Is intra-arterial hepatic chemotherapy painful?

BACKGROUND: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration. This pain is related to extrahepatic infusion and gastroduodenal ulceration. However, intense abdominal pain was observed under oxaliplatin IAHC specifically without any extrahepatic infusion. METHOD: We retrospectively reviewed the charts of 68 patients who received IAHC in our center between 2011 and 2015. Patient's demographics and disease characteristics were collected. Other variables such as the type, duration, and dosage of the chemotherapy administered, as well as the usage of painkillers before, during, or after intra-arterial administration, were also registered. RESULTS: The mean age of the patients was 59 years. 61.7% were male (n = 42). The mean dose of oxaliplatin administered was 162 mg per cure over 6.7-h course. Fifty percent were diagnosed with a left colon cancer, and 85.2% had synchronous liver metastasis. While 47% of patients received IAHC as a third-line therapy, the main chemotherapeutic drug was oxaliplatin (85.2% of cases; n = 58), then OPTILIV protocol (5FU, irinotecan, oxaliplatin) (13.3%; n = 9), and mitomycin C (1.5%; n = 1). A dose reduction of 23.6% had been noted in 58.8% (n = 40) cases due to adverse effects. Among patients who received opioids during IAHC (n = 40), 20% required opioids in intercure. Before, during, and after IAHC administration, patients complained of abdominal pain in 8.8%, 58.8%, and 19.1%, and opioids were used in 10.2%, 57.3%, and 19.1%, respectively. The main onset of pain occurs during the third cycle of chemotherapy. Among our patients, 11.7% and 22% had ulcer and extrahepatic perfusion, respectively, while 7.3% of them were asymptomatic. The mean occurrence of these signs was during the fourth cycle of IAHC. 33.8% and 52.9% of patients had abdominal pain while an extended and short infusion time, respectively. CONCLUSION: Lengthening of the infusion time did not prevent the occurrence of abdominal pain significantly but was nonetheless decreased compared with patients undergoing short infusion durations. Pain was more common in patients who did not have a dose reduction and who presented with ulcer and extrahepatic perfusion. Abdominal pain occurred on average one cycle before ulcer or extrahepatic perfusion diagnosis. In current practice, pain should be an alarming indicator in patients receiving IAHC, as it may be associated with ulcer or extrahepatic perfusion and thus requiring opioids.

[Rationale for a diagnostic approach in non-Graves' orbital inflammation--Report of 61 patients]. / Établissement d'un arbre décisionnel diagnostique dans les orbitopathies inflammatoires non basedowiennes chroniques--à propos de 61 patients.

INTRODUCTION: Orbital inflammatory syndromes include a wide variety of inflammatory intraorbital processes which are very different in terms of clinical presentation and prognosis. We currently prefer to differentiate so-called "specific" inflammations, for which an etiology is able to be identified, from idiopathic orbital inflammatory syndromes (IOIS), for which the etiology remains unknown and the histology is nonspecific. PURPOSE: To propose an efficient diagnostic approach for clinicians managing patients with non-Graves' orbital inflammations. MATERIALS AND METHODS: This is a retrospective and prospective study concerning 61 patients managed by the medical team for non-Graves' orbital inflammations between May, 1999 and May, 2013 in the ophthalmology departments of Nice and Limoges university hospitals in France. Seventeen specific inflammations, 19 orbital lymphomas and 25 idiopathic orbital inflammatory syndromes were included. Patients were divided into two groups. Thirty-six patients (group 1) underwent primary biopsy, while for the other 25 (group 2), therapy was begun empirically without biopsy. We could therefore compare both approaches in terms of diagnostic efficiency and time until identification of a specific etiology. RESULTS: Our statistical results show that an approach without primary biopsy leads to a number of specific diagnoses statistically much lower than that obtained by the approach with primary biopsy. Also, the risk of missing a specific inflammation (with as a consequence an inappropriate treatment and a risk of functional sequelae as well as a fatal risk of missing a lymphoproliferative pathology) is very clearly higher in the case of not performing primary biopsy. Finally, the average time elapsed between the initial consultation with the ophthalmologist and a specific diagnosis was one month in the case of the first approach, while this delay was almost three times higher with the second approach, with a mean of 2.91 months (P<0.01). DISCUSSION: Our study shows that biopsy should be the mainstay of diagnostic management. A trial of empiric treatment is only performed first in myositis or in locations where biopsy could jeopardize functional prognosis. It should only be done after biopsy in all other cases. Of course, in all cases of relapse or recurrence after treatment, biopsy should be performed or repeated. CONCLUSION: The diagnostic work-up of a patient with an orbital inflammatory process must of course include blood testing and orbital imaging, but also a systematic primary biopsy for histological examination in the vast majority of cases. It must be repeated at least in the case of any doubt about the diagnosis or in the case of any recurrence or resistance to treatment.

[Characterization and outcome of renal cancers ≤ 4cm treated by surgery]. / Caractéristiques cliniques, histologiques et évolutives des cancers du rein de taille inférieure ou égale à 4cm traités chirurgicalement.

PURPOSE: In a retrospective study, we described the characteristics and the outcome of renal cancers less than or equal to 4cm treated by surgical excision. MATERIAL: Two hundred and eighty four cancers less than or equal to 4cm on preoperative CT scan (T1a) were extracted from our database. We studied, the presence of symptoms, the ECOG and ASA scores, the size, the histological type and the Fuhrman grade. The follow up was clinical, biological and radiological. RESULTS: The mean age was 60.8 years. 21% of patients were symptomatic. The renal capsule was intact in 182 cases (64.08%), the urinary tract in 267 cases (94.01%). Seven patients (2.46%) were metastatic with tumors greater than or equal to pT3a. The most common histological types were the conventional renal cell carcinoma (78.52%) and the papillary renal cell carcinoma (16.55%). 76.06%. of the tumors were low grade. With a median of 66.9 months, 33 patients died (11.61%) . For N0M0 patients, with a median of 59.3 months, three specific deaths (1.19%) and 17 deaths from other causes (6.77%) were observed. The average survival of N0M0 group was 227.2 months. CONCLUSION: The renal cell carcinoma less than or equal to 4cm was a heterogeneous group including locally advanced and aggressive or metastatic tumors. For localized forms, surgical excision provided an effective long-term treatment regardless the histological type or the tumor grade.

MN/CA9: a potential gene marker for detection of malignant cells in effusions.

Many cancers cause malignant effusions. The presence of malignant cells in effusions has implications in diagnosis, tumour staging and prognosis. The detection of malignant cells currently presents a challenge for cytopathologists. New adjunctive methods are needed. Although the effusions provide excellent materials for molecular assay, the available molecular markers are extremely limited, which hinders its clinical application. MN/CA9 has proved to be a valuable marker in many cancers such as lung, breast, colon, kidney, etc. The present study was to evaluate MN/CA9 as a new molecular marker for the detection of cancer cells in pleural effusions. Seventy-one pleural effusions including 59 malignant effusions from patients with cancer, and 12 patients with benign diseases as a control, were subjected to RT-PCR for detection of MN/CA9 gene expression. MN/CA9 gene expression was detected in 53/59 (89.8%) pleural effusions from cancer patients (15/16 for breast cancers, 10/11 for lung cancers, 4/4 for ovary cancers, 2/3 for colon-rectal cancers, 5/6 for cancers of unknown site, 7/8 for mesothelioma and 10/11 for other cancers). Furthermore, MN/CA9 was positive in 13/18 (72.2%) of cytologically negative effusions of cancer patients. MN/CA9 was detected in only 1/12 (8.3%) effusions from the control patients (p < 0.01). The sensitivity and specificity of MN/CA9 gene expression were, respectively, 89.8% and 91.7%. Our preliminary results suggest that MN/CA9 could be a potential marker for the detection of malignant cells in effusions. A large-scale study is needed to confirm these results.

S100A1: a powerful marker to differentiate chromophobe renal cell carcinoma from renal oncocytoma.

AIMS: The common subtypes of renal tumours are conventional, papillary, chromophobe carcinoma and oncocytoma. The morphological differentiation between chromophobe carcinoma and oncocytoma may be difficult. The aim was to evaluate S100A1 as a new marker for the differentiation of the two subtypes. METHODS AND RESULTS: Thirty-nine tumour samples [nine clear cell renal cell carcinomas (RCCs), six papillary RCCs, nine chromophobe RCCs and 15 oncocytomas] were studied. The protein expression of S100A1 was evaluated by immunohistochemistry. The gene expression of S100A1 was analysed by reverse transcriptase-polymerase chain reaction. Nine oncocytomas showed strong immunoreactivity for S100A1. Four oncocytomas were scored as moderate and one as weak reactivity. In total, 14/15 (93%) of oncocytomas were considered to be immunopositive. In contrast, all nine chromophobe RCCs were considered to be immunonegative. There was a significant difference in the positive percentages of staining of S100A1 between these two subtypes (P < 0.01). S100A1 immunoreactivity was observed in 6/9 clear cell and 4/6 papillary carcinomas. The results of S100A1 gene expression corresponded well with the results of immunohistochemistry. CONCLUSION: S100A1 may be a potentially powerful marker to differentiate the chromophobe RCC from renal oncocytoma.

Successful treatment via chemotherapy and surgical resection of a femoral hemangiopericytoma with pulmonary metastasis.

Hemangiopericytoma (HPC) is a soft-tissue neoplasm composed of proliferating capillary pericytes. It has variable and unpredictable malignancy and most commonly occurs in the fifth or sixth decade of life. Diagnosis is based on the histological aspect. HPC is exceedingly rare in childhood. In both adults and children, curative surgery is the most important predictor of survival. The place of chemotherapy in the treatment of HPC is not well established. We describe a case of adult-type metastatic HPC of the thigh in a 13-year-old boy. The response to neoadjuvant chemotherapy was excellent, and local control of this initially unresectable tumor was achieved without radiation therapy or mutilating surgery. The child is alive and well and has had 8 years of follow-up after treatment.

[Giant aneurysm of the right coronary artery]. / Anévrysme pseudotumoral de l'artère coronaire droite.

INTRODUCTION: Giant coronary aneurysms are rare and often confused with cardiac tumours. OBSERVATION: We report a new case of this type of aneurysm occurring on the right coronary artery revealed by a cardiac congestion. COMMENTS: These aneurysms can be due to inflammatory diseases or dysplasia. But in these pseudotumoral forms, atherosclerosis is the main aetiology. The diagnosis and treatment require surgery and histological examination.

S100A1 and KIT gene expressions in common subtypes of renal tumours.

AIM: The aim of this study is to evaluate the S100A1 and KIT as gene markers for the differentiation of common subtypes of renal tumours. METHODS: Fifty-five tissue samples (15 clear cell RCCs, 15 papillary RCCs, 7 chromophobe RCCs, 8 oncocytomas and 10 normal renal tissues) were studied The gene expressions of S100A1 and KIT were analysed by one-step RT-PCR by using the specific primers. RESULTS: S100A1 was expressed in 2/15 clear cell RCCs, 11/15 papillary RCCs, 7/8 oncocytomas and in 0/7 chromophobe RCCs. KIT gene was expressed in 6/7 chromophobe RCCs and 7/8 oncocytomas while 0/15 clear cell RCCs and 1/15 papillary RCCs expressed kit gene. Normal tissue expressed neither S100A1 nor KIT gene. CONCLUSION: S100A1 and KIT can be used as gene markers for the differentiation of common subtypes of renal tumours.

Sentinel lymph node detection in primary melanoma with preoperative dynamic lymphoscintigraphy and intraoperative gamma probe guidance.

BACKGROUND: This study assessed the value of the radioisotopic method used alone, and factors influencing relapse rates, for sentinel lymph node (SLN) mapping in primary melanoma. METHODS: One hundred and thirty-three patients with a diagnosis of melanoma (thickness greater than 0.75 mm) underwent gamma probe-directed lymphatic mapping in a prospective single-centre study. RESULTS: Mean Breslow thickness was 3 mm. At least one SLN was identified in 132 patients (mean 1.8 nodes per patient); the success rate was 99.2 per cent. Twenty-two patients (16.7 per cent) had a metastasis within the SLN. The mean tumour thickness in patients with a metastatic SLN was 4.4 mm compared with 2.7 mm for patients with a negative SLN (P < 0.001). The median time to recurrence was 20.4 months in SLN-negative patients compared with 8.5 months in those with SLN metastasis (P < 0.001). Ten (9.1 per cent) of the 110 SLN-negative patients developed recurrence. Three patients relapsed in the previously mapped lymphatic basin after a median follow-up of 27.1 months. CONCLUSION: This study confirmed the reliability and accuracy of SLN mapping using a radioisotope technique, and also the importance of the SLN as a predictive factor for survival. There was a low risk of locoregional recurrence when the SLN was not involved.

[Microcystic meningiomas: comparison of histology and computed tomography]. / Aspects histologiques et tomodensitométriques des méningiomes microkystiques.

INTRODUCTION: Microcystic meningiomas are defined by large vacuolated and stellate shaped cells. We recently examined a microcystic meningioma mimicking a malignant tumor on computed tomography (CT). The aim of the current study was to compare the radiological features of microcystic meningiomas with their histological patterns. METHODS: We have diagnosed 7 intracranial microcystic meningiomas among 204 meningiomas registered in the files of our Department of Pathology from 1994 to 2001. All CT scans performed before surgery were reviewed. RESULTS: Three of the microcystic meningiomas appeared as entirely microcystic tumors. Two of them were homogeneously hypodense or isodense on CT scan. The third mening was heterogeneous, containing some blood. The histologic pattern of the 4 other meningiomas showed microcystic tumor cells associated with meningothelial or fibrous tumor cells. These meningiomas were heterogeneous on CT scan. All meningiomas seemed to be connected to the dura mater. Three tumors were strongly and homogeneously enhanced after contrast media injection while 3 others were heterogeneously enhanced. No enhanced CT scan was available for 1 case. Astrocytomas were incorrectly diagnosed by CT scan in the 3 heterogeneously enhanced tumors. Meningiomas were correctly diagnosed in the 3 strongly enhanced tumors. CONCLUSION: The presence of microcystic tumour cells in meningiomas often results in erroneous diagnosis on CT scan, particularly for those which are heterogeneously enhanced. In these cases, a diagnosis of astrocytoma is often made.

Does Switzerland train tomorrow's surgeons today? Today's reflections on tomorrow's surgeons.

Various factors are influencing the Swiss health care system, and therefore, surgeons' actual and future profession. Initiated by the current president of the Swiss Society of Surgery, a group of eight young Swiss surgeons constituted the ad hoc committee "Chirurgie 2020". The goal was to develop several scenarios of the surgeon's professional situation in 20 years. The future direction of surgery will be markedly influenced by medical innovation, political and economic relationships between Switzerland and Europe. However, the development of health care costs represents the most powerful factor predicting all further changes. The current situation of today's surgeons is best characterised as "hamsters in the treadmill" who try to fulfill a multitude of diverging tasks causing major demotivation. In order to retain a leading role in the health care system, surgeons must take part in social and political activities. To provide an excellent curriculum, university and county hospitals must join together to form clinical and educational networks. A clearly defined and structured curriculum must be introduced by the Swiss Society of Surgery. From our current point of view, only everyone's strong personal commitment will help to find solutions and to improve the current and future situation. In particular, today's surgical residents must actively take part in the development of tomorrow's surgery.

The expression of G250/mn/CA9 antigen by flow cytometry: its possible implication for detection of micrometastatic renal cancer cells.

Monoclonal antibody (mAb) G250 is a well characterized and specific mAb to renal cell carcinoma (RCC). The gene G250 was recently cloned and was proved to be homologous to MN/CA9. The G250/MN/CA9 antigen was recently explored as a potential marker for RCC. Flow cytometry (FCM) allows quantitative analysis of cells. The present study describes a flow cytometric method to detect this antigen in human cell lines and in malignant and normal renal tissues. Twelve human carcinoma cell lines (HeLa, Colo205, HT29, BxPC3, OVCAR3, SKOV3, ACHN, A704, CAKI-2, SKRC-59, SKRC-10, and SKRC-52), 10 specimens of normal peripheral blood mononuclear cells, and 38 malignant and 36 adjacent normal renal tissues were studied. The malignant and normal renal tissues were disaggregated mechanically into a single-cell suspension, stained by mAb G250, and analyzed by FCM. All 22 of the clear cell carcinomas, 6 of 8 mixed cell carcinomas, and 3 of 6 granular cell carcinomas were positive for G250/MN/CA9 antigen. SKRC-52 and SKRC-10 were strongly positive for G250/ MN/CA9. The G250/MN/CA9 antigen could also be detected in HeLa, SKOV3, HT29, and A704 cells. One chromophobic, one chromophilic cell carcinoma, the normal renal tissues, and normal peripheral blood mononuclear cells were considered as negative. Our results further confirmed that the G250/MN/CA9 antigen was an ideal marker for RCC, especially for clear cell carcinomas, and that this antigen was present in several types of malignant cells. FCM may serve as a fast tool of immunocytochemical detection of renal cancer cells. Flow cytometric detection of renal cancer cells by using mAb G250 should be further explored.

Epstein-Barr virus-associated Kikuchi disease in two children.

The authors describe two children with Kikuchi necrotizing lymphadenitis, the main manifestations of which were cervical lymphadenopathy, fatigue, and fever. The diagnosis was based on histopathologic findings after open biopsy. Results of serologic studies, immunoperoxidase staining for Epstein-Barr virus (EBV) latent membrane protein, in situ hybridization for Epstein-Barr encoded RNAs, and polymerase chain reaction amplification of EBV Epstein-Barr nuclear antigen-1 (EBNA) DNA suggested that EBV was the causative agent in both patients. The disease was mild and subsided after complete surgical resection in one patient, with a follow-up of 1 year. In the other patient, a short course of corticosteroids led to complete clinical remission within 2 months, but the child still has biologic signs of persistent EBV infection. He experienced relapse with a large cervical mass and fever 28 months after the initial onset. Histologic findings were identical to those at initial presentation. Symptoms again resolved spontaneously within 2 weeks, but the follow-up was short (12 mos) and the child's EBNA antibodies are still absent. No evidence of immunodeficiency was found in either child. The cause of Kikuchi disease is unknown, but a viral or postviral hyperimmune reaction has been proposed. Malignant lymphoma and systemic lupus erythematosus are differential diagnoses. Early recognition of Kikuchi disease minimizes potentially harmful and unnecessary investigations and treatments. These findings add Kikuchi disease to the protean manifestations of chronic EBV infection.

[Solitary congenital histiocytoma: two cases]. / Histiocytomes congénitaux : 2 cas.

BACKGROUND: Solitary histiocytoma is an uncommon form of Hashimoto-Pritzker syndrome and an exceptional type of histiocytosis with cells of undetermined origin. A solitary often ulcerated congenital nodule is generally observed. We report two cases, one of each form. CASE REPORTS: Both cases presented an ulcerative budding congenital tumefaction of the plantar aspect of the right foot for the first child and the parieto-axillary region in the second. Histology disclosed a granulomatous infiltrate of histiocytes positive for specific immunolabels (protein S100 and CD1a). In the first case, electron microscopy revealed histiocytes devoid of Birbeck granules and myelinoid bodies leading to the diagnosis of Langerhans histiocytosis with cells of unknown origin. In the second case, 18 p. 100 of the cells contained Birbeck granules. There has been no recurrence after a 5-year follow-up in a case. DISCUSSION: These cases recall the congenital nature of some types of solitary histiocytomas. Indeed, congenital Langerhans histiocytoma can occur as a unique nodule. The tumefaction may lie in any localization. Histological diagnosis is required. The benign nature of these lesions is confirmed by the absence of distant lesions and the lack of recurrence after complete excision. About a dozen cases have been reported. Most have been Hashimoto-Pritzker syndromes. Only one case has been reported with cells of undetermined origin. The diagnosis of histiocytosis with cells of undetermined origin is made when the ultrastructure study demonstrates the vacuity of the histiocyte cytoplasm. This condition is similar to Hashimoto-Pritzker syndrome by the absence of recurrence and systemic diffusion. It can however be observed in adults. The undetermined cell types would correspond different phases of Langerhans cell maturation or involution.

Flow cytometric analysis of antigen expression in malignant and normal renal cells.

UNLABELLED: Flow cytometry allows quantitative analysis of cancer cells. The aim of this study was to make a quantitative study of antigen expression in malignant and normal renal cells in order to find the efficient monoclonal antibodies (mAbs) for labelling renal cancer cells. MATERIAL AND METHODS: 15 malignant and adjacent normal renal tissues and three renal carcinoma cell lines (ACHN, A704 and CAKI-2) were analyzed. The malignant and normal renal tissues were dissociated mechanically into cell suspension. The mAbs and isotype controls were used for immunochemical labelling. The stained cells were analyzed by flow cytometry. RESULTS: Renal tumor associated antigen G 250 was frequently detected in malignant renal cells but not in normal renal cells. Renal tumor associated antigen gp200 recognized by 66.4.C2 and PN-15 was frequently detected in malignant cells, normal renal cells and also in all three carcinoma cell lines. Epithelial antigens were strongly positive in normal renal cells. Compared with MOC 31, Ber-EP4 and E 29, W-lD9 was mostly reactive to malignant renal cells. VU-1D9 was strongly positive on ACHN and A704. The carbohydrate carcinoma antigens CA 125, DF3 and Sialyl Lewis(a) were detectable in some of the malignant and normal renal cells. Sialyl Lewis(a) could be weakly detected on ACHN and A 704. Pan-cytokeratins and cytokeratin (CK) 8 were strongly expressed in malignant and normal renal cells and in all three cell lines. CONCLUSION: Our results indicated that G 250, 66.4.Ca, PN-15, VU-1D9, MNF116 and anti-ckg were efficient mAbs for labelling renal cancer cells. Their potential clinical application by flow cytometry should be explored.