Is a less-intensive follow-up for colon cancer in early stages reasonable?

PURPOSE: Patients with colon cancer are usually included in an intensive 5-year surveillance protocol after curative resection, independent of the tumor stage, though early stages have a considerably lower risk of recurrence. The aim of this study was to analyze the adherence to an intensive follow-up and the risk of recurrence in patients with colon cancer in UICC stages I and II. METHODS: In this retrospective study, we assessed patients who underwent resection for colon cancer in UICC stages I and II between 2007 and 2016. Data were collected on demographics, tumor stages, therapy, surveillance, recurrent disease, and oncological outcome. RESULTS: Of the 232 included patients, 43.5% (n = 101) reached the 5-year follow-up disease-free. Seven (7.5%) patients in stage UICC I and sixteen (11.5%) in UICC II had a recurrence, with the highest risk in patients with pT4 (26.3%). A metachronous colon cancer was detected in four patients (1.7%). The therapy of recurrence was intended to be curative in 57.1% (n = 4) of UICC stage I and in 43.8% (n = 7) of UICC stage II, but only in one of seven patients over 80 years. 44.8% (n = 104) of the patients were lost to follow-up. CONCLUSION: A postoperative surveillance in patients with colon cancer is important and recommended as a recurrent disease can be treated successfully in many patients. However, we suggest that a less intensive surveillance protocol is reasonable for patients with colon cancer in early tumor stages, especially in UICC stage I, as the risk of recurrent disease is low. With elderly and/or frail patients in a reduced general condition, who will not endure further specific therapy in case of a recurrence, the performance of the surveillance should be discussed: we recommend a significant reduction or even renunciation.

Emergency resection is an independent risk factor for decreased long-term overall survival in colorectal cancer: a matched-pair analysis.

BACKGROUND: Colorectal cancer is one of the most common malignant neoplasms worldwide. Up to 30% of the patients present in an emergency setting despite an established screening program. Emergency colorectal resection is associated with increased mortality and morbidity as well as worse oncological outcome. This study aims to analyze the impact on tumor recurrence and survival in patients with an emergency colorectal resection, independent of sex, age, and tumor stage. METHODS: Patients, who underwent an oncological resection for colorectal cancer at the Medical University of Innsbruck, Department of Visceral, Transplant and Thoracic Surgery, between January 2003 and December 2018 were analyzed retrospectively and screened for emergency resections. Matched pairs were formed to analyze the impact of emergency operations on long-term outcomes, considering tumor stage, sex, and age, comparing it with elective patients. RESULTS: In total, 4.5% out of 1297 patients underwent surgery in an emergency setting. These patients had higher UICC (Union internationale contre le cancer) stages than elective patients. After matching the patients for age, sex, and tumor stage, emergency patients still had higher mortality. The incidence of recurrence was higher (47.5% vs. 25.4%, p = 0.003) and the 5-year overall survival decreased (35.6% vs. 64.4%, p < 0.001) compared to the matched patients with elective resection. Correcting for 90-day mortality still a reduction in the 5-year overall survival was demonstrated (44% vs. 70%, p = 0,001). The left-sided colon tumors were more common in the emergency group (45.8% vs. 25.4%, p = 0.006) and the rectal tumors in the elective one (21.2% vs. 3.4%, p = 0.002). CONCLUSION: Patients undergoing emergency resection for colorectal cancer have a decreased tumor-specific and overall survival compared to patients after elective resection, independent of age, sex, and tumor stage, even after correcting for 90-day mortality. These findings confirm the importance of colorectal cancer awareness and screening to reduce emergency resections.

Damage control strategy in perforated diverticulitis with generalized peritonitis.

BACKGROUND: The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann's procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS. METHODS: DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24-48 h: definite reconstruction with colorectal anastomosis (-/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis). RESULTS: Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma. CONCLUSION: DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.

Prospectively Randomized Controlled Trial on Damage Control Surgery for Perforated Diverticulitis with Generalized Peritonitis.

INTRODUCTION: Damage control surgery (DCS) with abdominal negative pressure therapy and delayed anastomosis creation in patients with perforated diverticulitis and generalized peritonitis was established at our Institution in 2006 and has been published. The concept was adopted in other hospitals and published as a case series. This is the first prospectively controlled randomized study comparing DCS and conventional treatment (Group C) in this setting. METHODS: All consecutive patients from 2013 to 2018 with indication for surgery were screened and randomized to Group DCS or Group C. The primary outcome was the rate of reconstructed bowel at discharge and at 6 month. Informed consent was obtained. The trial was approved by the local ethics committee and registered at CinicalTrials.gov: NCT04034407. RESULTS: A total of 56 patients were screened; 41 patients gave informed consent to participate and ultimately 21 patients (9 female) with intraoperatively confirmed Hinchey III (n = 14, 67%) or IV (n = 7, 33%), and a median (range) age of 66 (42-92), Mannheim Peritonitis Index of 25 (12-37) and Charlson Comorbidity Index of 3 (0-10) were intraoperatively randomized and treated as Group DCS (n = 13) or Group C (n = 8). Per protocol analysis: A primary anastomosis without ileostomy (PA) was performed in 92% (11/12) patients in Group DCS at the second-look operation, one patient died before second look, and one underwent a Hartmann procedure (HP). In Group C 63% (5/8) patients received a PA and 38% (3/8) patients a HP. Two patients in Group C, but none in Group DCS experienced anastomotic leakage (AI). ICU and hospital stay was median (range) 2 (1-10) and 17.5 (12-43) in DCS and 2 (1-62) and 22 (13-65) days in group C. In Group DCS 8% (1/12) patients was discharged with a stoma versus 57% (4/7) in Group C (p = 0.038, n.s., α = 0.025); one patient died before discharge. The odds ratio (95% confidence interval) for discharge with a stoma is 0.068 (0.005-0.861). Intent to treat analysis: A PA was performed in 90% (9/10) of patients randomized to DCS, one patient died before the second look, and one patient received a HP. In group C, 70% (7/10) were treated with PA and 30% (3/10) with HP. 29% (2/7) experienced AI treated with protective ileostomy. In group DCS, 9% (1/11) were discharged with a stoma versus 40% (4/10) in group C (p = 0.14, n.s.). The odds ratio for discharge with a stoma is 0.139 (0.012-1.608). CONCLUSION: This is the first prospectively randomized controlled study showing that damage control surgery in perforated diverticulitis Hinchey III and IV enhances reconstruction of bowel continuity and can reduce the stoma rate at discharge.

Incisional hernia at the site of stoma reversal-incidence and risk factors in a retrospective observational analysis.

BACKGROUND: The closure of a stoma site has a high incidence of incisional hernia (IH) development, reaching 30% in some studies. Location and defect size in the abdominal wall depend on the type of stoma formed, most commonly a loop ileostomy or terminal sigmoid colostomy. METHODS: The retrospective single-centre study includes all consecutive patients who underwent stoma reversal between 2010 and 2016 at the Department of Visceral, Transplant and Thoracic Surgery in Innsbruck. Patient characteristics and follow-up examinations were evaluated for IH at both the stoma reversal site and at any other surgical access sites. RESULTS: A total of 181 patients (49% female, 51% male) had a stoma reversal operation. A parastomal hernia was present in 5% (n = 9). Follow-up data was available for 140 patients (77%). A postoperative IH at the stoma reversal site developed in 15.7% (n = 22) and in 18.6% (n = 26) at other surgical wounds to the abdominal wall during a median follow-up of 136 weeks. The combination of a preoperative parastomal hernia and a postoperative IH was observed in 2.8% (n = 5). Parastomal herniation, male sex, body mass index over 25, arterial hypertension and concomitant ventral hernia were associated with IH formation at the stoma reversal. CONCLUSION: The rate of IH at the stoma reversal site was lower than expected from the literature, whereas the rate of IH at other surgical wounds to the abdominal wall was within the expected range.

Perioperative chemotherapy versus neoadjuvant chemoradiation for patients with adenocarcinoma of the distal esophagus in Austria: a retrospective analysis.

BACKGROUND: The aim of this study was to compare the outcome of patients with adenocarcinoma of the distal esophagus (AEG type I) treated with neoadjuvant chemoradiation or perioperative chemotherapy. METHODS: Eligible patients from four Austrian centers were selected to conduct a retrospective analysis. All patients treated between January 2007 and October 2017 with chemotherapy according to EOX-protocol (Epirubicin, Oxaliplatin, Xeloda) or chemoradiation according to CROSS-protocol (carboplatin/paclitaxel + RTX 41.4 Gy), before esophagectomy were included. Primary outcomes disease-free survival (DFS) and overall survival (OS) as well as secondary outcomes downstaging of T- or N-stage and achievement of pathological complete response pCR (ypT0N0M0) were analyzed. Data of 119 patients were included. RESULTS: Complete data was available in 104 patients, 53 patients in the chemoradiation group and 51 patients in the chemotherapy group. The mean number of lymph nodes removed was significantly higher in the EOX group (EOX 29 ± 15.5 vs. CROSS 22 ± 8.8; p < 0.05). Median follow-up in the CROSS group was 17 months (CI 95% 8.8-25.2) and in the EOX group 37 months (CI 95% 26.5-47.5). In the chemotherapy group, the OS rate after half a year, - 1, and 3 years was 92%, 75%, and 51%. After chemoradiation, overall survival after half a year was 85 %, after 1 year 66%, and after 3 years 17%. In the EOX group DFS after ½, - 1, and 3 years was 90%, 73%, and 45%, in the chemoradiation group after half a year 81%, after 1 year 55% and after 3 years 15%. Pathological complete response (pCR) was achieved in 23% of patients after CROSS and in 10% after EOX (p < 0.000). CONCLUSIONS: There seem to be clear advantages for chemoradiation, concerning the major response of the primary tumor, whereas a tendency in favor for chemotherapy is seen in regards to systemic tumor control. Furthermore, the type of neoadjuvant treatment has a significant influence on the number of lymph nodes resected.

Perianal minimally invasive surgery (PAMIS) for rectal stump resection after previous colectomy.

PURPOSE: Resection of a long rectal stump after previous colectomy or Hartmann procedure often requires a combined transperitoneal and transperineal approach because of limited access through a perineal incision alone. Risks associated with this procedure include iatrogenic injury to bowels, nerves, ureters, vessels and sexual organs. This study reports on the feasibility and safety of perianal minimally invasive surgery (PAMIS) for the resection of long rectal stumps that would otherwise require a combined transperitoneal and perianal approach. METHODS: PAMIS utilizes standard laparoscopic equipment and a single access port to dissect the rectal stump following the mesorectal fascia into the pelvis after excision of the anal canal. Three PAMIS procedures were performed between February and April 2016. Feasibility, safety and outcome were analysed. RESULTS: Three patients with previous colectomy and ostomy creation due to colitis ulcerosa (n = 2) and idiopathic enteropathy (n = 1) underwent PAMIS. The rectal stump length ranged between 10 and 19 cm. The median postoperative length of stay was 9 (range 6 to 11) days and the median operating time was 90 (range 80 to 120) min. There were no perioperative complications. CONCLUSION: PAMIS is a feasible, safe and efficient procedure for rectal stump resection avoiding the transperitoneal approach for pelvic dissection.

Up-regulation of neutrophil gelatinase-associated lipocalin in colorectal cancer predicts poor patient survival.

BACKGROUND: Lipocalin-2 (Lcn-2) is expressed in human neutrophils and epithelial cells, particularly in the presence of inflammation or cancer. It was shown to be highly expressed in various human cancers. Increased protein levels were associated with decreased survival of patients with breast or gastric cancer. The main focus of this work was to analyze the implication of Lcn-2 up-regulation in the genesis of colon cancer. METHODS: Expression of Lcn-2 was analyzed in colorectal carcinoma cell lines, paired colorectal carcinoma tissues, and regular mucosa by Western blot analysis. Lcn-2 immunohistochemical staining was performed in 192 colorectal carcinoma resection specimens and correlated with clinicopathologic parameters. RESULTS: Western blot analysis of colorectal carcinoma tissues demonstrated Lcn-2 overexpression in carcinomas as compared with regular mucosa. Immunohistochemical staining revealed Lcn-2 expression in 179 (93.2%) colorectal carcinoma tissues. Intense immunoreactivity was significantly correlated with metastasis (p = 0.042) and UICC stage (p = 0.027). Survival analysis according to the Kaplan-Meier method revealed a significant association between Lcn-2 overexpressing tumors and overall survival (p < 0.001) and disease-free survival (p < 0.001). CONCLUSIONS: Our data provide evidence that Lcn-2 expression is up-regulated with tumor progression and was found to be a predictor of overall survival.

Results and complications after laparoscopic sleeve gastrectomy.

PURPOSE: Laparoscopic sleeve gastrectomy (SG) has gained popularity and acceptance among bariatric surgeons, mainly due its low morbidity and mortality. The purpose of the present study was to evaluate the efficacy of SG on weight loss, and to determine the postoperative course, clinical presentation and treatment of complications after SG. METHODS: Between January 2006 and October 2012, 153 consecutive patients underwent SG. All data were prospectively collected in a computerized database. RESULTS: This series comprised 119 females and 34 males with a median age of 46 years and a median preoperative BMI of 42.3 kg/m2. The median EWL was 53.0 % after 18.4 months of follow-up. The median postoperative BMI was 33.3 kg/m2 (range 19.7­56.1 kg/m2). Eight patients (5.2 %) required re-laparoscopy to manage postoperative hemorrhage (3.3 %) and leakage (1.9 %). Neither abdominal drains nor postoperative contrast-swallow studies were successful in diagnosing hemorrhage or leaks in our patients. CONCLUSION: SG is an effective procedure to achieve significant short-term weight loss. Clinical signs, such as tachycardia, pain, fever and hypotension, provide the best evidence of the presence of postoperative leakage or bleeding. An early diagnosis of these complications is the key to ensuring adequate treatment with immediate re-laparoscopy.

Long-term follow-up evaluation of revisional gastric bypass after failed adjustable gastric banding.

BACKGROUND: Disappointing long-term results, frequent band failure, and high rates of band-related complications increasingly necessitate revisional surgery after adjustable gastric banding. Laparoscopic conversion to gastric bypass has been recommended as the procedure of choice. This single-center retrospective study aimed to evaluate the long-term results of revisional gastric bypass after failed adjustable gastric banding. METHODS: The study included 108 consecutive patients who underwent laparoscopic conversion of gastric banding to gastric bypass from 2002 to 2012. Indications for surgery, operative data, weight development, morbidity, and mortality were analyzed. The median follow-up period was 3.4 years (maximum, 10 years). RESULTS: The most common indications for band removal were band migration, insufficient weight loss, and pouch dilation. The median interval between gastric banding and gastric bypass was 6.6 years. In 52 % of the cases, band removal and gastric bypass surgery were performed simultaneously as a single-stage laparoscopic procedure. The early postoperative morbidity rate was 10.2 %. The body mass index before gastric banding (43.3 kg/m(2)) decreased significantly to 37.9 kg/m(2) before gastric bypass and to 28.8 kg/m(2) 5 years after gastric bypass. CONCLUSIONS: This is the first report on the long-term outcome after conversion of failed adjustable gastric banding to gastric bypass. Findings have shown revisional gastric bypass to be a feasible bariatric procedure particularly for patients with insufficient weight loss that guarantees a constant and long-lasting weight loss.

Diverticulitis with coloenteric fistula mimicking gangrenous appendicitis with perityphlitic abscess. An uncommon presentation of a common disease - A case report.

INTRODUCTION: Diverticulitis is a common gastrointestinal disease usually presenting with a typical clinical picture depending on the stage of the disease. In complicated cases, the clinical presentation may be untypical, thus delaying diagnosis and treatment. PRESENTATION OF CASE: We present a case of a young patient who was initially treated for obscure intraabdominal abscesses presumably due to gangrenous appendicitis; however, intraoperative exploration revealed a normal appendix and a coloenteric fistula resulting from an unknown and untreated perforated diverticulitis. DISCUSSION: A patient with a perityphlitic abscess was initially managed with primary non-operative management (NOM) in accordance with the current Jerusalem guidelines, but surgery was eventually necessary due to failure of NOM. Intraoperative findings revealed a sigmoido-ileal fistula, a rare but potentially detectable complication of diverticulitis through colonoscopy. This case highlights the challenges in diagnosing and treating common surgical diseases with uncommon clinical presentations, emphasizing the importance of a detailed patient history and not relying solely on imaging studies. CONCLUSION: Intraabdominal abscesses require prompt treatment with non-operative management, while intestinal fistulae associated with diverticulitis are a rare consequence of chronic inflammation, often asymptomatic and often detected incidentally during surgery. In most cases simple fistulous tract resection is usually sufficient as first line therapy.

Small bowel neuroendocrine tumors: An analysis of clinical presentation, diagnostic workup and surgical approach-A single center retrospective study.

Background: Neurocrine neoplasms (NEN) of the small bowel (SBNEN) are a rare entity and mostly asymptomatic. The aim of this study was to explore trends in the clinical presentation, diagnostic workup, surgical approach and oncological outcome in patients with SBNEN at our surgical department. Materials and methods: All patients who underwent surgical resection for SBNEN from 2004 to 2020 at our department were enrolled in this single center retrospective study. Results: A total of 32 patients were included in this study. In most cases, the diagnosis was based on incidental findings during endoscopy or radiographic imaging (n = 23; 72%). Twenty cases had a G1 tumor and 12 cases a G2 tumor. The 1-, 3- and 5-year overall survival (OS) were 96%, 86% and 81%, respectively. Patients with a tumor more than 30 mm had a significantly lower OS (p = 0.01). For G1 tumors, the estimated disease-free survival (DFS) was 109 months. Again, the DFS was significantly lower when the tumor had more than 30 mm in diameter (p = 0.013). Conclusion: Due to the mostly asymptomatic presentation, the diagnostic workup can be difficult. An aggressive approach and a strict follow-up seem to be important for the oncological outcome.

Open abdomen treatment with dynamic sutures and topical negative pressure resulting in a high primary fascia closure rate.

BACKGROUND: Open abdomen (OA) treatment with negative-pressure therapy is a novel treatment option for a variety of abdominal conditions. We here present a cohort of 160 consecutive OA patients treated with negative pressure and a modified adaptation technique for dynamic retention sutures. METHODS: From May 2005 to October 2010, a total of 160 patients--58 women (36 %); median age 66 years (21-88 years); median Mannheim peritonitis index 25 (5-43) underwent emergent laparotomy for diverse abdominal conditions (abdominal sepsis 78 %, ischemia 16 %, other 6 %). RESULTS: Hospital mortality was 21 % (13 % died during OA treatment); delayed primary fascia closure was 76 % in the intent-to-treat population and 87 % in surviving patients. Six patients required reoperation for abdominal abscess and five patients for anastomotic leakage; enteric fistulas were observed in five (3 %) patients. In a multivariate analysis, factors correlating significantly with high fascia closure rate were limited surgery at the emergency operation and a Björk index of 1 or 2; factors correlating significantly with low fascia closure rate were male sex and generalized peritonitis. CONCLUSIONS: With the aid of initially placed dynamic retention sutures, OA treatment with negative pressure results in high rates of delayed primary fascia closure. OA therapy with the technical modifications described is thus considered a suitable treatment option in various abdominal emergencies.

Lessons Learned in 11 Years of Experience With Open Abdomen Treatment With Negative-Pressure Therapy for Various Abdominal Emergencies.

Introduction: Open abdomen (OA) treatment with negative-pressure therapy (NPT) was initiated for perforated diverticulitis and subsequently extended to other abdominal emergencies. The aim of this retrospective study was to analyze the indications, procedures, duration of NPT, and the outcomes of all our patients. Methods: All consecutive patients treated with intra-abdominal NPT from January 1, 2008 to December 31, 2018 were retrospectively analyzed. Results: A total of 438 patients (44% females) with a median (range) age of 66 (12-94) years, BMI of 25 (14-48) kg/m2, and ASA class I, II, III, and IV scores of 36 (13%), 239 (55%), 95 (22%), and 3(1%), respectively, were treated with NPT. The indication for surgery was primary bowel perforation in 163 (37%), mesenteric ischemia in 53 (12%), anastomotic leakage in 53 (12%), ileus in 53 (12%), postoperative bowel perforation/leakage in 32 (7%), abdominal compartment in 15 (3%), pancreatic fistula in 13 (3%), gastric perforation in 13 (3%), secondary peritonitis in 11 (3%), burst abdomen in nine (2%), biliary leakage in eight (2%), and other in 15 (3%) patients. A damage control operation without reconstruction in the initial procedure was performed in 164 (37%) patients. The duration of hospital and intensive care stay were, median (range), 28 (0-278) and 4 (0-214) days. The median (range) duration of operation was 109 (22-433) min and of NPT was 3(0-33) days. A trend to shorter duration of NPT was observed over time and in the colonic perforation group. The mean operating time was shorter when only blind ends were left in situ, namely 110 vs. 133 min (p = 0.006). The mortality rates were 14% at 30 days, 21% at 90 days, and 31% at 1 year. An entero-atmospheric fistula was observed in five (1%) cases, most recently in 2014. Direct fascia closure was possible in 417 (95%) patients at the end of NPT, but least often (67%, p = 0.00) in patients with burst abdomen. During follow-up, hernia repair was observed in 52 (24%) of the surviving patients. Conclusion: Open abdomen treatment with NPT is a promising concept for various abdominal emergencies, especially when treated outside normal working hours. A low rate of entero-atmospheric fistula formation and a high rate of direct fascia closure were achieved with dynamic approximation of the fascia edges. The authors recommend an early-in and early-out strategy as the prolongation of NPT by more than 1 week ends up in a frozen abdomen and does not improve abdominal sepsis.

Damage control with abdominal vacuum therapy (VAC) to manage perforated diverticulitis with advanced generalized peritonitis--a proof of concept.

PURPOSE: Perforated diverticulitis with advanced generalized peritonitis is a life-threatening condition requiring emergency operation. To reduce the rate of colostomy formation, a new treatment algorithm with damage control operation, lavage, limited closure of perforation, abdominal vacuum-assisted closure (VAC; V.A.C.), and second look to restore intestinal continuity was developed. METHODS: This algorithm allowed for three surgical procedures: primary anastomosis +/- VAC in stable patients (group I), but damage control with lavage, limited resection of the diseased colonic segment, VAC and second-look operation with delayed anastomosis in patients with advanced peritonitis or septic shock (group II), and Hartmann procedure was done for social reasons in stable patients (group III) RESULTS: All 27 consecutive patients (16 women; median age 68 years) requiring emergency laparotomy for perforated diverticulitis (Hinchey III/IV) between October 2006 and September 2008 were prospectively enrolled in the study. No major complications were observed in group I (n = 6). Nine patients in group II (n = 15) had intestinal continuity restored during a second-look operation, of whom one patient developed anastomotic leakage. The median length of stay at intensive care unit was 5 days. Considering an overall mortality rate of 26% (n = 7), the rate of anastomosis in surviving patients was 70%. CONCLUSIONS: Damage control with lavage, limited bowel resection, VAC, and scheduled second-look operation represents a feasible strategy in patients with perforated diverticulitis (Hinchey III and IV) to enhance sepsis control and improve rate of anastomosis.

Challenges in the treatment of a giant retroperitoneal liposarcoma.

BACKGROUND: Retroperitoneal soft-tissue sarcoma is a very rare neoplasm, the most frequent histological subtype is liposarcoma with up to 45% of all cases. Unspecific clinical presentation, late diagnosis and high local recurrence rate represent important problems in clinical practice. We present the case of an adult patient with an unusual large liposarcoma of the retroperitoneum analyzing diagnostic workup, surgical approach and therapeutic strategies. CASE REPORT: A 68-years old female was admitted with weight gain (+12 kg) and increasing abdominal girth. Computed tomography scan imaging showed a retroperitoneal tumor with 40 cm maximum diameter. Biopsy revealed a myxoid liposarcoma. The interdisciplinary curative surgical treatment included preoperative ureteral splinting, en-bloc tumorexstirpation, ileocecal resection, right ureteral resection and vascular reconstruction of the Arteria iliaca communis. The postoperative course was uneventful. After sixteen months the patient developed multifocal local recurrence requiring extensive surgical resection of tumor and retroperitoneal fat (Figs. 3, 4). However, thirteen months later the tumor reappeared and the patient was assigned to palliative chemotherapy. The patient is still alive with stable tumor disease. CONCLUSION: The removal of a huge retroperitoneal sarcoma is a significant challenge for the surgeon. Accurate planning, interdisciplinary treatment options, and radical surgery are essential. However, the recurrence risk is exceptionally high because of the enormous tumor dimensions and the big tumor surface, multimodal therapeutic approaches may improve the outcome in these patients. KEY WORDS: Liposarcoma, Retroperitoneum, Surgery.

Dickkopf-3 as a new potential marker for neoangiogenesis in colorectal cancer: expression in cancer tissue and adjacent non-cancerous tissue.

Gene expression of Dickkopf-3 (Dkk-3) has been shown to be upregulated in tumor endothelium of colorectal cancer (CRC). For the first time, we analyzed Dkk-3 protein expression in CRC and its potential as a marker for neoangiogenesis. We used tissue microarrays (TMAs) to investigate Dkk-3 in microvessels of 403 CRC samples, 318 appropriate adjacent non-cancerous samples and 127 normal colorectal samples. Of cancer samples with CD31-positive microvessels, 67.7% were positive for Dkk-3. Dkk-3 staining was demonstrated in endothelial cells of all microvessels in nearly all cases. Dkk-3-positive samples showed a higher mean microvessel count than did Dkk-3-negative samples (P=0.001). Dkk-3 expression increased with rising numbers of microvessels per sample (P<0.0001). In adjacent samples with CD31-positive microvessels, 56% were Dkk-3-positive in all microvessels. Similar to cancer samples, Dkk-3-positive adjacent samples had a higher mean microvessel count than did Dkk-3-negative samples (P<0.0001), and Dkk-3 expression also increased with rising numbers of microvessels (P<0.0001). All microvessels in normal mucosa samples were negative for Dkk-3. Dkk-3 can be considered a putative pro-angiogenic protein in neovascularization and may possibly be a marker for neoangiogenesis in CRC. Further investigations will elucidate whether Dkk-3 is a target structure for novel therapies.

Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells.

PURPOSE: The pathologic interactions between tumor and host immune cells within the tumor microenvironment create an immunosuppressive network that promotes tumor growth and protects the tumor from immune attack. In this study, we examined the contribution of the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) on this phenomenon. EXPERIMENTAL DESIGN: Expression of IDO was analyzed in colorectal cancer cell lines by reverse transcription-PCR and functional enzyme activity was assessed by high-pressure liquid chromatography. Semiquantitative immunohistochemistry was used to evaluate IDO expression in the tissue samples of 143 patients with colorectal carcinoma, and was then correlated with the number of tumor-infiltrating T cells and clinical variables. RESULTS: In vitro IDO expression and functional enzyme activity in colorectal cancer cells was found to be strictly dependent on IFN-gamma stimulation. Immunohistochemical scores revealed IDO-high expression in 56 of 143 (39.2%) tumor specimens, whereas 87 of 143 (60.8%) cases showed low IDO expression levels. IDO-high expression was associated with a significant reduction of CD3+ infiltrating T cells (46.02 +/- 7.25) as compared with tissue samples expressing low IDO (19.42 +/- 2.50; P = 0.0003). Furthermore, IDO-high immunoreactivity significantly correlated with the frequency of liver metastases (P = 0.003). Kaplan-Meier analysis showed the crossing of survival curves at 45 months. By multivariate Cox's analysis, IDO-high expression emerged as an independent prognostic variable (<45 months, P = 0.006; >45 months, P = 0.04). CONCLUSION: IDO-high expression by colorectal tumor cells enables certain cancer subsets to initially avoid immune attack and defeat the invasion of T cells via local tryptophan depletion and the production of proapoptotic tryptophan catabolites. Thus, IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer.

14-3-3sigma expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients.

PURPOSE: 14-3-3sigma is an intracellular, dimeric, phosphoserine binding protein that is expressed in epithelial cells and involved in cancer development. In this study, we examined the expression of 14-3-3sigma and evaluated its clinical significance in colorectal carcinoma. EXPERIMENTAL DESIGN: Expression of 14-3-3sigma was analyzed by Western blot in nine colorectal carcinoma cell lines, eight paired colorectal carcinoma tissues, and normal mucosas. Immunohistochemistry was used to evaluate expression of 14-3-3sigma in tissues of 121 colorectal carcinoma patients and to correlate it with clinical parameters. RESULTS: Western blot analysis of colorectal carcinoma cell lines and tissues revealed strong 14-3-3sigma expression in four of eight cell lines and 14-3-3sigma overexpression in carcinomas compared with normal mucosa in six of eight colorectal carcinoma tissue pairs. Immunohistochemical analysis revealed 14-3-3sigma overexpression in 38.8% of colorectal carcinoma samples. Furthermore, highly positive immunoreactivity was significantly correlated with tumor differentiation (P < 0.001) and pT stage (P < 0.003). In Kaplan-Meier analysis, 14-3-3sigma overexpression was associated with a significantly decreased survival time compared with negatively stained or low stained cases (P < 0.0096). In multivariate regression analysis, 14-3-3sigma expression emerged as a significant independent parameter (P < 0.037). CONCLUSIONS: These results provide evidence that 14-3-3sigma expression increases during carcinoma progression in a subset of colorectal carcinoma. The overexpression of this antigen identifies patients at high risk. It is tempting to suggest that 14-3-3sigma overexpression either promotes tumor proliferation and/or prevents apoptotic signal transduction in colorectal carcinoma. Thus, targeting 14-3-3sigma might be a new therapeutic strategy in colorectal carcinoma.