Current pathology keys of renal cell carcinoma

Context

Renal cell carcinoma (RCC) in adults comprises a heterogeneous group of tumours with variable clinical outcomes that range from indolent to overtly malignant. The application of molecular genetic techniques to the study of renal neoplasms has resulted in an improved classification of these entities and a better understanding of the biologic mechanisms responsible for tumour development and progression. The current 2004 World Health Organisation classification of adult renal epithelial neoplasms has expanded rapidly with new categories recently incorporated.

Objective

To review and evaluate the evidence implicating pathologic features and classification of RCC in adults as a tool to approach patients’ prognosis and modulate current therapy.

Evidence acquisition

Members of Committee 3: Pathology, under the auspices of the International Consultation on Urological Diseases and the European Association of Urology (ICUD-EAU) International Consultation on Kidney Cancer, performed a systematic review using PubMed. Participating pathologists discussed pathologic categories and diagnostic features of RCC in adults.

Evidence synthesis

We reviewed and discussed articles and the personal experiences of participating uropathologists.

Conclusions

The conclusions reached by the ICUD-EAU 2010 International Consultation on Kidney Cancer emphasise the appropriate pathologic diagnosis of RCC in adults as a tool to approach patients’ prognosis and modulate current therapy. Further emphasis should be placed on defining risk groups of RCC and diagnostic features of unusual tumours such as familial RCC, translocation RCC, and tubular mucinous and spindle cell carcinoma. A number of recently described entities and morphologic variants of classical categories deserves recognition because they can be important in differential diagnosis and therapy.     

Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men

INTRODUCTION: Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation. MATERIALS AND METHODS: 25 healthy men were administered goserelin acetate (GnRH analog) 3.6 mg subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (T(m)P/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests. RESULTS: Goserelin therapy decreased mean serum testosterone levels from 543+/-160 ng/dL to 33+/-15 ng/dL at week 4 (p<0.001), and to 20+/-10 ng/dL at week 12 (p<0.001). Serum phosphate increased significantly from 3.4+/-0.6 mg/dL to 3.9+/-0.4 mg/dL at week 4 (p=0.002), and to 4.3+/-0.4 mg/dL at week 12 (p<0.001). T(m)P/GFR increased significantly from 3.2+/-0.6 mg/dL to 3.6+/-0.5 mg/dL at week 4 (p<0.004), and to 4.1+/-0.6 mg/dL at week 12 (p<0.001). FGF-23 levels, however, did not change during the 12-week study. CONCLUSIONS: Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that supraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 dihydroxyvitamin D within this physiologic serum phosphate range.     

Versatility of the pedicled thoracodorsal artery perforator (TDAP) flap in soft tissue reconstruction

For the last decades, the latissimus dorsi skin-muscle flap has contributed to the efficient reconstruction of the loss of skin cover (especially in breast surgery) and in long-distance tissue defects. Unfortunately, the nonuse of such an important muscle as the latissimus dorsi for the patient, as well as the resulting thickness of the flap after reconstruction, has turned it into a second choice flap. However, this flap is still indicated in the reconstruction of areas which need a great amount of cutaneous and muscular tissue. The appearance of the perforator flaps and, specifically, thoracodorsal artery perforator (TDAP) flap, has meant a radical change in relation to lower morbidity of the donor site, thus highly ranking the use of these flaps in the reconstruction for similar defects. The aim of this publication is to present our experience with the pedicled TDAP flap in a series of 17 different cases. Of those, there were 14 cases of mammary reconstruction after sparing surgery, 2 cases of axillary reconstruction following severe recurrent hidradenitis, and a case of extensive substance loss in a patient's upper limb following a severe crush injury.     

Vascularised fibular grafts as a salvage procedure in failed intercalary reconstructions after bone tumour resection of the femur

Vascularised fibular grafts (VFGs) are widely used for primary reconstruction of long bones after bone tumour resections. The biological properties of VFGs are such that they can be a useful option even in failed intercalary reconstructions. The purpose of the current study was to investigate the results and the morbidity of VFGs as a salvage procedure in failed previous reconstructions after intercalary bone tumour resection of the femur. Our series included 12 patients, treated from April 1989 to March 2005, with an average age of 23 years (range 10–43 years) at presentation. The initial diagnosis was osteosarcoma in 10 cases and Ewing's sarcoma in two cases. All patients received chemotherapy and none received radiation therapy. Seven patients received VFG as biologic augmentation in intercalary allograft non-union and in the other five patients, a combination of allograft and VFG was used to replace a cement spacer with hardware failure (four patients) and a failed intercalary prosthesis (one patient). Three patients died during follow-up, in all cases because of metastatic disease. At an average follow-up of 147 months (range 11–260 months), the remaining nine patients were continuously disease-free. Complete healing of the osteotomy of both allograft and VFG was observed in 10 patients at final follow-up. Two major complications were observed that required surgical revision, eventually healing in one case and leading to a poor functional outcome in one case. Significant hypertrophy of the VFG was detected in seven of nine evaluable patients. At final follow-up the mean Musculoskeletal Tumour Society (MSTS)’93 functional score of the nine evaluable patients was 90% (range 66–100%). These results indicate that VFG is a valid salvage procedure in failed intercalary reconstructions of the femur after bone resection.     

The Bolognese surgeon Giuseppe Ruggi: how and why the aseptic surgery was introduced in Bologna in the middle half of the XIX century

Background

The first reliable statistic data about perioperatory mortality were published in 1841 by the French Joseph-Francois Malgaigne (1806–1863): he referred to a mean mortality of 60% for amputations and this bad result was to be attributed mainly to hospital acquired diseases. The idea of “hospital acquired disease” although vague, included five infective nosologic entities, which at that time were diagnosed more frequently: erysipelas, tetan, pyemia, septicemia, and gangrene. Nonetheless, the suppuration with pus production was considered from most of the surgeons and doctors of that time as a necessary and unavoidable step in the process of wound healing. During the end of the eighteenth century, hospitals of the main European cities were transforming into aggregations of several wards, where the high concentration of patients created poor sanitary conditions and a consistent increase of perioperatory mortality. In 1865, Lister applied his first antiseptic dressing on the surface of an exposed fracture. These experimental attempts lead to an effective reduction of wound infections respect to the dressing with strings used previously.

Discussion

Lister's innovations in the field of wound treatment were based on two brand new concepts: germs causing rot were ubiquitarious and the wound infection was not a normal step in the process of wound healing. The concept of antisepsis was hardly accepted in the European surgical world: “Of all countries, Italy is the most indifferent and uninterested in experimenting this method, which has been so favorably judged from the greatest surgical societies in Germany”. This quotation from the young surgeon Giuseppe Ruggi (1844–1925) from Bologna comes from his article where he presented his first experiences on aseptic medications started the previous year in the Surgical Department of Maggiore Hospital in Bologna. In his report, Ruggi described the adopted technique and suggested that the medication should be extended to all the surgical patients of the hospital:“… this is needed to totally remove from the hospital all those elements of infection which grow in the wounds dressed with the old method”. The experimentation of this new dressing for the few treated cases was rigorous and concerned both the sterilization of surgical tools with the fenic acid (5%) and the shaving of the skin. Ruggi also observed that there was no correlation between the seriousness of the wound and its extension or way of healing: when “simple” cases that “should heal without complication” showed fever he often realized that “it was often due to a medication performed without following the rules for an accurate disinfection and dressing”. Ruggi thought that the fever was connected to “reabsorption of pyrogenic substances, which can be removed cleaning and disinfecting the wound” in cases of wounds not accurately dressed and rarely medicated. Frequent postoperative medications of the wound were able to eliminate the fever within 2 h. Ruggi's attitude toward the fine reasoning lead him to introduce the concept of immunodeficiency related to physical deterioration: “… patients treated for surgical disease may sometimes suffer from complications of medical conditions, which initially escape the most accurate investigations… The surgical operation could, in some cases, hold the balance of power”.

Conclusions

The obtained results, published in 1879, appear extremely interesting. As he wrote in 1898, for the presentation of his case record of more than 1000 laparotomies, he had started “… operating as a young surgeon without any tutor, helped only by his mind and what he could deduce from publications existing at the moment …”.     

High‐Density Dependence But Low Impact on Selected Reproduction Parameters of Brucella suis Biovar 2 in Wild Boar Hunting Estates from South‐Western Spain

Porcine brucellosis is a disease caused by Brucella suis, which is characterized by reproductive disorders in pigs. The number of cases of swine brucellosis has risen in many European countries, likely because of the presence of a wild reservoir of B. suis in wild boar. This study aimed at evaluating factors that may influence the probability of infection with Brucella spp. in wild boar and at assessing the impact of a previous contact with Brucella spp. on reproductive parameters of wild boar. Two hundred and four wild boar living in Extremadura (south‐western Spain) were studied. The presence of anti‐Brucella antibodies was determined using an indirect ELISA, while the presence of living bacteria in genital organs was evaluated through microbiological cultures. Sex, age, density of wild boar in summer and presence of outdoor pigs were selected as possible risk factors for being seropositive for Brucella spp. in wild boar. In addition, reproductive parameters such as breeding status or potential fertility in females and testis weight in males were estimated and related to the presence of anti‐Brucella antibodies. A total of 121 animals were seropositive, resulting in a prevalence of 59.3% (95% CI). In addition, seven isolates of B. suis biovar 2 were obtained. Wild boar density in summer, as well as age and sex, was proposed as factors to explain the probability of Brucella seroconversion, although wild boar density in summer was the key factor. Current measures of reproductive parameters were not influenced by a previous contact with Brucella spp. Isolation of B. suis confirms that wild boar could represent a risk to domestic pig health in the study area. Wild boar density seems to have a great influence in the probability of infections with B. suis and suggests that density management could be useful to control Brucella infection in wild boar.     

Sentinel node mapping in high risk endometrial cancer after laparoscopic supracervical hysterectomy with morcellation

INTRODUCTIONOccult endometrial cancer after supracervical hysterectomy is very uncommon. Even if optimal management of those rare cases is still unproven, to guide the need for further therapies, restaging should be recommended in this situation.PRESENTATION OF CASEWe report of a 60-year old woman with occult high risk endometrial cancer after supracervical hysterectomy with morcellation. We describe the feasibility of laparoscopic intraoperative sentinel node identification with cervical stump removing to restage the suspicious early stage high risk endometrial cancer.DISCUSSIONIn high risk endometrial cancer surgical restaging is important, considering that 10–35% of cases can present pelvic nodal metastasis. To reduce the treatment related morbidity maintaining the benefit of surgical staging, with a negative preoperative PET/CT, we performed a laparoscopic SN mapping with cervical stump removing.CONCLUSIONThis report highlight the fact that SN mapping with cervical injection is a feasible and safe technique also without the uterine corpus after supracervical hysterectomy with morcellation.     

Back pain and disability after lumbar laminectomy: is there a relationship to muscle retraction?

OBJECTIVE: Preliminary studies have suggested that prolonged retraction of the paraspinal muscle during spinal surgery may produce ischemic damage. We report the continuous measurement of intramuscular pressure (IMP) during decompressive lumbar laminectomy and its relationship to subsequent back pain and disability. METHODS: Twenty patients undergoing two-level decompressive lumbar laminectomy for lumbar canal stenosis were recruited. Back pain and disability were assessed by use of the Visual Analog Score (VAS), Oswestry Disability Index (ODI), and Short-Form 36 (SF-36) Health Survey. During surgery, IMP was recorded continuously from the multifidus muscle by use of a pressure transducer. The intramuscular perfusion pressure (IPP) was estimated as the difference between the patient's mean arterial pressure and IMP. RESULTS: Two muscle retractors were used: the Norfolk and Norwich (n = 10) and the McCulloch (n = 10). The mean duration of deep muscle retraction was 62.7 +/- 8 minutes (range, 19-133 min). On application of deep muscle retraction, there was a rapid and sustained increase in IMP (P < 0.001), and overall, the calculated mean IPP approached 0 mm Hg or less during this period (P < 0.001). On release of deep muscle retraction, there was a rapid decrease in IMP to preoperative levels. The IPP was greater with the Norfolk and Norwich than the McCulloch retractor (P < 0.001). Compared with preoperative values, there was a decrease in ODI (P < 0.001) and VAS for back pain (P < 0.001) at discharge and 4 to 6 weeks and 6 months after surgery. In addition, there was a decrease in SF-36 scores at 6 months compared with preoperative values (P < 0.001). Total duration of muscle retraction greater than 60 minutes was associated with worse VAS scores for back pain and ODI and SF-36 scores for disability at 6 months after surgery (P < 0.05). There was no relationship between the VAS, ODI, and SF-36 scores and other parameters measured, including the mean IPP, retractor type, operating surgeon, and wound length. CONCLUSION: The McCulloch retractor generates a higher IMP than the Norfolk and Norwich retractor. However, postoperative improvement in VAS, ODI, and SF-36 scores in these patients was associated with a shorter duration of muscle retraction and not the degree of IMP or IPP generated. In this respect, periodic relaxation of the paraspinal muscle retractors during surgery to allow muscle perfusion may help to reduce postoperative back pain and disability.     

Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer.

Metastatic prostate cancer may respond initially to hormone suppression, with involution of tumor sites, but ultimate tumor progression is inevitable. Our aim was to detect the proportion of bone and soft-tissue lesions that represent metabolically active tumor sites in patients with progressive metastatic prostate cancer. METHODS: In a prospective study, we compared 18F-FDG and L-methyl-11C-methionine (11C-methionine) PET with conventional imaging modalities (CIM), which included the combination of 99mTc-methylene diphosphonate scintigraphy, CT, or MRI. Twelve patients with prostate cancer, increasing levels of prostate-specific antigen (PSA), and at least 1 site (index lesion) with new or increasing disease on CIM were studied. The total numbers of soft-tissue and bone-tissue lesions, in a site-by-site comparison, were calculated for all imaging modalities. RESULTS: The sensitivities of 18F-FDG PET and 11C-methionine PET were 48% (167/348 lesions) and 72.1% (251/348 lesions), respectively, with CIM being used as the 100% reference (348/348). 11C-Methionine PET identified significantly more lesions than 18F-FDG PET (P < 0.01). All 12 patients with progressive metastatic prostate cancer had at least 1 lesion site of active metabolism for 18F-FDG or 11C-methionine, which could be used as an index lesion to monitor the metabolic response to therapy. A significant proportion of lesions (26%) had no detectable metabolism of 18F-FDG or 11C-methionine. Although technical factors cannot be totally excluded, we believe that metabolically inactive sites may be necrotic or dormant. More than 95% (251/258) of metabolically active sites (72% of the total number of lesions detected by CIM) metabolize 11C-methionine. 18F-FDG uptake is more variable, with 65% of metabolically active sites (48% of the total number of lesions detected by CIM). CONCLUSION: These findings reflect the different biologic characteristics of the lesions in a heterogeneous tumor such as prostate cancer and suggest that a time-dependent metabolic cascade may occur in advanced prostate cancer, with initial uptake of 11C-methionine in dormant sites followed by increased uptake of 18F-FDG during progression of disease.     

Langerhans cell histiocytosis of the vulva: two case reports

This report describes the histopathologic results of Langerhans cell histiocytosis of the vulva and options for treatment. We present two new cases demonstrating vulvar manifestations of disease and their course of treatment with a review of the literature. Langerhans cell histiocytosis of the female genital tract is rare. The disease cannot be diagnosed without biopsy of cutaneous lesions. Langerhans cell histiocytosis of the vulva is a rare disorder with few options for treatment.