M. I. van Berge Henegouwen

In vitro comparison and evaluation of seven gastric closure modalities for natural orifice transluminal endoscopic surgery (NOTES)

BACKGROUND AND STUDY AIMS Secure transluminal closure is the most fundamental prerequisite for the safe introduction of natural orifice transluminal endoscopic surgery (NOTES). The aim was to compare acute strength of various gastrotomy closure techniques in an in vitro porcine stomach model by assessing leak pressures. METHODS Standardized gastrotomies were closed manually, without the use of an endoscope, by one of seven NOTES closure devices: (i) T tags, (ii) purse string modified T tags, (iii) Eagle Claw VIII, (iv) Resolution clips, (v) flexible stapler; (vi) purse string suturing device, and (vii) flexible Endostitch. After closure, each specimen was fixed on the experimental apparatus and the pressure was gradually increased. By linking the pressure gauge and two cameras, the leak location and pressure could be determined in detail. We began by collecting gold standard reference values, by testing 15 gastrotomies closed with interrupted surgical sutures; these were associated with a mean leak pressure of 206 mmHg (SD 59). Using a noninferiority design, a sample size of 11 specimens for each NOTES closure technique was determined. RESULTS The Resolution clips ( P = 0.0285), Eagle Claw VIII ( P = 0.0325), flexible stapler ( P < 0.001) and flexible Endostitch ( P = 0.002) produced noninferior closures in comparison with the predetermined gold standard; T tags ( P > 0.6775), purse string modified T tags ( P > 0.999), and the purse string suturing device ( P = 0.9875) resulted in inferior closures. CONCLUSIONS The Eagle Claw VIII, Resolution clips, flexible stapler and flexible Endostitch produced noninferior closures in comparison with surgical closure in this model. These techniques seem to be the prime candidates for further testing in animal experiments before human trials can be initiated.

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS)

BackgroundA surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial.Methods/designThe CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm.The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up.DiscussionThis study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen.Trial registrationISRCTN80832026

Risk of Lymph Node Metastasis Associated with Deeper Invasion by Early Adenocarcinoma of the Esophagus and Cardia: Study Based on Endoscopic Resection Specimens

BACKGROUND Most risk estimations for lymph node metastasis in adenocarcinoma of the esophagus and cardia (AEC) with invasion into the muscularis mucosae (m3) or submucosa are based on surgical series. This study aimed to correlate the lymph node metastasis rate with m3 and submucosal infiltration depth of AEC in endoscopic resection specimens. METHODS Patients undergoing endoscopic resection for AEC between January 2000 and March 2008 at two centers were included if the endoscopic resection specimen showed m3 or submucosal cancer. Infiltration into the muscularis mucosae was defined as m3. Submucosal invasion was classified as sm1 (≤ 500 µm) or sm2/3 (> 500 µm). Exclusion criteria were chemotherapy or radiotherapy and nonradical endoscopic resection. RESULTS 82 patients included 57 with m3, 12 with sm1, and 13 with sm2/3 cancers. Of the tumors, 13 were poorly differentiated and five showed lymphovascular invasion. After initial endoscopic resection, seven patients underwent surgery and 75 endoscopic therapy. No lymph node metastases were found in 158 lymph nodes of the esophagectomy specimens and none of the endoscopically treated patients were diagnosed with lymph node metastasis during a median follow-up of 26 months (interquartile range [IQR] 14 - 41). CONCLUSION This study suggests that lymph node metastasis risk for m3 and submucosal AEC may be lower than has been assumed on the basis of surgical series, and that current guidelines are valid regarding suitability of m3 AECs for endoscopic therapy. It may also suggest that selected patients with submucosal cancers are also eligible for endoscopic management. Confirmation of these results is needed in larger series with longer follow-up.

Prospective, randomized trial on the effect of cyclic versus continuous enteral nutrition on postoperative gastric function after pylorus-preserving pancreatoduodenectomy.

OBJECTIVE The effect of a cyclic versus a continuous enteral feeding protocol on postoperative delayed gastric emptying, start of normal diet, and hospital stay was assessed in patients undergoing pylorus-preserving pancreatoduodenectomy (PPPD). SUMMARY BACKGROUND DATA Delayed gastric emptying occurs in approximately 30% of patients after PPPD and causes prolonged hospital stay. Enteral nutrition through a catheter jejunostomy is used to provide postoperative nutritional support. Enteral infusion of fats and proteins activates neurohumoral feedback mechanisms and therefore can potentially impair gastric emptying and prolong postoperative gastroparesis. METHODS From September 1995 to December 1996, 72 consecutive patients underwent PPPD at the Academic Medical Center, Amsterdam. Fifty-seven patients were included and randomized for either continuous (CON) jejunal nutrition (0-24 hr; 1500 kCal/24 hr) or cyclic (CYC) enteral nutrition (6-24 hr; 1125 kCal/18 hr). Both groups had an equal caloric load of 1 kCal/min. The following parameters were assessed: days of nasogastric intubation, days of enteral nutrition, days until normal diet was tolerated orally, and hospital stay. On postoperative day 10, plasma cholecystokinin (CCK) levels were measured during both feeding protocols. RESULTS Nasogastric intubation was 9.1 days in the CON group (n = 30) and 6.7 days in the CYC group (n = 27) (not statistically significant). First day of normal diet was earlier for the CYC group (15.7 vs. 12.2 days, p < 0.05). Hospital stay was shorter in the CYC group (21.4 vs. 17.5 days, p < 0.05). CCK levels were lower in CYC patients, before and after feeding, compared with CON patients (p < 0.05). CONCLUSIONS Cyclic enteral feeding after PPPD is associated with a shorter period of enteral nutrition, a faster return to a normal diet, and a shorter hospital stay. Continuously high CCK levels could be a cause of prolonged time until normal diet is tolerated in patients on continuous enteral nutrition. Cyclic enteral nutrition is therefore the feeding regimen of choice in patients after PPPD.

Safety and efficacy of multiband mucosectomy in 1060 resections in Barrett's esophagus

INTRODUCTION Multiband mucosectomy (MBM) is a relatively new technique for endoscopic resection in Barretts esophagus. This ligate-cut technique uses a modified variceal band ligator allowing for six consecutive resections without prior submucosal lifting. The aim was to evaluate the safety of MBM and its efficacy for complete endoscopic removal of delineated target areas in Barretts esophagus. METHODS Prospective registration of all MBM procedures in Barretts esophagus was carried out between November 2004 and October 2009 in two hospitals. Prior to MBM, the target area was delineated with coagulation markings, followed by endoscopic resection until the delineated area was completely resected. Primary end points were acute (during procedure) plus early complications (<30 days) and the rate of complete endoscopic resection of the delineated target area. RESULTS A total of 243 MBM procedures, with 1060 resections, were performed in 170 patients. MBM was performed for focal lesions (n=113), for Barretts esophagus removal as part of a (stepwise) radical endoscopic resection protocol (n=117), and as escape treatment after radiofrequency ablation (n=13). The only acute complication was bleeding (in 3%, endoscopically managed); no perforations occurred despite absence of submucosal lifting. Early complications consisted of delayed bleeding (in 2%, endoscopically managed) and stenosis, which occurred in 48% of patients treated in a (stepwise) radical resection protocol; patients treated for focal lesions or in escape treatment showed no stenosis. Complete endoscopic resection was achieved in 91% of the focal lesions, in 86% of cases treated under the (stepwise) radical endoscopic resection protocol, and 100% for escape treatment after radiofrequency ablation. CONCLUSION MBM is a safe and effective technique for the removal of delineated target areas in Barretts esophagus.

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

Objectives:We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Background:Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently “sterilize” regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Methods:Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. Results:One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12–27) and 14 (9–21), with 2 (1–6) and 0 (0–1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P = 0.007), but not in the multimodality arm (hazard ratio 1.00; P = 0.98). Conclusions:The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Novel over-the-scope-clip system for gastrotomy closure in natural orifice transluminal endoscopic surgery (NOTES): an ex vivo comparison study

BACKGROUND AND STUDY AIMS Secure transluminal closure remains a fundamental barrier to clinical introduction of natural orifice transluminal endoscopic surgery (NOTES). Current NOTES closure modalities either do not provide secure closure or are too challenging to apply in vivo. The aims of this study were to evaluate gastric closure using the over-the-scope clip (OTSC) system in a previously described experimental setup, comparing the acute strength with a gold standard (hand surgical suturing). METHODS Comparison was done using an ex vivo porcine stomach experimental setup. The gastric opening was created by a needle knife puncture followed by dilation with 18-mm balloon. Control gastrotomies (n = 15; surgical suturing) showed a mean leak pressure of 206 mmHg (SD 59). A noninferiority design required a sample size of 11 specimens for the OTSC group. Closure comprised: (i) approximation of muscular layers using a flexible twin grasper; (ii) pulling the tissue into the OTSC cap at the tip of the scope; (iii) releasing the clip. Main outcome measures were leak pressure of closed gastrotomies, leak location, and time needed for adequate closure. RESULTS Closure was successful in all specimens in a median of 3 minutes. Closed gastrotomies showed air leakage at mean pressure of 233 mmHg (SD 47), which was non-inferior compared with the predetermined gold standard (P = 0.003). CONCLUSIONS Closure of gastric incisions to meet a predetermined leak pressure criterion was attainable and easy with the OTSC system. In vivo survival animal experiments are needed to further evaluate this promising closure modality.

Pylorus-preserving pancreatoduodenectomy: influence of a Billroth I versus a Billroth II type of reconstruction on gastric emptying

Background/Aim: Delayed gastric emptying (DGE) is a frequent problem after pylorus-preserving pancreatoduodenectomy. Important risk factors are the presence of intra-abdominal complications. Searching for other causes, this study evaluates the influence of the type of reconstruction after a pancreatoduodenectomy (Billroth I vs. Billroth II; B I vs. B II on DGE. Methods: A retrospective study was performed evaluating consecutive patients from two surgical institutes. 174 patients were included (B II type of reconstruction n = 123, period 1992–1996; B I type of reconstruction n = 51, period 1988–1998). DGE was defined by gastric stasis requiring nasogastric intubation for 10 days or more or the inability to tolerate a regular diet on or before the 14th postoperative day. Results: After a B I type of reconstruction, there was significantly longer nasogastric intubation period as compared with a B II type of reconstruction (B I median 13 days, range 4–47, B II median 6 days, range 1–40; p < 0.05). There was no difference in postoperative commencement of a normal diet. Also significantly more patients had DGE after a B I (76%) as compared with a B II type of reconstruction (32%; p < 0.05). Conclusions: The results of this study indicate a significantly higher incidence of DGE after a B I type of reconstruction as compared with a B II type reconstruction. The etiology remains speculative.

Laparoscopic reintervention for anastomotic leakage after primary laparoscopic colorectal surgery.

Anastomotic leakage is associated with high morbidity and mortality rates. The aim of this study was to assess the potential benefits of a laparoscopic reintervention for anastomotic leakage after primary laparoscopic surgery.

The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers

Background—Octreotide is used in many centres to prevent complications after pancreatic surgery. Delayed gastric emptying is a another complication occurring in around 30% of patients after pancreatoduodenectomy (PD) and causes prolonged hospital stay. The influence of octreotide on this complication is doubtful. Aims—To assess the effect of octreotide, at the clinical dosage used after pancreatic surgery, on gastric emptying in healthy volunteers. Subjects and methods—Eight healthy male volunteers (mean age 22.5 years) participated in this double blind, placebo controlled study. On day 1 subjects received 100 μg of octreotide or placebo subcutaneously, three times daily and on day 2, one hour after the fourth injection, gastric emptying, postprandial cholecystokinin (CCK) release, and mouth to caecum transit time (MCTT) were measured. This protocol was repeated after one week, in a crossover design. On the test day subjects received a liquid test meal (1.57 MJ/300 ml) and gastric emptying measurements were performed with applied potential tomography, a non-invasive, validated technique which measures gastric emptying through impedance differences. From the gastric emptying curves, lag time, t50, and postlag emptying rate were measured. MCTT was measured using the hydrogen breath test. Results—Lag time decreased from 29.6 (6.3) (mean (SEM)) to 12.2 (4.6) minutes (p<0.05) during octreotide treatment; t50 decreased from 87.8 (12.0) to 47.5 (8.2) minutes (p<0.02) and there was a trend towards an increased postlag emptying rate (0.8 to 1.6% per minute; p=0.07). MCTT increased from 150 (12.7) to 229 (17.9) minutes during octreotide treatment (p<0.01). Octreotide suppressed postprandial CCK release (p<0.05). Conclusions—MCTT was delayed by octreotide, suggesting impairment of small bowel transit. Octreotide administered at the clinical dosage for pancreatic surgery accelerates gastric emptying, mainly by shortening the lag time. Suppression of postprandial CCK release may be involved in this process. Octreotide administration is therefore not a contributing factor in the pathogenesis of delayed postoperative gastric emptying after PD and might even play a role in preventing this complication.