Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction.

In adenocarcinoma of the esophagus or gastroesophageal junction, little attention has been paid to the biologic significance of extracapsular lymph node involvement (LNI). In the present study, a consecutive series of 251 patients with lymph node dissemination were reviewed. All patients underwent esophagectomy for adenocarcinoma and were prospectively followed. A total of 1562 positive lymph nodes were reexamined. Extracapsular LNI was identified in 456 lymph nodes (29%) in 166 patients (66%). Extracapsular LNI was confined to one lymph node in 63 patients (38%). The occurrence of extracapsular LNI increased significantly with the depth of invasion, presence of positive resectable truncal nodes, number of resected nodes, number of positive nodes, and lymph node ratio. The median potential follow-up period was 58 months (range, 12-143 months). In this period, 178 patients died of recurrent disease. The pattern of recurrence was comparable between patients with and without extracapsular LNI (P = 0.938). The median survival in patients with extracapsular LNI was 15 months (95% confidence interval, 12-18 months) compared with 41 months (95% confidence interval, 19-64 months) in those without extracapsular LNI (P < 0.001). Median survival of patients with 2 or more lymph nodes was 12 months (95% confidence interval, 8-15 months). Multivariate analysis demonstrated that T-stage, extracapsular LNI, and lymph node ratio were independent prognostic factors. The presence of extracapsular LNI identifies a subgroup with a significantly worse long-term survival. Together with the T-stage and the lymph node ratio, extracapsular LNI reflects a particularly aggressive biologic behavior and has significant prognostic potential.

Microscopically incomplete resection offers acceptable palliation in pancreatic cancer.

BACKGROUND: Because mortality and morbidity of pancreatic surgery have decreased to acceptable levels, the complex question arises whether pancreatic resection should be performed in patients with preoperatively doubtful resectable pancreatic cancer. METHODS: Perioperative parameters and outcome of 80 patients who underwent a microscopically incomplete (R1) resection were compared with those of 90 patients who underwent a bypass for locally advanced disease for pancreatic adenocarcinoma. All patients initially underwent exploratory laparotomy with the intention to perform a resection. Quality of life was assessed by analyzing readmissions and their indications. RESULTS: Groups were similar with respect to age, presenting symptoms, and preoperative health status. Tumors were significantly larger in the bypass group (3.5 cm vs 2.9 cm, P < .01). Hospital mortality was comparable: zero after R1 resection and 2% after bypass. Of all severe complications, only intra-abdominal hemorrhage occurred significantly more frequently after resection (10% vs 2%; P = .03). Hospital stay after resection was significantly longer than after bypass (16 vs 10 days; P < .01). Survival was significantly longer after R1 resection (15.8 vs 9.5 months, P < .01). Sixty-one percent of patients were readmitted for a total of 215 admissions, equally distributed between groups. After R1 resection, 0.58% of the total survival time after initial discharge was spent in the hospital, after bypass, 0.69%, which was not significantly different. CONCLUSIONS: R1 pancreatic resection and bypass for locally advanced disease can be performed with comparable low mortality and morbidity rates. Readmission rates are also comparable between groups and time spent in the hospital after initial discharge is low. Because resection offers adequate palliation in pancreatic cancer, a more aggressive surgical approach in patients who are found to have a doubtfully resectable tumor could be advocated, even if only an R1 resection can be achieved.

Incidence and management of biliary leakage after hepaticojejunostomy.

This study analyzes the change in the management of biliary leakage after hepaticojejunostomy. Between 1993 and 2003 all patients (n = 1033) were studied with a hepaticojejunostomy as part of a pancreatoduodenectomy (n = 486), proximal bile duct resection (without liver resection) (n = 35), and biliodigestive bypass for malignant (n = 302) and benign (n = 210) disease. Biliary leakage was defined as the presence of bile-stained fluid (>50 mL) in the abdominal drain more than 24 hours after surgery, proven radiologically or at relaparotomy. The studied patients were divided into two equal periods to analyze the change in management. Overall, 24 of 1033 patients (2.3%) had biliary leakage. In multivariate analysis, a body mass index greater than 35 kg/m2 (P = .012), endoscopic biliary drainage (P = .044), and an anastomosis on the segmental bile ducts (P < .001) were independent predictors of leakage. Management in the first half of the study period (1993-1998) versus the second half (1999-2003) was maintenance of operatively placed drains (18% vs. 15%, respectively, P = 1.000), percutaneous transhepatic biliary drainage (18% vs. 69%, respectively, P = .012), surgical drainage (55% vs. 8%, respectively, P = .023), and re-hepaticojejunostomy (9% vs. 8%, respectively, P = 1.000). There was no mortality in the patients with biliary leakage. Leakage after a hepaticojejunostomy is a relatively rare complication without mortality and can safely be managed with percutaneous transhepatic biliary drainage.

A prospective evaluation of anorectal function after total mesorectal excision in patients with a rectal carcinoma.

BACKGROUND: Rectum resection with total mesorectal excision (TME) and neorectal anastomosis often compromises anorectal function. Insight into the underlying mechanisms is lacking. Therefore, a prospective study was designed to investigate the relationship between clinical and functional outcomes preoperatively and postoperatively. METHODS: Eleven patients with rectal cancer were examined before and 4 and 12 months after surgery and compared with 11 healthy volunteers (HVs). Anorectal (neorectal) function was examined by clinical outcome questionnaire, anal manometry, rectal compliance, and sensation. Six HVs also underwent barostat measurements in the sigmoid colon. RESULTS: Clinical parameters of soiling and passive incontinence (loss of stool without sensation) increased significantly until 12 months postoperatively, whereas urgency and tenesmus increased temporarily, returning to preoperative values at 12 months. In anorectal measurements, anal sphincter function was grossly preserved; however, rectal-anal inhibitory reflex (RAIR) was decreased at 4 months but recovered after 1 year. Neorectal compliance was similar to that of HV sigmoid, increasing slightly after 12 months but still significantly lower than that of normal rectum. Neorectal sensation to pressure distention was similar to that of normal rectum, however accompanied by smaller volumes. Neorectal distention induced contractions of large amplitude at 4 months, returning to normal after 12 months. CONCLUSIONS: Our results suggest that the transient increase in urgency and tenesmus after surgery results from a temporary increase in neorectal "irritability" accompanied by some adaptation of compliance in time. In contrast, episodes of incontinence and soiling are increased after 1 year most likely because of reduced neorectal capacity and RAIR recovery in the presence of a low basal anal sphincter pressure.

Indicators of prognosis after transhiatal esophageal resection without thoracotomy for cancer.

BACKGROUND: Various techniques have been described for the surgical treatment of esophageal cancer. The transhiatal approach has been debated for its safety and oncologic results. STUDY DESIGN: Between January 1993 and September 1996, 115 patients underwent a transhiatal esophagectomy with curative intent for adenocarcinoma or squamous cell carcinoma of the middle or distal esophagus or esophagogastric junction. Procedure-related hazards, pathologic results, and prognostic factors for survival were evaluated. Median duration of postoperative followup was 27 months (range 1 to 74 months) for all patients and 45 months (range 30 to 74 months) for those alive at final followup. RESULTS: No emergency thoracotomies were experienced. In-hospital mortality was 3.5%. Vocal cord dysfunction (24%) and pulmonary complications (23%) were the most frequent early postoperative complications. A microscopically radical resection was achieved in 73% of patients. Overall survival was 45% at 3 years. In univariate analysis, the most pronounced indicators of longterm survival (p < 0.0001) were radicality of the resection, lymph node involvement, lymph node ratio (ie, the ratio of invaded to removed lymph nodes), and pathologic tumor stage. Multivariate analysis identified the lymph node ratio (p < 0.0001) as the strongest independent predictor of long-term survival, followed by radicality of the resection (p = 0.0064) and duration of ICU stay (p = 0.027). CONCLUSION: Transhiatal esophagectomy without thoracotomy can be considered a safe procedure for resectable cancer of the midesophagus, distal esophagus, or esophagogastric junction. Radicality and survival results were in line with the data reported for traditional transthoracic approaches. A prognostic value of the lymph node ratio was observed. It emphasizes the need for controlled trials aimed at delineating the prognostic impact of an extended lymph node dissection.

Recurrent disease after microscopically radical (R0) resection of periampullary adenocarcinoma in patients without adjuvant therapy.

The survival rate after microscopically radical resection of pancreatic duct adenocarcinoma is still poor. Patients with ampulla of Vater and distal common bile duct adenocarcinoma indicate a much more favorable prognosis. Controversy exists as to whether adjuvant therapy could improve the outcome in these patients after resection. The aim of the present study was to analyze the pattern of recurrence in patients with periampullary adenocarcinoma after pancreatoduodenectomy. Between January 1992 and December 2002, all patients with an R0 resection were identified and used for this analysis. A total of 190 patients underwent a microscopically radical resection and received no adjuvant therapy. Of those, 72 patients were diagnosed with pancreatic duct adenocarcinoma, 86 patients were diagnosed with ampulla of Vater adenocarcinoma, and 31 patients were diagnosed with distal common bile duct adenocarcinoma. Recurrent disease was indicated in 81% of the patients with pancreatic duct adenocarcinoma, 50% of the patients with ampulla of Vater adenocarcinoma, and in 74% of the patients with bile duct adenocarcinoma. Multivariate analysis revealed that lymph node metastases were prognostic for recurrent disease in patients with pancreatic duct adenocarcinoma (P = 0.038). The depth of invasion (T4, P < 0.032) and lymph node metastases (P < 0.001) were prognostic in patients with ampulla of Vater adenocarcinoma. Poor tumor differentiation (P < 0.001) was prognostic in patients with distal bile duct adenocarcinoma. Selected patients with periampullary malignancies exhibited a high recurrence rate and should be encouraged to enroll in clinical trials for adjuvant treatment including local therapy (radiotherapy) according to the identified prognostic factors.

Emergency medicine in the Netherlands, the necessity for changing the system: results from two questionnaires.

OBJECTIVE: To obtain information about patient, staff and organization characteristics of Emergency Departments in the Netherlands, and evaluate the changes between 1996 and 1999. METHODS: The heads of the Emergency Departments of all hospitals in the Netherlands were sent a questionnaire concerning patient, staff, and organization characteristics, as well as questions about intended future developments. The results were compared with data obtained from a comparable questionnaire in 1996. RESULTS: In the Netherlands, 113 hospitals (113/126) have an Emergency Department; 105/113 returned the questionnaire (93%). Ninety-two percent of the hospitals reported an increase in annual Emergency Department census and in the number of self-referred patients. The number of Emergency Departments staffed by only surgical residents decreased (52% in 1996 versus 41% in 1999), whereas the number of hospitals employing emergency physicians increased (24% in 1996 versus 45% in 1999). In 92% of the hospitals, nurses who work in the Emergency Department receive specific training. For emergency physicians, a specific training programme is not available, and in fact 30% of the physicians did not have any specific emergency medicine training. Therefore, none of the emergency physicians were fully trained in emergency medicine. According to 88% of all responders, there is a future for emergency medicine as an independent speciality in the Netherlands, and 35% of all hospitals intend to initiate a training programme for emergency physicians in the future. CONCLUSION: Almost all hospitals in the Netherlands reported an increase in the number of patients visiting the Emergency Department, especially in the number of self-referred patients. A majority of the Emergency Departments are now staffed by emergency physicians instead of surgical residents. Developing specific training programmes for emergency physicians should be a priority for the Netherlands in the future.

Preoperative prediction of the occurrence and severity of complications after esophagectomy for cancer with use of a nomogram.

BACKGROUND: Predicting the severity of complications after esophagectomy may supply important information for both patient and surgeon. The aim of the present study was to develop a nomogram based on preoperative risk factors to predict the severity of complications in patients who undergo esophagectomy for cancer. METHODS: A consecutive series of 663 patients who underwent esophagectomy between January 1993 and August 2005 was used to develop a prognostic model. The model was validated in a second group of patients who were operated between August 2005 and November 2006. Ordinal logistic regression analysis was performed to predict the severity of complications. Diverse simple and conventional preoperative risk factors were evaluated. A nomogram was developed to enhance clinical applicability. RESULTS: Patients were divided into three complication categories: those who suffered from no complications (n = 197); minor complications (n = 354); and major complications (n = 112). The following predictors remained in the model after multivariate analysis: higher age (p = 0.014); cerebrovascular accident/transient ischemic attack (CVA/TIA) (p = 0.009) or myocardial infarction in the medical history (p = 0.066); lower forced expiratory volume in the first second of expiration (FEV(1)) (p = 0.030); presence of electrocardiogram-changes (p = 0.008); and more extensive surgery (p < 0.001). A nomogram based on these variables was constructed. Overall agreement between the predicted probabilities and the observed frequencies was good in the development and the validation set. CONCLUSIONS: The nomogram predicts the severity of complications for individual patients and may help in informing the patient before undergoing esophagectomy for cancer and in choosing the optimal extent of surgery. When externally validated, the nomogram may play a role in risk-adjusted audit of morbidity after esophagectomy.

The importance of complete excision of the caudate lobe in resection of hilar cholangiocarcinoma.

BACKGROUND: The numbers of margin-negative resections and survival times have greatly improved because of a more aggressive surgical approach to resectable hilar cholangiocarcinoma (Klatskin tumour). It was shown initially by Japanese authors that complete resection of the caudate lobe together with partial hepatectomy leads to more margin-negative resections. However, this concept has not been unanimously taken up by Western authors. The aim of this study was to examine the role of complete caudate lobe resection in our series of resected hilar cholangiocarcinomas. METHODS: Between January 1993 and January 2003, 54 patients underwent resection for Klatskin tumours. These patients were divided into two groups, according to the two 5-year periods in which they had been operated. In the first period, patients did not routinely undergo complete excision of the caudate lobe, whereas in the second period, partial liver resection was combined with complete excision of the caudate lobe in 15 patients. These two patient groups were evaluated with respect to postoperative morbidity and mortality, microscopic tumour margins and survival time. RESULTS: Postoperative complications occurred in 59% of patients in total, while overall mortality was 11%. No difference was found in postoperative morbidity or mortality between the two periods. A significantly higher number of margin-negative resections was found in the second 5-year period, together with improved survival. CONCLUSION: Concomitant complete excision of segment 1 for patients with hilar cholangiocarcinoma did not lead to increased morbidity or mortality. Therefore the addition of complete excision of segment 1 is a safe procedure contributing to a higher rate of R0 resections and improved survival.

Incidence and management of chyle leakage after esophagectomy.

BACKGROUND: Postoperative chyle leakage is a rare but well-recognized complication after esophageal surgery. The aim of this study was to identify its incidence and potentially predisposing factors and to assess the consequences and management. METHODS: A consecutive series of 536 patients who underwent esophagectomy for malignant disease of the esophagus or gastroesophageal junction was reviewed. RESULTS: There were 20 patients (3.7%) with chyle leakage. After transthoracic esophagectomy the risk for the development of chyle leakage was higher than after transhiatal resection (p = 0.006). Chyle leakage was associated with more positive nodes (p = 0.041). Patients with chyle leakage had significantly more pulmonary complications (p < 0.001) and longer intensive care unit (p = 0.015) and hospital stays (p = 0.001). No patient with chyle leakage died. Conservative management, consisting of no enteral feeding and total parenteral nutrition, was instituted in all patients, but was abandoned in 4 patients (20%) because of persistence of high chyle output through the chest tube. In contrast to patients who were successfully treated with conservative measures, patients who eventually needed a reoperation had a drain output of more than 2 L on the day conservative therapy was started and 1 and 2 days later. CONCLUSIONS: Chyle leakage is seen more often in patients who undergo transthoracic esophagectomy and in patients who have more positive nodes. Patients with chyle leakage have more pulmonary complications. Conservative therapy is often successful, but operative therapy should be seriously considered in patients with a persistently high daily output of more than 2 L after 2 days of optimal conservative therapy.

Delayed massive hemorrhage after pancreatic and biliary surgery: embolization or surgery?

OBJECTIVE: To analyze the management of delayed massive hemorrhage (DMH) after major pancreatic and biliary surgery. SUMMARY BACKGROUND DATA: Despite a decreased mortality rate for pancreatic and biliary surgery, DMH is still an important cause of postoperative mortality. The aim of the present study was to analyze the management of DMH after pancreatic and biliary surgery, and specifically to assess the role of embolization and surgical intervention. METHODS: The study group (SG) consisted of 1010 patients from 1994 to 2002 who underwent pancreatic or biliary surgery (cholecystectomy excluded). Patients from a previous study (1983-1993, n = 686) were used as a historical control group (HCG). RESULTS: The incidence of DMH (SG 2.3% vs. HCG 3.2%) declined somewhat but did not differ significantly between both periods. The number of patients with a septic complication (SG 74% vs. HCG 50%) and a sentinel bleed (SG 78% vs. HCG 100%) before the onset of DMH did not differ significantly. Embolization (SG 2 of 2 patients vs. HCG 0 of 2 patients) was not used frequently. Successful outcome after surgical intervention (SG 14 of 16 patients vs. HCG 8 of 14 patients) and the surgical procedures performed to obtain hemostasis were comparable and overall mortality (SG 22% vs. HCG 29%) was comparable. CONCLUSIONS: The incidence of DMH declined somewhat from 3.2% to 2.3% over the past years. Most patients present with septic complications and a sentinel bleed before onset of DMH. Despite general acceptance of embolization in our unit, it was used infrequently in patients with DMH. Aggressive surgical intervention was the treatment of choice in patients with DMH after pancreatic or biliary surgery.

Immune responses and prediction of major infection in patients undergoing transhiatal or transthoracic esophagectomy for cancer.

OBJECTIVE: To investigate alterations in immune responses after transhiatal versus transthoracic esophageal resection and to evaluate the role of preoperative immune functions in predicting postoperative infectious complications. SUMMARY BACKGROUND DATA: Impaired immune defense is associated with a decreased resistance to infection. Patients undergoing esophageal resection via a transhiatal or transthoracic approach are prone to develop infectious complications. There are no randomized data on immune responses after two major surgical interventions. METHODS: The study group consisted of 20 patients who were randomly allocated to a limited transhiatal or extended transthoracic esophagectomy for cancer. Blood samples were taken before the operation and at regular intervals thereafter from day 1 to day 10. Monocyte and T-helper type 1 (Th1) and type 2 (Th2) lymphocyte functions were assessed in stimulated whole blood cultures. RESULTS: Both surgical groups had severely depressed in vitro production of interleukin (IL)-12, IL-10, interferon-gamma, IL-2, IL-4, and IL-13 on postoperative day 1. Depression of Th2-type cytokine production was more profound after transthoracic than after transhiatal esophagectomy (IL-4, P=.005; IL-13,P=.007). Postoperative reduction in Th1-type cytokine production was similar between the two groups (interferon-gamma, P=.40; IL-2, P=.06). Irrespective of the surgical approach, patients who developed major infectious complications after surgery presented with a diminished T-cell cytokine production before the operation compared to those who had a relatively uneventful recovery (IL-4, P=.045; interferon-gamma, P=.064). In regression analysis, the occurrence of postoperative major infection was best predicted by increased duration of anesthesia ( P<.0001) and low preoperative interferon-gamma production ( P=.006). CONCLUSIONS: Both transhiatal and transthoracic esophagectomy induced severely depressed monocyte and T-lymphocyte cytokine production. The extent of the surgical procedure had a differential immunosuppressive impact on Th2-type but not on Th1-type cell activity, indicating that the two Th pathways were downregulated through distinct mechanisms. Preoperative interferon-gamma determination would be useful to anticipate the occurrence of postoperative major infectious complications.

The need for a prophylactic gastrojejunostomy for unresectable periampullary cancer: a prospective randomized multicenter trial with special focus on assessment of quality of life.

OBJECTIVE: To evaluate the effect of a prophylactic gastrojejunostomy on the development of gastric outlet obstruction and quality of life in patients with unresectable periampullary cancer found during explorative laparotomy. SUMMARY BACKGROUND DATA: Several studies, including one randomized trial, propagate to perform a prophylactic gastrojejunostomy routinely in patients with periampullary cancer found to be unresectable during laparotomy. Others suggest an increase of postoperative complications. Controversy still exists in general surgical practice if a double bypass should be performed routinely in these patients. METHODS: Between December 1998 and March 2002, patients with a periampullary carcinoma who were found to be unresectable during exploration were randomized to receive a double bypass (hepaticojejunostomy and a retrocolic gastrojejunostomy) or a single bypass (hepaticojejunostomy). Randomization was stratified for center and presence of metastases. Patients with gastrointestinal obstruction and patients treated endoscopically for more than 3 months were excluded. Primary endpoints were development of clinical gastric outlet obstruction and surgical intervention for gastric outlet obstruction. Secondary endpoints were mortality, morbidity, hospital stay, survival, and quality of life, measured prospectively by the EORTC-C30 and Pan26 questionnaires. It was decided to perform an interim analysis after inclusion of 50% of the patients (n = 70). RESULTS: Five of the 70 patients randomized were lost to follow-up. From the remaining 65 patients, 36 patients underwent a double and 29 a single bypass. There were no differences in patient demographics, preoperative symptoms, and surgical findings between the groups. Clinical symptoms of gastric outlet obstruction were found in 2 of the 36 patients (5.5%) with a double bypass, and in 12 of the 29 patients (41.4%) with a single bypass (P = 0.001). In the double bypass group, one patient (2.8%) and in the single bypass group 6 patients (20.7%) required (re-)gastrojejunostomy during follow-up (P = 0.04). The absolute risk reduction for reoperation in the double bypass group was 18%, and the numbers needed to treat was 6. Postoperative morbidity rates, including delayed gastric emptying, were 31% in the double versus 28% in the single bypass group (P = 0.12). Median postoperative length of stay was 11 days (range 4-76 days) in the double versus 9 days (range 6-20 days) in the single bypass group (P = 0.06); median survival was 7.2 months in the double versus 8.4 months in the single bypass group (P = 0.15). No differences were found in the quality of life between both groups. After surgery most quality of life scores deteriorated temporarily and were restored to their baseline score (t = -1) within 4 months. CONCLUSIONS: Prophylactic gastrojejunostomy significantly decreases the incidence of gastric outlet obstruction without increasing complication rates. There were no differences in quality of life between the two groups. Together with the previous randomized trial from the Hopkins group, this study provides sufficient evidence to state that a double bypass consisting of a hepaticojejunostomy and a prophylactic gastrojejunostomy is preferable to a single bypass consisting of only a hepaticojejunostomy in patients undergoing surgical palliation for unresectable periampullary carcinoma. Therefore, the trial was stopped earlier than planned.