Expert consensus on a train-the-trainer curriculum for robotic colorectal surgery.

AIM: Robotic techniques are being increasingly used in colorectal surgery. There is, however, a lack of training opportunities and structured training programmes. Robotic surgery has specific problems and challenges for trainers and trainees. Ergonomics, specific skills and user-machine interfaces are different from those in traditional laparoscopic surgery. The aim of this study was to establish expert consensus on the requirements for a robotic train-the-trainer curriculum amongst robotic surgeons and trainers. METHOD: This is a modified Delphi-type study involving 14 experts in robotic surgery teaching. A reiterating 19-item questionnaire was sent out to the same group and agreement levels analysed. A consensus of 0.8 or higher was considered to be high-level agreement. RESULTS: Response rates were 93-100% and most items reached high levels of agreement within three rounds. Specific requirements for a robotic faculty development curriculum included maximizing dual-console teaching, theatre team training, nontechnical skills training, patient safety, user-machine interface training and telementoring. CONCLUSION: A clear need for the development of a train-the-trainer curriculum has been identified. Further research is needed to assess feasibility, effectiveness and clinical impact of a robotic train-the-trainer curriculum.

Recurrence following curative intended surgery for an adenocarcinoma in the gastroesophageal junction: a retrospective study.

Recurrence following a resection for an adenocarcinoma of the gastroesophageal junction leads to reduced long-term survival. This study aims to identify risk factors associated with recurrence, recurrence localization, time to recurrence, and long-term survival. All patients undergoing curative intended resection for an adenocarcinoma of the gastroesophageal junction at Rigshospitalet between June 2003 and December 2011 were identified through a prospectively maintained nationwide database and enrolled in this study. Only histologically verified recurrence was considered eligible. Recurrence within six months, microscopically incomplete resection margins, and death within eight weeks were excluded. A total of 348 patients were included in this study. Biopsy-verified recurrence occurred in 120 patients (34.5%), with 32 local (9.2%), and 88 distant (25.3%) recurrences. Lymph node metastases was associated with an increased risk of recurrence (hazard ratio; [95% confidence interval]: HR = 2.7; [1.7-4.3], P < 0.001). Median time to local versus distant recurrence was 18 months (interquartile range (IQR): 9-37 months) versus 17 months (IQR: 11-27 months), P = 0.96, respectively. A trend toward local recurrence was identified if patients had anastomotic leakage (HR = 2.64; [0.89-7.86], P = 0.08). Survival was inversely associated with recurrence, but a survival comparison between local and distant recurrences showed no significant difference: median survival time was 28 months (IQR: 17-43 months) versus 24 months (IQR: 16-36 months), P = 0.45, respectively. A trend toward local recurrence was seen if the patient had an anastomotic leakage event. However, no factors were associated with site-specific recurrence (local vs. distant).

Changes in treatment and outcome of oesophageal cancer in Denmark between 2004 and 2013.

BACKGROUND: Since 2003, care for patients with oesophageal cancer has been centralized in a few dedicated centres in Denmark. The aim of this study was to assess changes in the treatment and outcome of patients registered in a nationwide database. METHODS: All patients diagnosed with oesophageal cancer or cancer of the gastro-oesophageal junction who underwent oesophagectomy in Denmark between 2004 and 2013, and who were registered in the Danish clinical database of carcinomas in the oesophagus, gastro-oesophageal junction and stomach (DECV database) were included. Quality-of-care indicators, including number of lymph nodes removed, anastomotic leak rate, 30- and 90-day mortality, and 2- and 5-year overall survival, were assessed. To compare quality-of-care indicators over time, the relative risk (RR) was calculated using a multivariable log binomial regression model. RESULTS: Some 6178 patients were included, of whom 1728 underwent oesophagectomy. The overall number of patients with 15 or more lymph nodes in the resection specimen increased from 38·1 per cent in 2004 to 88·7 per cent in 2013. The anastomotic leak rate decreased from 14·8 to 7·6 per cent (RR 0·66, 95 per cent c.i. 0·43 to 1·01). The 30-day mortality rate decreased from 4·5 to 1·7 per cent (RR 0·51, 0·22 to 1·15) and the 90-day mortality rate from 11·0 to 2·9 per cent (RR 0·46, 0·26 to 0·82). There were no statistically significant changes in 2- or 5-year survival rates over time. CONCLUSION: Indicators of quality of care have improved since the centralization of oesophageal cancer treatment in Denmark.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

A bridging stent to surgery in patients with esophageal and gastroesophageal junction cancer has a dramatic negative impact on patient survival: A retrospective cohort study through data acquired from a prospectively maintained national database.

This study aimed to assess the impact of esophageal stenting on postoperative complications and survival in patients with obstructing esophageal and gastroesophageal junction (GEJ) cancer. All patients treated without neoadjuvant therapy that had an R0-resection performed for esophageal and GEJ cancer between January 2003 and December 2010 were identified from a prospectively maintained database. Data on stenting, postoperative mortality, morbidity, recurrence-free survival, complications, and length of hospital stay were collected. Kaplan-Meier plots for survival and recurrence-free survival curves were constructed for R0 resected patients. Data were compared between the stent and no-stent group by nonparametric tests. Two hundred seventy three consecutive R0 resected patients with esophageal or GEJ cancer were identified. Of these patients, 63 had a stent as a bridge to surgery. The male/female ratio was 2.64 (198/75) with a median age in the stent group (SG) of 65.1 versus 64.3 in the no stent group (NSG). Patients were comparable with respect to gender, age, smoking, TNM-classification, oncological treatment, hospital stay, tumor location, and histology. The median survival in the SG was 11.6 months compared with 21.3 months for patients treated without a bridging stent (P < 0.001). There were no statistically significant differences in 30-day mortality between the two groups, but NSG patients exhibited a significantly better two-year survival (P = 0.017). The median recurrence-free survival was 9.1 months for the SG compared with 15.2 months for the NSG. The use of a stent as a bridging procedure to surgery in patients treated without neaoadjuvant therapy for an esophageal or GEJ cancer that later underwent R0 resection decreased the two year survival and the recurrence-free survival.

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

BACKGROUND: Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS: Patients with stage I-III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS: Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P = 0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P = 0·839) for exercise and usual care respectively. CONCLUSION: Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).

ANTECEDENTES: El tratamiento del cáncer de la unión gastroesofágica (gastroesophageal junction, GEJ) puede determinar un deterioro considerable y persistente de la condición física y de la calidad relacionada con la salud (health-related quality of life, HRQoL). El objetivo de este estudio controlado de seguimiento fue investigar la factibilidad y seguridad del entrenamiento físico postoperatorio. MÉTODOS: Pacientes con cáncer de GEJ en estadio I-III fueron asignados a 12 semanas de entrenamiento postoperatorio simultáneo aeróbico y de resistencia o a cuidados médicos habituales. Se evaluaron los cambios en el estado cardiorrespiratoria, fuerza muscular y HRQoL. Se recogieron datos de la adherencia a la quimioterapia adyuvante, hospitalizaciones y supervivencia global a 1 año para evaluar la seguridad. RESULTADOS: Se estudiaron un total de 49 pacientes. El grupo con ejercicio asistió al 69% de todas las sesiones planificadas. Después del ejercicio, la fuerza muscular y el estado cardiorrespiratorio aumentaron y volvieron a los niveles previos al tratamiento. Si bien al año de seguimiento, el grupo con ejercicio presentó una mejoría de la HRQoL (+13,5 puntos (i.c. del 95% 2,2 a 24,9)), sin cambios en el grupo con atención médica habitual (+3,7 puntos (i.c. del 95% −5,9 a 13,4)), no hubo diferencias entre los grupos en ese momento (+9,8 puntos (i.c. del 95% −5,1 a 24,8)). El ejercicio fue seguro, sin diferencias entre el ejercicio o la atención médica habitual en pacientes que recibían quimioterapia adyuvante 87,5% versus 84,2% (RR 1,04 (i.c. del 95% 0,74 a 1,44)), intensidad relativa de la dosis de quimioterapia adyuvante 56,8% versus 63,3% (P = 0,479), hospitalizaciones 36,8% versus 26,1% (RR 1,41 (i.c. del 95% 0,57 a 3,49)) o supervivencia global a 1 año 80,0% versus 79,3% (P = 0,839). CONCLUSIÓN: El ejercicio en el periodo postoperatorio es seguro y puede tener potencial para mejorar la condición física en pacientes con cáncer de GEJ. No se observaron diferencias en los resultados pronósticos o en la HRQoL.

Safety and feasibility of preoperative exercise training during neoadjuvant treatment before surgery for adenocarcinoma of the gastro-oesophageal junction.

Background: Neoadjuvant chemotherapy or chemoradiotherapy is used widely before tumour resection in cancer of the gastro-oesophageal junction (GOJ). Strategies to improve treatment tolerability are warranted. This study examined the safety and feasibility of preoperative exercise training during neoadjuvant treatment in these patients. Methods: Patients were allocated to a standard-care control group or an exercise group, who were prescribed standard care plus twice-weekly high-intensity aerobic exercise and resistance training sessions. The primary endpoint was the incidence of serious adverse events (SAEs) that prevented surgery, including death, disease progression or physical deterioration. Preoperative hospital admission, postoperative complications, changes in patient-reported quality of life and pathological treatment response were also recorded. In the exercise group, adherence to exercise and changes in aerobic fitness, muscle strength and body composition were measured. Results: The incidence of SAEs was not increased in the exercise group. The risk of failure to reach surgery was 5 versus 21 per cent in the control group (risk ratio (RR) 0·23, 95 per cent c.i. 0·04 to 1·29), the risk of preoperative hospital admission was 15 versus 38 per cent respectively (RR 0·39, 0·12 to 1·23) and the risk of postoperative complications was 58 versus 57 per cent (RR 1·06, 0·61 to 1·73). The exercise group attended a mean of 17·5 sessions, and improved fitness, muscle strength and Functional Assessment of Cancer Therapy - Esophageal (FACT-E) total score compared with the baseline level. Conclusion: Preoperative exercise training during neoadjuvant treatment in patients with GOJ cancer is safe and feasible, with improvements in fitness, strength and quality of life. Preoperative exercise training may be associated with a lower risk of critical SAEs that preclude surgery or result in hospitalization.

The occurrence of Enterococcus faecium and faecalis Is significantly associated With anastomotic leakage After pancreaticoduodenectomy.

BACKGROUND AND AIMS: Enterococcus has emerged as a virulent species; Enterococcus faecium especially has arisen as a source of nosocomial infections. Furthermore, specific Enterococcus faecalis species are significantly associated with anastomotic leakage in rodent studies. The objective of this study was to investigate whether the occurrence of Enterococci ( E. faecium and E. faecalis) obtained from drain samples was associated with leakage in humans undergoing pancreaticoduodenectomy. MATERIALS AND METHODS: All patients undergoing pancreaticoduodenectomy had a peritoneal drain sample sent for culturing between postoperative days 3 and 10. Postoperative pancreatic fistulas were defined and classified according to the International Study Group of Pancreatic Fistula. Bile leakage was radiologically verified. Postoperative complications were classified according to the Dindo-Clavien classification. RESULTS: A total of 70 patients were eligible and enrolled in this study. Anastomosis leakage was observed in 19 patients; 1 leakage corresponding to the hepaticojejunostomy and 18 pancreatic fistulas were identified. In total, 10 patients (53%) with leakage had Enterococci-positive drain samples versus 12 patients (24%) without leakage [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 1.4-19.4, p = 0.02]. Preoperative biliary drainage with either endoscopic stenting or a percutaneous transhepatic cholangiography catheter was associated with the occurrence of Enterococci in drain samples (OR = 5.67, 95% CI = 1.8-12.9, p = 0.003), but preoperative biliary drainage was not associated with leakage (OR = 0.45, 95% CI = 0.1-1.7, p = 0.23). CONCLUSION: Enterococci in drain sample cultures in patients undergoing pancreaticoduodenectomy occurs significantly more among patients with anastomotic leakage compared to patients without leakage.

Ghrelin secretion in humans - a role for the vagus nerve?

BACKGROUND: Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa. Circulating levels rise in the preprandial phase, suggesting an anticipatory or cephalic phase of release, and decline in the postprandial phase, suggesting either the loss of a stimulatory factor or inhibition by factors released when nutrients enter the intestine. We hypothesized that vagal signals are not required for the (i) preprandial increase or (ii) postprandial suppression of ghrelin levels. Further, we wanted to investigate the hypothesis that (iii) glucagon-like peptide-1 might be implicated in the postprandial decline in ghrelin levels. METHODS: We measured ghrelin levels in plasma from sham-feeding and meal studies carried out in vagotomized individuals and controls, and from a GLP-1 infusion study carried out in fasting healthy young individuals. KEY RESULTS: We find that (i) ghrelin secretion is unchanged during indirect vagal stimulation as elicited by modified sham-feeding in vagotomized individuals and matched controls, (ii) ghrelin secretion is similarly suppressed after meal ingestion in vagotomized individuals and controls, and (iii) infusion of GLP-1 does not lower ghrelin levels. CONCLUSIONS & INFERENCES: We conclude that for postprandial suppression of circulating ghrelin levels, a circulating factor (but not GLP-1) or short (duodeno-gastric) reflexes seem to be implicated.

Diagnostic performance of computed tomography colonography and colonoscopy: a prospective and validated analysis of 231 paired examinations.

BACKGROUND: Detection of colorectal tumors with computed tomography colonography (CTC) is an alternative to conventional colonoscopy (CC), and clarification of the diagnostic performance is essential for cost-effective use of both technologies. PURPOSE: To evaluate the diagnostic performance of CTC compared with CC. MATERIAL AND METHODS: 231 consecutive CTCs were performed prior to same-day scheduled CC. The radiologist and endoscopists were blinded to each other's findings. Patients underwent a polyethylene glycol bowel preparation, and were scanned in prone and supine positions using a single-detector helical CT scanner and commercially available software for image analysis. Findings were validated (matched) in an unblinded comparison with video-recordings of the CCs and re-CCs in cases of doubt. RESULTS: For patients with polyps >/=5 mm and >/=10 mm, the sensitivity was 69% (95% CI 58-80%) and 81% (68-94%), and the specificity was 91% (84-98%) and 98% (93-100%), respectively. For detection of polyps >/=5 mm and >/=10 mm, the sensitivity was 66% (57-75%) and 77% (65-89%). A flat, elevated low-grade carcinoma was missed by CTC. One cancer relapse was missed by CC, and a cecal cancer was missed by an incomplete CC and follow-up double-contrast barium enema. CONCLUSION: CC was superior to CTC and should remain first choice for the diagnosis of colorectal polyps. However, for diagnosis of lesions >/=10 mm, CTC and CC should be considered as complementary methods.

Severe Postoperative Complications may be Related to Mesenteric Traction Syndrome during Open Esophagectomy.

BACKGROUND: During abdominal surgery, traction of the mesenterium provokes mesenteric traction syndrome, including hypotension, tachycardia, and flushing, along with an increase in plasma prostacyclin (PGI2). We evaluated whether postoperative complications are related to mesenteric traction syndrome during esophagectomy. METHODS: Flushing, hemodynamic variables, and plasma 6-keto-PGF1α were recorded during the abdominal part of open ( n = 25) and robotically assisted ( n = 25) esophagectomy. Postoperative complications were also registered, according to the Clavien-Dindo classification. RESULTS: Flushing appeared in 17 (open) and 5 (robotically assisted) surgical cases ( p = 0.001). Mean arterial pressure was stable during both types of surgeries, but infusion of vasopressors during the first hour of open surgery was related to development of widespread (Grade II) flushing ( p = 0.036). For patients who developed flushing, heart rate and plasma 6-keto-PGF1α also increased ( p = 0.001 and p < 0.001, respectively). Furthermore, severe postoperative complications were related to Grade II flushing ( p = 0.037). CONCLUSION: Mesenteric traction syndrome manifests more frequently during open than robotically assisted esophagectomy, and postoperative complications appear to be associated with severe mesenteric traction syndrome.

Dysphagia is not a Valuable Indicator of Tumor Response after Preoperative Chemotherapy for R0 Resected Patients with Adenocarcinoma of the Gastroesophageal Junction.

BACKGROUND: Monitoring treatment response to preoperative chemotherapy is of utmost importance to avoid treatment toxicity, especially in non-responding patients. Currently, no reliable methods exist for tumor response assessment after preoperative chemotherapy. Therefore, the aim of this study was to evaluate dysphagia as a predictor of tumor response after preoperative chemotherapy and as a predictor of recurrence and survival. METHODS: Patients with adenocarcinoma of the gastroesophageal junction, treated between 2010 and 2012, were retrospectively reviewed. Dysphagia scores (Mellow-Pinkas) were obtained before and after three cycles of perioperative chemotherapy together with clinicopathological patient characteristics. A clinical response was defined as improvement of dysphagia by at least 1 score from the baseline. The tumor response was defined as down staging of T-stage from initial computer tomography (CT) scan (cT-stage) to pathologic staging of surgical specimen (pT-stage). Patients were followed until death or censored on June 27th, 2014. RESULTS: Of the 110 included patients, 59.1% had improvement of dysphagia after three cycles of perioperative chemotherapy, and 31.8% had a chemotherapy-induced tumor response after radical resection of tumor. Improvement of dysphagia was not correlated with the tumor response in the multivariate analysis (p = 0.23). Moreover, the presence of dysphagia was not correlated with recurrence (p = 0.92) or survival (p = 0.94) in the multivariate analysis. CONCLUSION: In our study, improvement of dysphagia was not valid for tumor response evaluation after preoperative chemotherapy and was not correlated with the tumor response. The presence of dysphagia does not seem to be a predictor of recurrence or survival.

The Multidisciplinary Team Conference's Decision on M-Staging in Patients with Gastric- and Gastroesophageal Cancer is not Accurate without Staging Laparoscopy.

BACKGROUND: The implementation of the multidisciplinary team conference has been shown to improve treatment outcome for patients with gastric- and gastroesophageal cancer. Likewise, the staging laparoscopy has increased the detection of patients with disseminated disease, that is, patients who do not benefit from a surgical resection. The aim of this study was to compare the multidisciplinary team conference's decision in respect of M-staging with the findings of the following staging laparoscopy. METHODS: Patients considered operable and resectable within the multidisciplinary team conference in the period 2010-2012 were retrospectively reviewed. Patient data were retrieved by searching for specific diagnosis and operation codes in the in-house system. The inclusion criteria were as follows: biopsy-verified cancer of the esophagus, gastroesophageal junction or stomach, and no suspicion of peritoneal carcinomatosis or liver metastases on multidisciplinary team conference before staging laparoscopy. Furthermore, an evaluation with staging laparoscopy was required. RESULTS: In total, 222 patients met the inclusion criteria. Most cancers were located in the gastroesophageal junction, n = 171 (77.0%), and most common with adenocarcinoma histology, n = 196 (88.3%). The staging laparoscopy was M1-positive for peritoneal carcinomatosis in eight patients (16.7%) with gastric cancer versus nine patients (5.3%) with gastroesophageal junction cancer. Furthermore, liver metastases were evident in zero patients (0.0%) and four patients (2.3%) with gastric- and gastroesophageal junction cancer, respectively. The staging laparoscopy findings regarding peritoneal carcinomatosis were significantly different between gastric- and gastroesophageal junction cancers, p = 0.01. No significant differences were found regarding T-/N-stage or histological tumor characteristics between the positive- and negative-staging laparoscopy group. CONCLUSION: The M-staging of the multidisciplinary team conference without staging laparoscopy lacks accuracy concerning peritoneal carcinomatosis. Staging laparoscopy remains an essential part of the preoperative detection of disseminated disease in patients with gastric- and gastroesophageal cancer.

Comparative Investigation of Postoperative Complications in Patients With Gastroesophageal Junction Cancer Treated With Preoperative Chemotherapy or Surgery Alone.

BACKGROUND AND AIM: Gastroesophageal junction cancer is one of the leading causes to cancer-related death and the prognosis is poor. However, progress has been made over the last couple of decades with the introduction of multimodality treatment and optimized surgery. Three-year survival rates have improved to 50% in patients receiving neoadjuvant therapy. Only a few studies have focused on the difference of postoperative complications in patients receiving neoadjuvant therapy in relation to a comparative surgery-only group. The aim of this study was to compare the prevalence of postoperative complications of patients with cancer at the gastroesophageal junction treated with either neoadjuvant chemotherapy or surgery alone in patients from "The Danish Clinical Registry of Carcinomas of the Esophagus, the Gastro-Esophageal Junction and the Stomach." MATERIALS AND METHODS: A historical follow-up study, comparing postoperative complications between two cohorts before and after implementation of chemotherapy was completed. RESULTS: In all, 180 consecutive patients treated with perioperative chemotherapy and a comparative surgery-only group of patients were identified from The Danish Clinical Registry of Carcinomas of the Esophagus, the Gastro-Esophageal Junction and the Stomach. No difference was found in demographics between the two groups, except for alcohol consumption and a lower T and N stage in the surgery-only group, and no difference in complication rates was found. Furthermore, no variable in the multivariate analysis was significantly associated with anastomotic leakage which was considered the most severe complication. CONCLUSION: Since perioperative chemotherapy does not appear to increase surgical complications, the future challenges include defining the optimal combination of chemo- and/or radiotherapy, but more importantly also to select the patients who will benefit the most from the different neoadjuvant strategies.

Post-endoscopic retrograde cholangiopancreaticography complications in liver transplanted patients, a single-center experience.

BACKGROUND: Complications in the biliary tract occur in 5%-30% after liver transplantation and the main part of the complications is successfully managed with endoscopic retrograde cholangiopancreaticography (ERCP). The incidence and risk factors for post-ERCP complications in liver transplantation patients are not well described. Our objective was to define the frequency of post-ERCP complications in liver transplantation patients at the Abdominal Center, Rigshospitalet, the only Liver Transplantation Center in Denmark. METHODS: Retrospective study of all ERCPs performed in liver transplantation patients during a 9-year period. RESULTS: A total of 292 ERCPs were included. Overall post-ERCP complications occurred in 24 procedures (8.2%): pancreatitis in 8 (2.7%), bleeding in 5 (1.7%), and cholangitis in 13 (4.5%) procedures. Simultaneous pancreatitis and cholangitis, and simultaneous bleeding and cholangitis occurred after two procedures, respectively. Multivariate analysis concerning overall complications identified biliary sphincterotomy (p = 0.006) and time since liver transplantation within 90 days postoperatively (p = 0.044) as risk factors for post-ERCP complications. Specifically concerning post-ERCP pancreatitis (PEP), it was found that pre-ERCP cholangitis was another independent risk factor for PEP (p = 0.026). Stent in the biliary tract prior to ERCP seemed to be protective (p = 0.041). CONCLUSIONS: Complications were of surprisingly mild degree. The rates of post-ERCP complications in our study were in line with previous studies with liver transplantation patients. Cholangitis prior to ERCP may be another risk factor for post-ERCP pancreatitis.

Two daily doses of sucralfate or cimetidine in the healing of gastric ulcer. A comparative randomized study.

A double-blind, randomized study compared the healing of gastric ulcer during a twice-daily regimen of 2 g sucralfate or 400 mg cimetidine. The patients received the tablets one-half hour before breakfast and one-half hour before bedtime. The study included 76 patients with endoscopically proven gastric ulcer. Patients with ulcers less than 3 cm from the pyloric ring and patients with ulcers less than 3 mm in diameter were excluded from the study. Sixty-four patients completed the study. Healing was endoscopically assessed at four-week intervals for 12 weeks. After four, eight, and 12 weeks, the healing rates for cimetidine were 55, 81, and 94 percent, respectively; the healing rates for sucralfate were 52, 79, and 91 percent, respectively. No statistically significant difference was found between the two regimens. At 12 weeks, the risk of overlooking a difference in favor of one of the two dosage regimens was less than 20 percent. The results suggest that 2 g sucralfate twice daily is as effective in the healing of gastric ulcer as 400 mg cimetidine twice daily.

Pulsed dose rate (PDR) brachytherapy of anal carcinoma.

BACKGROUND AND PURPOSE: With radiotherapy of anal carcinomas, sphincter preservation can be obtained at survival rates similar to those obtained with radical surgery. By combining external beam irradiation with interstitial irradiation, superiority over standard external irradiation has been obtained. With the introduction of pulsed dose rate equipment, where a single high activity source moves through catheters, a more individualized dose distribution and a further elimination of radiation exposure to the staff can be achieved. MATERIALS AND METHODS: Between June 1993 and November 1994, 17 patients with anal carcinoma (T1:4, T2:4, T3:6, T4:3) have been treated at the Finsen Center. The treatment consisted of three-field external irradiation 46 Gy/23 fractions with five fractions a week to the anal canal and regional pelvic lymph nodes. Seven to 33 days after completion of external irradiation, the tumorspace was given 25.2 Gy PDR brachytherapy with 42 pulses of 0.6 Gy, one pulse every hour. RESULTS: One isolated local recurrence has been noted 13 weeks after implantation. One additional local recurrence was seen in a patient with concomitant hepatic and inguinal recurrence. In three patients inguinal recurrence had occurred, two of these patients were irradiated without any further evidence of disease, and one patient with a primary advanced tumour, had local failure. So far necrosis has been observed in 13 patients within 1-49 weeks (median 16 weeks) after implantation. Eight of these patients required colostomy. No relation was observed between the number of implanted needles and the occurrence of necrosis. CONCLUSIONS: The results indicate that the treatment is highly effective, but with substantial toxicity.

Human skin fibroblast in vitro tetraploidy. Flow cytometric DNA assay used to confirm metaphase assay in patients with various colonic diseases.

One hundred twenty-two patients with various colon pathologies (43 colorectal carcinoma patients exclusive of the known autosomal dominant colorectal cancer syndromes, 31 patients with solitary colorectal adenomas, 27 patients with ulcerative colitis, and 21 controls with no evidence of colorectal cancer) were investigated for in vitro tetraploidy in dermal fibroblasts cultures using a metaphase assay for determination of numerical chromosomal alterations. Later, stationary cultures of these skin fibroblasts were investigated with DNA flow cytometry. There was good correlation between the percentage of tetraploid metaphase cells and the percentage of nuclei with a flow cytometric DNA index of 2. Using a linear discrimination function to classify the flow cytometric data, the peak with DNA index of 2 was the most important parameter, supplemented by the region with DNA index greater than 2, whereas the region with DNA index between 1 and 2 probably represented a different subpopulation. We have thus demonstrated that only the region with a DNA index of 2 or greater is suitable in determining in vitro tetraploidy in stationary skin fibroblast cultures.

Correlation between in vitro tetraploidy in skin fibroblasts and development of sporadic colorectal carcinomas.

In vitro tetraploidy (IVT) in skin fibroblasts cultures measured by flow cytometry was compared with histological type and degree of dysplasia in 22 patients with adenomas of the colon and rectum. Furthermore, IVT was compared with stage and differentiation in 36 patients with carcinoma of the colon and rectum. In vitro tetraploidy in skin fibroblasts was correlated to type as well as dysplasia in adenomas and differentiation in carcinomas but was not correlated to Dukes' stage in carcinomas. Skin fibroblast genetic instability, expressed as increased IVT (IVT+), has been reported to reflect a genetic predisposition to colorectal cancer in the hereditary nonpolyposis colorectal cancer syndrome. Because IVT+, which appears to be associated with the progression of adenomas to carcinomas, also is found in many of the non-syndrome colorectal cancers, we suggest that development of colorectal cancer is considerably influenced by the constitutive genetic instability of the autosomal dominant colorectal cancer syndromes.

Pancreatic tissue pressure and pain in chronic pancreatitis.

Pancreatic tissue pressure (PTP) was measured peroperatively by the needle technique in 14 patients with chronic pancreatitis undergoing drainage operations for pseudocysts (six patients) or dilated ducts (eight patients). All patients suffered from severe abdominal pain before the operation, and a pain evaluation was made at discharge and after 8-18 months of observation. PTP was increased in all patients and was not different in the two groups. PTP decreased significantly in both groups after drainage. Pain relief at discharge was good or fair in 12 patients and poor in one (one patient died postoperatively). During observation, pain returned in four patients. Long-term pain relief was not related to PTP decrease, PTP after operation, type of operation, or patency of anastomosis as seen by endoscopic retrograde pancreaticography.