Long-term prognostic impact of surgical complications in the German Rectal Cancer Trial CAO/ARO/AIO-94.

BACKGROUND: The influence of postoperative complications on survival in patients with locally advanced rectal cancer undergoing combined modality treatment is debatable. This study evaluated the impact of surgical complications on oncological outcomes in patients with locally advanced rectal cancer treated within the randomized CAO/ARO/AIO-94 (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society) trial. METHODS: Patients were assigned randomly to either preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) or postoperative CRT between 1995 and 2002. Anastomotic leakage and wound healing disorders were evaluated prospectively, and their associations with overall survival, and distant metastasis and local recurrence rates after a long-term follow-up of more than 10 years were determined. Medical complications (such as cardiopulmonary events) were not analysed in this study. RESULTS: A total of 799 patients were included in the analysis. Patients who had anterior or intersphincteric resection had better 10-year overall survival than those treated with abdominoperineal resection (63·1 versus 51·3 per cent; P < 0·001). Anastomotic leakage was associated with worse 10-year overall survival (51 versus 65·2 per cent; P = 0·020). Overall survival was reduced in patients with impaired wound healing (45·7 versus 62·2 per cent; P = 0·009). At 10 years after treatment, patients developing any surgical complication (anastomotic leakage and/or wound healing disorder) had impaired overall survival (46·6 versus 63·8 per cent; P < 0·001), a lower distant metastasis-free survival rate (63·2 versus 72·0 per cent; P = 0·030) and more local recurrences (15·5 versus 6·4 per cent; P < 0·001). In a multivariable Cox regression model, lymph node metastases (P < 0·001) and surgical complications (P = 0·008) were the only independent predictors of reduced overall survival. CONCLUSION: Surgical complications were associated with adverse oncological outcomes in this trial.

Surgical options for locally recurrent rectal cancer--review and update.

Locally recurrent rectal tumours in the pelvis are found in about 6% following treatment for rectal cancer. This type of tumour can cause serious local complications and symptoms. The aim of modern surgical oncology is to offer a curative treatment option embedded in an interdisciplinary network of specialities to the patient. Due to advancements in surgical techniques and procedures, especially regarding surgical reconstruction, the possibilities of a curative treatment regarding recurrent cancers have been expanded and established. To aim for a curative treatment one must introduce a multimodal therapy including radio- and chemotherapy, and a radical oncological surgery with en bloc resection of the tumour and affected surrounding organs to achieve a R0-resection.

[Plastic surgery of extended defects after exenteration of the pelvis]. / Plastische Deckung ausgedehnter Defekte nach exenterativen Eingriffen im Becken.

Extended resections of pelvic malignancies, especially in cases of recurrent malignancies, result in the formation of large tissue defects in the region of the pelvic floor and perineum, which are difficult to deal with. Both after extra levator rectal excision and pelvic exenteration, wound healing deficiencies and local infections of the perineal wound are frequent. Primary closure is often impossible due to a lack of tissue substance after resection and an additional previous radiotherapy in most cases. This can result in poor or non-healing wounds, a consecutive need of complex care and an increased risk of secondary problems including tumour recurrences. A permanent wound closure of good quality can therefore only be achieved by plastic surgery. This can be done by local or distant muscle flaps with or without skin, for example, the gluteus maximus flap, the vertical rectus abdominis muscle flap (VRAM) or free flaps such as the latissimus dorsi flap.

Survival of patients with initially unresectable colorectal liver metastases treated with FOLFOX/cetuximab or FOLFIRI/cetuximab in a multidisciplinary concept (CELIM study).

BACKGROUND: Initially, unresectable colorectal liver metastases can be resected after response to chemotherapy. While cetuximab has been shown to increase response and resection rates, the survival outcome for this conversion strategy needs further evaluation. PATIENTS AND METHODS: Patients with technically unresectable and/or ≥5 liver metastases were treated with FOLFOX/cetuximab (arm A) or FOLFIRI/cetuximab (arm B) and evaluated with regard to resectability every 2 months. Tumour response and secondary resection data have been reported previously. A final analysis of overall survival (OS) and progression-free survival (PFS) was carried out in December 2012. RESULTS: Between December 2004 and March 2008, 56 patients were randomised to arm A, 55 to arm B. The median OS was 35.7 [95% confidence interval (CI) 27.2-44.2] months [arm A: 35.8 (95% CI 28.1-43.6), arm B: 29.0 (95% CI 16.0-41.9) months, HR 1.03 (95% CI 0.66-1.61), P = 0.9]. The median PFS was 10.8 (95% CI 9.3-12.2) months [arm A: 11.2 (95% CI 7.2-15.3), arm B: 10.5 (95% CI 8.9-12.2) months, HR 1.18 (95% CI 0.79-1.74), P = 0.4]. Patients who underwent R0 resection (n = 36) achieved a better median OS [53.9 (95% CI 35.9-71.9) months] than those who did not [21.9 (95% CI 17.1-26.7) months, P < 0.001]. The median disease-free survival for R0 resected patients was 9.9 (95% CI 5.8-14.0) months, and the 5-year OS rate was 46.2% (95% CI 29.5% to 62.9%). CONCLUSIONS: This study confirms a favourable long-term survival for patients with initially sub-optimal or unresectable colorectal liver metastases who respond to conversion therapy and undergo secondary resection. Both FOLFOX/FOLFIRI plus cetuximab, appear to be appropriate regimens for 'conversion' treatment in patients with K-RAS codon 12/13/61 wild-type tumours. Thus, liver surgery can be considered curative or alternatively as an additional 'line of therapy' in those patients who are not cured. CLINICAL TRIAL NUMBER: NCT00153998, www.clinicaltrials.gov.

[Oesophageal perforation: a retrospective analysis of aetiology, diagnosis and therapy]. / Osophagusperforation: Eine retrospektive Analyse über Atiologie, Diagnostik und Therapie.

Oesophageal perforation is commonly a rare diagnosis which is associated with a high mortality rate. Decisive for a good clinical outcome are localisation and depth of the perforation, risk factors, the time until diagnosis and a rapid therapy. The data we collected agree with those in the published papers. In cases of an early diagnosis sometimes an endoscopic therapy is possible. In -cases of surgical therapy the smallest intervention is the most favourable. A resection with the necessity for a later reconstruction is considered as the ultima ratio.

[Treatment of retroperitoneal sarcoma in Germany : Results of a survey of the German Society of General and Visceral Surgery, the German Interdisciplinary Sarcoma Study Group and the advocacy group Das Lebenshaus]. / Behandlung retroperitonealer Sarkome in Deutschland : Eine Umfrage der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie, der Deutschen Interdisziplinären Studiengruppe Sarkome und der Patientenorganisation Das Lebenshaus.

OBJECTIVE: Retroperitoneal sarcomas (RPSs) are rare cancers with some variability in clinical and histopathological presentation. In Germany, general treatment strategies of retroperitoneal sarcoma are unknown since centralized registries do not exist. The objective of this survey was to access the medical care of RPS patients in Germany. METHODS: In cooperation with the German Society of General and Visceral surgery, the German Interdisciplinary Sarcoma Study Group and the patient advocacy group Das Lebenshaus we designed an online survey assessing diagnostic and treatment strategies (e. g. performance of tumor biopsies, administration of multimodal therapies and surgical strategy). All departments for general and visceral surgery in Germany were addressed (n = 976). RESULTS: Responses were received from 191 of 976 departments. Only 11 surgical departments treat more than 10 RPS patients per year. A multidisciplinary sarcoma board exists in 19 hospitals. Staging is generally performed by cross-sectional imaging. In 54% of the departments pretreatment tumor biopsy is a standard procedure. Surgery is performed as compartment resection in 85% of the departments. A systematic lymph node dissection is done in 40%. Adjuvant radio- or chemotherapy is performed as a standard treatment in 27% and 22% departments, respectively. CONCLUSION: The survey demonstrates a large heterogeneity in RPS diagnostic and treatment strategies. Dedicated education programs and centralized treatment strategies are warranted to improve the standard of care.

[R1 resection in rectal cancer]. / Die R1-Resektion beim Rektumkarzinom.

R1 resections in rectal cancer particularly affect the circumferential resection margin (CRM) and lead to increased local recurrence rates, more distant metastases and a poorer prognosis. The proximity of the tumor to the CRM is already sufficient to increases these risks; therefore, according to the guidelines, it is now necessary to distinguish between R0 wide (≥1 mm distance), R0 close (<1 mm) and R1. The surgical technique is decisive for avoiding R1 situations. The preparation follows the boundary layers and envelope fascia in a standardized radical way and if necessary deviates away from these structures and the tumor under en bloc resection of neighboring structures. Neoadjuvant therapy also contributes to the reduction of R1 situations but cannot compensate for inadequate surgical procedures.

[Rare lesion in hepatoduodenal ligament]. / Seltene Raumforderung im Ligamentum hepatoduodenale.

A 60-year-old man was admitted for surgical treatment with a diagnosis of distal oesophageal carcinoma. A lymph node metastasis in the area of the hepatoduodenal ligament was suspected by preoperative CT scan and endosonographic examination. During the course of the oesophagectomy, a saccular tumour encircling the common hepatic artery was shown. The vessel and surrounding tumour were resected en bloc. Histology demonstrated a completely thrombosed true aneurysm of the common hepatic artery.

Treatment of Esophageal Perforation: A Single-Center Expertise.

BACKGROUND AND AIMS: Esophageal perforation is a rare diagnosis, which is associated with a high morbidity and mortality. There is only small scientific background regarding the best choice of treatment. Parameters indicating a good clinical outcome seem to be localization, depth of the defect, pre-existing risk factors, and time interval between the event and start of treatment. MATERIAL AND METHODS: We evaluate retrospective data from 39 patients who were treated with a esophageal perforation in our hospital between 2004 and 2012. RESULTS AND CONCLUSIONS: Our collected data agree with the available published literature. Endoscopic treatment seems to be favorable in early diagnosis.

Pituitary adenylate cyclase-activating polypeptide: a potent activator of human intestinal ion transport.

To investigate the effects of PACAP-27 on electrolyte transport across the isolated human intestinal mucosa, changes in short-circuit current (Isc) were measured in Ussing chamber experiments. Serosally added PACAP-27 increased Isc in a concentration-dependent manner, eliciting a similar maximal effect in both the jejunal and the colonic mucosa. Bumetanide inhibited Isc responses, indicating stimulation of Cl- secretion. The potency and efficacy of PACAP-27 were comparable to those of VIP, suggesting that both peptides activate intestinal secretion by way of a common receptor located in the basolateral membrane of the intestinal epithelium.

Uroguanylin: gene structure, expression, processing as a peptide hormone, and co-storage with somatostatin in gastrointestinal D-cells.

Guanylin/GCAP-I and uroguanylin/GCAP-II are two structurally related peptides which play an important role in the regulation of water/electrolyte balance within the gut. In order to enable the investigation and comparison of both peptide hormones at the genomic level, we decided to clone the corresponding genes. The human gene for guanylin/GCAP-I and its 5'-flanking region have been described recently. Here, we report the three exon/two intron structure of the human uroguanylin/GCAP-II gene and its localization on chromosome 1 p35-34, as determined by radiation hybrid mapping. Together with data obtained for the guanylin/GCAP-I gene we show that these genes are localized in the same chromosomal area with other guanlyl cyclase-activating peptides like ANP etc. Northern hybridization revealed that the expression of the uroguanylin/GCAP-II gene is highest in the intestinal mucosa, especially in the ileum and colon. By means of polymerase chain reaction (PCR), an expression was also observed in the stomach where no guanylin/GCAP-I expression is detectable. Using immunohistochemical methods, uroguanylin/GCAP-II immunoreactive material was distinctly localized in D-type gastric and intestinal endocrine cells. Although the comparable data on the genomic organisation of both peptide hormones verify their high degree of relationship, this finding indicates a special task of uroguanylin/GCAP-II within the stomach, such as regulatory functions in gastric secretion. The redundant expression of the GCAP/GC-C system in the small and large intestine, however, is as yet unclear.

[Limitations of surgery for rectal cancer]. / Grenzen der Chirurgie beim Rektumkarzinom.

This article presents and summarizes different treatment options for rectal cancer. The aim of this article is an historical review of treating primary and recurrent rectal cancer, highlighting the development and advancement in surgical and multimodal therapy. Limitations, specifically regarding recurrent rectal cancer are discussed and reviewed. A R0 resection can almost always be achieved in primary rectal cancer. In recurrent rectal cancer a R0 resection with extended surgical resection can be achieved in up to 70 % of the cases. In addition, surgical therapy plays a crucial role in the case of metastatic disease but should be incorporated into a multimodal network. The analysis of tumor genetics and predictive parameters will lead to the emergence of new treatment concepts shifting the limits of the current gold standard. Oncological long-term survival and improving the quality of life are the main focal points.

[Preoperative management for malnourished patients in abdominal surgery. Practical treatment regimen for reduction of perioperative morbidity]. / Präoperatives Management bei Mangelernährten in der Viszeralchirurgie : Praktischer Behandlungspfad zur Reduktion perioperativer Morbidität.

The incidence of malnutrition in oncological and visceral surgical units can be high. The screening of malnourished patients is very important, especially in the preoperative setting. The available published literature provides crucial knowledge about the risks inherent to malnutrition and subsequent perioperative morbidity and mortality. The preoperative screening of malnourished patients followed by a subsequent renutrition is the key to decreasing rates of postoperative morbidity and mortality. The data and guidelines given by the European Society of Parenteral and Enteral Nutrition (ESPEN) in 2006 for the preoperative nutritional conditioning are clear and give no doubt regarding the necessity of preparation of malnourished patients for elective abdominal surgery. Despite this fact, the observance and application of these guidelines among German surgical units remain low. To fill this void a model of systematic screening and treatment of malnutrition in the preoperative setting for elective abdominal surgery was created and implemented at the university hospital of Oldenburg. A practical treatment regimen was designed to prepare malnourished patients within 2-3 weeks before elective surgery. Initial results regarding the feasibility of preoperative home renutrition therapy were moderate but encouraging. The success of such a conditioning process depends on cooperation between the surgical unit, the general practitioner (GP) and the homecare environment. In the German healthcare system the prescription of home nutrition (i.e. enteral feeding) can lead to the prescription limits of a GP being exceeded and has to be justified to the medical insurance company in each case. This article presents a simple yet applicable way of screening and preparing malnourished patients a few weeks prior to elective surgery. Therefore, simple tools which can be promptly used in daily clinical life, especially in the outpatient surgical consultations prior to elective visceral surgery are proposed.

[Retroperitoneal mass]. / Raumforderung im Retroperitoneum.

Castleman's disease is presented in the following article in more detail using the case report of a 55-year-old patient with abdominal pain without any significant pre-existing medical conditions. A computer tomography of the abdomen demonstrated a retroperitoneal tumor in the lower abdomen below the aortic bifurcation. Because malignancy of the tumor could not be excluded, surgical extirpation was performed without complications. Histopathological examination revealed the diagnosis of a localized castleman's tumor. Castleman's disease is a rare disease of the lymph nodes of unknown etiology. In the prognosis, benign forms can be distinguished from malignant forms.

Treatment of recurrent rectovaginal/pouch-vaginal fistulas by gracilis muscle transposition - a single center experience.

PURPOSE: Rectovaginal fistulas constitute a serious burden for the affected patient and a major challenge for the attending surgeon. Definitive surgical treatment of the fistula depends on the size and location of the fistula, the underlying disease, and any previous therapies. In regards to complicated recurrent rectovaginal fistulas, transposition of the gracilis muscle is one of the well-established therapeutic options with a success rate of up to 70%. MATERIAL AND METHODS: Between 01/2004 and 06/2010, ten patients diagnosed with a recurrent rectovaginal fistula were treated in the surgical department of Klinikum Oldenburg by gracilis muscle transposition; their data were collected and analyzed. Post-operative evaluation was performed using a standardized telephone interview. All patients had a protective stoma. The primary endpoint of assessment was the long-term healing of the fistula following stoma reversal, and the comparison between those who were treated successfully versus those who were not. RESULTS: Over a time span of 6years, ten women with a complicated rectovaginal fistula underwent fistula repair with the gracilis muscle transposition. Patient age ranged from 29 and 64years. There were five rectovaginal fistulas, four pouch-vaginal fistulas, and one anovaginal fistula. The underlying disease was rectal cancer in seven patients, Crohn's disease in one patient, previous complicated gynecologic surgery in one patient, and idiopathic anal fistula in one patient. All seven patients with rectal cancer underwent radiochemotherapy with 50.4Gy (n=6 neo-adjuvant, n=1 adjuvant). All ten patients had previously undergone repair by a different surgical approach while five presented with a second or third recurrence. Post-operative complications were noted in two patients (perineal wound defect, thigh hematoma). Follow-up of the patients ranged from 8 to 60months. Recurrent rectovaginal fistula occurred in four patients. Evaluation of the data failed to identify statistically significant criteria for treatment failure of rectovaginal fistula repair. CONCLUSION: Our results are similar to previous studies in this area. For the majority of the patients, the gracilis muscle transposition was a long-term effective treatment of recurrent rectovaginal fistulas, however recurrences were noted in 40% of cases. Predictive criteria for treatment failure could not be established.

[Locally recurrent rectal cancer]. / Lokalrezidiv des Rektumkarzinoms.

Over the last decades the therapy of rectal carcinoma has shown continuous improvement. Due to improvements in operative techniques, such as the establishment of total mesorectal excision (TME) and the combination of surgery and (neo-) adjuvant radiochemotherapy, the incidence of locally recurrent rectal cancer could be improved from nearly 50% to less then 10%. Nevertheless recurrent rectal carcinoma remains a severe problem. Predictive factors relating to locally recurrent rectal cancer are surgical experience, localization of the tumor, circumferential resection margins, stage-oriented multimodal therapy and a suitable oncological procedure for the primary tumor. In addition the tumor-specific biology also seems to be a relevant risk factor for recurrence. Operative treatment of locally recurrent rectal cancer was seen for a long time as a palliative procedure. Newer data show that resection of locally recurrent rectal cancer can be carried out with a curative intention in experienced institutions with a long-term 5 year survival of about 30% and mortality around 5%. The composite sacropelvic resection technique is a reasonable option in the curative treatment of locally recurrent rectal cancer. For the future the focus must be on improvements in the primary therapy of rectal carcinoma to avoid local recurrence. In addition early diagnosis of local recurrence and multimodal therapies will be of decisive importance.

[Therapy of locally recurrent rectal carcinoma]. / Therapie des Lokalrezidivs nach Rektumkarzinom.

During the last decade no gastrointestinal tumor underwent such profound modifications in diagnostics and therapy as rectal cancer (total mesorectal excision, multimodal therapy). Despite all efforts and continuous improvements in the results of oncological treatment, local recurrence of rectal carcinoma is still a considerable problem. Optimized surgery methods and multimodal therapies allow a local recurrence rate lowered to about 6%. Without surgical intervention the 5-year survival rate after local recurrence is approximately 4%, and the median survival time in a palliative situation is about 13 months and often associated with considerable restriction of quality of life. Morbidity after complex pelvic surgery is still high, but its mortality rate in highly professional surgical centers has reached an acceptable level of about 6%. Surgical oncology today has the ability for remarkable improvement in the prognosis of locally recurrent rectal cancer. After R0 resection the 5-year survival rate is nearly 30%.