specificity and sensitivity for the diagnosis of vascular infiltration were 100% and 94% for EUS and 100% and 44% for CT, giving a diagnostic accuracy of 97% for EUS vs 74% for CT (p <0.001). CONCLUSIONS: EUS proved to be more sensitive and specific than CT in the loco-regional staging of pancreatic carcinoma. Its diagnostic accuracy is especially high in assessing vascular infiltration and loco-regional nodal metastases. CT still remains the examination of choice for staging pancreatic carcinoma and for assessing its resectability as it affords a panoramic view and ability to rule out distant metastases. Candidates to resection should all be examined by EUS, as, due to its high accuracy in loco-regional staging and assessing vascular infiltration, it might allow a large proportion of patients to be spared the operation.

Is colonoscopy a suitable investigation in the preoperative staging of ovarian cancer patients?

BACKGROUND: During ovarian cancer surgery, colorectal resection may be required. In our institution, preoperative colonoscopy is performed in order to assess visceral involvement. AIMS: The aim of this study was to evaluate the utility of preoperative colonoscopy in ovarian cancer patients and the prevalence of adenomas in this population. PATIENTS: This retrospective study involved 144 consecutive patients with a supposed primary ovarian cancer. METHODS: Mucosal infiltration, bowel wall elasticity and bowel fixation were used to predict colorectal infiltration. Endoscopic and pathological findings were compared. All the polyps observed were removed. RESULTS: Six patients (4.2%) were excluded because of a misdiagnosed colorectal cancer metastatic to the ovary. Eight (6%) patients were considered, at endoscopy, to have a bowel infiltration and eight (6%), an uncertain infiltration. In 116 (88%), no signs of bowel infiltration were observed. The pathological analysis showed that colonoscopy had a low sensitivity (44%) in identifying bowel infiltration. Specificity was 100%, positive predictive value 100% and negative predictive value 92%. The overall accuracy was about 90%. Thirty-six adenomas were removed in 26 (20%) women. CONCLUSIONS: Colonoscopy identifies a not insignificant number of ovarian cancer patients requiring colorectal surgery. An increased prevalence of adenomas was not observed in this population.

Iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy.

BACKGROUND/AIMS: Various percentages of iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy have been reported in the literature. The aim of this study was to analyze a homogeneous cohort of patients in order to evaluate the evolution and management of this complication. METHODOLOGY: We retrospectively reviewed the clinical charts of 80 patients with primary or metastatic liver tumors who received 186 hepatic arterial infusion chemotherapy courses of 5-fluorouracil, cisplatin and mitomycin-C. All of the patients complaining of upper gastrointestinal symptoms during or after hepatic arterial infusion underwent esophagogastroduodenoscopy. RESULTS: Esophagogastroduodenoscopy was performed in 14 patients, all of whom had gastroduodenal ulcers. Two of ten investigated patients were Helicobacter pylori positive. All of the patients were treated with a proton pump inhibitor and five also received major analgesics. All of the ulcers healed without complications. Six patients did not continue with hepatic arterial infusion for reasons other than ulcers. Eight patients received a subsequent hepatic intra-arterial chemotherapy course, five despite the persistence of an active ulcer. CONCLUSIONS: Iatrogenic gastroduodenal ulcers are probably due to ischemia and the direct toxicity of the anticancer agents. They are Helicobacter pylori independent and do not represent an absolute contraindication for the continuation of hepatic intra-arterial chemotherapy.