Primary and locally recurrent retroperitoneal soft-tissue sarcoma: local control and survival.

AIM: To evaluate local control for long-term prognosis in retroperitoneal soft-tissue sarcoma (primary tumors (PT) and local recurrence (LR)). METHODS: A total of 110 patients underwent surgery between 1988 and 2002. Prospectively gathered clinicopathological data were analyzed. Kaplan-Meier estimations and Cox regression analyses were performed. RESULTS: Resectability was 90%, being comparable for PT (n=71) and LR (n=39). Morbidity, mortality, blood loss, and operation time did not differ for PT or LR (24% vs. 31%, p=0.41; 7.0% vs. 5.1%, p=1.0; 1000 ml vs. 1500 ml, p=0.17; 240 min vs. 255 min, p=0.13). Hospitalization was comparable in both groups (median, 12 days (PT) and 13 days (LR)). Follow-up was 89 months (median, IQR 37-112 months). Local 3- and 5-year control rates after complete resection of PT were 66% and 59% (19% and 9% for LR, p<0.001). The mean number of operations were 1.4 for PT and 2.4 for LR (p=0.0047). The 5-year survival rates after complete resection were 51% for PT and 43% for LR (p=0.39). The 5-year survival rates were 65%, 4%, and 0% for complete resection, incomplete resection, and exploration, respectively (p<0.001). Multivariate analysis showed high-grade and blood loss with a poor prognosis. CONCLUSIONS: Comparable resectability rates and perioperative outcome were observed for surgery of PT and LR. Consequent reoperation leads to respectable long-term survival rates after resection of LR. The prognosis in retroperitoneal sarcomas varies significantly according to resectability, grade and blood loss.

Recognition of distress and psychiatric morbidity in cancer patients: a multi-method approach.

BACKGROUND: This study aimed to determine the prevalence of psychiatric morbidity and distress among 189 consecutively recruited cancer patients upon admission to surgical oncology wards, and to investigate the recognition of distressed patients by medical staff. PATIENTS AND METHODS: Assessment consisted of a diagnostic psychiatric interview (SCID, DSM-IV), patient-reported distress using a standardised questionnaire (Hospital Anxiety and Depression Scale), and physicians' and nurses' estimates of patients' distress. Twenty-eight per cent of patients were assigned a psychiatric diagnosis, with adjustment disorder predominating. RESULTS: Surgeons accurately recognised marked distress in 77% of patients with a psychiatric disorder and nurses did so in 75%. Because of low specificity, the positive predictive value was only 39% in surgeons and 40% in nurses. However, recognition of distress translated into referral to the psychosocial liaison service for only a minor proportion of distressed patients. CONCLUSIONS: Since a remarkable proportion of distressed patients remained unrecognised by the medical staff, only systematic screening of patients upon admission allows timely support to those who are most in need.

Hematogenous tumor cell dissemination during colonoscopy for colorectal cancer.

BACKGROUND: It has long been suspected that mechanical influences may enhance the release of viable colorectal cancer cells into the circulation. The objective of this study was to determine the extent of hematogenous tumor cell spread in colorectal cancer patients during colonoscopy. METHODS: Peripheral venous blood samples were taken before and after colonoscopy from 44 patients with colorectal cancer. Blood samples were examined using a reverse-transcriptase polymerase chain reaction assay to amplify cytokeratin 20 transcripts. RESULTS: Eleven patients with colorectal cancer displayed circulating tumor cells before and after colonoscopy (25%), whereas tumor cells were detected in six of 44 patients (14%) only after the procedure (p = 0.03, McNemar's test: tumor cell detection before after colonoscopy). All control samples consistently tested negative. CONCLUSIONS: Mechanical forces may result in enhanced release of viable colorectal cancer cells into the circulation; however, the clinical significance of these results needs to be clarified.

Laparoscopically assisted colectomy and ileoanal pouch procedure with and without protective ileostomy.

BACKGROUND: Apart from an obviously better cosmetic situation, there is controversy on the actual benefit of laparoscopic and laparoscopically assisted techniques in restorative proctocolectomy. The need for a protective ileostomy remains unclear. METHODS: Fifty-nine consecutive patients with ulcerative colitis and familial polyposis were included in this prospective cohort study. The colon was mobilized laparoscopically with a four-trocar technique, facilitating vascular dissection, rectal resection, and ileoanal pouch construction to be done through a Pfannenstiel incision. A protective ileostomy was constructed only in patients where the operation was difficult or where the anastomosis was under tension. Intra- and postoperative data were recorded; statistical analyses were performed by exact logistic regression. RESULTS: Laparoscopic mobilisation was successful in 54 patients (91.2%). Two patients had to be primarily converted because of exceeding the set time limit; 3 other patients had to have an additional median laparotomy. These 5 patients all had an increased body mass index (BMI), which was a statistically significant risk factor for failure of the laparoscopic technique. 18.6% of patients developed major complications (n = 11). Nine patients required secondary ileostomies; all of them either were under high dose immunosuppressants (n = 5) or had an increased BMI (average 28.42 kg/m2). Failure of the laparoscopic technique was associated with major complications. CONCLUSION: Laparoscopically assisted restorative proctocolectomy is technically feasible; an increased BMI is a relevant risk factor for failure. The minimally invasive approach probably does not reduce the need for a protective ileostomy in selected patients. The selection criteria for the addition or omission of a protective ileostomy in minimally invasive restorative proctocolectomy remain to be clearly defined.

Glutathione depletion with L-buthionine-(S,R)-sulfoximine demonstrates deleterious effects in acute pancreatitis of the rat.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.

Glutamine distribution in patients with ulcerative colitis and in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy.

BACKGROUND AND AIMS: Restorative proctocolectomy with construction of an ileoanal pouch (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP). This procedure imposes an essential change in function on the terminal ileal mucosa and pouch mucosa. Glutamine is one of the major nutrients for the small-bowel mucosa; it is metabolized into glutamate and subsequently alanine in the human enterocyte. In a prospective clinical trial we compared glutamine distribution in patients with UC to that in patients with FAP before and after restorative proctocolectomy. METHODS AND PATIENTS: Concentrations of glutamine, glutamate, and alanine were measured pre- and postoperatively in the terminal ileal mucosa, pouch mucosa, skeletal muscle and venous blood of patients undergoing IPAA for UC or FAP. Healthy individuals served as controls for skeletal muscle glutamine concentration. RESULTS: After IPAA the glutamine concentration in UC patients was decreased in skeletal muscle. In the mucosa glutamine remained unaltered while glutamate and alanine concentrations increased. In plasma the glutamine concentration increased, the glutamate level fell, and the alanine level increased. In FAP patients the glutamine level was unchanged in skeletal muscle after IPAA. In mucosa the glutamine level did not change, but glutamate and alanine increased. In plasma the glutamine level remained unaltered, glutamate decreased, and alanine increased. CONCLUSION: Patients with UC or FAP before surgical therapy do not suffer from glutamine depletion. IPAA resulted in changes in the distribution of glutamine and its metabolites in skeletal muscle, plasma, and ileal pouch mucosa, particularly in patients with UC. Further studies should investigate whether characteristics in the glutamine distribution have any impact for the long-term outcome after IPAA.

The effect of virtual reality and training on liver operation planning.

OBJECTIVE: The three-dimensional relation of a liver tumour to the intrahepatic vascular trees is basis of operation planning in liver surgery. Yet it has not been proven whether 3D reconstruction and further computerised processing will enhance precision of operation planning in liver surgery which has been based on the liver segment classification of Couinaud up to now. DESIGN: Our interdisciplinary group (department of Surgery, German Cancer Research Center and Department of Radiology) has developed a new interactive computer-based quantitative 3D operation planning system for liver surgery which is being introduced into the clinical routine. The system quantifies the organ structures semiautomatically, defines resection planes depending on safety margins and the vascular trees, and presents the data in digital movies as well as in quantitative reports. We conducted a clinical trial to evaluate whether 3D reconstruction will lead to an improved operation planning. Data of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumours had to be assigned to a liver segment and subsequently drawn together with the operation proposals into a liver model. The precision of both was measured quantitatively for each surgeon and stratified concerning 2D and different types of 3D presentations. RESULTS: The 3D anatomy can be visualised in high quality which results in good perception of the third dimension (depth). Tumour assignment to liver segments was significantly correlated to the level of training (p < 0.05). There was a significant increase (p < 0.001) in the precision of tumour localisation by 51% and resection proposal from 2D through 3D reconstructions by 13%-21%. Quantitative differences of the simplified Couinaud's classification of the liver segments compared to the true vascular anatomy of up to 40% were found. CONCLUSION: The impact of individual 3D-reconstruction on surgical planning has been proven to be significant and increases precision quantitatively. The merit of Couinaud's classification may be enhanced by individualisation of the segment borders in future.

Impact of diagnostic laparoscopy on the management of gastric cancer: prospective study of 120 consecutive patients with primary gastric adenocarcinoma.

BACKGROUND: Peritoneal seeding or liver metastases found at laparotomy usually preclude curative treatment in patients with gastric adenocarcinoma. Such exploratory laparotomies may be avoided by diagnostic laparoscopy. However, routine diagnostic laparoscopy does not benefit those patients who proceed to laparotomy after negative laparoscopy. The aim of this study was to evaluate prospectively the selective use of laparoscopy in uncertain situations. METHODS: One hundred and twenty consecutive patients with primary gastric adenocarcinoma were studied prospectively. Diagnostic laparoscopy was performed in patients with clinical T4 tumours or suspected metastases, unless laparotomy was required for symptomatic disease. RESULTS: Ninety-six of 120 patients were selected for immediate laparotomy with curative intent (n = 81) or for palliation (n = 15). In two of the 81 patients gastrectomy was abandoned because of unexpected peritoneal carcinomatosis. Fifteen patients underwent diagnostic laparoscopy, which identified intra-abdominal metastases in six; the other nine patients proceeded to laparotomy, which revealed peritoneal metastases not detected at laparoscopy in four patients. The remaining nine patients had overt metastases and were referred for systemic chemotherapy without abdominal exploration. CONCLUSION: Diagnostic laparoscopy in selected patients effectively limits the number of unnecessary invasive staging procedures. Routine use of diagnostic laparoscopy in all patients with gastric adenocarcinoma is not warranted.

Outcome after septic complications in J pouch procedures.

BACKGROUND: Despite the wide range of surgical approaches for pouch salvage, septic complications are among the main causes of pouch failure. METHODS: This study analysed the mode and outcome of various therapeutic approaches for pouch salvage and the impact of time of diagnosis, localization and form of septic complications on the risk of pouch failure in 131 patients with septic complications of a total of 706 patients undergoing a J pouch procedure. RESULTS: Septic complications consisted of 76.3 per cent fistulas, 15.3 per cent anastomotic breakdowns and 8.4 per cent pelvic abscesses. A total of 107 patients (81.7 per cent) with septic complications required a mean of 2.2 surgical procedures. The frequency of permanent defunctioning and excision of the pouch in the 131 patients with septic complications was 23.7 and 6.1 per cent respectively. The estimated cumulative 3-, 5- and 10-year rate of pouch failure in patients with septic complications was 19.6, 31.1 and 39.2 per cent respectively. The risk of pouch failure was significantly affected by the site of origin of septic complications (P = 0.02). The 5-year pouch failure rate increased in a subgroup of patients with septic complications at the pouch-anal anastomosis when the anal sphincter was involved (50.1 versus 29.2 per cent; P = 0.18). CONCLUSION: Pouch failure as a result of septic complications may occur several years after ileal pouch-anal anastomosis. For prevention of pouch failure, surgery for septic complications is required in a high percentage of patients and repeated attempts are justified. Follow-up studies are required for further analysis of pouch failure.

One- or two-stage procedure for restorative proctocolectomy: rationale for a surgical strategy in ulcerative colitis.

OBJECTIVE: To analyze the results of different strategies for restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) in ulcerative colitis. SUMMARY BACKGROUND DATA: No commonly accepted criteria exist for choosing between the one-stage or the two-stage procedure (with or without temporary diverting ileostomy) for IPAA. The authors analyzed the outcome of patients principally suitable for either of the two alternative surgical strategies. METHODS: A matched-pair control study was performed, comparing surgical details and the early and late outcome of the one-stage (study group, n = 57) versus the two-stage procedure (control group, n = 114), for IPAA. RESULTS: No differences were found between the study group and the control group regarding the matching criteria gender, median age at IPAA, systemic corticoid medication, or activity of colitis. Comparing the patients who underwent a one-stage procedure with those who underwent a two-stage procedure, the proportion of patients without complications was significantly higher (P =.0042) and the frequency of late complications was significantly lower (P =.0022) in patients who underwent the one-stage procedure. The percentage of patients with anastomotic strictures was significantly higher in the control group than in the study group (P =.0022). No significant difference was found between the two groups regarding early complications, pouch-related septic complications, pouchitis, median duration of surgery for IPAA, median blood loss, need for transfusion, or median hospital stay. CONCLUSIONS: In patients with ulcerative colitis in whom there is a choice between a one-stage procedure or a two-stage procedure with a defunctioning ileostomy, the one-stage procedure is clearly superior. This finding is of great clinical relevance both for the subjective interests of the patient and from an economic point of view.

Surgical strategies and minimal residual disease detection.

The ultimate goal in the treatment of cancer patients is the elimination of all tumor cells. A cure by surgery alone is possible only if the tumor is still confined locally. Detection of disseminated tumor cells may help to individually tailor the surgical procedure to each patient: extended or limited resections may be indicated depending on the individual state of tumor cell dissemination. In cases of systemic tumor cell dissemination, surgery alone cannot cure the patient. Thus, by detecting disseminated tumor cells, patients with a higher risk for relapse, who might benefit from multimodal therapeutic regimes, could be defined. A second aspect is the possibility of tumor cell shedding induced by manipulation during surgical procedures, which could be demonstrated for several tumor entities. Intraoperative tumor cell dissemination could be prevented by alternative operative strategies. In addition, perioperative antibody or cytotoxic therapy may prevent tumor cell implantation. Well-designed clinical studies are now of major importance to evaluate the clinical impact of individualized patient management and altered surgical procedures.

Serum tenascin-C is an indicator of inflammatory bowel disease activity.

Tenascin-C is a multifunctional matrix protein that is induced in inflammation and neoplasia. In the colonic mucosa of ulcerative colitis patients tenascin-C indicates tissue repair, and mucosal concentrations are correlated with local disease activity. We prospectively examined the relationship between serum concentrations of tenascin-C parameters of disease activity in surgically treated patients with ulcerative colitis and patients with inflammatory bowel disease (IBD). Perioperative serum concentrations were quantified by ELISA in 58 patients admitted for restorative proctocolectomy; controls were 37 patients with familial adenomatous polyposis receiving the same treatment. We also measured tenascin-C serum levels in 47 patients with ulcerative colitis and Crohn's disease who were receiving nonsurgical treatment. Preoperative serum tenascin-C levels were significantly higher in ulcerative colitis patients than in controls (17.2 +/- 14.6 microg/ml vs. 3.2 +/- 1.7 microg/ml) and were significantly correlated with clinical and histological parameters of disease activity; levels decreased significantly after restorative proctocolectomy. Serum tenascin-C levels were also correlated with the course of disease activity in conservatively treated IBD patients. Tenascin-C is thus not disease-specific. However, it does indicate the activity of IBD and may reflect the degree of tissue remodeling. The tenascin-C levels therefore offers a novel serum parameter for assessing disease activity and monitoring therapy in patients with IBD.

Evaluation of Bethesda guidelines in relation to microsatellite instability.

PURPOSE: The Bethesda guidelines were developed for selection of patients whose tumors should be tested for high microsatellite instability. This study examined the validity of the different Bethesda criteria in relation to microsatellite instability status to simplify their use in clinical practice. METHODS: A total of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer-associated cancers were registered on the basis of the Amsterdam criteria without age limitations (11 cases), multiple tumors (2 cases), the accumulation of colorectal cancer in the family (no first-degree relatives affected or the index patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13 cases), morphologic and histopathologic manifestations (right-sided colorectal cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria (92 cases). The microsatellite instability status of tumors was determined using the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high microsatellite instability tumors were identified in our hereditary nonpolyposis colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent (27/92) of the Bethesda-positive patients displayed high microsatellite instability compared with 6 percent of patients (4/72) not meeting these criteria (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different distribution of the microsatellite instability status when compared with those of the remaining patients registered (P < or = 0.001). These three criteria detected high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36), and 31 percent (21/67) of patients, respectively. When applying these criteria only, a cumulative detection rate of 77 percent of all (24/31) high microsatellite instability cases was found, thereby identifying 89 percent of high microsatellite instability tumors among the Bethesda-positive patients. Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline mutations and tumor-specific loss of protein expression. CONCLUSION: In our hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria showed the highest sensitivity to identify patients with high microsatellite instability tumors. However, for general medical practice outside academic centers, three criteria are reasonably accurate for adequate high microsatellite instability tumor selection.

Association of decreased perfusion of the ileoanal pouch mucosa with early postoperative pouchitis and local septic complications.

BACKGROUND: After ileoanal pouch operation, 5% to 40% of patients with ulcerative colitis and 2% to 8% of patients with familial adenomatous polyposis develop pouchitis. Seven percent to 32% of all patients have local septic complications. Pouch ischemia is discussed as a pathophysiologic factor. Tonometry is a minimally invasive method for estimating intramucosal pH (pHi), with a decreased pHi showing intramucosal acidosis characteristic of hypoperfusion. HYPOTHESIS: Decreased perfusion of the iloanal pouch measured by pHi is associated with local septic complications and the development of pouchitis. DESIGN: Prospective cohort study. SETTING: Surgical department of a university hospital. PATIENTS AND METHODS: The pHi in the ileoanal pouch of 98 patients was measured directly after the pouch procedure and correlated to the clinical course. Endoscopic examination of the pouch with biopsy and blinded histologic assessment, including calculation of a histologic pouchitis score, were routinely performed 3 months postoperatively. MAIN OUTCOME MEASURES: Development of pouchitis and local septic complications in correlation to pHi. RESULTS: A decreased pHi was statistically significantly associated with the development of pouchitis and the rate of local septic complications. All 3 patients with anastomotic stenosis had a pHi less than 7.00. The diagnosis of ulcerative colitis just failed in statistical significance as a risk factor for pouchitis. An increased body mass index just failed as a statistically significant risk factor for complications but was a risk factor for the development of acute pouchitis. CONCLUSION: Pouch hypoperfusion is a risk factor for the development of pouchitis and local septic complications.

Intraoperative fluorescence visualization of the parathyroid gland in rats.

Bilateral neck exploration is the standard procedure of primary hyperparathyroidism. Preoperative localization is not mandatory. Intraoperative visualization methods help to avoid unsuccessful explorations and to reduce morbidity rates. In our study, the application of 5-Aminolevulinic acid (5-ALA), a precursor in the heme biosynthesis pathway, led to Protoporphyrin IX (PpIX) accumulation within the parathyroid gland (PTG). PpIX, a metabolite of 5-ALA, causes red fluorescence (635 nm) when stimulated by light of a defined wavelength. Largely invisible under conventional illumination, all PTGs were fluorescence positive and detectable after PpIX targeting and blue light excitation (380-440 nm). Point spectrometry to measure fluorescence intensities, showed a fluorescence ratio between PTG and surrounding thyroid gland tissue of 5.7:1 (p < 0.001). Fluorescence guided PTG biopsies showed no false positive findings in histology. 5-ALA induced PpIX fluorescence to detect PTGs suggests to be a highly sensitive intraoperative visualization method. Hence, the performance of minimally invasive video-assisted parathyroidectomy will be facilitated by this innovative technique.

[Tumor related prognostic factors--established and hypothetical aspects]. / Tumorbezogene Prognosefaktoren--Belegtes und Hypothetisches.

The prognostic assessment of cancer patients is of special importance clinically and scientifically. Prognostic factors are divided into three groups: patient-, treatment- and tumor-related factors. Only a minority of those factors, for example the UICC TNM classification, have been proven by multivariate studies to be of prognostic significance and have an impact on patient management, even then only as prognostic groups. The individual prognosis of a specific patient, which would allow an individualized therapy, cannot yet be adequately assessed. New prognostic factors may result in improved prognostic predictions; currently it is unclear whether this will be accomplished by molecular prognostic parameters assessed on the basis of the primary tumor or rather by the detection of disseminated cancer cells. Of major importance are well-designed clinical studies, in order to prove the clinical benefit of an individualized patient management.

Surgical treatment of parathyroid carcinoma (Review).

Cancer of the parathyroid gland is rare and most patients suffer from hyperparathyroidism (HPT). Therefore it is often difficult to distinguish between benign HPT and malignant disorders. Prognosis as well as therapeutic approaches are still limited. Surgical treatment should be considered the therapy of choice for primary and recurrent manifestation of parathyroid carcinoma. The initial operation includes en-bloc resection of the tumor and the ipsilateral thyroid lobe. Surgery may cure some patients, but is often only palliative and aims to control hypercalcemia. In some patients hypercalcemia may be refractory to repeated surgery and medical treatment can provide short- or middle-term effects.

Adenocarcinoma in the ileal pouch: late risk of cancer after restorative proctocolectomy.

Restorative proctocolectomy and ileal pouch-anal anastomosis is the surgical treatment of choice for patients with ulcerative colitis. As a long-term complication of this procedure, chronic pouchitis impairs the outcome in a number of patients. Aneuploidia and dysplasia have been observed after long-lasting inflammation of ileal mucosa. The question arises whether chronic inflammation of ileal mucosa predisposes to malignant transformation similar to the situation in the chronically inflamed colon. Cancer of the ileal mucosa has been reported in patients with Brooke's ileostomy and in patients with Kock pouch but not as yet in those with an ileoanal pouch. We report a patient with carcinoma in an ileoanal pouch originating from terminal ileal mucosa who had been suffering from pancolitis with long-term backwash ileitis before, and from chronic pouchitis after, restorative proctocolectomy. This case demonstrates the importance of regular follow-up with pouchoscopy and random biopsies in all patients with long-standing inflammation of the ileal mucosa.