Long-term Recurrence-free Survival Research Articles

PD-0004 Perioperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer; A Multicenter, Single Arm Phase I/II Trial: Asso Lm1

ABSTRACT Introduction Patients with colorectal cancer (CRC) and liver metastases may benefit from pre- and postoperative chemotherapy and disease resection. Best treatment sequence, length and combination still needs to be determined. We evaluated Bevacizumab and XELOX in a multicenter approach. Resectabilty was the primary endpoint, periOP morbidity, response rate, recurrence-free and overall survival the secondary end points. Methods Patients with liver metastases from CRC potentially curable by resection were eligible for this trial. Patients received Bevacizumab 5mg/kg (day 1), oxaliplatin 85mg/m2 (day 1) and Capecitabine 3000mg/m2/day (days 1–7) of a 2-week cycle for six cycles. The sixth cycle did not include Bevacizumab, resulting in 5 weeks between the last Bevacizumab dose and surgery. Therapy with Bevacizumab plus XELOX was restarted 5 weeks after surgery for another six cycles. Response rates were assessed by the PIs and after central review, pathological response was assessed centrally according to Rubbia-Brandt. Results 43 patients (pts) with a median age of 66 years (38-80) were enrolled into this multicenter trial. 78% of these pts had synchronous disease, 51% of these started treatment without primary tumor resection. The median number of metastases was 2 (1-10) and median Fong score was 3 (0-4). In total of 8 pts were ineligible for resection, 1 due to PD, 7 due to protocol violation or personal reason. Resectability of operated patients was 97% with 34 R0 resections and one R1 resection. Postoperative morbidity occurred in 22% of the pts, 3 operative revisions were related to the primary tumor resection. Efficacy results for response in 38 eligible patients confirm an ORR of 66%, 31% SD and 3% PD according to RECIST. Preoperative grade 3/4 adverse events were 17% diarrhea, 5% HFS, 2% neuropathy and 5% thromboembolic events. Histological assessment of resected metastases revealed a major histological response in 56%, a partial histological response in 28%, and no histological response in 16%. Recurrence-free (RFS) and overall survival (OS) significantly differed dependent upon the fulfillment of the adjuvant treatment cycles in curative resected patients (24 pts completed periOP CTx vs 10 pts neoCTx only): median RFS was 26.2 months in patients receiving postsurgical Bev + Xelox vs. 7.4 months in those without postOP therapy (p Conclusion These data demonstrate that Bevacizumab and XELOX provide substantial response rates with well-known adverse events in this potentially curative mCRC setting. In patients eligible for resection after 3 months of neoadjuvant therapy perioperative morbidity is not increased compared to studies without Bevacizumab. Long-term recurrence-free and overall survival was significantly prolonged in our study in patients receiving postoperative chemotherapy plus Bevacizumab.

術後7年無再発生存中の紡錘細胞型退形成性膵管癌の1例

症例は63歳男性で，心窩部痛と黄疸を主訴に発症した．膵鈎頭部に2.5 cm大の乏血性腫瘤を認め, 膵鈎頭部癌の診断で膵頭十二指腸切除術を施行．病理組織学的検査の結果，紡錘細胞型退形成性膵管癌（anaplastic ductal carcinoma of the pancreas；以下，ADCと略記）と診断された．補助化学療法は施行せず，術後7年無再発生存中である．ADCは浸潤性膵管癌の一亜型であり，まれで予後不良な腫瘍である．その細胞形態から紡錘細胞型を含め4型に分類されるが，これまでに紡錘細胞型における長期生存例の報告はない．ADC本邦報告例に自験例を加えた検討を行い，報告する．

Patients with non-[18F]fludeoxyglucose-avid advanced hepatocellular carcinoma on clinical staging may achieve long-term recurrence-free survival after liver transplantation

There is increasing evidence that a relevant number of patients with hepatocellular carcinoma (HCC) exceeding the Milan criteria may benefit from liver transplantation (LT). We retrospectively analyzed the prognostic significance of [(18) F]fludeoxyglucose ([(18) F]FDG) positron emission tomography (PET) for identifying appropriate LT candidates with advanced HCC on clinical staging. Between 1995 and 2008, 111 patients with HCC were listed for LT. All underwent a pretransplant PET evaluation. LT was performed for 91 of these patients. The tumor recurrence rate after LT was 3.6% for patients with non-[(18) F]FDG-avid (PET(-) ) tumors, but it was 54.3% for patients with [(18) F]FDG-avid (PET(+) ) tumors (P < 0.001). The 5-year recurrence-free survival rates were comparable for patients with tumors meeting the Milan criteria (86.2%) and patients with PET(-) HCC exceeding the Milan criteria (81%) at LT, but these rates were significantly higher than the rate for liver recipients with [(18) F]FDG-avid advanced HCC (21%, P = 0.002). In a multivariate analysis, negative PET findings (odds ratio = 21.6, P < 0.001), an alpha-fetoprotein level <400 IU/mL (odds ratio = 3.3, P = 0.013), and a total tumor diameter <10 cm (odds ratio = 3.0, P = 0.022) were identified as pretransplant prognostic variables for recurrence-free survival. A PET(+) status was assessed as the only independent clinical predictor of tumor-related patient dropout from the waiting list (hazard ratio = 5.7, P = 0.01). Patients with non-[(18) F]FDG-avid HCC beyond the Milan criteria according to clinical staging may achieve excellent long-term recurrence-free survival after LT.

Fish oil attenuates surgery-induced immunosuppression, limits post-operative metastatic dissemination and increases long-term recurrence-free survival in rodents inoculated with cancer cells

Omega-3 fatty acids (ω-3FA) attenuate postoperative immunosuppression vis-à-vis infection. Since immune-surveillance targets metastasizing cancer cells, we assessed the effect of ω-3FA consumption on 1) early post-operative Natural Killer cell (NK) cytotoxicity and metastases and 2) long-term recurrence-free survival, in two rodent models of surgery-promoted metastases. C57BL/6J mice were fed standard, ω-3FA-enriched, or ω-6FA-enriched chow, beginning one week before subcutaneous footpad implantation of syngeneic melanoma cells. When tumors reached the volume of 110μl, the tumor-bearing footpad was amputated, and long-term recurrence-free survival was assessed. Also, F344 rats were fed ω-3FA or ω-6FA for a month before undergoing or not undergoing laparotomy, and were intravenously inoculated with radio-labeled syngeneic adenocarcinoma cells. Marginating-pulmonary (MP)-leukocytes were harvested, and lung tumor retention (LTR) of metastases was assessed. ω-3FA consumption did not affect the growth of footpad tumors, but significantly enhanced post-amputation recurrence-free survival in mice. Surgery had a deleterious effect on NK cell activity and LTR whereas ω-3FA had large beneficial effects in non-operated rats and an even greater impact in operated rats. ω-3FA feeding attenuates or even overcomes postoperative NK cell suppression, increases resistance to experimental and spontaneous metastasis, and enhances recurrence-free survival following excision of metastasizing primary tumors. These findings warrant clinical studies of ω-3FA-based nutrition in patients undergoing resection of a primary tumor.

Frühes Ösophaguskarzinom: Pro chirurgische Resektion

Endoscopic methods are increasingly propagated as oncologically adequate and less invasive treatment modalities for early esophageal cancer compared to surgery. The superiority or equality of endoscopic treatment has, however, so far not been proven by controlled trials. Current guidelines and an analysis of recently published data support surgical resection and lymphadenectomy as the standard of care for early esophageal cancer. This is based on the following arguments: 1) a reliable complete tumor resection with clear margins in all directions (R0 resection) including removal of all precancerous and precursor lesions can currently only be achieved by surgical resection, 2) none of the currently available staging tools allows definitive exclusion of lymphatic spread. A potentially curative surgical lymphadenectomy should thus only be omitted in well-defined subgroups. 3) In experienced hands surgical resection and lymphadenectomy can be performed with low mortality and morbidity, 4) reproducible and reliable data on long-term recurrence-free survival and quality of life are currently only available for surgical series. Thus, endoscopic therapy for early esophageal cancer is an alternative to surgical resection with lymphadenectomy only in patients unfit for surgery and in strictly defined low-risk situations.

Long-term Outcomes After Percutaneous Radiofrequency Ablation for Renal Cell Carcinoma

To assess the long-term oncological efficacy of radiofrequency ablation (RFA) for treatment of renal cell carcinoma (RCC). In this institutional review board-approved, retrospective study, the records and imaging studies for all RCC patients treated with percutaneous RFA before 2005 were reviewed and analyzed. A total of 48 RCCs in 41 patients were treated with RFA. Median size of RCC treated was 2.6 cm (range: 0.7-8.2 cm). Of the 48 treated RCCs, 5 (12%) had recurrent tumor after a single ablation session. The median size of the index lesion in the cases with recurrence was 5.2 cm (interquartile range [IQR]: 4-5.3) compared with 2.2 cm (IQR: 1.7-3.1, P = .0014) without local recurrence. There were no recurrences when RCCs less than 4 cm were treated. Seventeen (41%) patients with 18 treated RCCs died during the follow-up period at a median time of 34 (IQR: 10-47) months. One patient (2%) died of metastatic RCC, whereas 16 died of unrelated causes. Twenty-four patients with 30 RCCs treated with RFA survived. For the remaining 30 RCCs, median follow up was 61 months (IQR: 54-68). No patients in this group of survivors had metastatic RCC, 1 had recurrence diagnosed at 68 months. The long-term recurrence-free survival rate was 88% after RFA. RFA can result in durable oncological control for RCCs less than 4 cm. RFA is an effective treatment option for patients with RCCs less than 4 cm who are poor surgical candidates. For patients with larger RCCs alternative treatments should be considered.

Improving Postoperative Immune Status and Resistance to Cancer Metastasis

Surgical procedures, including primary tumor resection, have been suggested to suppress immune competence and to promote postoperative infections and cancer metastasis. Catecholamines and prostaglandins were recently implicated in these processes, and in directly promoting tumor angiogenesis and invasion. To examine the integration of 2 complementary approaches to reduce postoperative immunosuppression and metastatic progression: (1) perioperative immunostimulation with CpG-C and (2) pharmacological blockade of the tumor-promoting and immunosuppressing effects of catecholamines and prostaglandins, using propranolol (P) and etodolac (E), respectively. F344 rats were treated before surgery with CpG-C, P+E, both interventions, or vehicles, and were intravenously inoculated with syngeneic MADB106 mammary adenocarcinoma cells. Blood was withdrawn, marginating-pulmonary leukocytes were harvested, and NK activity and lung MADB106 tumor retention were assessed. In addition, C57BL/6 mice were implanted with syngeneic B16F10.9 melanoma cells. When tumors reached 100 mm, mice were treated with CpG-C/vehicle, and 24 hours later the tumor was excised along with P+E/vehicle treatment. Recurrence-free survival was monitored thereafter. Each of the regimens alone, CpG-C or P+E, showed improvement in most indices examined, including improved long-term recurrence-free survival rates. Most importantly, the combined treatment yielded additive or synergistic effects, further improving tumor clearance from the lungs and enhancing NK numbers and cytotoxicity via different, but complimentary, mechanisms. Treatment aimed at perioperative enhancement of CMI and simultaneous inhibition of excessive catecholamine and prostaglandin responses, employing CpG-C, propranolol, and etodolac, could be successful in limiting postoperative immunosuppression and metastatic progression, more so than each treatment alone.

Long-term recurrence-free survival in a patient with pancreatic carcinosarcoma: A case report with a literature review

Here, we presented a case of carcinosarcoma of the pancreas in a 53-year-old woman. The carcinosarcoma was in the head of pancreas. She underwent a pancreaticoduodenectomy. The tumor was grossly yellowish-whitish. Histologic evaluation of the tumor revealed 2 elements separated from each other. One component was conventional pancreatic ductal adenocarcinoma, and the other component showed sarcomatous growth pattern composed of pleomorphic spindle cells. Immunohistochemically, the adenocarcinoma component was reactive for antibodies to cytokeratin 18 and epithelial membrane antigen. The sarcomatous component was reactive for smooth muscle antibody. These findings led to a diagnosis of pancreatic carcinosarcoma. The patient was treated with gemcitabine, adriamycin, and cisplatin after the operation. Although previously reported patients with pancreatic carcinosarcoma showed a very poor outcome, this patient has remained free of recurrence for 20 months, which is the longest recurrence-free survival time recorded for this type of cancer. This treatment plan may be a feasible option.

Tumor control probability in radiation treatment

Patients undergoing radiation therapy (and their physicians alike) are concerned with the probability of cure (long-term recurrence-free survival, meaning the absence of a detectable or symptomatic tumor). This is not what current practice categorizes as "tumor control (TC);" instead, TC is taken to mean the extinction of clonogenic tumor cells at the end of treatment, a sufficient but not necessary condition for cure. In this review, we argue that TC thus defined has significant deficiencies. Most importantly, (1) it is an unobservable event and (2) elimination of all malignant clonogenic cells is, in some cases, unnecessary. In effect, within the existing biomedical paradigm, centered on the evolution of clonogenic malignant cells, full information about the long-term treatment outcome is contained in the distribution Pm(T) of the number of malignant cells m that remain clonogenic at the end of treatment and the birth and death rates of surviving tumor cells after treatment. Accordingly, plausible definitions of tumor control are invariably traceable to Pm(T). Many primary cancers, such as breast and prostate cancer, are not lethal per se; they kill through metastases. Therefore, an object of tumor control in such cases should be the prevention of metastatic spread of the disease. Our claim, accordingly, is that improvements in radiation therapy outcomes require a twofold approach: (a) Establish a link between survival time, where the events of interest are local recurrence or distant (metastatic) failure (cancer-free survival) or death (cancer-specific survival), and the distribution Pm(T) and (b) link Pm(T) to treatment planning (modality, total dose, and schedule of radiation) and tumor-specific parameters (initial number of clonogens, birth and spontaneous death rates during the treatment period, and parameters of the dose-response function). The biomedical, mathematical, and practical aspects of implementing this program are discussed.

Long-term recurrence-free survival in a patient with stage IVB uterine carcinosarcoma

Uterine carcinosarcomas are rare and highly aggressive tumors with a poor prognosis. Due to early metastasis and disease progression, it is known to be far more aggressive than matched grade 3 endometroid endometrial carcinomas. Five-year survival for stage IV is reported to be 10% and overall survival for stage IVB is expected to be very poor. The authors report one case after experiencing long-term survival (over 5 years) for stage IVB carcinosarcoma of uterus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed to 56 year old patient for uterine myoma. On pathology report, uterine carcinosarcoma was diagnosed and image studies were performed. With the impression of stage IVB uterine carcinosarcoma, 6 cycles of chemotherapy (ifosfamide and cisplatin) was conducted as adjuvant. Up to recently (over 5 years), she maintains good performance scale without evidence of tumor recurrence or disease progression.

A Case of Long-term Recurrence-free Survival after Resection of Colon Cancer and Chest Wall Metastasis

症例は66歳の女性で，1995年3月にRa直腸癌に対して低位前方切除を行い，同年5月に肝転移（S2，S3-4，S8）切除術を施行した．1999年2月に右前胸部の圧痛を自覚し，胸部CTで右前胸壁に石灰化を伴う腫瘍を認めた．穿刺細胞診で腺癌と診断され，摘出可能と判断したため1999年3月に摘出術を施行した．2000年5月には左肺転移（S10）に対して，手術を施行した．現在，原発巣切除から15年，胸壁転移切除から11年が経過したが，再発所見なく健在である．大腸癌胸壁転移の報告例は少ないが，切除により予後の改善が期待できるので，根治性が得られれば積極的に手術をすべきと考えられる．

Sustained low hepatitis B viral load predicts good outcome after curative resection in patients with hepatocellular carcinoma

Little is known about the role of hepatitis B virus (HBV) factors in the long-term prognosis of hepatocellular carcinoma (HCC) after resection. The objective of the present study was to identify the changing patterns of HBV levels and its effect on outcome after resection. This study recruited 188 patients with HBV-related HCC who underwent curative resection. Among the 188 patients, 115 were alive without recurrence at 12 months, and had serial measurements of viral levels. The mean age was 53 years and the mean follow-up period was 48.5 months. With multivariate analysis, tumor size > 5 cm (P = 0.047), Child-Pugh class B (P = 0.017), vascular invasion (P = 0.028), and HBV DNA > 10(4) copies/mL at the time of resection (P = 0.003) were independently predictive of HCC recurrence for the entire population. For the 115 patients with serial measurements of viral levels, tumor size > 5 cm, HBV DNA > 10(4) copies/mL at resection, and the absence of sustained HBV DNA level < 10(4) copies/mL, the presence of cirrhosis, and elevated aminotransferase levels (> 40 IU/L) were marginally or significantly associated with HCC recurrence and overall survival. However, on multivariate analysis, sustained HBV DNA level < 10(4) copies/mL was the only factor for both low recurrence (P = 0.002; odds ratio [OR] 3.13; 95% confidence interval [CI] 1.55-6.35) and longer survival (P = 0.002; OR 3.76; 95% CI 1.61-8.78). A high HBV replication state is among the most important predictors of adverse outcome after resection of HBV-related HCC. The sustained suppression of HBV below 10(4) copies/mL is a strong protective factor for long-term recurrence-free and overall survival.

Liver transplantation for T3 lesions has higher waiting list mortality but similar survival compared to T1 and T2 lesions

Background. Restrictive staging criteria for liver transplant (LT) patients with HCC in the U.S. have resulted in favorable long-term recurrence-free survival, but these criteria exclude a subgroup of patients who, despite tumor size beyond T2 stage, demonstrate an acceptable outcome. The aim of this study was to assess the waiting list and post-transplant mortality of patients with HCC tumors greater than Milan T2 stage.Methods. The U.S. OPTN standard transplant dataset was analyzed for patients with a diagnosis of HCC who were listed for liver transplantation between February 2002 and 2008. Those patients with Milan T3 stage tumors were compared to patients with T1 and T2 lesions. Multivariate survival models were developed to investigate independent predictors of death or tumor recurrence post-transplant.Results. 7,391 patients with HCC were identified. 351 (4.75%) had T3 lesions. Compared to non-T3 patients, total tumor burden was greater and total alpha-fetoprotein (AFP) was higher in the T3 patients. T3 patients also were more likely to receive pretransplant locoregional therapy. There were no significant differences between T3 patients and non-T3 patients in demographic variables or physiologic MELD score at the time of transplant, waiting time, or donor risk index. Waiting list mortality was increased for T3 patients compared to non-T3 and tumor progression while waiting was higher. Independent predictors of waiting list mortality included physiologic MELD score at the time of listing, total tumor burden, and serum AFP. There was significant regional variation in the utilization of exceptions for T3 patients and UNOS regions 4, 9, and 10 performed a higher percentage of their transplants in T3 patients compared to other regions. There was no difference in post transplant survival between T3 and non-T3 patients. Independent predictors of post-transplant mortality included physiologic MELD score at the time of transplant, recipient age, and donor risk index. In patients with T3 tumors, total tumor burden was not an independent predictor of post transplant survival.Conclusions. Patients who are listed for liver transplantation with Milan stage T3 HCC have higher waiting list mor-tality but have similar post-transplant survival compared to patients with T1 and T2 HCC.

Indications and Oncologic Outcome of Radical Cystectomy for Urothelial Bladder Cancer†

Abstract Context Radical cystectomy (RC) offers the best opportunity for ultimate cure of high-grade and high-risk invasive bladder cancer (BCa). Objective To review the available literature on indications for and oncologic outcomes of RC for urothelial carcinoma of the bladder. Evidence acquisition A database search of the US National Library of Medicine (PubMed) was performed for relevant medical articles using the Medical Subject Headings invasive bladder cancer and radical cystectomy with restrictions to English-language publications. Evidence synthesis Immediate or early RC should be offered as a treatment of choice to all patients with recurrent or multifocal high-grade T1 tumours, T1 tumours at high risk of progression, failures of bacillus Calmette-Guerin treatment, and muscle-invasive bladder tumours. RC offers excellent recurrence-free survival (RFS) and disease-specific survival rates as well as local tumour control in patients with organ-confined and node-negative disease. Tumour control in non–organ-confined tumours is still satisfactory, with long-term RFS rates of about 50%. For node-positive disease, surgery may only be curative in approximately one-fourth of patients. Conclusions Evidence from the literature supports early, aggressive surgical management for invasive BCa. Risk stratification of patients with BCa based on pathologic features at initial transurethral resection or at recurrence can select those patients most appropriate for RC early. In patients with organ-confined, lymph node–negative urothelial bladder carcinoma, excellent long-term survival rates can be achieved.

Phase 2 trial of primary systemic therapy with doxorubicin and docetaxel followed by surgery, radiotherapy, and adjuvant chemotherapy with cyclophosphamide, methotrexate, and 5‐fluorouracil based on clinical and pathologic response in patients with stage IIB to III breast cancer

This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross-resistant adjuvant chemotherapy. Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor-positive patients only). Eighty-eight patients were evaluable. Seventy-four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5-year recurrence-free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5-year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5-year OS rates were 82% for initially operable and 21% for initially inoperable patients (P < or = .001) Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long-term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS.

Beyond Milan criteria – chances and risks of expanding transplantation criteria for HCC patients with liver cirrhosis

Orthotopic liver transplantation (OLT) is, apart from resection, one important curative treatment for hepatocellular carcinoma (HCC) in liver cirrhosis, and especially attractive because it eliminates both the tumor and the underlying liver disease. The application of restrictive inclusion criteria for OLT in HCC patients resulted in favorable long-term recurrence-free survival. These criteria, however, exclude a subgroup of patients which, despite advanced tumor size, demonstrate an acceptable outcome. As a consequence, expansion of the strict Milan criteria has been discussed. However, this will also deteriorate the average outcome of OLT in HCC patients. Considering that we run short of donor organs, more sophisticated prediction models for survival after OLT for HCC patients are needed to identify patients who benefit best from OLT. Neoadjuvant treatment that is frequently applied as a bridging technique for patients on the waiting list for OLT could provide useful information on tumor behavior to better predict the risk of post-OLT tumor recurrence. This might also allow expansion of the Milan criteria to patients with good response to downstaging methods without negatively affecting post-OLT survival. Furthermore, alternative scoring systems have been suggested to identify HCC patients that might still benefit from resection instead of OLT, and molecular tools are being explored to provide predictive information on HCC biology. This review discusses the advantages and risks of extended inclusion criteria for OLT and the currently available data on alternative prediction models and bridging methods in HCC patients.

Long-term Recurrence-free Survival in a Patient with Primary Hepatic Carcinosarcoma: Case Report with a Literature Review

A 72-year-old man was found to have a 40 mm mass in liver segment VIII during follow-up abdominal ultrasonography for type C viral hepatitis. Abdominal ultrasound showed a well-defined mass containing a cystic component, and computed tomographic hepatic arteriography showed heterogeneous enhancement except for cystic necrosis. Under a pre-operative diagnosis of atypical hepatocellular carcinoma (HCC), partial resection of liver segment VIII was performed. The encapsulated tumor consisted of a peripheral solid component with a central necrotic area. Histologically, the solid component had a two-layer structure, an HCC component in the external area and a sarcomatous component with neoplastic osteoid formation in the internal area, showing histological transition. Immunohistochemically, the HCC component was positive for hepatocyte antigen and negative for vimentin. The Ki-67 labeling index was found to increase from 5% to 58% with increasing histologic atypia. The sarcomatous component was positive for vimentin and negative for pan-keratin and hepatocyte antigen, with a Ki-67 labeling index of >90%. These findings led to a diagnosis of primary hepatic carcinosarcoma. Although previously reported patients with hepatic carcinosarcoma showed early metastasis with a very poor outcome, this patient has remained free of recurrence for 30 months, which is the longest recurrence-free survival time recorded for this type of cancer. Since relatively early-stage hepatic carcinosarcoma rarely seems to present as a small tumor showing a concentric growth pattern, we report this case with a review of the literature.

Eight-Year Outcomes of Tricuspid Annuloplasty Using Autologous Pericardial Strip for Functional Tricuspid Regurgitation

Although several techniques of tricuspid annuloplasty have been used to treat tricuspid regurgitation (TR), TR can persist or recur with redilatation of the annulus or disease progression. We compared the long-term results of newly developed tricuspid annuloplasty procedure using autologous pericardial strip with that of conventional suture annuloplasty. From January 1997 to April 2006, 334 patients (mean age, 52.7 years) underwent tricuspid annuloplasty for functional TR. Concomitant procedures included mitral valve replacement in 261 patients and mitral-aortic valve replacement in 73. We performed conventional suture annuloplasty (De Vega or Kay) in 117 patients and autologous pericardial strip annuloplasty in 217 patients. There were 8 in-hospital deaths (mortality, 2.4%). Mean follow-up was 42.1 months, and total follow-up duration was 1,145 patient-years. Significant TR before discharge was noted in 34 patients (11.1%). The severity of TR improved with time in the autologous pericardial strip annuloplasty group; however, it became worse in conventional suture annuloplasty group (p = 0.05). Multivariate analysis demonstrated that preoperative severity of TR and conventional suture annuloplasty were significant predictors of recurrent TR. Overall survival was comparable between two groups (p = 0.742); however, recurrence-free survival was better for the autologous pericardial strip annuloplasty group than for the conventional suture annuloplasty group (86.8% versus 71.9%; p = 0.039). The long-term recurrence-free survival after autologous pericardial strip annuloplasty appeared to be better than that of conventional suture annuloplasty. Autologous pericardial strip annuloplasty appears to be a simple, easily reproducible, and valid option for surgical treatment of functional TR.

Der solid pseudopapilläre Pankreastumor (SPT) – eine seltene Raumforderung der Bauchspeicheldrüse

In general, the rare SPT is a tumour of low malignancy predominantly affecting young women. The outcome after radical resection is favourable. In exceptional cases the tumour presents as solid pseudopapillary carcinoma (SPC) with typical malignant features and even metastases. Unresectable liver metastases can be treated with RFA, TACE or chemotherapy. We retrospectively reviewed the surgical approach, immunohistochemistry and clinical outcome in five female patients (1998--2007). The mean age was 16 years (range: 13-47 years). For radical tumour removal a pancreato-duodenectomy (n = 3), a distal pancreatectomy (n = 1) and an enucleation (n = 1) were performed. We encountered a mean tumour diameter of 8 cm (range: 6-15 cm), an angioinvasion (3/5) and a lymphatic infiltration (1/5). After 30 to 101 months follow-up four patients were free of recurrence. Chemotherapy has resulted in a survival of over 98 months in a case of SPC with liver metastases. SPT is a tumour of low malignancy. Radical resection is recommended for long-term recurrence-free survival. Chemotherapy may prolong survival in SPC with unresectable metastases.

Current approach to down-staging of hepatocellular carcinoma prior to liver transplantation

Orthotopic liver transplantation is currently the best curative treatment for hepatocellular carcinoma within conventional Milan criteria. Recent data have suggested that modest expansion of tumor size limits could still preserve acceptable long-term recurrence-free survival. Down-staging of hepatocellular carcinoma initially exceeding conventional criteria for transplantation provides a unique perspective on tumor biology in that those with more favorable tumor biology are more likely to be successfully down-staged and do well after transplantation. This article reviews the principles and published data on down-staging of hepatocellular carcinoma prior to orthotopic liver transplantation. Several groups have examined the use of loco-regional therapy such as chemoembolization and radiofrequency ablation for tumor down-staging before Orthotopic liver transplantation. According to the latest results from the University of California, San Francisco involving 61 patients with hepatocellular carcinoma exceeding Milan criteria but meeting specific criteria for tumor size and number, 70% were successfully down-staged to within Milan criteria by an intention-to-treat analysis, with no posttransplant recurrence and a 4-year posttransplant survival of 92%. Strictly defined upper limits of tumor size and number for patient inclusion, as well as criteria for response to loco-regional therapy, are essential in achieving excellent posttransplant outcome following tumor down-staging.