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.

A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

BACKGROUND: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. PATIENTS AND METHODS: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. RESULTS: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. CONCLUSION: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. CLINICALTRIALSGOV: NCT02409472.

Robotic colectomy: is it necessary?

More than 20 years ago the introduction of laparoscopic surgery represented a paradigm shift in the management of colorectal cancer. In most recent years robotic surgery is becoming a viable alternative to laparoscopic and traditional open surgery. The major clear advantages of robotic surgery in comparison with laparoscopy are the lower conversion to open surgery rates and the shorter learning curve. However, the role of robotics in colorectal surgery is still largely undefined and different with respect to its application in abdominal versus pelvic surgery. As for colon cancer there are emerging data that laparoscopic and robotic surgery have the same advantages in terms of faster recovery, although robotic-assisted colectomy is associated with costs increase of care without providing clear reduction in overall morbidity or length of stay. Long-term outcomes for laparoscopic versus robotic colonic resections remain still largely undetermined and randomized controlled clinical trials are required to establish a possible difference in outcomes. Interesting issues for the educational aspects are associated with robotic surgery, as the double console allows the resident to take part actively at the surgical procedure since the beginning of his surgical experience.

Role of robotic surgery in colorectal resections for cancer.

In recent years, robotic surgery is becoming a valid alternative in colorectal diseases treatment to laparoscopic and traditional open surgery. The most relevant reported technical advantages of the robotic surgery are 3D-view, tremor-filtering, seven degree-free motion and a higher comfortable setting for the surgeon. Both case series and comparative studies available in Literature report only short and mid-term outcomes. These studies are able to demonstrate that robotic surgery is as safe and feasible as laparoscopic surgery regarding perioperative outcomes. Trials with long term follow up are needed to establish the real safety and effectiveness of the robotic surgery especially concerning resections for cancer. The robotic surgery could be considered a promising surgical field. The high costs represent one of the most relevant drawbacks.

Comparison of oral polyethylene glycol plus a large volume glycerine enema with a large volume glycerine enema alone in patients undergoing colorectal surgery for malignancy: a randomized clinical trial.

AIM: Recent meta-analyses and randomized clinical trials have concluded that mechanical bowel preparation (MBP) before elective colorectal surgery is not associated with a reduction of surgical site infection (SSI). The aim of this randomized clinical trial was to evaluate the impact of preoperative MBP for colon and rectal cancer surgery in comparison with a single glycerine enema. METHOD: Patients scheduled for radical colorectal resection for malignancy with primary anastomosis were randomized to preoperative MBP (4 l of polyethylene glycol) (group 1, 114 patients) plus a glycerine 5% enema (2 l) or a single glycerine 5% enema (2 l) (group 2, 115 patients). The postoperative incidence of SSI was recorded prospectively. Patients undergoing minimally invasive surgery (laparoscopy or robotic) accounted for 55 and 51 in groups 1 and 2 respectively. RESULTS: In all, 229 patients were included in the study, 114 in group 1 and 115 in group 2. At least one SSI was reported in 16 (14.0%) group 1 and in 20 (17.8%) group 2 patients (P=0.475). Perioperative mortality was nil. The incidence of SSI was comparable also in the 73 patients who had a low anterior resection (seven of 33 vs eight of 40, P=1.000), and for the 106 patients who underwent a minimally invasive procedure (nine of 55 vs four of 51, P=0.241). CONCLUSION: A single large-volume glycerine enema is effective bowel preparation before colorectal resection whether performed by an open or minimally invasive technique.

[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.

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial.

BACKGROUND: Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS: Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patient's death or ending of the study. RESULTS: Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS: Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

Mini-invasive surgery may be advised in oncology.

In the last decade mini-invasive surgery has consistently developed with good results, but also with some unjustified clinical applications. This review is aimed at defining evidence based indications and procedures ('clinical practice') and those still worthy of controlled studies in oncologic centers with expertise in mininvasive surgery ('clinical research'). At present, diagnostic and staging laparoscopy and thoracoscopy represent the 'standard' for different tumors. Conversely, therapeutic indications according to evidence based medicine criteria are still limited. Tumors treatment by mini-invasive surgery requires 'expertise' on the part of the surgical team; this can be achieved by extensive training of a correct use of instruments and methods following the general surgical principles of traditional 'open surgery'.

Long-term, totally implantable central venous access ports connected to a Groshong catheter for chemotherapy of solid tumours: experience from 178 cases using a single type of device.

The aim of this study was to examine the early and late complications rate of central venous access ports connected to the Groshong catheter for long-term chemotherapy delivering. All patients suffering from a neoplastic disease, who required long-term chemotherapy and underwent insertion of implantable ports during a 21-month period (1 October 1994-30 June 1996) were prospectively studied. A single type of port was used, constructed of titanium and silicone rubber (Dome Port, Bard Inc., Salt Lake City, U.S.A), connected to an 8 F silastic Groshong catheter tubing (Bard Inc.). A team of different operators (two general surgeons, one interventional radiologist and four anaesthesiologists) was involved in inserting the port. All devices were placed in the operating room under fluoroscopic control. A central venous access form was filled in by the operator after the procedure and all ports were followed prospectively for device-related and overall complications. Data from the follow-up of these patients were entered in the form and collected in a database. Follow-up continued until the device was removed, the patient died or the study was closed. 178 devices, comprising a total of 32,089 days in situ, were placed in 175 patients. Three patients received a second device after removal of the first. Adequate follow-up was obtained in all cases (median 180 days, range 4-559). 138 devices (77.5%) were still in situ when the study was closed. Early complications included six pneumothoraxes, three arterial punctures and two revisions for port and/or catheter malfunction (overall early complications in 8 patients). Late complications included 3 cases (1.68% of devices) of catheter rupture and embolisation (0.093 episodes/1000 days of use), 2 cases (1.12% of devices) of venous thrombosis (0.062 episodes/1000 days of use), 1 case (0.56% of devices) of pocket infection (0.031 episodes/1000 days of use), and 4 cases (2.24% of devices) of port-related bacteraemias (0.124 episodes/1000 days of use). Infections were caused by coagulase-negative Staphylococcus aureus (4 cases) and Bacillus subtilis (1 case); they required port removal in 3 out of 5 cases. This study represents the largest published series of patients with totally implantable access ports connected to Groshong catheters; this device is a good option for long-term access to central veins and delivery of chemotherapeutic regimens, including continuous intravenous infusions. The low incidence of major complications related to implantation and management of these devices support increased use in oncology patients.

Totally implantable central venous access ports for high-dose chemotherapy administration and autologous stem cell transplantation: analysis of overall and septic complications in 68 cases using a single type of device.

Sixty-eight patients suffering from breast cancer, ovarian cancer, lymphoma or multiple myeloma were treated with high-dose chemotherapy and autologous stem cell transplantation. They underwent placement of a central venous port via the subclavian vein for delivery of chemotherapy and reinfusion of stem cells. All patients were followed prospectively for device-related and overall complications, comprising a total of 18,213 days in situ (median: 267 days, range: 90-480). One patient experienced a pneumothorax (1.4%) spontaneously resolved, as an acute toxicity. Two patients (2.8%, 0.1 episodes/1000 days of use) were forced to have the port removed due to infection, caused by Streptococcus mitis in one case, while the causative agent was not identified by laboratory tests in the second. The other 66 patients completed the therapeutic programme, including peripheral stem cell reinfusions and supportive care, such as i.v. antibiotics, antiemetics or fluid administration and blood sample collection, without additional complications. In conclusion, the use of totally implantable central venous access ports has resulted in good long-term access to central veins, in spite of the severe neutropenia and increased septic risk of this category of oncology patients.

Clinical relevance of serological markers in the detection and follow-up of pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is a relatively common malignancy and its incidence is increasing. Prognosis in these patients is poor, and surgery, the only effective treatment, saves only a minority of patients. The number in this small group of patients might be increased by early detection of pancreatic tumours. This review examines the current status of pancreatic tumour associated proteins in the detection of pancreatic cancer. As well as existing markers, the review also reports on newer markers that may offer advantages over existing ones in the detection of pancreatic adenocarcinoma. This is particularly important because recent studies have identified high-risk groups susceptible to pancreatic cancer. Future research in pancreatic cancer should be directed at earlier detection, and tumour markers may play an important role in this process.

Complications and long-term outcome of 80 oncology patients undergoing needle catheter jejunostomy placement for early postoperative enteral feeding.

Some findings suggest that needle catheter jejunostomy (NCJ) is associated with a significant rate of potentially dangerous complications. The purpose of this study was to prospectively evaluate the rate and type of early and late complications associated with NCJ in patients with surgical treatment of upper gastrointestinal malignancy. Eighty patients underwent NCJ implant at the end of their scheduled surgical procedure. Enteral nutrition programme was started on postoperative day 1 in the surgical ICU. NCJ was always removed in the outpatient clinic after hospital discharge. One case of tube blockage has been observed as single short-term complication in this series. No long-term complications have been detected after a mean follow-up of 12 months. Routine use of NCJ in malnourished patients undergoing major surgical procedures on upper gastrointestinal tract is safe and effective.

Sentinel node localization in primary melanoma: learning curve and results.

Ninety primary melanoma patients were studied to investigate the importance of adopting the simultaneous use of patent blue dye (PBD) and lymphoscintigraphy plus gamma detection probe to locate the sentinel node (SN). In total 135 SNs in 105 basins were visualized preoperatively under a gamma camera after lymphoscintigraphy. When a SN was identified intraoperatively, its radioactivity level and colour were verified and documented. Two of the SNs seen on lymphoscintigraphy were not found. Using PBD 78.52% of the SNs were identified; 95.5% were identified using the gamma detection probe. Using both methods together 98.5% of the SNs were detected. Twenty-two patients (24.4%) had pathologically positive SNs. The surgical learning curve was assessed for the two techniques. The learning curve associated with the methodology was important in finding the SN when using PBD associated with lymphoscintigraphy, but not when the gamma detection probe was used; we found a statistically significant reduction in the percentage of stained SNs found using PBD in the initial 14 SNs biopsied compared with the subsequent 121 nodes. This is important as not all institutions have access to a gamma probe. The time required to identify each SN was documented and analysed. The duration of the procedure was significantly shorter for stained SNs than for non-stained SNs, which support the use of both PBD and the gamma probe. In conclusion, SN biopsy should be performed by surgeons and nuclear medicine doctors in co-operation, both methods being adopted simultaneously to reduce the percentage of procedure failures.

Role of hepatic histologic findings in the prognosis and treatment of bleeding esophageal varices.

In the period from 1976 to 1986, we performed 329 hepatic needle biopsies using a posterior extraperitoneal approach in patients with bleeding esophageal varices. The histologic findings subdivided according to a four-stage classification were correlated significantly with immediate survival. Specifically, 21 of 23 stage IV patients with severe degenerative and necrotic parenchymal lesions died after immediate emergency surgery, whereas 26 of 48 stage IV patients who did not undergo emergency surgery survived. Stage IV patients appeared unable to withstand major surgery. According to our data, histologic stage and Child's class are independent parameters, especially in emergency situations, since they quantify different aspects of functional liver failure. Therapeutic implications are presented based on cumulative analysis of histologic stages and Child's classes.

Medical decision making for melanoma of the glans penis.

This case report describes a rare presentation of penile melanoma in which 3 successive primaries arose and were operated from an area of melanosis on the glans penis and prepuce. One of the major factors accounting for the poor prognosis of this patient was the long delay in presentation. This was largely due to the patient's reluctance because of the site of the disease. When diffuse melanotic areas are present in the genital region, in particular given the reluctance of patients with skin lesions in this region to present, the index of suspicion should be high with respect to the risk of transformation and an aggressive follow-up policy should be advocated. Treatment guidelines should not significantly differ from the usual approach of cutaneous melanoma.

Rare presentation of small bowel leiomyosarcoma with liver metastases.

Intraabdominal sarcomas are rare tumours usually diagnosed at an advanced stage. These lesions at presentation are bulky and symptoms are often related to pressure effects on adjacent organs. This case report describes a rare presentation of a small bowel leiomyosarcoma whose initial presentation was free haemorrhage into the abdominal cavity and concomitant liver metastases. This case report also demonstrates that, even with such a rare presentation, an aggressive surgical approach is indicated in this type of tumour and helps a patient with advanced disease to live a few disease-free months with a good quality of life.

Percutaneous ultrasonic lithotripsy of intrahepatic gallstones under endoscopic control.

Percutaneous ultrasonic lithotripsy in association with endoscopic control and balloon catheter dilatation of stenosed cholangiojejunostomy was successfully used in the treatment of a 53-year-old man with intrahepatic gallstones and severe cholestasis. Previously, he had undergone several biliary surgery operations, but all interventions were complicated by stenosis. The good results obtained in this case lead us to consider percutaneous ultrasonic lithotripsy a possible alternative to surgical treatment of complicated gallstones.

Comparison of continuous versus intermittent hepatic pedicle clamping in an experimental model.

BACKGROUND/AIMS: The tolerance of the liver to ischemia obtained with intermittent clamping of the hepatic pedicle or continuous Pringle maneuver was tested. METHODOLOGY: Ninety rats were divided into three groups undergoing total duration of clamping ischemia of 60, 90, and 120 min. Each group of rats were subdivided to receive continuous Pringle maneuver, 30-min or 15-min intermittent clamping. The clamp release time between the periods of liver ischemia was 5 min. Survival at 7 days and postoperative changes of liver function (transaminase enzymes, bilirubin, and adenosine-5'-triphosphate levels (hepatocellular damage index) were recorded. RESULTS: Intermittent clamping of the hepatic pedicle was better tolerated than the continuous clamping method. With continuous clamping the rat survival rates inversely correlated with the duration of ischemia. Survival rates at 15-min and 30-min intermittent ischemia groups were significantly higher than in the continuous clamping group. CONCLUSIONS: This data suggest that when the Pringle maneuver is adopted, it should be applied intermittently rather than continuously.

[Prognostic significance of postoperative septic complications in surgery of rectal carcinoma]. / Significato prognostico delle complicanze settiche postoperatorie nella chirurgia del carcinoma rettale.

AIM: To assess whether there is a correlation between the onset of postoperative sepsis and the 5-years survival rate in patients undergoing surgery for rectal cancer. EXPERIMENTAL DESIGN: A retrospective study of all patients, undergoing rectal cancer surgery during the period January 1981-December 1987. PLACE: General Surgery Unit, Hospital Arnau de Vilanova. PATIENTS: All patients operated with Duke's stage B and C colorectal neoplasms, excluding cases with postoperative complications not directly correlated to surgery: pneumonia, thromboblebitis, urinary infection or fever of unknown origin. FINDINGS: Postsurgical complications distinguished as minor (wall abscess) or major (anastomotic dehiscence, peritoneal abscess). 5-year survival rate. RESULTS: The actuarial 5-year survival rate of patients with major septic complications was significantly lower (p < 0.05) than that in noncomplicated cases. No difference was observed in the survival of patients with and without minor septic complications. CONCLUSION: Major septic complications secondary to colorectal surgery are still a threat in spite of improved techniques and antibiotic prophylaxis, and negatively influence the long-term survival rate.