Conserved proline residues prevent dimerization and aggregation in the ß-lactamase BlaC.

Evolution leads to conservation of amino acid residues in protein families. Conserved proline residues are usually considered to ensure the correct folding and to stabilize the three-dimensional structure. Surprisingly, proline residues that are highly conserved in class A ß-lactamases were found to tolerate various substitutions without large losses in enzyme activity. We investigated the roles of three conserved prolines at positions 107, 226, and 258 in the ß-lactamase BlaC from Mycobacterium tuberculosis and found that mutations can lead to dimerization of the enzyme and an overall less stable protein that is prone to aggregate over time. For the variant Pro107Thr, the crystal structure shows dimer formation resembling domain swapping. It is concluded that the proline substitutions loosen the structure, enhancing multimerization. Even though the enzyme does not lose its properties without the conserved proline residues, the prolines ensure the long-term structural integrity of the enzyme.

[Consultations by senior physicians in general and abdominal surgery for other medical disciplines over 10 years at a tertiary center-Is a fast time-consuming processing necessary? : Spectrum of clinical findings, diagnoses and treatment decision making]. / Allgemein- und viszeralchirurgische Oberarztkonsile für andere medizinische Disziplinen über 10 Jahre an einem tertiären Zentrum ­ ist eine schnelle, zeitaufwendige Abarbeitung notwendig? : Klinisches Befund­, Diagnose- und therapeutisches Entscheidungsspektrum.

BACKGROUND: The challenges of an adequate, efficient and rational medical treatment and care of patients are always associated with an interprofessional activity of several specialist disciplines. AIM: The spectrum of variable diagnoses and the profile of surgical decision-making with further surgical measures within the framework of senior physician consultation in general and visceral surgery for neighboring medical disciplines were analyzed on a representative patient cohort over a defined observational time period. PATIENTS AND METHODS: All consecutive patients (n = 549 cases) were documented as part of a clinical systematic prospective single center observational study at a tertiary center using a computer-based patient registry over 10 years (1 October 2006-30 September 2016). The data were analyzed with respect to the spectrum of clinical findings, diagnoses, treatment decisions and the influencing factors as well as gender and age differences and time-dependent developmental trends using χ2-tests and U­tests. RESULTS (KEY POINTS): The predominant discipline for requests for surgical consultation was cardiology (19.9%) followed by surgical disciplines (11.8%) and gastroenterology (11.3%). Disorders of wound healing (7.1%) and acute abdomen (7.1%) were predominant in the diagnostic profile. In 11.7% of the patients the indications for immediate surgery were derived, whereas in 12.9% elective surgery was recommended. The conformity rate of suspected and definitive diagnoses was only 58.4%. CONCLUSION: The surgical consultation work is an important mainstay of a sufficient and especially timely clarification of surgically relevant questions in nearly all medical institutions and especially in a center. This serves i) the quality assurance of surgery in the clinical care of patients with need of additional interdisciplinary needs for surgical treatment in the daily practice of general and abdominal surgery in research on clinical care, ii) clinical marketing and monetary aspects in the sense of patient recruitment and iii) last but not least to provide emergency care of patients. Due to the high proportion of 12% of subsequent emergency operations, which were derived from requests for general and visceral surgical consultations, such requests must be processed promptly during working hours.

Robotic and laparoscopic liver resection-comparative experiences at a high-volume German academic center.

PURPOSE: Minimally invasive liver surgery (MILS) is a feasible and safe procedure for benign and malignant tumors. There has been an ongoing debate on whether conventional laparoscopic liver resection (LLR) or robotic liver resection (RLR) is superior and if one approach should be favored over the other. We started using LLR in 2010, and introduced RLR in 2013. In the present paper, we report on our experiences with these two techniques as early adopters in Germany. METHODS: The data of patients who underwent MILS between 2010 and 2020 were collected prospectively in the Magdeburg Registry for Minimally Invasive Liver Surgery (MD-MILS). A retrospective analysis was performed regarding patient demographics, tumor characteristics, and perioperative parameters. RESULTS: We identified 155 patients fulfilling the inclusion criteria. Of these, 111 (71.6%) underwent LLR and 44 (29.4%) received RLR. After excluding cystic lesions, 113 cases were used for the analysis of perioperative parameters. Resected specimens were significantly bigger in the RLR vs. the LLR group (405 g vs. 169 g, p = 0.002); in addition, the tumor diameter was significantly larger in the RLR vs. the LLR group (5.6 cm vs. 3.7 cm, p = 0.001). Hence, the amount of major liver resections (three or more segments) was significantly higher in the RLR vs. the LLR group (39.0% vs. 16.7%, p = 0.005). The mean operative time was significantly longer in the RLR vs. the LLR group (331 min vs. 181 min, p = 0.0001). The postoperative hospital stay was significantly longer in the RLR vs. the LLR group (13.4 vs. LLR 8.7 days, p = 0.03). The R0 resection rate for solid tumors was higher in the RLR vs. the LLR group but without statistical significance (93.8% vs. 87.9%, p = 0.48). The postoperative morbidity ≥ Clavien-Dindo grade 3 was 5.6% in the LLR vs. 17.1% in the RLR group (p = 0.1). No patient died in the RLR but two patients (2.8%) died in the LLR group, 30 and 90 days after surgery (p = 0.53). CONCLUSION: Minimally invasive liver surgery is safe and feasible. Robotic and laparoscopic liver surgery shows similar and adequate perioperative oncological results for selected patients. RLR might be advantageous for more advanced and technically challenging procedures.

Oncological outcome after hyperthermic isolated limb perfusion for primarily unresectable versus locally recurrent soft tissue sarcoma of extremities.

INTRODUCTION: The management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP. PATIENTS AND METHODS: Data about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed. RESULTS: The cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13-142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events. DISCUSSION: ILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.

A falciform ligament flap surface sealing technique for laparoscopic and robotic-assisted liver surgery.

Whether sealing the hepatic resection surface after liver surgery decreases morbidity is still unclear. Nevertheless, various methods and materials are currently in use for this procedure. Here, we describe our experience with a simple technique using a mobilized falciform ligament flap in minimally invasive liver surgery (MILS). We retrospectively analyzed the charts from 46 patients who received minor MILS between 2011 and 2019 from the same surgical team in a university hospital setting in Germany. Twenty-four patients underwent laparoscopic liver resection, and 22 patients received robotic-assisted liver resection. Sixteen patients in the laparoscopic group and fourteen in the robotic group received a falciform ligament flap (FLF) to cover the resection surface after liver surgery. Our cohort was thus divided into two groups: laparoscopic and robotic patients with (MILS + FLF) and without an FLF (MILS-FLF). Twenty-eight patients (60.9%) in our cohort were male. The overall mean age was 56.8 years (SD 16.8). The mean operating time was 249 min in the MILS + FLF group vs. 235 min in the MILS-FLF group (p = 0.682). The mean blood loss was 301 ml in the MILS + FLF group vs. 318 ml in the MILS-FLF group (p = 0.859). Overall morbidity was 3.3% in the MILS + FLF group vs. 18.8% in the MILS-FLF group (p = 0.114). One patient in the MILS-FLF group (overall 2.2%), who underwent robotic liver surgery, developed bile leakage, but this did not occur in the MILS + FLF group. Covering the resection surface of the liver after minor minimally invasive liver resection with an FLF is a simple and cost-effective technique that does not prolong surgical time or negatively affect other perioperative parameters. In fact, it is a safe add-on step during MILS that may reduce postoperative morbidity. Further studies with larger cohorts will be needed to substantiate our proof of concept and results.

Mesothelial cyst of the round ligament.

Mesothelial cyst of the round ligament is a rare finding in females, with only a few cases reported so far. A case of a 25 year old female patient presenting with a palpable mass in her right inguinal region is presented. The preoperative investigation through ultrasound (U/S), computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of an intraabdominal cystic lobular mass in the inguinal canal, in contact with the femoral vessels. The mass was excised and the diagnosis of a benign mesothelial cyst was made through pathological examination. Even though it is a rare condition, it is advisable that clinicians consider in the differential diagnosis when evaluating a non-reducible mass in the inguinal region of a female patient.

[Robotic-Assisted Liver Surgery]. / Roboterassistierte Leberchirurgie.

BACKGROUND: The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of ≤ 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria. RESULTS: Malignant liver tumours were removed in 10 patients (71%) and benign symptomatic liver tumors in 3 patients (21%), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7%) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21%) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14%). One patient (7%) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively. CONCLUSION: Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.

[Surgery for metastases, anatomical and ethical limits. Special aspect: oligometastases]. / Metastasenchirurgie - anatomische und ethische Grenzen. Besonderer Aspekt: Oligometastasierung.

The surgical resection of metastases is nowadays feasible in selected patients with multifocal metastatic disease due to the implementation of interdisciplinary multimodal therapeutic options. Anatomical limitations do not seem to represent obstacles which cannot be overcome because of the development of new surgical techniques. The cornerstone of the selection of patients is the correct staging diagnosis achieved through modern diagnostic tools; however, surgery alone does not always offer acceptable survival and recurrence-free rates. Furthermore, in every complex surgical procedure there is the risk of morbidity and mortality; therefore, parameters such as alternative therapeutic modalities, the individual situation of the patient and tumor biology have to be considered in order to make the correct selection of patients. This is one of the major future challenges and should never be driven by unfounded hopes and expectations of the patients. The same principle also applies for brain metastases, which represent the most common brain tumors. Approximately 70 % of patients with brain metastases have 1-3 lesions (oligometastases). Treatment is now individualized and the goal of therapy has shifted towards long-term survival (≥ 24 months) and improved quality of life. Under this aspect surgery is one of the important treatment options, particularly in patients with a single metastasis or oligometastases. Furthermore, approximately 20 % of patients who have recurrent brain metastases, successfully undergo a complete resection of tumors and with a Karnofsky performance status (KPS) score > 70 show a long-term survival of ≥ 24 months.

[Results of surgical treatment of hiatal hernia]. / Ergebnisse der operativen Therapie großer Hiatushernien.

BACKGROUND: Hiatus hernias are considered as the most prominent form of diaphragmatic hernias. The passage is defined through the oesophageal hiatus, resulting in a superdiaphragmatic displacement of parts of the stomach or the complete stomach, respectively. In our work we investigated the treatment of partial thoracic stomach with both open and minimally invasive surgical procedures emphasising the view on operating data, the success of the surgery and recurrence rates. Patients with mesh insertion for hernia defect closures were considered separately. MATERIAL AND METHOD: 94 Patients were treated in the period from 01.01.2003 to 01.06.2010. The ratio male/female was 2 : 1. The median age was 66 years. All data were prospectively collected by means of surgical protocols and data from the central patient records and analysed retrospectively. The statistical analyses were performed with SPSS 18.0 (SPSS Inc., Chicago, IL, USA). Any existing significances were determined using the T-test. RESULTS: Of the 94 patients, 65 were operated laparoscopically. In the case of nine patients an initial laparoscopic surgery had to be changed to an open procedure. The reasons for switching surgical procedures were splenic bleeding in the case of 2 patients, intestinal injury due to perforation by the trocar in one case and unclear surgical situs in 6 cases. The postoperative complication rate was 24 %. The main reasons were a delayed achievement of passage. The mortality rate was 0 %. The comparison between laparoscopic and open groups showed, by comparable complication and recurrence rates, a shorter recovery time in favour of patients operated on laparoscopically. Additionally it can be stated that a bridge closure with mesh (ePTFE) had no significant influence on the postoperative outcome. Therefore we cannot confirm the postulated poor postoperative results of other groups. CONCLUSION: In summary, the clear trend in the surgical treatment of hiatus hernias is to minimally invasive surgery. Only for patients with multiple previous operations, who are expected to have strong adhesions, the operation with comparable morbidity and mortality rates can also be planned primarily as open. In this case, however, longer postoperative recovery times must be expected. Large defects can be treated with comparable complication and recurrence rates by mesh insertion (ePTFE).

Liver transplantation for hepatitis B-induced liver disease: long-term outcome and effectiveness of antiviral therapy for prevention of recurrent hepatitis B infection.

OBJECTIVE: The aim of this study was to examine the efficacy of preoperative, perioperative, and long-term treatment in liver transplant (OLT) patients suffering hepatitis B (HBV)-induced liver disease, in terms of graft and survivals as well as disease recurrence. MATERIALS AND METHODS: We reviewed the medical records of 19 HBV-infected patients who underwent OLT between 2000 and 2010 using antiviral treatment with either lamivudine (LAM, n = 14) and/or adefovir/entecavir/tenofovir (n = 8) before OLT. Fifteen subjects showed a HBV DNA-negative status prior to OLT. All patients were administered HBIG (antiHBs immunoglobulin) perioperatively: 10,000 international units (IU) in the anhepatic phase and 2.000 IU/d until day 7 after OLT. The preoperative antiviral regimen was continued as maintenance prophylaxis from day 1 after OLT. In cases of the YMMD mutation the antiviral treatment was switched to combination therapy with entecavir and tenofovir. RESULTS: Patient follow-up as of December 2011 or till time of death ranged from 6 to 129 months (median = 47). All patients were prescribed tacrolimus. None of them experienced HBV-related graft dysfunction or graft loss. All subjects were HBV DNA negative at 6 months after OLT. HBV recurrence in the post-OLT phase was discovered in 3 patients, 2 of whom had undergone OLT because of acute liver failure due to hepatitis B. They showed LAM-resistant mutations at the time of recurrence and underwent entecavir/tenofovir therapy to achieve HBV DNA negative status. CONCLUSIONS: Our study demonstrated excellent long-term outcomes among patients after successful preoperative antiviral treatment for HBV. Patients should be given a high dosage of HBIG during the first week after OLT in combination with the preoperatively established antiviral treatment. In presence of a LAM-resistance mutation, antiviral treatment should be adapted individually to achieve HBV recurrence freedom and graft survival.

Long-term outcome of liver transplantation as treatment modality in patients with hepatocellular carcinoma in cirrhosis: a single-center experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most frequent malignant diseases worldwide. In the vast majority of cases, it is associated with liver cirrhosis. Liver transplantation (OLT) is potentially the gold standard treatment for patients suffering HCC in cirrhosis, because of synchronous eradication of HCC and of the underlying hepatic disease. The aim of this study was to evaluate long-term outcomes of OLT in HCC patients. MATERIAL AND METHODS: Between January 2000 and December 2011, 43 patients who were diagnosed with HCC in liver cirrhosis and underwent OLT in our department, were identified from a prospective database. All patients received their grafts from deceased donors. We analyzed demographic data, laboratory values, number and size of lesions, primary liver disease, diagnostic methods, bridging therapy modalities, and postoperative outcomes, including complications, recurrences, and their treatment. RESULTS: Patient follow-up as of January 2012 or to death ranged from 0 to 138 months (median, 59; mean, 63). None of the patients were lost to follow-up. The gender bias was 85%:15% (male:female) and the median age, 57.8 years (range, 44-69). The most common underlying diseases for cirrhosis and HCC were alcoholic (n = 12) and hepatitis C (n = 16). Thirty-one subjects underwent bridging therapy through transarterial chemoembolization (TACE), and/or radiofrequency ablation. All patients underwent OLT within the Milan criteria according to the preoperative evaluation and histopathologic examination of the explanted liver. Twenty-one of them suffered postoperative complications (48.8%). HCC recurrence, which occurred in 5 (10.4%), was treated by surgery (n = 3), systemic chemotherapy with sorafenib (n = 1), or TACE (n = 1). CONCLUSIONS: OLT for HCC in cirrhosis, displays a relatively high complication rate. It shows good survivals with and low recurrence.

The diagnostic value of systolic acceleration time and resistive index as noninvasive modality for detection of graft rejection after orthotopic liver transplantation.

BACKGROUND: Acute cellular and chronic graft rejection are major disorders in the postoperative setting after orthotopic liver transplantation (OLT). An immediate diagnosis and successful therapy are essential for graft survival. We sought to determine whether quantitative and qualitative analysis of Doppler sonography data was predictive and sensitive as noninvasive diagnostic tools for rejection episodes. MATERIALS AND METHODS: We prospectively recorded and retrospectively analyzed the medical records of patients who underwent OLT between January 2000 and November 2011, identifying patients with acute cellular (ACR) and chronic rejection (CR) and the grade classified the activity index according to BANFF criteria. Analyzed parameters included resistive index (R/I), systolic acceleration time (SAT) in the hepatic artery, laboratory values, histopathologic grade and therapy as well as graft and patient survival. RESULTS: Patient follow-up as of December 2011 or to the time of death ranged from 2 to 132 months (median follow- up: 79 months, mean = 83 months). We registered 29 rejection episodes (ACR n = 20 and CR n = 9) in 20 subjects. The majority of patients received a tacrolimus-based immunsuppressive regimen (n = 14, trough level: 7-12 ng/mL) in addition to high-dose corticosteroids, and sometimes a third drug. One patient displayed a corticosteroid-resistant ACR and 4 CR cases, graft loss followed by retransplantation. R/I was calculated for all patients and SA for those who underwent OLT since 2009. As a control group we used subjects with delayed SAT and high R/I without graft rejection. In all patients with a high R/I (>0.7, range: 0.71-0.91) and in all patients who suffered graft rejection since 2009 (n = 14), we observed a delayed SAT (>0.08, range: 0.08-0.18). The sensitivity and specificity for R/I were 82%, and 54.9%; for SAT 100% and 78%, respectively. CONCLUSION: Delayed SAT (>0.08) and high R/I (>0.7) were sensitive indices of graft rejection episode. The limitation of these diagnostic parameters is their specificity, especially in the immediate postoperative period, where early vascular disorders trigger similar sonographic results. Nevertheless SAT and R/I may be considered to be important diagnostic tools, in combination with elevated laboratory liver values they can provide an early diagnosis of graft rejection.

Is there a disadvantage to radical lymph node dissection in colon cancer?

BACKGROUND: The necessity for radical lymph node dissection for solid tumours was discussed in the past controversially. The aim of this study was to correlate the oncologic results of radical surgery for colon cancer with potential complications. METHODS: A total of 1,453 patients with R0-resected colon cancer operated on between 1978 and 2004 were analysed in a prospective database. The follow-up was at least 5 years. Rates of survival, locoregional and distant recurrences and complications were calculated. RESULTS: To compare the oncological outcome, the time frame was divided into five periods. In the last cohort (2000-2004), we observed in stage I-III tumours a 5-year cancer-related survival rate of 90.1 %, compared to 82.1 % in the first cohort (1978-1984) (p = 0.061). The local recurrence rate could be reduced from 6.5 to 3.2 % in the same cohorts (p = 0.059). It reached the level of significance in the multivariate analysis. The rates of distant metastases did not change. For patients with stage III, the 5-year cancer survival rates increased from 62.0 to 81.8 % (p = 0.005). Morbidity and mortality were comparable to other studies even to those with limited lymph node dissections. CONCLUSION: Radical lymph node dissection in colon cancer is not associated with obvious disadvantages to the patient. Specific considerable side effects were not observed when the preparation is performed in embryonic planes preserving the autonomous nerves. The complication rates were not increased compared to other studies, even to those with limited lymphatic dissection. In addition, radical lymph node dissection in colon cancer may improve survival.

The value of pre-emptive therapy for cytomegalovirus after liver transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R-) casses. We investigated whether this strategy was safe and effective to prevent CMV disease. METHODS: One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL. RESULTS: Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R-) developed CMV infections significantly more often than D-/R- serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349). CONCLUSION: Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.

Spigel hernia: a single center experience in a rare hernia entity.

INTRODUCTION: Spigelian Hernia (SH) is a rare ventral hernia with a high incarceration and obstruction risk. The purpose of this study is to present our experience in diagnosis and treatment of this rare hernia entity. MATERIALS AND METHOD: Sixteen patients underwent surgery for SH between 2000 and 2010. Analysis parameters included demographic data, location of defect, diagnostic methods, mode of surgery, mode of anesthesia and postoperative outcome. RESULTS: Mean follow-up was 98 months. The gender bias was 37.5 %: 62.5 % (man: woman) with mean age of 56 years. The SH was right-sided in 56.25 %, left-sided in 37.5 % and bilateral in 6.25 % of the cases. The preoperative diagnosis was correct in 25 % of the cases. Eight patients (50 %) underwent elective surgery, and the other 8 patients (50 %) underwent surgical treatment on emergency basis. Two patients underwent open hernia repair by primary suture, 13 patients underwent open mesh repair and one patient underwent a laparoscopic mesh repair. Neither a major hernia repair-related complication nor mortality could be registered. CONCLUSION: SH is a rare entity with a wide clinical spectrum and difficulties in preoperative diagnosis. Once the diagnosis of SH is established, a surgical treatment is indicated because of the high complication risk.

Outcome of operative therapy of hepatic metastatic stomach carcinoma: a retrospective analysis.

BACKGROUND: In general, hepatic metastasis from stomach carcinoma has an unfavorable prognosis. In addition, there are often further metastases in other organs, such as peritoneal carcinomatosis. The major aim of the present study was to investigate a potential curative surgical approach in these patients. MATERIAL AND METHODS: Thirty-one patients with hepatic metastases from stomach cancer were treated in the University Clinic Erlangen-Nürnberg. The data were collected retrospectively from 1972 to 1977 and prospectively since 1978 at the Erlangen Cancer Registry. The time frame of this retrospective analysis from patients who had surgical resection of hepatic metatases from gastric cancer was from 1972 to 2008. The median age of the patients was 65 years, and the ratio of men to women was 2:1. RESULTS: Atypical or anatomical resections of segments were possible in 21 cases. Larger operations, such as hemihepatectomy (right/left), were performed in 10 patients. The postoperative complication rate was 29%, and the hospital mortality was 6%. The five-year survival rate was 13%; R0 resection was achieved in 23 patients. We also found a significant difference in the 5-year survival rate between synchronous and metachronous metastases (0 vs. 29%; p < 0.001) and R0 resected patients (p = 0.002). Patients with solitary metastases had a significantly better median survival than patients with multiple metastases (21 vs. 4 months; p < 0.005.) CONCLUSIONS: The overall survival in our study was 13%; therefore gastric cancer with liver metastases is not in every case a palliative situation. It seems that patients with liver metastases benefit from resection, especially if the metastases are metachronous (p < 0.001) and solitary, provided that a curative R0 resection has been achieved. An interdisciplinary approach with neoadjuvant chemotherapy appears useful. Additional controlled studies should be conducted.

Impact of the conversion of the immunosuppressive regimen from prograf to advagraf or to sirolimus in long-term stable liver transplant recipients: indications, safety, and outcome.

BACKGROUND: Compliance problems have arisen due to the twice a day administration of calcineurin inhibitors (CNI). We examined the safety, indications, and efficacy in terms of graft and patient survivals after conversion from tacrolimus to sirolimus or advagraf. PATIENTS AND METHODS: Between January 2006 and December 2009, 36 orthotopic liver transplantation patients underwent conversion of the immunosuppressive regimen from prograf to either sirolimus (group 1; n=10) or advagraf (group 2; n=26). A group of patients taking prograf was used as a control group (group 3; n=15). We identified 51 patients of mean age 57 years and male:female percentages of 57%:43% from a prospective database. Renal and liver graft functions, patient survival, as well as laboratory and clinical data over at least 12 months (mean, 38) were the investigated parameters. RESULTS: Patients converted to sirolimus did not show significantly improved renal function at 12 months as evidenced by creatinine levels (1.31 mg/dL+/-0.47 vs 1.34 mg/dL+/-0.78) and glomerular filtration rate (GFR, 57+/-16 vs 56+/-16 mL/min). However, there were significant antiproliferative effects. Patients with a hepatocellular carcinoma in the pretransplantation phase remained without a recurrence. The side effects including ankle edema, aphthae, and tachyarrhythmia absoluta, required reconversion to the CNI. Patients prescribed advagraf reported a better life quality because of the single administration and a slight, insignificant improvement in renal function. An acute rejection episode was evidenced under either immunosuppresant. CONCLUSION: Sirolimus is a safe immunosuppressive option in liver transplant recipients suffering from hepatocellular carcinoma. Advagraf showed a lower incidence of side effects than prograf and probably is not as harmful for renal function, offering better compliance and better life quality.

The effect and safety of the treatment of recurrent hepatitis C infection after orthotopic liver transplantation with pegylated interferon α2b and ribavirin.

INTRODUCTION: Recurrent hepatitis C infection in the posttransplant setting is a serious problem. The aim of this study was to evaluate the efficacy, safety, indications, optimal time of administration and adequate duration of antiviral therapy with pegylated interferon alpha 2 b (PEG-IFN) and ribavirin (RIB). PATIENTS AND METHODS: Between 2003 and 2009, 16 patients received antiviral therapy (PEG-IFN: 0.8-1.6 µg/kg/wk, RIB 800-1200 mg/d) for at least 6 months. Patients with a biochemical without a virologicalresponse after 12 months of therapy received antiviral treatment for a further 6 months. Hepatitis C virus load was determined at 1, 3, 6, and 12 months after start of therapy. Liver biopsy was performed in all patients before the beginning and after the end of treatment. RESULTS: The mean period of antiviral therapy was 14 months. The four patients who received the full-length treatment (12 months, 33%) showed sustained virological responses (SVR) and 8 showed virological and biochemical responses (VR, BR). Patients with SVR showed significant improvement in the grading and staging of HAI (histological activity index; P=.03). Nine patients had several side effects under antiviral treatment. Acute rejection episodes were not observed. CONCLUSION: The antiviral treatment combination using PEG-IFN and RIB for recurrent hepatitis C is effective procedure. The SVR of 33% after 12 months of treatment with significant improvement in HAI grading and staging and stable HAI in all treated patients favor early initiation and 12-month administration of antiviral treatment. Furthermore, all patients with BR without VR, who underwent antiviral treatment for a further 6 months, achieved a VR. However, the optimal duration of treatment needs to be investigated in large prospective studies.

Biliary tract complications after orthotopic liver transplantation: still the "Achilles heel"?

Postoperative biliary tract complications after liver transplantation (LT) still lead to early and late morbidity and mortality. Modern interventional endoscopic techniques can replace surgical repair as the first line of treatment. Nevertheless surgical intervention plays an important role in specific situations. We performed a retrospective analysis of patients with biliary complications after LT over a 12-year period. We compared treatment programs based on duration and success rate. The rate of biliary complications was 24.5% (60/245). The side-to-side choledocholedochostomy (CDC) technique showed the significantly lowest rate. The rate of complications after hepaticojejunostomy (HJS) was considerably lower, albeit not significantly. Eighty-one percent of complications after CDC were treated with interventional endoscopy. The duration of treatment of strictures, was 10 times greater than that of leakages. Surgical repair was necessary for 19% of complications occurring after CDC. The treatment options after HJS largely comprised surgical repairs. From a surgical standpoint, choosing the correct method for biliary reconstruction and ensuring normal arterial flow are the best preventive techniques to avoid biliary complications. Over the past 10 years, the primary treatment regimen has moved from surgical repair to interventional endoscopy. Only when endoscopy fails, should one consider surgical repair. The treatment after HJS is still primarily surgical. Percutaneous transhepatic approaches should be avoided. Creation of an inspection stoma to allow endoscopic access is an option.

Procalcitonin in the setting of complicated postoperative course after liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is a treatment for end-stage liver disease. The shortage of available organs leads to the acceptance of marginal grafts, thereby increasing the risk of perioperative complications such as acute rejection, infection, and graft dysfunction Procalcitonin (PCT) has been shown to be a reliable marker for a complicated course after traumatic injury as well as in the courses of systemic inflammatory response syndrome and sepsis. The aim of our study was to evaluate PCT as an early prognostic marker for the occurrence of complication during the postoperative course after OLT. METHOD: We analyzed PCT levels and clinical and paraclinical data of 32 patients who underwent 33 OLTs. The highest PCT was termed as peak-PCT. Patients were stratified into noncomplication and complication groups. Renal replacement therapy, respiratory insufficiency, postoperative bleeding, refractory ascites, pleural effusion, rejection, sepsis, and fatal outcome were defined as complications. A secondary stratification, using a peak-PCT of 5 ng/mL, was used to analyzed the risk of a complication. We also analyzed the course of PCT after OLT in each group. RESULTS: The peak-PCT, which occurred between the first and third postoperative day in 30 patients, was followed by halving of the value every second day. Three subjects died because of sepsis. A constantly rising PCT or a secondary rise observed in 2 patients was associated with a fatal outcome. The noncomplication group included 18 patients, 8 of them showing a peakPCT <5 ng/mL and 10 above. The complication group included 14 patients who underwent 15 transplantations; Only 1 displayed a peakPCT <5 ng/mL. When the peak-PCT was >5 ng/mL, the odds ratio of a complication was 11.2 (95% Confidence interval, 10.81-11.59; P < .025). However, not before the 7th postoperative day was the course of mean PCT levels significantly different between the complication and noncomplication groups. In transplant patients, an elevation of PCT was observed only in the presence of bacterial infection and not rejection or wound infection. PCT rose during respiratory failure and sepsis, but not renal replacement therapy, ascites, pleural effusion, rejection, or bleeding. CONCLUSION: PCT was a reliable marker. A decline was observed in 31 cases with subject, who both had fatal outcomes showing a constantly rising level. An initial high PCT indicated a poor prognosis; some members of the noncomplication group also had levels >15 ng/mL. The patients in the complication group showed a higher mean PCT, which was significant at 7 days, most probably because of the high variation among levels. Still, a peak-PCT >5 ng/mL showed an odds ratio of 11.2 for patients to experience a complication.