Conversion to Rapamycin Immunosuppression for Malignancy After Kidney Transplantation

Introduction

Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro.

Methods

Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6).

Results

Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up.

Conclusion

Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.     

Ductal prostate cancer: contemporary management and outcomes

OBJECTIVES: To evaluate contemporary management and outcomes of ductal prostate cancer (PCA). MATERIALS AND METHODS: We reviewed all patients with ductal PCA and at least 6 months of follow-up seen at UTMB from 1990 to 2005, which comprised 17 patients (mean age: 67.7 years, range 55-87). At time of diagnosis, 11 patients had localized disease (Group 1) and 6 patients had distant metastasis (Group 2). RESULTS: Treatment of Group 1 patients included radiation and endocrine treatment for at least 2 years (n = 7), radiation alone (n = 2), and radical surgery (n = 2). At a mean follow-up of 3.6 years (r = 1-12 years) 8 patients (67.7%) remained free of recurrence, 1 patient had biochemical recurrence alone, 1 patient had recurrence in the anterior urethra, and the other had progression with metastasis to the brain and subsequent death. In addition to metastasis to regional/distant lymph nodes and bone in Group 2, metastatic sites included brain (n = 1), peritoneum (n = 1), and lung (n = 1). Mean follow-up was 2.3 years (r = 8 months to 4 years). All patients received androgen deprivation. One patient had progression of disease despite lack of biochemical recurrence and is alive at 2.5 years. One patient died from other causes while the 4 remaining patients are in remission at last follow-up. CONCLUSIONS: Contemporary management of localized ductal PCA with radiation and endocrine therapy yields adequate disease-free survival. Metastatic sites include brain, lung, peritoneum, and anterior urethra, and most patients respond well to endocrine treatment.     

Measurement of chemoresistance markers in patients with stage III non-small cell lung cancer: a novel approach for patient selection

BACKGROUND: The long-term survival of patients with stage III non-small cell lung cancer treated with a combination of chemotherapy and radiation is 10% to 20%. Survival could potentially be increased and toxicity limited if one could identify patients most likely to respond to a particular treatment regimen. This project prospectively evaluated a panel of potential immunohistochemical markers of chemoresistance in a population of patients with pathology-confirmed stage III non-small cell lung cancer in order to determine the prognostic value of each marker in relation to response to chemotherapy or survival. METHODS: Immunohistochemical staining was performed on histologically positive mediastinal nodal specimens obtained from 59 patients (mean age, 62 years; range, 41 to 79 years) without evidence of distant metastatic disease treated with navelbine-based chemotherapy and external beam radiation therapy between 1996 and 2001. Included were markers for apoptosis (p53, bcl-2), drug efflux/degradation (MDR, GST-pi), growth factors (EGFr, Her2-neu), and mismatch repair (hMLH1, hMSH2). After chemotherapy, patients underwent radiologic evaluation for response measured by standard criteria. RESULTS: After a median 41 months of follow-up (range, 17 to 55 months), 43 patients had recurrent disease and 38 of these patients were dead of cancer (median cancer-free survival of 10 months and overall survival of 18 months). Patients who demonstrated a complete or partial response (n = 38) had a significantly improved survival (p = 0.002) compared with those with stable or progressive cancer (n = 21). Multivariable Cox step-wise regression analysis of marker expression associated overexpression of p53 and low expression of hMSH2 with poor treatment response and cancer death. CONCLUSIONS: These preliminary data suggest that marker expression may allow the separation of patients into low- and high-risk groups with respect to survival after combined navelbine-based chemotherapy and XRT. This could represent a novel method of selecting patients for a particular treatment regimen if these data are reproduced in a larger prospective trial.     

An open prospective pilot study on the use of rapamycin after penetrating high-risk keratoplasty

BACKGROUND: The purpose of this study was to prove efficacy and safety of systemic immunosuppression with rapamycin following penetrating high-risk keratoplasty. Rapamycin has shown its immunosuppressive potential in the rat keratoplasty model and is a component of several immunosuppressive protocols after solid organ transplantation. In this pilot study, we compared the efficacy and safety of rapamycin and mycophenolate mofetil (MMF). METHODS: Ten patients (group 1) undergoing high-risk keratoplasty were included in this study, receiving rapamycin as postoperative immunoprophylaxis. Rapamycin was administered orally once daily (blood trough level 4-10 ng/ml) for 6 months. Thereafter, it was tapered over 2 weeks. The control group (group 2) consisted of 24 patients who received 1000 mg MMF twice daily for 6 months. All of the patients received postoperative medication with fluocortolone 1 mg/kg/day (tapered over 3 weeks) and prednisolone acetate eyedrops 5 times per day (tapered over 5 months). RESULTS: Mean follow-up of all patients (n=34) was 739 days. No immune reaction was observed in groups 1 and 2 during the first 6 months under immunosuppression. Two immune reactions occurred in group 1, and five in group 2 within a 2-year follow-up. All of the immune reactions were reversible. The side effects observed in both groups were mostly reversible. CONCLUSIONS: Rapamycin and mycophenolate mofetil seem to be similarly efficacious in preventing immune reactions after high-risk keratoplasty, as long as they are administered. However, we observed a broad spectrum of side effects from rapamycin.     

Evidence of differential risk for posttransplantation malignancy based on pretransplantation cause in patients undergoing liver transplantation

Organ transplant recipients are considered to be at greater risk for developing malignancy because of the prolonged immunosuppression associated with organ grafting. The purpose of this study is to determine risk factors, clinical characteristics, and outcomes of de novo nonlymphoid malignancies after liver transplantation from a large single-center series. All patients undergoing liver transplantation at the King's College Hospital (London, UK) between January 1988 and December 1999 were analyzed retrospectively for the development of de novo malignancy in the posttransplantation period. Records were evaluated for age at diagnosis of malignancy, cause of liver disease, interval from transplantation to diagnosis of malignancy, predisposing factors for the development of cancer, immunosuppression regimen, treatment of malignancy, rejection episodes, and patient survival. Of 1,140 patients undergoing 1,271 liver transplantations, 30 patients (2.6%) developed de novo nonlymphoid malignancy after transplantation. Skin cancers were the most common (n = 13), followed by oropharyngeal carcinoma (n = 2), bladder carcinoma (n = 2), acute leukemia (n = 2), breast carcinoma (n = 2), and various other malignancies (n = 9). The mean time of presentation of the malignancy after transplantation was 45.1 ± 32 months (range, 6 to 133 months), and mean age at diagnosis of malignancy was 55 years (range, 34 to 71 years). The incidence of de novo malignancy was significantly greater in patients who underwent transplantation for alcoholic liver disease compared with other groups (P < .001). Although the incidence of de novo nonlymphoid malignancy after liver transplantation is low, patients who underwent transplantation for alcoholic cirrhosis appear to have an increased risk for developing posttransplantation malignancy. (Liver Transpl 2002;8:482-487.)     

Efficacy of a second course of immunosuppressive therapy in patients with membranous nephropathy and persistent or relapsing disease activity.

BACKGROUND: A single course of immunosuppressive treatment improves renal survival in patients with idiopathic membranous nephropathy (iMN) and renal insufficiency. However, not all patients respond and relapses occur within 5 years in 30% of patients. It is unknown if a second course of immunosuppressive therapy is effective in such patients. METHODS: We have prospectively studied and evaluated the clinical course in 15 patients (14 male, one female; age: 52+/-12 years) with iMN who have received a repeated course of immunosuppressive therapy because of deteriorating renal function associated with relapsing or persistent nephrotic syndrome. RESULTS: The first course of immunosuppression was started 8 months (range: 0-143 months) after renal biopsy and consisted of chlorambucil (n = 8) or cyclophosphamide (n = 7); the second course consisted of cyclophosphamide in all patients. The interval between the first and second course was 40 months (range: 7-112 months). Total follow-up was 110 months (range: 46-289 months). Renal function and proteinuria improved at least temporarily in all patients after the second course. During follow-up, an additional course of therapy was given in four patients. Status at the end of follow-up was complete remission (n = 2), partial remission (n = 8), persistent proteinuria (n = 3), end-stage renal disease (n = 1) and death (n = 1, due to cardiovascular disease while nephrotic). Renal survival was 86% at 5 and 10 years of follow-up. The repeated courses of immunosuppression have resulted in a gain of dialysis-free survival time of > or =93 months (range: 43-192 months). CONCLUSIONS: Our results indicate that patients with iMN who do not respond well or relapse after a first course of immunosuppressive therapy and have renal insufficiency should be offered a second course of immunosuppression. Such a strategy maintains renal function in the majority of patients.     

Immunosuppression withdrawal after auxiliary liver transplantation for acute liver failure

BACKGROUND: The potential for immunosuppression withdrawal is the rationale for auxiliary liver transplantation (AUX) in patients with acute liver failure (ALF). PATIENTS AND METHODS: Forty-four AUX were performed in 28 adults and 16 children with ALF secondary to seronegative hepatitis (n = 20; 45%), paracetamol hepatotoxicity (n = 14; 32%), acute viral hepatitis (hepatitis B virus [HBV] n = 3, Epstein-Barr virus n = 1; 9%), drug-induced hepatitis (n = 3; 7%), autoimmune hepatitis (n = 2; 5%), and mushroom poisoning (n = 1; 2%). All patients fulfilled the King's College Hospital transplant criteria for ALF. After partial hepatectomy, 38 patients received a segmental auxiliary graft and six, a whole auxiliary graft. Immunosuppression was based on calcineurin inhibitors and steroids. RESULTS: Thirty-four patients (77%) are alive after a median follow-up of 30 months (range 4 to 124). Eight adults and two children died of sepsis (n = 6; 14%) at a median interval of 30 days (range 2 to 66), intraoperative cardiac failure (n = 1), brain edema on postoperative day 8 (n = 1), sudden death on day 35 (n = 1), and multiple organ failure associated with HBV recurrence 4 years after transplantation (n = 1). Three patients underwent retransplantation for small-for-size graft syndrome with sepsis on postoperative day 15 (n = 1) and for ductopenic rejection 4 and 15 months after AUX (n = 2). In 10/31 (32%) survivors (6/18 adults and 4/13 children) immunosuppression was completely withdrawn after a median of 19 months. CONCLUSION: Complete immunosuppression withdrawal can be achieved in a significant proportion of patients after AUX for ALF.     

Intermittent androgen suppression in the treatment of metastatic prostate cancer

BACKGROUND: To assess the feasibility of intermittent androgen suppression in patients with metastatic prostate cancer and to quantify the improvement in the quality of life. METHODS: Forty-three patients with M1 b prostate cancer were treated by intermittent hormonal deprivation using luteinizing hormone-releasing hormone (LHRH) analogue alone (n = 11), or associated with an antiandrogen (n = 32). The prospective nonrandomized study required an initial therapy period of 12 months with a stable biological response during 6 months (PSA, testosterone). Treatment was resumed when the serum PSA value recovered to 20 ng/ml, or when local failure or new bone metastasis occurred. The assessment of quality of life was carried out using the EORTC QLQ-C30. RESULTS: The mean follow-up time was 43.7 months. After the initial 12 months of androgen suppression, one patient with a minimal disease was off-therapy with a follow-up of 18 months. For the 42 other patients, the mean off-therapy period was 6.7 months. In the second therapy period (9-12 months), 7 patients were hormono-independent and died with a mean survival time of 27 months; 35 patients were responders. The mean off-therapy length in the second cycle was short (3.8 months). After this time, androgen suppression therapy was reintroduced permanently, but 10 patients were hormono-independent. No difference was observed in the EORTC QLQ-C30 between therapy and off-therapy periods, only a rapid decrease in adverse events due to the hormonal deprivation was reported in all cases during the off-therapy period. CONCLUSIONS: Intermittent androgen suppression in patients with M1 b prostate cancer could be associated with a significant period off-therapy in the first cycle (55.8%), and with a chance of second hormone response. But in the second cycle, the off-therapy period length was short and required a careful follow-up.     

Outcomes for laparoscopic bilateral adrenalectomy

BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has become the preferred surgical approach to manage adrenal disorders. Bilateral adrenalectomy is performed for diseases that are unresponsive to medical management and, frequently, for neoplastic disease. The aim of this study was to review our experience with laparoscopic bilateral adrenalectomy and to evaluate its safety, efficacy, and outcomes. PATIENTS AND METHODS: Between July 1996 and May 2001, five male and two female patients with a mean age of 46 years (range 15-69 years) presented for bilateral adrenalectomy (pheochromocytoma [N = 3], Cushing's disease [N = 3], and metastatic cancer [N = 1]). All procedures were performed using a lateral transperitoneal approach. One gland was excised, the patient was repositioned to the opposite lateral decubitus position, and the remaining gland was removed. RESULTS: Laparoscopic bilateral adrenalectomy was completed in all seven patients. The mean tumor/gland size on the right was 5.0 cm (range 3.1-7.0 cm) and on the left was 5.6 cm (range 3.6-7.0 cm). The mean operative time was 308 minutes (range 190-430 minutes), and the mean estimated blood loss was 138 mL (range 30-300 mL). One patient with a pheochromocytoma experienced intraoperative hypertension necessitating treatment. There were no postoperative complications. The mean postoperative hospital stay was 5.1 days (range 3-9 days). All patients have been treated postoperatively with daily hydrocortisone and fludrocortisone replacement. After a mean follow-up of 33 months (range 2-45 months), six patients are alive. The patient undergoing bilateral adrenalectomy for metastatic lung cancer died from recurrent disease 13 months after resection. CONCLUSION: Laparoscopic bilateral adrenalectomy is safe and effective. Patients are discharged postoperatively in a relatively short time with few complications. Appropriate steroid replacement and close follow-up allows these patients to return to self-reliance.     

Metastasenresektion nach neoadjuvanter Systemtherapie mit Multityrosinkinaseinhibitoren beim metastasierten Nierenzellkarzinom

Background

Metastatic renal cell carcinoma (mRCC) still poses a challenge to therapists in spite of the availability of multiple innovative molecular treatment options. Complete remission is rare and in cases of partial remission it is often unclear if necrosis or vital carcinoma tissue persists. We report on a cohort of patients who underwent metastasectomy after neoadjuvant therapy with multi-tyrosine kinase inhibitors (MTKI).

Methods

In 2009 a total of 11 patients (7 male and 4 female) underwent metastasectomy after achievement of ≥ 3 months stable partial remission. All patients received either sunitinib (n=7, mean 5.5 cycles), bevacizumab and interferon (IFN)-α2a (n=2, mean 8.5 months), temsirolimus (n=1, mean 9 months) or a combination of sunitinib followed by temsirolimus (n=1). Of the patients 7 presented with retroperitoneal lymph node metastases with a mean diameter of 3.5-12?cm, 2 patients with pulmonary metastases, 1 patient with lymph node and pancreas tail metastases and 1 female patient showed residual disease in the vena cava.

Results

All metastases were completely resected with negative surgical margins. In 82% of the cases histologically active, Ki-67 positive renal cell cancer tissue was identified. The following adjunctive interventions were necessary: vena cava resection with vascular prosthesis and reimplantation of the renal vein (n=3), partial liver resection (n=1), splenectomy (n=1) and pancreas tail resection (n=1). There were no significant perioperative complications but 1 patient developed fascial dehiscence and underwent revision surgery and 1 patient developed clinically insignificant pancreatitis. After a median follow-up of 12 months (range 8-19 months) 5 patients had no recurrence and 6 of the patients showed liver (n=3), lung (n=2) or bone (n=1) recurrences from which 3 patients died.

Conclusions

Metastasectomy of mRCC is associated with a low rate of complications in experienced centers. Surgical resection of metastatic disease is indicated to achieve complete remission with a favorable prognosis because of biologically active kidney cancer tissue. Patients with isolated and resectable metastases are ideal candidates for such a procedure.     

Genitourinary Tumor Following Kidney Transplantation: A Multicenter Study

Renal transplantation has been advocated as the treatment of choice for end-stage renal disease. Immunosuppression increases the incidence of cancer and promotes the growth of neoplasms in solid organ recipients. There have been a few reports on the incidence of cancer from transplant registries. It is difficult to precisely compare the incidence with that in the general population using data from small, single-center studies. Thus, we sought to study the prevalence of genitourinary cancer development in Iranian renal transplant recipients. We collected data from 5 kidney transplant centers in Iran between 1984 and 2008, seeking to detect the incidence, type, and outcome of cancers after kidney transplantation. Only histologically confirmed tumors, which occurred after renal transplantation, were included in the analysis. Of the 5532 patients who underwent kidney transplantation, genitourinary tumors were detected in 21 subjects (0.38%), namely, 12 males and 9 females. Transitional cell carcinoma (TCC) of the bladder, the most common genitourinary cancer (n = 7) was followed by renal cell carcinoma (RCC; n = 5), ovarian cancer (n = 3), breast cancer (n = 3), prostate cancer (n = 1), seminoma (n = 1), and uterine cancer (n = 1). The overall mean age of the patients was 46 ± 12 years (range, 19-72 years) and the median time to diagnosis after transplantation was 72 months (range, 4-240 months). Seven patients died during the follow-up. There was a male predominance among TCC of the bladder and RCC (5:2 and 4:1, respectively). In conclusion, TCC of the bladder was the most common genitourinary tumor following kidney transplantation. It was predominant in male patients.     

Viremia Negativization After BK Virus Infection in Kidney Transplantation: A National Bicentric Study

BackgroundBK virus (BKV) infection represents a potentially dreadful complication after kidney transplantation (KT). When BK viremia is detected, the best therapeutic approach remains not entirely clarified. Critical elements of BK viremia treatment are immunosuppression minimization and introduction of drugs like leflunomide, everolimus, and fluoroquinolones. The study aimed to analyze the results of the BK viremia management in 2 collaborative Italian centers.MethodsTen patients undergoing KT in the 2 collaborative Italian centers of Sapienza University of Rome and University of L’Aquila from January 2013 to December 2017 and showing a post-KT diagnosis of BK viremia were retrospectively investigated.ResultsMean time from KT to BKV positivity was 7 months (range: 1-19 months). At diagnosis, the mean viral load was 683,842 copies/mL (range: 5800-4,052,415 copies/mL), with an average zenith of 2,428,410 copies/mL (range: 6762-18,022,500 copies/mL). In the 5 patients with BKV nephropathy, we observed a switch from antimetabolite to leflunomide (n = 5), a switch from tacrolimus to everolimus (n = 3), or an introduction of fluoroquinolones (n = 3). BKV clearance was achieved in 3 patients.ConclusionsEarly BKV diagnosis and stepwise minimization of immunosuppression remain the first-line approach in patients with BK viremia. In the presence of BKV nephropathy, a combination of antiviral drugs like leflunomide and fluoroquinolones/everolimus should favor viremia clearance.     

Radiofrequency ablation of pulmonary malignant tumors in nonsurgical candidates

OBJECTIVE: Radiofrequency ablation applies thermal energy with a catheter delivery system, resulting in coagulation necrosis. Radiofrequency ablation is frequently used for hepatic malignant tumors, but few reports exist regarding its use for lung tumors. We report our experience with radiofrequency ablation for the treatment of pulmonary malignant tumors. METHODS: We evaluated the results of lung radiofrequency ablation for patients not considered surgical candidates. Indications for radiofrequency ablation were pulmonary malignant tumors in patients with medical comorbidities, pulmonary compromise, or refusal of surgery. RESULTS: Thirty-three lung tumors in 18 patients (12 male, 6 female) were treated with radiofrequency ablation. Tumors included metastatic carcinoma (n = 8), sarcoma (n = 5), and lung cancer (n = 5). Mean age was 60 years (range 27-95 years). Thoracic surgeons performed radiofrequency ablation by minithoracotomy (n = 5) or computed tomography-guided percutaneous methods (n = 13) with patients under general anesthesia in the operating room. Mean length of stay was 3 days (range 1-7 days). Complications included procedure-related pneumothorax in 7 of 13 percutaneous procedures (53.8%), delayed pneumothorax (1/18), pneumonitis/pneumonia (4/18), small pleural effusion (9/18) and transient renal failure (1/18). One death occurred as a result of hemoptysis 19 days after radiofrequency ablation of a central nodule. This patient had also received recent brachytherapy. After a mean follow-up of 6 months (range 1-14 months), radiofrequency ablation had achieved a radiographically determined response in 8 of 12 patients with treated tumors smaller than 5 cm (66.6%). Death with progressive metastatic disease occurred in 7 of 18 patients (38%) during follow-up. CONCLUSION: This pilot study demonstrates the feasibility of radiofrequency ablation for small peripheral lung tumors. Larger tumors responded poorly. Additional trials are needed to determine safety and efficacy.     

Successful treatment of BK viremia using reduction in immunosuppression without antiviral therapy

BACKGROUND: Treatment of BK virus (BKV) infection in renal transplant recipients remains controversial. This retrospective analysis evaluated efficacy and safety of reducing immunosuppression without antiviral therapy. METHODS: This single center analysis included 24 patients diagnosed with BK viremia between September 2001 and December 2003. Sixteen patients (66%) presented with BKV nephritis and eight patients (34%) presented with viremia without evidence of nephritis on renal biopsy. RESULTS: At time of diagnosis, mean plasma BKV DNA (copies/mL) was 460,409 (range 10,205-1,920,691). Mean doses reduction of mycophenolate mofetil and tacrolimus were 44% and 41%, respectively, from time of diagnosis of BKV infection to complete resolution of viremia. A decline in BK viral load was noticed within 15 to 30 days, with successful elimination of viremia over a mean period of 5.8 months (range, 1-9.5). Mean serum creatinine at time of diagnosis of BK viremia was 1.8 mg/dL (range, 1.2-2.8). Mean follow-up period is 30.9 months postdiagnosis. At the most recent visit, serum creatinine was 2.0 mg/dL (range, 1.0-3.6) (P=0.14). With reduction in immunosuppressive therapy, three patients (13%) developed acute cellular rejection and were treated successfully with intravenous bolus steroids. During follow-up, one patient had a relapse of BKV nephritis during pregnancy and lost her graft. After mean follow-up period of 43.5 months posttransplantation, all 24 patients are alive and 23 have a functioning graft. Seventeen patients (71%) have stable or improved graft function. CONCLUSION: Our analysis shows that reduction in immunosuppression therapy alone results in clearance of the BK viremia with good long-term outcome.     

Sarcomatoid carcinoma of the prostate: a study of 42 cases

Sarcomatoid carcinoma of the prostate is a rare type of prostatic cancer. With the exception of 1 study, the morphologic features and patient outcomes have been reported only in relatively small case series and individual reports. We examined transurethral resection, needle biopsy, and radical prostatectomy specimens from 42 patients with sarcomatoid carcinoma of the prostate, all of which were received in consultation. Clinical information on 32 patients was obtainable. Five patients were lost to follow-up and information on the 5 remaining patients could not be obtained. Prior prostatic adenocarcinoma: The majority of patients (n=21; 66%) had a prior history of acinar adenocarcinoma of the prostate. Of the 14 men with available data, reported Gleason scores were 6 (n=7), 8 (n=4), and 10 (n=3). Of the remaining patients for whom this information was known, 11 patients presented with de novo sarcomatoid carcinoma. The time between the original diagnosis of acinar adenocarcinoma and diagnosis of sarcomatoid carcinoma ranged from 6 months to 16 years (mean 6.8 y). Concurrent adenocarcinoma: The majority of patients demonstrated a concurrent high grade acinar carcinoma of Gleason score 7 (n=3), 8 (n=9), 9 (n=10), and 10 (n=10). A subset of patients contained an admixed ductal adenocarcinoma (n=4), small cell carcinoma (n=3), squamous cell carcinoma (n=3), or other unusual pattern of prostate carcinoma (n=3). In 1 case, the diagnosis was based on immunohistochemical evidence of epithelial differentiation along with the history of prior adenocarcinoma. Morphology of the sarcomatoid component: The percentage of sarcomatoid growth ranged from 5% to 99% (mean 65%). Bizarre atypia with giant cells was present in 55% of cases. Admixed heterologous elements were identified in 10 cases (29%), including osteosarcomatous (n=7), chondrosarcomatous (n=5), and rhabdomyosarcomatous (n=2) elements. Of the 12 cases with received immunostains of the sarcomatoid component, 5/7 cases were at least focally positive for cytokeratin, 1/1 case was focally positive for Cam5.2, and 3/6 cases were focally positive for prostate acid phosphatase. The sarcomatoid component did not demonstrate immunoreactivity for prostate-specific antigen in 8 cases. Prognosis: approximately half of all patients developed metastatic disease either at time of presentation or subsequently. Of patients with meaningful follow-up, 6/7 died within 1 year of the diagnosis of sarcomatoid carcinoma; 20 were alive yet with very short follow-up (median 1 y; mean 2.3 y). Kaplan-Meier analysis revealed that the actuarial risk of death at 1 year after diagnosis of sarcomatoid carcinoma was 20%. No correlation was identified between patient survival and morphologic features, before radiation or hormone therapy, or concurrent high-grade prostate cancer. Sarcomatoid carcinoma demonstrates diverse spindle and epithelial cell morphologies. The sarcomatoid component often has heterologous elements and, in 1 case, no epithelial component was seen on hematoxylin and eosin-stained sections. The epithelial component is typically high-grade acinar adenocarcinoma, yet other aggressive tumor subtypes such as ductal adenocarcinoma and small cell carcinoma may also be seen. Sarcomatoid carcinoma is an aggressive form of prostate cancer, the prognosis of which is dismal regardless of other histologic or clinical findings.     

甲状腺转移癌35例的临床特点及诊治分析

目的 探讨甲状腺转移癌的临床特点、诊断、治疗方式及预后.方法 回顾性分析1958至2010年收治的35例甲状腺转移癌患者的临床资料,均经细胞学或组织学病理确诊.结果 35例患者中,除了3例原发肿瘤不明外,其余原发肿瘤依次为肺癌16例、食管癌9例、乳腺癌2例、肾癌2例、下咽癌1例、鼻咽癌1例、软腭腺样囊性癌1例.其中12例以甲状腺转移癌为首发症状,其余23例从诊断原发肿瘤到发现甲状腺转移癌,时间间隔为0～168个月,中位时间为24个月,其中有6例时间间隔＞3年.所有患者均经病理学证实,其中细针吸取细胞学诊断7例,手术标本组织病理学诊断24例,两种手段结合使用诊断4例.发现甲状腺转移癌后,全部患者的中位生存期为11.5个月,1、3、5年生存率分别为43.8%、27.8%和11.9%.有28例患者接受手术治疗,7例接受非手术治疗,手术组整体生存率明显高于非手术组(P＜0.01).在合并颈淋巴结转移患者中,接受甲状腺切除合并颈清扫组的中位生存期与接受单纯甲状腺切除组相比差异无统计学意义(P＞0.05).结论 甲状腺转移癌临床少见,细针吸取细胞学可以有效的诊断甲状腺转移癌.甲状腺转移癌是恶性肿瘤的晚期表现,预后较差.     

Urothelial papilloma of the bladder: a review of 34 de novo cases

BACKGROUND: Urothelial papilloma of the bladder is an uncommon entity when using restrictive diagnostic criteria. DESIGN: We retrospectively studied 34 patients who were diagnosed with urothelial papilloma of the bladder using the criteria of the 1998 WHO/ISUP classification system. Six cases were in-house and the remaining 28 were referred from other institutions as consults to one of the authors. In all cases, the diagnosis of papilloma was the first manifestation of urothelial neoplasia. RESULTS: The mean age of the patients at diagnosis was 57.8 years (range, 23-87 years). The male-to-female ratio was 2.4:1 (24 males and 10 females). The tumor size averaged 3.3 mm (range, 1-20 mm; median, 2 mm). Simple papillary fronds were seen in all cases; in 5 cases the additional finding of secondary budding off of small fronds from larger ones was also seen. In all cases, the fronds had a round morphology; yet in 4 cases elongated fronds were also noted. In 5 cases, dilated lymphatics within the fibrovascular fronds were apparent. One case had foamy histiocytes within the fibrovascular stalks. In all cases, the lining consisted of normal-appearing urothelium without hyperplasia, dysplasia, and/or mitotic figures. Some of the distinctive histologic features seen were changes in the umbrella cells: vacuolization (n = 4), prominence with cytologic atypia (n = 2), eosinophilic syncytial morphology (n = 1), apocrine-like morphology (n = 1), and mucinous metaplasia (n = 1). Follow-up was available in 26 cases with a mean follow-up for those without evidence of progression of 28.9 months (range, 3-127 months). Three patients (8.8%) developed recurrent papilloma 4, 15, and 18 months after the initial diagnosis of papilloma; 1 of these patients also showed progression to noninvasive low-grade urothelial carcinoma at the time of recurrence (15 months). Three patients (8.8%) progressed to higher-grade disease: 2 to noninvasive low grade urothelial carcinoma (11 and 15 months after the original diagnosis) and 1 to a papillary urothelial neoplasm of low malignant potential at 104 months and a noninvasive low-grade urothelial carcinoma at 141 months from the initial diagnosis of papilloma. None of the patients demonstrated progression to either lamina propria (T1) or muscularis propria (T2) invasion. Two patients died of unrelated causes. None of the patients died of bladder cancer. CONCLUSION: Patients with urothelial papillomas have a low incidence of recurrence and rarely progress to develop urothelial carcinoma. It seems reasonable to avoid labeling these patients as having cancer. It remains to be studied whether and when patients with papillomas who have no evidence of recurrence or progression no longer need to be followed.     

九例腹腔镜解剖性肝Ⅷ段切除的可行性与策略分析

目的:探讨完全腹腔镜解剖性肝Ⅷ段切除的策略、安全性及近期疗效。方法:回顾分析湖南省人民医院2015年1月至2019年12月行腹腔镜解剖性肝Ⅷ段切除9例患者资料,其中男性6例,女性3例,年龄范围29～67岁,平均年龄53.6岁。观察手术时间、术中失血量、术后住院时间、术后并发症等指标。出院后随访生存和复发情况。结果:9例...     

Hepatic resection for recurrent metastatic ovarian cancer

BACKGROUND: The role for liver resection in metastatic ovarian cancer has not been defined. The aim of the current study was to investigate the validity of hepatic resection as a treatment option in metastatic ovarian cancer. METHODS: Retrospective review of a single institution's experience of patients undergoing hepatic resection for metastatic ovarian cancer from 1998-2006. RESULTS: Ten patients underwent resection for metastatic ovarian cancer. Primary tumor type included serous cystadenocarcinoma (n = 8), granulosa cell (n = 1), and yolk sac (n = 1). Median disease-free interval was 48 months. Liver resections included trisegmentectomy (n = 4), lobectomy (n = 4), and bisegmentectomy(n = 1). Additional surgeries included diaphragm resection (n = 60), bowel resection, (n = 30), and adrenalectomy (n = 10). The median overall survival following liver resection was 33 months. CONCLUSION: Liver resection for metastatic ovarian cancer is safe and is associated with long-term survival in some patients. Larger analysis may lead to the identification of prognostic factors associated with improved outcomes.     

Atypical cribriform lesions on prostate biopsy

Atypical cribriform lesions on prostate needle biopsy specimens are rare and difficult to diagnose. Of 574 high-grade prostatic intraepithelial neoplasia (PIN) lesions on needle biopsy seen at our institution over 75 months, we identified 23 consult cases in which the differential diagnosis was cribriform high-grade PIN versus infiltrating cribriform carcinoma. Prebiopsy prostate-specific antigen (PSA) averaged 6.5 ng/mL (range, 0.3 to 37.3). A positive digital rectal examination (DRE) was present in 12 of 22 (55%) patients for whom information was available. Ordinary high-grade PIN was present elsewhere in the biopsy specimens in 32% of cases. The following architectural features of cribriform glands were evaluated: number (mean, 5; range, 1 to 21); largest size (mean, 0.5 mm; range, 0.1 to 1 mm); necrosis (14%); detached cribriform fragments (18%); stromal fibrosis (18%); and bilaterality (22%). Cytologically, there was cellular maturation toward the center of the cribriform glands (45%); identifiable basal cells on hematoxylin and eosin sections (36%); marked nuclear atypia (9%); and mitoses (23%). Nucleoli were not visible in 18% of cases, small in 36%, and prominent in 45%. With a mean follow-up of 13.8 months for those without progression (25.9 months' overall follow-up), a repeat biopsy diagnosis of cancer was seen in 10 of 22 men [by report: Gleason score (Gs) 4 (n = 1); Gs 6 (n = 3); Gs 7 (n = 4); Gs 9 (n = 2); three biopsy specimens showed ductal features]. An additional two men developed bone metastases without biopsy. Overall, 12 of 22 (55%) patients had cancer on follow-up (one patient lost to follow-up). Four clinicopathologic findings predicted carcinoma on follow-up: positive DRE (p = 0.02); positive transrectal ultrasound (p = 0.02); bilateral atypical cribriform glands (p = 0.02); and detached cribriform glands (p = 0.04).