Does Routine Endoscopy or Contrast Swallow Study After Esophagectomy and Gastric Tube Reconstruction Change Patient Management?

BACKGROUND: Anastomotic leakage is a severe complication after esophagectomy. The objective was to investigate the diagnostic and predictive value of routine contrast swallow study and endoscopy for the detection of anastomotic dehiscence in patients after esophagectomy. METHODS: All patients who underwent contrast swallow and/or endoscopy within 7 days after oesophagectomy for cancer between January 2005 and December 2009 were selected from an institutional database. RESULTS: Some 173 patients underwent endoscopy, and 184 patients underwent a contrast swallow study. The sensitivity of endoscopy for anastomotic leakage requiring intervention is 56 %, specificity 41 %, positive predictive value (PPV) 8 %, and negative predictive value (NPV) 95 %. The sensitivity of contrast swallow study for detecting leakage requiring intervention in patients without signs of leakage was 20 %, specificity 20 %, PPV 3 %, and NPV 97 %. CONCLUSIONS: In patients without clinical suspicion of leakage, there is no benefit to perform routine examinations.

Prednisolone does not affect direct-acting antivirals against hepatitis C, but inhibits interferon-alpha production by plasmacytoid dendritic cells.

BACKGROUND: Chronic hepatitis C virus (HCV) infection compromises long-term outcomes of liver transplantation. Although glucocorticosteroid-based immunosuppression is commonly used, discussion is ongoing on the effect of prednisolone (Pred) on HCV recurrence and response to antiviral therapy post transplantation. Recently, new drugs (direct-acting antivirals) have been approved for the treatment of HCV, however, it remains unknown whether their antiviral activity is affected by Pred. The aim of this study was to investigate the effects of Pred on the antiviral activity of asunaprevir (Asu), daclatasvir (Dac), ribavirin (RBV), and interferon-alpha (IFN-α), and on plasmacytoid dendritic cells (PDCs), the main IFN-α-producing immune cells. METHODS: The effects of Pred and antiviral compounds were tested in both a subgenomic and infectious HCV replication model. Furthermore, effects were tested on human PDCs stimulated with a Toll-like receptor-7 ligand. RESULT: Pred did not directly affect HCV replication and did not inhibit the antiviral action of Asu, Dac, RBV, or IFN-α. Stimulated PDCs potently suppressed HCV replication. This suppression was reversed by treating PDCs with Pred. Pred significantly decreased IFN-α production by PDCs without affecting cell viability. When Asu and Dac were combined with PDCs, a significant cooperative antiviral effect was observed. CONCLUSION: This study shows that Pred acts on the antiviral function of PDCs. Pred does not affect the antiviral action of Asu, Dac, RBV, or IFN-α. This implies that there is no contraindication to combine antiviral therapies with Pred in the post-transplantation management of HCV recurrence.

Induction chemotherapy followed by surgery for advanced oesophageal cancer.

BACKGROUND: Patients with locoregionally advanced oesophageal tumours or disputable distant metastases are referred for induction chemotherapy with the aim to downstage the tumour before an oesophagectomy is considered. STUDY DESIGN: Patients who underwent induction chemotherapy between January 2005 and December 2012 were identified from an institutional database. Treatment plan was discussed in the multidisciplinary team. Response to chemotherapy was assessed by CT. Survival was calculated using the Kaplan Meier method. Uni- and multivariable analyses were performed to identify prognostic factors for survival. RESULTS: In total 124 patients received induction chemotherapy mainly for locoregionally advanced disease (n = 80). Surgery was withheld in 35 patients because of progressive disease (n = 16) and persistent unresectability (n = 19). The median overall survival of this group was 13 months (IQR: 8-19). The remaining 89 patients underwent surgery of which 13 still had unresectable tumour or distant metastases. Of the 76 patients that underwent an oesophagectomy, 50 patients had tumour free resection margins (66%) with an estimated 5-year survival of 37%. A positive resection margin (HR 4.148, 95% CI 2.298-7.488, p < 0.0001) was associated with a worse survival in univariable analysis, but only pathological lymph node status with increasing hazard ratio's (6.283-10.283, p = 0.001) remained significant after multivariable analysis. CONCLUSION: Induction chemotherapy downstages the tumour and facilitates a radical oesophagectomy in patients with advanced oesophageal cancer. Pathological lymph node status is an independent prognostic factor for overall survival.

Translational research on esophageal adenocarcinoma: from cell line to clinic.

Human esophageal adenocarcinoma (EAC) cell lines have made a substantial contribution to elucidating mechanisms of carcinogenesis and drug discovery. Model research on EAC relies almost entirely on a relatively small set of established tumor cell lines because appropriate animal models are lacking. Nowadays, more than 20% of all fundamental translational research studies regarding EAC are partially or entirely based on these cell lines. The ready availability of these cell lines to investigators worldwide have resulted in more than 250 publications, including many examples of important biomedical discoveries. The high genomic similarities (but certainly not completely identical) between the EAC cell lines and their original tumors provide rational for their use. Recently, in a collaborative effort all available EAC cell lines have been verified resulting in the establishment of a reliable panel of 10 EAC cell lines. It could be expected that the value of these cell lines increases as unlimited source of tumor material because new biomedical techniques require more tumor cells and the supply of viable tumor cells is diminishing because of neoadjuvant chemo(radio)therapy of patients with EAC. Here, we review the history of the EAC cell lines and their utility in translational research and biomedical discovery.

Umbilical hernia management during liver transplantation.

PURPOSE: Patients with liver cirrhosis scheduled for liver transplantation often present with a concurrent umbilical hernia. Optimal management of these patients is not clear. The objective of this study was to compare the outcomes of patients who underwent umbilical hernia correction during liver transplantation through a separate infra-umbilical incision with those who underwent correction through the same incision used to perform the liver transplantation. METHODS: In the period between 1990 and 2011, all 27 patients with umbilical hernia and liver cirrhosis who underwent hernia correction during liver transplantation were identified in our hospital database. In 17 cases, umbilical hernia repair was performed through a separate infra-umbilical incision (separate incision group) and 10 were corrected from within the abdominal cavity without a separate incision (same incision group). Six patients died during follow-up; no deaths were attributable to intraoperative umbilical hernia repair. All 21 patients who were alive visited the outpatient clinic to detect recurrent umbilical hernia. RESULTS: One recurrent umbilical hernia was diagnosed in the separate incision group (6 %) and four (40 %) in the same incision group (p = 0.047). Two patients in the same incision group required repair of the recurrent umbilical hernia; one of whom underwent emergency surgery for bowel incarceration. The one recurrent hernia in the separate incision group was corrected electively. CONCLUSION: In the event of liver transplantation, umbilical hernia repair through a separate infra-umbilical incision is preferred over correction through the same incision used to perform the transplantation.

Barrett's esophagus and esophageal adenocarcinoma are common after treatment for achalasia.

BACKGROUND: Achalasia is characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES). This contrasts with an insufficient LES, predisposing to gastro-esophageal reflux and Barrett's esophagus. The co-incidence of achalasia and BE is rare. Pneumatic dilatation (PD) may lead to gastro-esophageal reflux, Barrett's esophagus development, and esophageal adenocarcinoma. AIMS: To determine the incidence of Barrett's esophagus and esophageal adenocarcinoma in achalasia patients treated with PD. METHODS: We performed a single-center cohort follow-up study of 331 achalasia patients treated with PD. Mean follow-up was 8.9 years, consisting of regular esophageal manometry, timed barium esophagram, and endoscopy. RESULTS: Twenty-eight (8.4%) patients were diagnosed with Barrett's esophagus, one at baseline endoscopy. This corresponds with an annual incidence of Barrett's esophagus of 1.00% (95% CI 0.62-1.37). Hiatal herniation was present in 74 patients and 21 developed Barrett's esophagus compared to seven of 257 patients without a hiatal hernia. Statistical analysis revealed a hazard ratio of 8.04 to develop Barrett's esophagus if a hiatal hernia was present. Post-treatment LES pressures were lower in patients with Barrett's esophagus than in those without (13.9 vs. 17.4 mmHg; p = 0.03). Two (0.6%) patients developed esophageal adenocarcinoma during follow-up. CONCLUSIONS: Barrett's esophagus is incidentally diagnosed in untreated achalasia patients despite high LES pressures, but is more common after successful treatment, especially in the presence of hiatal herniation. Patients treated for achalasia should be considered for GERD treatment and surveillance of development of Barrett's esophagus, in particular, when they have low LES pressures and a hiatal herniation.

Genetic polymorphisms in innate immunity receptors do not predict the risk of bacterial and fungal infections and acute rejection after liver transplantation.

INTRODUCTION: We studied the influence of a broad range of genetic variants in recipient and donor innate immunity receptors on bacterial and fungal infections and acute rejection after liver transplantation (LT). METHODS: Seventy-six polymorphisms in TLR 1-10, NOD2, LBP, CD14, MD2, SIGIRR, Ficolins 1, -2, and -3, MASP 1, -2, and -3, and the complement receptor C1qR1 were determined in 188 LT recipients and 135 of their donors. Associations with clinically significant infections and acute rejection were analyzed for 50 polymorphisms. Significant associations were validated in an independent cohort of 181 recipients and 167 donors. RESULTS: Three recipient polymorphisms and 3 donor polymorphisms were associated with infections in the identification cohort, but none of these associations were confirmed in the validation cohort. Three donor polymorphisms were associated with acute rejection in the identification cohort, but not in the validation cohort. CONCLUSION: In contrast to their effect in the general population, 50 common genetic variations in innate immunity receptors do not influence susceptibility to bacterial/fungal infections after LT. In addition, no reproducible associations with acute rejection after LT were observed. Likely, transplant-related factors play a superior role as risk factors for bacterial/fungal infections and acute rejection after LT.

Impact of age and co-morbidity on surgical resection rate and survival in patients with oesophageal and gastric cancer.

BACKGROUND: Major surgery for cancer has become safer, including for elderly patients with co-morbidity. The aim of this study was to investigate the association between patient characteristics, resection rates and survival among patients with oesophageal or gastric cancer. METHODS: The prospective Dutch population-based Eindhoven Cancer Registry for oesophagogastric cancers diagnosed between 1995 and 2009 was studied retrospectively for patient characteristics including co-morbidity. Logistic regression analysis was performed to assess the likelihood of resection in patients with tumour node metastasis (TNM) stage I-III lesions. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for survival. RESULTS: The database contained information on 923 patients with oesophageal squamous cell carcinoma, 1181 with distal oesophageal, 942 with cardia and 3177 with subcardia cancer. Of patients with TNM stage I-III disease, 20·8 per cent (557 of 2680 patients) did not undergo resection. Age 70 years or above was associated with a lower likelihood of resection for distal oesophageal (odds ratio (OR) 0·24, 95 per cent confidence interval (c.i.) 0·14 to 0·41) and gastric (cardia: OR 0·41, 0·22 to 0·76; subcardia: OR 0·68, 0·48 to 0·97) cancer. The 30-day mortality rate increased with age (4·7 per cent in patients aged less than 70 years versus 11·9 per cent in those aged 70 years or more; P < 0·001) and co-morbidity (no co-morbidity, 3·6 per cent; 1 co-morbidity, 8·6 per cent; 2 or more co-morbidities, 11·2 per cent; P = 0·015). Surgery (compared with no surgery) was independently associated with better survival for all tumour types. After adjustment for treatment differences, age 70 years or above and presence of two or more co-morbidities were independently associated with poorer survival, especially in patients with subcardia carcinoma (age 70 years or more: HR 1·27, 95 per cent c.i. 1·17 to 1·48; co-morbidity: HR 1·33, 1·21 to 1·62). CONCLUSION: Surgical compared with non-surgical treatment of oesophagogastric cancer was associated with better survival, but postoperative mortality was increased in patients of advanced age and with greater co-morbidity.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

A prospective study on elective umbilical hernia repair in patients with liver cirrhosis and ascites.

BACKGROUND: Patients with both cirrhosis and ascites have a 20% risk of developing umbilical hernia. A retrospective study from our center comparing conservative management of umbilical hernia with elective repair in these patients showed a significant risk of mortality as a result of hernia incarceration in conservatively treated patients. The goal of this study was to assess the safety and efficacy of elective umbilical hernia repair in these patients prospectively. METHODS: Patients with liver cirrhosis and ascites presenting with an umbilical hernia were included in this study. For all patients, the expected time to liver transplantation was more than 3 months, and they did not have a patent umbilical vein in the hernia sac. The following data were collected prospectively for all patients: Child-Pugh-Turcotte (CPT) classification, model for end-stage liver disease (MELD) score, kidney failure, cardiovascular comorbidity, operation-related complications, and duration of hospital stay. Mortality rates were registered in hospital records and verified in government records during follow-up. Mortality rates were registered in hospital records and verified in government records during follow-up. On completion of the study, a retrospective survey was performed to search for any patients who met the study inclusion criteria but were left out of the study cohort. RESULTS: In total, 30 patients (25 males) underwent operation at a mean age of 58 years (standard deviation [SD] ± 9 years). Of these 30 patients, 6 were classified as CPT grade A (20%), 19 (63%) as grade B, and 5 (17%) as grade C. The patients' median MELD score was 12 (interquartile range [IQR], 8-16). In 10 (33%) of the 30 patients hernia repair was performed with mesh. The median duration of hospital stay was 3 days (IQR, 2-4). None of the patients were admitted to the intensive care unit. Postoperative complications included pneumonia and decompensation of cirrhosis (1 case each,) resulting in prolonged hospital stay for those 2 patients. After a median follow-up period of 25 months (IQR, 14-34), 2 (7%) of the 30 patients died; neither of the deaths were attributable to the umbilical hernia repair. A total of 2 patients suffered recurrence. CONCLUSION: Elective umbilical hernia repair is safe and the preferred approach in cirrhotic patients with ascites.

Results of a two-center study comparing hepatic fibrosis progression in HCV-positive liver transplant patients receiving cyclosporine or tacrolimus.

A 2-center retrospective analysis was performed in 60 patients undergoing liver transplantation for hepatitis C virus (HCV)-related disease (cyclosporine in 20, tacrolimus in 40). Mean (±SEM) follow-up was 23.6 ± 22.5 and 22.3 ± 13.7 months in patients receiving cyclosporine or tacrolimus, respectively. Clinically indicated biopsies were performed in 15/20 cyclosporine patients (75%) and 22/40 tacrolimus patients (55%; P = .17). The Ishak fibrosis score was significantly lower in cyclosporine-treated patients versus tacrolimus-treated patients (mean 1.7 ± 0.4 vs 3.1 ± 0.4; P = .023), as was percentage of fibrosis grade Ishak ≥4 (7% vs 41%; P = .028). The mean time to moderate fibrosis (Ishak score ≥3) was 38.2 ± 15.1 months in cyclosporine patients (4/15) and 23.5 ± 12.6 months in tacrolimus patients (14/22); the difference was not statistically significant (P = .09). This retrospective study suggests that cyclosporine-based immunosuppression is associated with less severe hepatic fibrosis in HCV-positive liver transplant recipients compared with tacrolimus-based regimens, but a larger prospective comparative trial is necessary to confirm these findings.

Surgical management of submucosal esophageal cancer: extended or regional lymphadenectomy?

INTRODUCTION: Radical esophagectomy is considered the standard therapy for tumors that infiltrate the submucosa of the esophagus (T1b), as the prevalence of lymph node metastases has been reported in up to 40% of these patients. It remains unclear whether radical esophagectomy with extended lymphadenectomy is needed or whether a surgical procedure with only regional lymphadenectomy suffices. The aim of this study was to compare outcomes of patients who underwent esophagectomy for T1b cancer through a transthoracic approach with extended lymphadenectomy (TTE) with those of patients in whom transhiatal esophagectomy (THE) was performed with a regional lymph node dissection. METHODS: Patients who underwent esophagectomy for T1b cancer between 1990 and 2004 and who did not receive (neo)adjuvant therapy were included. Data were collected from prospective databases of 4 centers. In Leuven, Belgium (n = 101), and Los Angeles, CA (n = 31), patients with T1b tumors had been operated on via TTE with extended lymphadenectomy, whereas in Amsterdam (n = 43) and Rotterdam (n = 47), the Netherlands, THE with regional lymphadenectomy had been performed. RESULTS: The 2 patient groups (TTE, n = 132; THE, n = 90) were comparable with regard to age, body mass index, and ASA classification. Operative time was longer in patients who underwent TTE (390 minutes) versus THE (250 minutes) (P < 0.001). The yield of lymph nodes resected was higher in the TTE group (median: 32) versus THE (median: 10) (P < 0.001). Overall morbidity, in-hospital mortality, and length of hospital stay were comparable between both the groups. In the TTE group, 27.3% of complications were classified as major versus 14.4% in the THE group (P < 0.001); however, the reoperation rate was higher after THE (12.2%) versus TTE (3.8%) (P = 0.01). There was no difference in pathological outcomes (infiltration depth, pN stage, pM stage, positive lymph node ratio) between both groups. Overall, 5-year survival (63.4% TTE vs 69.4% THE; P = 0.55) and disease-free 5-year survival (76.9% TTE vs 78.3% THE; P = 0.65) were comparable between both the groups. In patients with N1 disease, disease-free 5-year survival was 49.8% in the TTE group versus 40.0% in the THE group (P = 0.57). CONCLUSIONS: In patients with submucosal esophageal cancer (T1b), TTE with extended lymphadenectomy and THE with regional lymphadenectomy had similar short-term outcome and long-term survival. In the selected group of T1bN1 patients, TTE may be the preferred operative technique because of a potential disease-free survival benefit; in patients with T1bN0 disease, THE with en bloc dissection of the esophagus and regional lymph nodes offers an oncologically safe and less invasive treatment.

Prognostic value of body mass index on short-term and long-term outcome after resection of esophageal cancer.

INTRODUCTION: Cachexia and obesity have been suggested to be risk factors for postoperative complications. However, high body mass index (BMI) might result in a higher R0-resection rate because of the presence of more fatty tissue surrounding the tumor. The purpose of this study was to investigate whether BMI is of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer. METHODS: In 556 patients who underwent esophagectomy (1991-2007), clinical and pathological outcome were compared between different BMI classes (underweight, normal weight, overweight, obesity). RESULTS: Overall morbidity, mortality, and reoperation rate did not differ in underweight and obese patients. However, severe complications seemed to occur more often in obese patients (p = 0.06), and the risk for anastomotic leakage increased with higher BMI (12.5% in underweight patients compared with 27.6% in obese patients, p = 0.04). Histopathological assessment showed comparable pTNM stages, although an advanced pT stage was seen more often in patients with low/normal BMI (p = 0.02). A linear association between BMI and R0-resection rate was detected (p = 0.02): 60% in underweight patients compared with 81% in obese patients. However, unlike pT-stage (p < 0.001), BMI was not an independent predictor for R0 resection (p = 0.12). There was no significant difference in overall or disease-free 5-year survival between the BMI classes (p = 0.25 and p = 0.6, respectively). CONCLUSIONS: BMI is not of prognostic value with regard to short-term and long-term outcome in patients who undergo esophagectomy for cancer and is not an independent predictor for radical R0 resection. Patients oncologically eligible for esophagectomy should not be denied surgery on the basis of their BMI class.

Long-term esophageal cancer risk in patients with primary achalasia: a prospective study.

OBJECTIVES: Achalasia patients are considered at increased risk for esophageal cancer, but the reported relative risks vary. Identification of this risk is relevant for patient management. We performed a prospective evaluation of the esophageal cancer risk in a large cohort of achalasia patients with long-term follow-up. METHODS: Between 1975 and 2006, all patients diagnosed with primary achalasia in our hospital were treated and followed by the same protocol. After graded pneumatic dilatation, all patients were offered a fixed surveillance protocol including gastrointestinal endoscopy with esophageal biopsy sampling. RESULTS: We surveyed a cohort of 448 achalasia patients (218 men, mean age 51 years at diagnosis, range 4-92 years) for a mean follow-up of 9.6 years (range 0.1-32). Overall, 15 (3.3%) patients (10 men) developed esophageal cancer (annual incidence 0.34 (95% confidence interval 0.20-0.56)). The mean age at cancer diagnosis was 71 years (range 36-90) after a mean of 11 years (range 2-23) following initial presentation, and a mean of 24 years (range 10-43) after symptom onset. The relative hazard rate of esophageal cancer was 28 (confidence interval 17-46) compared with an age- and sex-identical population in the same timeframe. Five patients received a potential curative treatment. CONCLUSIONS: Although the gastro-esophageal cancer risk in patients with longstanding achalasia is much higher than in the general population, the absolute risk is rather low. Despite structured endoscopical surveillance, most neoplastic lesions remain undetected until an advanced stage. Efforts should be made to identify high-risk groups and develop adequate surveillance strategies.

Effects of a rehabilitation programme on daily functioning, participation, health-related quality of life, anxiety and depression in liver transplant recipients.

PURPOSE: Fatigue is a chronic problem in liver transplant recipients and may influence daily functioning and health-related quality of life (HRQoL). This study aimed to evaluate the effects of a fatigue-reducing physical rehabilitation programme on daily functioning, participation, HRQoL, anxiety and depression among liver transplant recipients. METHOD: Eighteen fatigued liver transplant recipients (mean age 51 years, 10 men/8 women) participated in a 12-week rehabilitation programme, which included supervised exercise training and daily physical activity counselling. We assessed pre- and post-programme health-related daily functioning, participation, HRQoL, anxiety and depression using questionnaires. RESULTS: After the programme, patients showed improvements in daily functioning (23.6%, p = 0.007), the participation domain 'autonomy outdoors' (34.1%, p = 0.001), and the HRQoL domains 'physical functioning' (11.5%, p = 0.007) and 'vitality' (21.5%, p = 0.022). Anxiety and depression were unchanged post-programme. CONCLUSIONS: Rehabilitation using supervised exercise training and daily physical activity counselling can positively influence daily functioning, participation and HRQoL among fatigued liver transplant recipients.

Dysphagia after an L-shaped reconstruction technique of the free jejunum graft.

BACKGROUND: The free jejunum graft is a well-established reconstruction technique after total laryngopharyngectomy. However, besides necrosis of the jejunum graft, the two most important complications are pharyngocutaneous fistula formation and dysphagia due to stricture formation. OBJECTIVES: This study aims to develop an L-shaped reconstruction technique of the free jejunum graft to decrease pharyngocutaneous fistula formation and long-term stricture formation after total laryngopharyngectomy. METHODS: An L-shaped side-to-end anastomosis was performed at the proximal end of the jejunum graft in six patients treated for piriform sinus carcinoma. Patient and operation characteristics and follow-up were recorded. RESULTS: A successful jejunum transfer was performed in all six patients. No pharyngocutaneous fistula or stricture formation occurred during a median follow-up of 23 months (range: 18-30 months). Swallowing rehabilitation started at the median 12th postoperative day (range: 5-150 days). Four patients developed dysphagia at a median of 2 months (range: 1-6 months) after oral intake was started. X-barium swallow revealed a redundant pouch of the transferred jejunum graft, which resulted in compression on the jejunum interposition during swallowing. In three patients, an operation was required to resolve these problems. After the revision operation, no dysphagia occurred during a median follow-up of 12 months (range: 7-13 months). CONCLUSIONS: Because of dysphagia complaints in the majority of our patients, we cannot recommend the described technique and should find other means to improve direct postoperative results and long-term quality of life in this difficult-to-treat group of patients.

Salvage or what follows the failure of a free jejunum transfer for reconstruction of the hypopharynx?

AIM: To analyse the cases of failure of free jejunum transfer with subsequent secondary reconstruction methods after ablative surgery for malignant tumours of the laryngopharyngeal region and the cervical oesophagus with reconstruction using a jejunum interposition. MATERIALS AND METHODS: Four cases in which failure of the jejunum interposition was managed with a second free or pedicle transfer were identified. The electronic files of patients were studied and analysed for patient characteristics and failure of reconstruction; type of salvage surgery and outcome; swallowing function and rehabilitation; postoperative complications; recurrence of tumour; patient survival and cause of death. RESULTS: Failure of the interposition occurred within 11 days in all patients, with oral bleeding being the most prominent sign. To replace the failed jejunum transfer, two new free jejunum transfers, two gastric pull-ups and one colon interposition after the second failure of a jejunum transfer were used. Three patients started swallowing rehabilitation, of which two achieved complete oral intake, defined as the redundancy of a feeding tube. The median disease-free period and overall survival was 28 and 42 months, respectively. CONCLUSION: Failure of a free jejunum transfer is a rare but inevitable complication when performed in a high-risk patient population, with oral bleeding being the most important sign of necrosis. Salvage of the buried jejunum interposition is hardly ever possible and secondary reconstruction can be performed using a new jejunum interposition or gastric pull-up procedure with considerable early postoperative complications, but relatively good results regarding swallowing rehabilitation and patient survival.

Chemotherapy followed by surgery in patients with carcinoma of the distal esophagus and celiac lymph node involvement.

BACKGROUND: Patients with carcinoma of the distal esophagus and metastatic celiac lymph nodes (M1a) have a poor prognosis and are often denied surgery. In this study, we evaluated our treatment strategy of chemotherapy followed by surgery in patients with M1a disease. METHODS: Thirty-eight patients who received chemotherapy for carcinoma of the distal esophagus with celiac lymph node involvement between 2000 and 2007 were identified from a prospective database. Clinical and histopathological responses to chemotherapy were analyzed and follow-up comprised review of medical charts. RESULTS: Twelve non-responding patients were not eligible for surgery. Twenty-six patients with partial responses or stable disease were operated on. The resectability rate was 96% (25/26) and tumor-free resection margins (R0) were achieved in 68% (17/25). The overall survival of patients with M1a disease was 16 months. Patients who received chemotherapy alone had a median survival of 10 months; patients who underwent additional surgery had a median survival of 26 months (log-rank P < 0.001). CONCLUSION: The overall survival of patients with carcinoma of the distal esophagus and clinical celiac lymph node involvement is poor. Tumor-free resection margins (R0) in M1a patients with clinical response to chemotherapy are likely to be achieved and contributes to prolonged survival.

Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the Rotterdam experience.

Multimodality treatment is increasingly used in the treatment for esophageal cancer. We determined the tumor regression grade after preoperative chemoradiation and correlated the effect of specific pathologic and clinical findings to overall survival. For this purpose esophageal biopsies and surgical specimens of 67 patients treated with neoadjuvant paclitaxel and carboplatin concurrent with radiotherapy were reviewed. Neoadjuvant chemoradiotherapy led to a significant downstaging. Complete tumor regression was found in 24% of the patients resulting in a trend towards better survival. It was found more frequently in poorly differentiated tumors. Patients with pre-treatment nodal involvement, assessed by endoscopic ultrasound, had a significantly worse survival compared to patients without. Contrastingly, this was not found for post-treatment nodal involvement, as determined by pathological examination, speculating that survival is more determined by (submicroscopic) distant disease, than by locoregional tumor cells.

Centralization of esophageal cancer surgery: does it improve clinical outcome?

BACKGROUND: The volume-outcome relationship for complex surgical procedures has been extensively studied. Most studies are based on administrative data and use in-hospital mortality as the sole outcome measure. It is still unknown if concentration of these procedures leads to improvement of clinical outcome. The aim of our study was to audit the process and effect of centralizing oesophageal resections for cancer by using detailed clinical data. METHODS: From January 1990 until December 2004, 555 esophagectomies for cancer were performed in 11 hospitals in the region of the Comprehensive Cancer Center West (CCCW); 342 patients were operated on before and 213 patients after the introduction of a centralization project. In this project patients were referred to the hospitals which showed superior outcomes in a regional audit. In this audit patient, tumor, and operative details as well as clinical outcome were compared between hospitals. The outcome of both cohorts, patients operated on before and after the start of the project, were evaluated. RESULTS: Despite the more severe comorbidity of the patient group, outcome improved after centralizing esophageal resections. Along with a reduction in postoperative morbidity and length of stay, mortality fell from 12% to 4% and survival improved significantly (P = 0.001). The hospitals with the highest procedural volume showed the biggest improvement in outcome. CONCLUSION: Volume is an important determinant of quality of care in esophageal cancer surgery. Referral of patients with esophageal cancer to surgical units with adequate experience and superior outcomes (outcome-based referral) improves quality of care.