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.

[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.

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.

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.

Endoscopic argon plasma coagulation for palliative treatment of malignant airway obstructions: early results in 47 cases.

Argon plasma coagulation (APC) is a new method of non-contact electrocoagulation, using high frequency current by means of ionized argon gas (argon plasma). Recently, this technique has become available for flexible endoscopic delivery through special probes. Aim of this study is to evaluate the efficacy, indications and the possible side effects of APC use in the palliative treatment of malignant airway obstructions and/or bleeding. Over a 24-month period, 47 patients underwent APC treatment for malignant neoplasms of the tracheobronchial system causing obstruction and/or recurrent bleeding. Immediate airway patency and haemostasis were obtained in 91.5% of cases (43/47). No complications or side effects caused by the treatment were observed. In two patients, the treatment allowed a radical surgical approach after induction chemotherapy. In all cases, APC proved to be highly effective and easy to perform. In our experience, APC has proven to be easy to perform, rapidly effective, safe and well tolerated by the patient, even after repeated application. This study highlights the value of endoscopic APC in the palliative management of tracheobronchial neoplasms.

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.

Flexible sigmoidoscopy as a colorectal cancer screening test in the general population: recruitment phase results of a randomized controlled trial in Lombardia, Italy.

UNLABELLED: A two arm multicentre randomized controlled trial is in progress to evaluate the efficacy of flexible sigmoidoscopy (FS) as a screening test for colorectal cancer in the general population. AIMS: To determine the acceptance rate and feasibility of FS as a colorectal cancer screening test in average-risk asymptomatic volunteers. Average-risk, asymptomatic subjects, aged 55-64 years and assisted by 244 general practitioners (GPs) in Lombardy, Italy, were invited by postal questionnaire (PQ) to enter a study for the prevention of colorectal cancer and asked to indicate their interest in, and willingness to undergo, screening: those responding positively were randomized to the intervention or control arms. GPs were trained in colorectal cancer screening and proposed free FS to their patients randomized to the intervention arm. All sigmoidoscopies were performed by experienced endoscopists. Small polyps were removed at FS. Colonoscopy was indicated for high risk polyps (size more than 5 mm, more than two adenomas, villous histology, severe dysplasia or malignancy). 40,945 subjects were invited. 667 PQs were returned undelivered due to postal failure. 7,892 (19.59%) subjects responded, 2,116 of whom (26.81%) were not included, presenting 1 or more exclusion criteria. We randomized 5,778 volunteers and performed 1,582 sigmoidoscopies out of 2,885 subjects in the intervention arm (54.84% acceptance rate). Although the screening procedure had a good attendance rate in the intervention group, involvement of the people invited was lower than expected. Future FS screening programmes will require a keener focus on recruitment strategies, mainly with participation of GPs.

[Preoperative staging of gastric carcinoma using endosonography (EUS)]. / Stadiazione pre-operatoria del carcinoma gastrico mediante endosonografia (EUS).

Accurate staging of gastric malignancy can only be obtained at surgery and after detailed histological examination of the resection specimen. Endoscopic ultrasonography may provide accurate detection and staging of gastric cancer because of its ability to visualize both the intramural and extramural extent of the lesion and any adjacent lymph node involvement. From february 90 to april 91, 29 patients with a gastric carcinoma were studied endosonographically before surgery. All studies were performed with an Olympus EU-M3. Preoperative TNM classification and a prediction of the resectability of gastric cancer were done in every patient. The results were matched with those obtained with the histology of resected specimens according to the TNM classification 1987. Endoscopic ultrasonography was accurate in assessing the extent and depth of tumor infiltration. The overall accuracy rate was 90.5% (19 out of 21 patients). Overstaging occurred in 9.5% of the cases (2 patients); none understaging occurred. EUS was less accurate in assessment of lymph node metastasis; the overall accuracy rate was 57.1%. Distinction between reactive lymph node and small micrometastatic lymph node involvement could be hard. Local resectability was correctly diagnosed with EUS in each of 23 patients; in two patients an intramural mass with a deep infiltration into the surrounding tissue was correctly diagnosed. In our opinion EUS is an essential diagnostic procedure in the clinical staging of the gastric cancer.

[Comparison of 67 pancreatic head tumors and 27 periampullary tumors]. / Confronto tra 67 tumori della testa pancreatica e 27 tumori periampollari.

The authors, in the period from Jan. 1980 to Dec. 1990, observed 67 patients with tumor located in the head of pancreas and 27 patient with periampullary tumors. These included 18 tumors originated from the ampulla of Vater and 9 from distal common bile duct. Operability rate ranged from 62.6% pancreatic carcinoma to 94.4% tumors of ampulla, according to the tumor location. Resectability rate ranged from 9.5% for pancreatic adenocarcinoma for 94.1% to ampullary tumors. Considering 23 resections, 18 were pancreatoduodenectomies and 5 local excisions for tumor of ampulla. Mortality was 7.7% after non resectional treatment and two patients (8.7%) died in the immediate postoperative period after radical resection. Multivariate analysis on all patients operated (n. 65) revealed that 5 years survival rate was significantly related to intent of operation (palliative = 0 - curative = 8.6%), histologic type, and site. In fact no patient with pancreatic adenocarcinoma achieved a 5 years survival rate. Two patients with adenocarcinoma of ampulla survived 5 years. Cancer of the head of pancreas is quite malignant because, owing to pancreas position, an early diagnosis is very hard. Most times resective surgical treatment is impossible because of the cancer diffusion.

[A point about obstructive non-neoplastic pathology of the duodeno-biliary-pancreatic junction]. / Il punto sulla patologia ostruente non neoplastica del giunto duodeno-bilio-pancreatico.

Various benign pathological conditions of Oddi's sphincter may give origin to clinical manifestations due to hindrances to biliary flow into the duodenum; the hypertonic dyskinesia, proper, odditis and fibrosclerotic dystrophies. Such forms develop very big problems from a diagnostic and therapeutical point of view, even if an adequate therapy permits in most cases to reach definite results. Therapy in inflammatory forms (odditis) must be first of all of medical type; only when these are changing into fibrosclerotic forms or are manifest in an acute way it is meet to proceed surgically on the sphincter. The action on the sphincter, either by means of endoscopy or surgery, is performed with caution in the forms of hypertonic dyskinesia (only when such forms are going on and have had a long duration, or even resistant to any pharmacological therapy) because of the high percentage of painful recurrences. The cutting of Oddi's sphincter is on the contrary the first therapeutical choice in the fibrosclerotic forms, with immediate success on the symptoms and the results in the long run are optimal.

[Primary gastric lymphoma: our experience]. / Il linfoma gastrico primitivo: nostra esperienza.

The authors report their experience with 10 cases of primary gastric lymphoma observed in 10 years. Nonspecific symptomatology and bioptic features often misleading to benign lesions (pseudolymphoma) explain why an early diagnosis is difficult to achieve. A correct surgical treatment, with careful pre- and intraoperative staging, associated to pre- and postoperative chemo- and radiotherapy, allows good results in terms of survival.

[Early gastric carcinoma: short and long term results of surgical treatment]. / Carcinoma gastrico iniziale: risultati a breve e lungo termine della terapia chirurgica.

This paper reports Authors' experience in 58 cases of early gastric cancer observed between 1972 and 1990. The diagnosis of E.G.C. was frequently obtained in patients with recent dyspeptic symptoms. The diagnostic importance of endoscopic procedures, upper gastrointestinal X-rays and endoscopic ultrasonography is underlined. The choice of total gastrectomy with the standardized dissection of regional lymph nodes in order to treat multicentric or upper gastric malignancies v.s. distal gastrectomy for antral lesions is discussed. The cumulative survival rate was 84.4%; local recurrence rate was 4.2%.

[Cancer of the gallbladder]. / II cancro della colecisti.

The Authors report their experience about 20 patients operated on since 1975 for primary carcinoma of the gallbladder. They remark their disappointment because of the poor percentage of preoperative and early diagnosis, that only allows a radical surgical therapy. More attention, therefore, should be payed to this not so rare pathology in the hope the survival of the patients radically operated will increase.