[Palliative Surgery in Colorectal Cancer - Which Factors Should Influence the Choice of the Surgical Procedure?] / Palliativchirurgie beim kolorektalen Karzinom ­ welche Faktoren können bei der Wahl des operativen Vorgehens helfen?

BACKGROUND: The surgical procedure for patients with colorectal cancer (CRC) in the palliative situation cannot be adequately standardised. The present study was initiated to identify criteria for the decision for resection of the malignancy with or without anastomosis. PATIENTS/MATERIAL AND METHODS: In a unicentric retrospective analysis, 103 patients after palliative resection with or without anastomosis due to CRC were examined. Using univariate and logistic regression analysis, the influence of a total of 40 factors on postoperative morbidity and mortality was assessed. RESULTS: In 46 cases, resection with primary anastomosis and in 57 cases a discontinuity resection was performed. Postoperative morbidity was 44.7% and mortality 17.5%. After one-stage resection with anastomosis, nicotine abuse (OR 4.2; p = 0.044), hypalbuminaemia (OR 4.0; p = 0.012), ASA score > 2 (OR 3.7; p = 0.030) and liver remodelling/cirrhosis (OR 3.6; p = 0.031) increased the risk for postoperative complications. Hypalbuminaemia (OR 1.8; p = 0.036), cachexia (OR 1.8; p = 0.043), anaemia (OR 1.5; p = 0.038) and known alcohol abuse (OR 1.9; p = 0.023) were identified as independent risk factors for early postoperative mortality. After discontinuity resection, renal failure (OR 2.1; p = 0.042) and cachexia (OR 1.5; p = 0.045) led to a significant increase in the risk of postoperative morbidity, alcohol abuse (OR 1.8; p = 0.041) in mortality. Hypalbuminaemia (OR 2.8; p = 0.019) and an ASA score > 2 (OR 2.6; p = 0.004) after resection and reconstruction increased the risk of major complications according to Clavien-Dindo, while pre-existing renal failure (OR 1.6; p = 0.023) increased the risk after discontinuity resection. In univariate analysis, an ASA score > 2 (p = 0.038) after simultaneous tumour resection and reconstruction, and urgent surgery in both groups with or without primary anastomosis were additionally identified as significant parameters with a negative influence on mortality (p = 0.010 and p = 0.017). CONCLUSION: Palliative resections of colorectal carcinomas have high morbidity and mortality. Especially in cases of pre-existing alcohol abuse and/or urgent indication for surgery, more intensive monitoring should be performed. In the case of anaemia, cachexia, hypalbuminemia and an ASA score > 2, discontinuity resection may be the more appropriate procedure.

Predictive factors of early outcome after palliative surgery for colorectal carcinoma.

OBJECTIVES: A significant number of patients with colorectal cancer are presented with various conditions requiring surgery in an oncologically palliative setting. We performed this study to identify risk factors for early outcome after surgery to facilitate the decision-making process for therapy in a palliative disease. METHODS: We performed a retrospective chart review of 142 patients who underwent palliative surgery due to locally advanced, complicated, or advanced metastatic colorectal carcinoma between January 2010 and April 2018 at the "Elbland" Medical Center Riesa. We performed a logistic regression analysis of 43 factors to identify independent predictors for complications and mortality. RESULTS: Surgery included resections with primary anastomosis (n=31; 21.8%) or discontinuous resections with colostomy (n=38; 26.8%), internal bypasses (n=27; 19.0%) and stoma formation only (n=46; 32.4%). The median length of hospitalization was 12 days (2-53 days), in-hospital morbidity was 50.0% and the mortality rate was 18.3%. Independent risk factors of in-hospital morbidity were age (HR: 1.5, p=0.046) and various comorbidities of the patients [obesity (HR: 1.8, p=0.036), renal failure (HR: 1.6, p=0.040), diabetes (HR: 1.6, p=0.032), alcohol abuse (HR: 1.3, p=0.023)] as well as lung metastases (HR: 1.6, p=0.041). Arteriosclerosis (HR: 1.4; p=0.045) and arterial hypertension (HR: 1.4, p=0.042) were independent risk factors for medical complications in multivariate analysis. None of the analyzed factors predicted the surgical morbidity after the palliative procedures. Emergency surgery (HR: 10.2, p=0.019), intestinal obstruction (HR: 9.2, p=0.006) and ascites (HR: 5.0, p=0.034) were multivariate significant parameters of in-hospital mortality. CONCLUSIONS: Palliatively treated patients with colorectal cancer undergoing surgery show high rates of morbidity and mortality after surgery. In this retrospective chart review, independent risk factors for morbidity and in-hospital mortality were identified that are similar to patients in curative care. An adequate selection of patients before palliative operation should lead to a better outcome after surgery. Especially in patients with intestinal obstruction and ascites scheduled for emergency surgery, every effort should be made to convey these patients to elective surgery by interventional therapy, such as a stent or minimally invasive stoma formation.

Total Parathyroidectomy With Routine Thymectomy and Autotransplantation Versus Total Parathyroidectomy Alone for Secondary Hyperparathyroidism: Results of a Nonconfirmatory Multicenter Prospective Randomized Controlled Pilot Trial.

OBJECTIVE: This randomized controlled multicenter pilot trial was conducted to find robust estimates for the rates of recurrence of 2 surgical strategies for secondary hyperparathyroidism (SHPT) within 36 months of follow-up. BACKGROUND: SHPT is a frequent consequence of chronic renal failure. Total parathyroidectomy with autotransplantation (TPTX+AT) and subtotal parathyroidectomy (SPTX) are the standard surgical procedures. Total parathyroidectomy alone (TPTX) might be a good alternative, as morbidity and recurrence rates are low according to small-scale retrospective studies. METHODS: The trial was performed as a nonconfirmatory randomized controlled pilot trial with 100 patients on long-term dialysis with otherwise uncontrollable SHPT to generate data on the rate of recurrent disease within a 3-year follow-up period after TPTX or TPTX+AT. Parathyroid hormone (PTH) and calcium levels, recurrent or persistent hyperparathyroidism, parathyroid reoperations, morbidity, and mortality were evaluated during a 3-year follow-up. RESULTS: A total of 52 patients underwent TPTX and 48 TPTX+AT. Patient characteristics, preoperative baseline data, duration of surgery (02:29 vs 02:47 hrs, P = 0.17) and mean hospital stay (10 ± 7.1 vs 8 ± 3.7 days, P = 0.11) did not differ significantly. Persistent SHPT developed in 1 TPTX and 2 TPTX+AT patients. None of the TPTX patients required delayed parathyroid AT to treat permanent hypoparathyroidism. Serum-calcium values were similar (2.1 ± 0.3 vs 2.1 ± 0.2, P = 0.95) whereas PTH rose by time in the TPTX+AT group and was significantly higher at the end of follow-up when compared with the TPTX group (31.7 ± 43.6 vs 98.2 ± 156.8, P = 0.02). Recurrent SHPT developed in 4 TPTX+AT and none of the TPTX patients. CONCLUSIONS: TPTX+AT and TPTX seem to be safe and equally effective for the treatment of otherwise uncontrollable SHPT. TPTX seems to suppress PTH more effectively and showed no recurrences after 3 years. The hypothesis that TPTX is superior to TPTX+AT referring to the rate of recurrent SHPT has to be tested in a large-scale confirmatory trial. Nevertheless, TPTX seems to be a feasible alternative therapeutic option for the surgical treatment of SHPT.

Colorectal liver metastases: an update on palliative treatment options.

Only approximately 30% of patients with colorectal cancer liver metastasis qualify for curative therapy, which is in most cases liver lesion resection. Due primarily to the extent of the tumors and patient comorbidities, palliative therapy remains the only option in non-resection cases. Palliation enables local, symptomatic control and prolonged survival in some cases. As established methods are continuously improved, new palliative therapy methods are tested in clinical trials and subsequently introduced into clinical practice. The present review provides an overview of current colorectal liver metastasis treatment when resection is not an option. This review gives the basis for an interdisciplinary decision making process for the treatment of liver metastasis.

Diagnostic evaluation, surgical technique, and perioperative management after esophagectomy: consensus statement of the German Advanced Surgical Treatment Study Group.

PURPOSE: Correct diagnosis, surgical treatment, and perioperative management of patients with esophageal carcinoma remain crucial for prognosis within multimodal treatment procedures. This study aims to achieve a consensus regarding current management strategies in esophageal cancer by questioning a panel of experts from the German Advanced Surgical Treatment Study (GAST) group, comprised of 9 centers specialized in esophageal surgery, with a combined total of >220 esophagectomies per year. MATERIALS AND METHODS: The Delphi method, a systematic and interactive, evidence-based approach, was used to obtain consensus statements from the GAST group regarding ambiguities and disparities in diagnosis, patient selection, surgical technique, and perioperative management of patients with esophageal carcinoma. After four rounds of surveys, agreement was measured by Likert scales and defined as full (100% agreement), near (≥66.6% agreement), or no consensus (<66.6% agreement). RESULTS: Full or near consensus was obtained for essential aspects of esophageal cancer staging, proper surgical technique, perioperative management and indication for primary surgery, and neoadjuvant treatment or palliative treatment. No consensus was achieved regarding acceptability of minimally invasive technique and postoperative nutrition after esophagectomy. CONCLUSION: The GAST consensus statement represents a position paper for treatment of patients with esophageal carcinoma which both contributes to the development of clinical treatment guidelines and outlines topics in need of further clinical studies.

Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.

BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting. METHODS: Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or > or =5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4-6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998. FINDINGS: 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI -8 to 30; odds ratio [OR] 1.62, 0.74-3.59; p=0.23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35-8.66; p=0.0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p<0.0001). INTERPRETATION: Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. FUNDING: Merck-Serono, Sanofi-Aventis, and Pfizer.

Quantitative perfusion analysis of transabdominal contrast-enhanced ultrasonography of pancreatic masses and carcinomas.

BACKGROUND & AIMS: Preoperative differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) and focal masses in patients with chronic pancreatitis (CP) can be challenging. There are fine differences in the vascularization of these lesions; ultrasound contrast agents can aid in their differentiation. We evaluated the value of software-aided quantitative analysis of transabdominal contrast-enhanced ultrasonography for differential diagnosis of PDAC vs focal masses. METHODS: Sixty patients for whom it was not possible to differentiate between an inflammatory focal lesion of the pancreas and a pancreatic carcinoma underwent contrast-enhanced ultrasonography with a second-generation contrast agent. Time-intensity curves were obtained for all exams in 2 regions of interest within the lesion and within the normal pancreatic tissue. Images were processed using Axius ACQ software; the following parameters were obtained: maximum intensity, arrival time, time-to-peak, and area under the curve. Absolute values and differences between the lesion and the normal tissue were evaluated. RESULTS: Histology analysis revealed 45 PDACs and 15 inflammatory masses in patients with CP. Time-dependent parameters (arrival time and time to peak) were significantly longer in PDACs compared to focal masses. Although markedly lower than in healthy pancreata, the maximum intensity and area under the curve parameters were not significantly different between PDACs and focal lesions in patients with CP. CONCLUSIONS: In cases of CP, PDAC and focal masses exhibit different perfusion patterns at a capillary level that can be visualized using the small microbubbles of ultrasound contrast agents. Contrast quantification software supplements a subjective visual assessment with objective criteria to facilitate the differential diagnosis of focal lesions in pancreatic cancer and chronic pancreatitis.

Who profits from neoadjuvant radiochemotherapy for locally advanced esophageal carcinoma?

BACKGROUND: Patients suffering from locally advanced esophageal carcinoma are generally treated using multimodal therapies. This prospective, non-randomized trial was performed to evaluate the survival benefit of neoadjuvant radiochemotherapy prior to surgery in comparison with surgery only. PATIENTS & METHODS: Histopathological outcomes and survival were compared between 61 patients who underwent neoadjuvant radiochemotherapy and 64 comparable control patients who had been under-staged. After neoadjuvant therapy, tumor regression was assessed using the method described by Mandard in 1994. Survival curves for the two groups were estimated using the Kaplan-Meier method, and compared with the log-rank test. RESULTS: Median and 3-year recurrence-free survival for the entire group were 26 months and 39.7%, respectively. The median and 3-year overall survival reached 34 months and 48.1%. Patients who showed complete response to neoadjuvant therapy had significantly improved survival (35 months) compared to patients with residual tumor cells (28 months), patients with tumors unresponsive to radiochemotherapy (22 months), or patients who received surgery only (control group, 29 months). Patients with nodal-negative carcinomas showed significantly longer survival after surgery only and after neoadjuvant therapy compared to patients with lymph node-positive cancers. CONCLUSIONS: Complete response after neoadjuvant radiochemotherapy is associated with significantly improved survival. Negative nodal status is a major determinant of outcomes following primary operation or neoadjuvant treatment.

Surgical therapy of intrapancreatic metastasis from renal cell carcinoma.

BACKGROUND: Pancreatic metastases from renal cell carcinoma (RCC) are clinically rare but highly resectable. The aim of this article is to identify patients who profit from pancreatic resection of RCC despite the invasiveness of the surgery. METHODS: Between January 1996 and December 2007, data from 744 patients were collected in a prospective pancreatic surgery database, and patients with metastasis into the pancreas from RCC were identified. RESULTS: Resective surgery was performed in 14 patients with metastasis to the pancreas from RCC. Most patients were clinically asymptomatic. The median interval between primary treatment of RCC and occurrence of pancreatic metastasis was 94 months (range 32-158). The morbidity rate was 42.8%. Patients with a metastasis size <2.5 cm had a much better survival after resection (100 months) than those with a metastasis size >2.5 cm (44 months). Moreover, the number of metastases predicts the survival after resection. CONCLUSIONS: In patients with pancreatic metastases from RCC who have only limited disease, complete resection of all lesions can be successfully performed with a low rate of complications. Thus, patients with a history of RCC should be monitored for more than 10 years after nephrectomy to detect recurrence.

Colorectal liver metastasis surgery: analysis of risk factors predicting postoperative complications in relation to the extent of resection.

BACKGROUND/AIMS: Despite advances in diagnosis and treatment, the rate of complications after resection for colorectal liver metastases remains high. An awareness of risk factors is essential for the rates of morbidity and mortality to fall to optimal levels. MATERIALS AND METHODS: Of the 240 patients who underwent resection for the first manifestation of colorectal liver metastases, 49 patients with lobectomy or extended hepatectomy (major resections) and 58 with wedge resections within only one liver segment (minor resections) form the basis of this report. A total of 16 variables were analyzed to find the risk factors linked to postoperative morbidity and mortality. RESULTS/FINDINGS: Thirty-four patients (31.8%) suffered postoperative complications, and one patient died during the hospital stay (0.9%). In the major resection group, multivariate analysis showed that neoadjuvant chemotherapy [odds ratio (OR): 2.4; p = 0.005], vascular clamping (OR: 1.4; p = 0.008), and intraoperative blood loss with transfusion of three to six packed red cell units (OR: 1.2; p = 0.029) were significantly associated with postoperative morbidity. Vascular clamping was an independent predictor for biliary fistula (OR: 1.2; p = 0.029). Postoperative temporary liver failure was influenced by neoadjuvant chemotherapy (OR: 3.4; p = 0.010), vascular clamping (OR: 1.5; p = 0.015), and requirement of blood transfusion (OR: 2.1; p = 0.016). After minor resections, only a decreased postoperative serum cholinesterase B level was an independent predictor for complications (OR: 2.2; p = 0.001), as well as for hemorrhage (OR: 1.6; p = 0.023). Postoperative mortality was not predicted by any of the factors that were analyzed. INTERPRETATION/CONCLUSION: Factors for complications differ depending on the extent of colorectal liver metastasis resection. Only knowledge and particular consideration of these factors may provide for an optimal postoperative outcome for the individual patient.

Prognostic factors and evaluation of a clinical score for predicting survival after resection of colorectal liver metastases.

BACKGROUND: Patient outcome after resection of colorectal liver metastases can be predicted by various prognostic factors. AIMS: Development of a model for risk stratification based on analysis of prognostic factors. METHODS: Data of 201 patients were collected prospectively and included in a single-centre trial. A total of 20 factors were analysed as to their influence on recurrence-free and overall survival. Independent prognostic factors were entered into a model of a clinical risk score. RESULTS: Median recurrence-free survival reached 24 months for all patients; median overall survival was 50 months. Only a synchronous manifestation of primary colorectal carcinoma and liver metastases, the presence of four or more metastases and a carcino-embryonic antigen level of 200 ng/ml or more significantly influenced recurrence-free and overall survival in the multivariate analysis. The derived risk stratification grouped the patients according to the following criteria: low risk, zero prognostic factors (n=112); intermediate risk, one factor (n=74); high risk, two or more factors (n=15). The median recurrence-free survival for low, intermediate and high risk were 30.0, 23.0 and 11.0 months, respectively; the median overall survival was 94.0, 40.0 and 33.0 months. Compared with the low-risk group, patients with intermediate risk demonstrated an increased hazard ratio (HR) of 1.57-fold for recurrence (P=0.018) and 1.91-fold for mortality (P=0.007). For the high-risk group, the HR rose significantly to 3.26 for recurrence (P<0.0005) and to 3.10 for mortality (P=0.001). CONCLUSIONS: The presented clinical score may allow for patients with colorectal liver metastases to be stratified appropriately and for optimization of their subsequent therapeutic management.

Resection of colorectal liver metastases: is a resection margin of 3 mm enough? : a multicenter analysis of the GAST Study Group.

BACKGROUND: A safety margin of > or =10 mm is generally accepted in surgery for colorectal metastases. It is reasonable that modern methods of liver parenchyma dissection may allow for a reduction in this distance. METHODS: A total of 333 patients were included in a multicenter trial after resection of colorectal liver metastases. Dissection of the liver had been performed with a CUSA, UltraCision, or water-jet dissector. The size of the resection margin was correlated with recurrence risk and survival. RESULTS: The median hepatic recurrence-free survival reached 35 months for all patients; median recurrence-free survival was 24 months and overall survival was 41 months. Univariate analysis of different groups denoting the extent of resection margin (> or =10 mm, 6-9 mm, 3-5 mm, 1-2 mm, 0 mm (R1)) indicated that a margin of 1-2 mm leads to a significantly reduced median hepatic recurrence-free survival of 20 months (p = 0.004) and recurrence-free survival of 19 months (p = 0.011). Patients with R1 resection had the worst prognosis. Overall survival was not influenced by the size of the resection margin. Surgical margins were significantly reduced in simultaneous resections of four or more liver metastases and in cases in which metastatic infiltration of central liver segments was present. At multivariate analysis, resection margins of 1-2 mm and 0 mm were independent predictors of hepatic recurrence and overall recurrence. CONCLUSION: The indication for resection of metastases can be safely extended to cases in which tumors sit closer than 1 cm to nonresectable structures.

Location of liver metastases reflects the site of the primary colorectal carcinoma.

OBJECTIVE: The present study was designed to investigate whether the different venous return of different locations of colorectal carcinomas affects the lobar distribution of metastases to the liver, due to the "streaming" within the portal vein. MATERIAL AND METHODS: The site of the primary colorectal carcinoma was divided into the right- and left hemicolon according to the different venous drainage via the superior and the inferior mesenteric/splenic vein. Both groups were analyzed for the distribution of the metastases in the liver. The anatomic site of the liver metastases was detected by intraoperative exploration and differentiated between the two lobes using the Cantlie line. RESULTS: Out of a total of 178 patients, 109 men and 69 women with 264 metastases were eligible for the study. The ratio of metastases in the right and left hemiliver was 3.6:1 for 35 right-sided primary tumors (p=0.002) compared with 2.1:1 for 143 left-sided primary tumors (p=NS). No significant differences were evident for the sub-analysis of involved liver segments. CONCLUSIONS: The results of our study support the existence of the "streaming" effect in the portal vein. Right-sided colon carcinomas predominantly involve the right hemiliver, while left-sided colon carcinomas involve the liver homogeneously, considering the size ratio of the right to left liver lobe, which is about 2:1. Knowledge of streaming may help us to understand the spread of abdominal malignancies and may provide a reference concerning the possible primary site depending on metastatic distribution in the liver.

Prospective evaluation of the retrograde percutaneous translaryngeal tracheostomy (Fantoni procedure) in a surgical intensive care unit: technique and results of the Fantoni tracheostomy.

BACKGROUND: Controversy surrounds the safety and practicality of the retrograde percutaneous translaryngeal tracheostomy (Fantoni procedure) compared with other percutaneous methods. METHODS: We used the Fantoni tracheostomy for 245 patients in our intensive care unit (ICU) over a period of 3 years 6 months and conducted a prospective analysis. RESULTS: We are able to report a low incidence of complications (1.2%) with the Fantoni procedure. Advantages of the method are reduced tissue trauma and optimal adaptation of the stoma to the cannula, leading to less stomal bleeding and fewer infectious complications. We observed no procedure-related mortality. Under mandatory bronchoscopic control, proper puncture location and cannula placement are ensured, which prevents tracheal wall injury and paratracheal placement of the cannula. CONCLUSIONS: Our experience shows that the major advantage of the use of the Fantoni tracheostomy is the retrograde dilatation of the stoma, which prevents serious complications compared with other techniques.

Malignant fibrous histiocytoma masquerading as germ cell tumor by producing beta-human chorionic gonadotropin and neuron-specific enolase.

Neuron-specific enolase and beta-human chorionic gonadotropin are serum markers frequently found associated with germ cell tumors. To our knowledge, we report the first case of a malignant fibrous histiocytoma producing both markers and discuss the significance of this unusual condition in the differential diagnosis of retroperitoneal tumors.