Prognostic Significance of the Microenvironment in Human Papillomavirus Oropharyngeal Carcinoma: A Systematic Review.

OBJECTIVE: The immune microenvironment of HPV-associated (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) (HPV+OPSCCs) differs from that of HPV-independent oropharyngeal cancers (HPV-independent OPSCCs). The literature on the subject is very abundant, demanding an organized synthesis of this wealth of information to evaluate the hypothesis associating the favorable prognosis of HPV+OPSCC patients with a different immune microenvironment. A systematic review of the literature was conducted regarding the microenvironment of HPV+OPSCCs. DATA SOURCE: MEDLINE/PubMed, Embase, and Cochrane Library databases. REVIEW METHODS: A literature search was performed following PRISMA guidelines (Moher D. PLoS Med. 2009). The PEO (Population, Exposure, and Outcome) framework is detailed as follows: P: patients with oropharyngeal squamous cell carcinomas, E: human papillomavirus (HPV), and O: histological and immunological composition of the tumoral microenvironment (TME). No meta-analysis was performed. RESULTS: From 1,202 studies that were screened, 58 studies were included (n = 6,474 patients; n = 3,581 (55%) HPV+OPSCCs and n = 2,861(45%) HPV-independent OPSCCs). The presence of tumor-infiltrating lymphocytes (TIL), CD3+ in 1,733 patients, CD4+ in 520 patients, and CD8+ (cytotoxic T lymphocytes (CTL)) in 3,104 patients, and high levels of PD-L1 expression in 1,222 patients is strongly correlated with an improved clinical outcome in HPV+OPSCCs. CONCLUSION: This systematic review provides the most comprehensive information on the immune microenvironment of HPV+OPSCCs to date. Tumor-infiltrating lymphocytes and PD-L1 expression are associated with a favorable prognosis. B, CD8+ and resident memory cells densities are higher in HPV+OPSCCs. The importance of myeloid lineages is still a matter of debate and research. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1507-1516, 2024.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.

OBJECTIVE: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). METHODS: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. RESULTS: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). CONCLUSION: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO.

[MRI-guided breast microbiospy or macrobiopsy: which is the best option for a small tumor?]. / Micro- ou macrobiopsie mammaire guidée par IRM : quel est le meilleur choix pour une petite tumeur ?

The choice of the optimum therapeutic strategy for breast cancer depends on the histological diagnosis of the sample obtained by biopsy. The microbiopsy is the preferred method as it provides an accurate diagnosis of the histological type as well as the main prognostic factors, whilst being simple, fast and inexepensive. However, some infraclinic breast tumors are not accessible by conventional guidance due to excessive depth inside the breast, their small size or technical inability to image them by mammography or ultrasonography. In those cases, the MRI guidance may help to perform the biopsy. Most MRI biopsies are made by large-core needle that are known to alter the histological structure of the tumor and to disturb the anatomopatholgical analysis (size and surgical margin). Those are very important elements to know before treatment. Our case report details an original technique of MRI microbiopsy of a deep 4mm opacity found on the occasion of a patient's mammography. The operative specimen revealed an invasive ductal carcinoma of 4mm diameter which scored III on the Elston and Ellis scale (oestrogen and progesterone receptors tested negative and HER-2 was over-expressed). It was associated with a high grade in situ ductal carcinoma. No systemic treatment was prescribed due to the small size of the carcinoma. The development of partially or totally amagnetic microbiopsy pistols would help perform microbiopses guided by MRI.

[Breast cancer after Hodgkin disease]. / Cancer du sein après maladie de Hodgkin.

Secondary breast cancer represents 6 to 9% of secondary neoplasia after treatments for Hodgkin Disease (HD). Mostly, they appear 10 years after the end of treatments for HD. The most important risk factors are mantle field irradiation and the young age. The means of screening and treatments are still in discussion. We report a case of bilateral intraductal and invasive carcinoma that occurred 16 years after treatments for HD, developing its particularities in diagnosis and treatment, particularly place of conservative treatments and sentinel lymph node biopsy.

High yield synthesis, purification and characterisation of the RNase L activators 5'-triphosphate 2'-5'-oligoadenylates.

Upon viral infection, double-stranded viral RNA is detected very early in the host cell by several cellular 2'-5' oligoadenylate synthetases, which synthesize 2'-5' adenylate oligonucleotides that activate the cellular RNase L, firing an early primary antiviral response through self and non-self RNA cleavage. Transfecting cells with synthetic 2'-5' adenylate oligonucleotides activate RNase L, and thus provide a useful shortcut to study the early steps of cellular and viral commitments into this pathway. Defined 2'-5' adenylate oligonucleotides can be produced in vitro, but their controlled synthesis, purification, and characterisation have not been reported in detail. Here, we report a method suitable to produce large amounts of 2-5As of defined lengths in vitro using porcine OAS1 (pOAS) and human OAS2 (hOAS). We have synthesized a broad spectrum of 2-5As at the milligram scale and report an HPLC-purification and characterisation protocol with quantified yield for 2-5A of various lengths.

Long-term outcome of surgically-treated habitual patellar dislocation in children with coexistent patella alta. Minimum follow-up of 11 years.

We retrospectively reviewed the operative treatment carried out between 1988 and 1994 of eight patients with habitual patellar dislocation. In four the condition was bilateral. All patients had recurrent dislocation with severe functional disability. The surgical technique involved distal advancement of the patella by complete mobilisation of the patellar tendon, lateral release and advancement of vastus medialis obliquus. The long-term results were assessed radiologically, clinically and functionally using the Lysholm knee score, by an independent observer. The mean age at operation was 10.3 years (7 to 14) with a mean follow-up of 13.5 years (11 to 16). One patient required revision. At the latest follow-up, all patellae were stable and knees functional with a mean Lysholm knee score of 98 points (95 to 100). In those aged younger than ten years at operation there was a statistically significant improvement in the sulcus angle at the latest follow-up (Student's t-test, p = 0.001). Two patients developed asymptomatic patella infera as a late complication. This technique offers a satisfactory treatment for the immature patient presenting with habitual patellar dislocation associated with patella alta. If performed early, we believe that remodelling of the shallow trochlea may occur, adding intrinsic patellofemoral stability.

[Results of resection for ductal adenocarcinoma of the pancreatic head]. / Résultats carcinologiques de l'exérèse chirurgicale du cancer glandulaire céphalique du pancréas.

INTRODUCTION: Pancreaticoduodenectomy (PD) is the only curative treatment for adenocarcinoma of the pancreatic head but is associated with a significant early morbidity and a poor long term survival. Therefore, its value is still debated. The aim of this study was to evaluate early and distant results of PD for pancreatic adenocarcinoma, and to identify prognostic factors. SUMMARY: Seventy-nine patients who underwent PD with curative intent for adenocarcinoma of the pancreatic head from 1982 to 2002 were studied retrospectively. The following data were evaluated: operative mortality, long-term survival, prognostic factors (through univariate and multivariate analysis), and characteristics of 5-year survivors. RESULTS: Mortality rate was 1.3%. Survival at 1, 3 and 5 years was 46%, 26% and 11%. The median survival was 12 months. The prognostic factors were the T stage (T.N.M. classification) and radicality of resection. After multivariate analysis, radicality of resection was the only independent prognostic factor. Five patients survived for more than 5 years. They did not differ of the other patients but none had positive margin or venous invasion. CONCLUSIONS: These results (low mortality, significant distant survival including some long term survivors) suggest that PD for pancreatic adenocarcinoma must be indicated in most low-risk patients. PD remains the only curative treatment allowing prolonged survival.

[Late intestinal fistula following implantation of parietal abdominal prostheses]. / Fistules intestinales tardives après implantation de prothèse pariétale abdominale.

STUDY AIM: The aim of this retrospective study was to describe an unusual complication of the nonabsorbable meshes used for repair of incisional hernia or inguinal hernia. PATIENTS AND METHODS: This study included eight observations of intestinal fistulas that occurred between 1 and 13 years after using Mersilène (Dacron) mesh for repair of an incisional hernia (7 cases) and an inguinal hernia (1 case). There were 6 men and 2 women (mean age: 58 years, range: 35-85 years) with an external intestinal fistula (n = 6) or an internal intestinal fistula (n = 2). All the patients required a reoperation for extraction of the mesh and treatment of the bowel injuries. RESULTS: There was one secondary death in a 85 years old woman in relation with a vascular complication after incomplete excision of the prosthesis. In five patients out of six, there was a recurrence of the incisional hernia. CONCLUSION: The intestinal fistulas associated with prosthetic repair of the abdominal wall are mostly observed with intraperitoneal mesh but this factor is not exclusive. Their frequency after repair of incisional or inguinal hernia with non absorbable mesh is estimated between 0.3 and 3.5%. The use of nonabsorbable mesh should be limited to the indications of strict necessity, without any septic context or emergency surgery. The contact of the mesh with the bowel should be formally avoided.

[Costal chondroma and chondrosarcoma]. / Chondromes et chondrosarcomes costaux.

The aim of this study was to report two cases of chondrosarcoma located on the chest wall, in order to emphasize the difficulty encountered by the pathologist to differentiate a chondrosarcoma from a chondroma and the importance, in our opinion, of performing a large resection with wide margins in all cases.

3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation.

gamma-Irradiation of several amino acids (Val, Leu, Ile, Lys, Pro, and Glu) in the presence of O2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO* attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3-hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4-hydroxyhexanoic acid], (2S, 5R)-5-hydroxylysine [(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5-hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA and histone H1) exposed to HO./O2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.

Management of fibular hemimelia: amputation or limb lengthening.

We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia treated by amputation or limb lengthening to evaluate these methods of treatment. There were 12 boys and 10 girls, all with associated anomalies in the lower limbs. Twelve patients (13 limb segments) had early amputation and prosthetic fitting and ten had tibial lengthening using the Ilizarov technique. At the latest follow-up, the twelve patients who had amputation were functioning well and had few complications. The ten patients who had lengthening had suffered numerous complications, and all had needed either further corrective surgery or to wear braces or shoe-raises. Two of the ten lengthened limbs required late amputation for poor function or cosmesis. There were fewer hospital admissions, clinic visits, and periods of absence from school in the amputation group. Our findings suggest that amputation is a more effective method of management than limb-lengthening in severe fibular hemimelia. The Ilizarov method is an attractive alternative for selected patients, but its exact role is not yet established. One problem is that families often have unrealistic expectations of the surgical and prosthetic technology available and may refuse amputation when this has been recommended.

Insecticidal activity of a recombinant baculovirus containing an antisense c-myc fragment.

Attempts to develop baculovirus-based insecticides by insertion of genes encoding enzyme inhibitors, neuropeptides or toxins have met with some success. However, it is often difficult to ensure correct processing or secretion of the encoded peptides. Here we tested a simpler strategy by insertion of an antisense fragment of a host gene to block translation of a protein essential for larval growth and development. We selected the c-myc gene for two main reasons: (i) its protein is known to be well conserved in evolution and to have multiple essential functions during development; and (ii) c-myc family genes have yet to be characterized in insects, thus blockage of essential genes by anti-sense transcripts from a strong virus promoter could provide a sensitive test for the existence of myc-like gene products. An appropriate fragment of the human c-myc gene was inserted downstream from the polyhedrin promoter of Autographa californica nucleopolyhedrovirus and tested in bioassays on Spodoptera frugiperda larvae. Western blot analysis with a human c-myc antibody revealed an endogenous protein band which bound specifically to these antibodies. This band disappeared more rapidly from cells infected with the antisense c-myc recombinant virus than from those infected with c-myc-negative virus. Results of bioassays showed that the antisense construct stopped feeding as soon as the polyhedrin promoter-driven transcripts accumulated, followed shortly by death of the larvae. These results suggest that c-myc-like protein(s) exist in insects and that the antisense strategy is an effective approach to virus insecticide productions.

Effects of UV and visible radiation on DNA-final base damage.

Several mechanisms are likely to be involved in the solar radiation-mediated modifications of cellular DNA. Direct excitation of DNA bases by the UVB component (290-320 nm) of solar light gives rise, mostly through oxygen independent reactions, to the formation of dimeric pyrimidine lesions including cyclobutadipyrimidines, pyrimidine (6-4) pyrimidone photoproducts and related valence Dewar isomers. In addition, photoexcitation of cytosine and guanine may lead to the formation in relatively minor yields of 6-hydroxy-5,6-dihydrocytosine and 8-oxo-7,8-dihydroguanine, respectively. A second mechanism that requires the participation of endogenous photosensitizers together with oxygen is at the origin of most of the DNA damage generated by the UVA (320-400 nm) and visible light. Singlet oxygen, which arises from a type II mechanism, is likely to be mostly involved in the formation of 8-oxo-7,8-dihydroguanine that was observed within both isolated and cellular DNA. However, it may be expected that the latter oxidized purine lesion together with DNA strand breaks and pyrimidine base oxidation products are also generated with a lower efficiency through Fenton type reactions. A more definitive assessment of these mechanisms would require further studies aimed at the identification and quantification of the different DNA photolesions including both dimeric pyrimidine photoproducts and photooxidized lesions.

Effect of chronic renal failure on the expression of erythropoietin message in a murine model.

The anemia of chronic renal failure (CRF) is largely due to decreased production of erythropoietin (EPO) by the kidney. A small amount of EPO also originates from extra-renal sources, and this would be expected to assume a more important role in maintaining erythropoiesis when renal production is impaired. In this study, we examined the production of EPO mRNA by RT-PCR in kidney, liver, and bone marrow tissues isolated from normal mice, mice rendered acutely anemic by phlebotomy, and from mice with surgically induced CRF. The induction of acute anemia results in an expected increase in the expression of EPO mRNA in renal and hepatic tissue. In contrast, while the expression of EPO mRNA was expectedly reduced in the kidney from CRF mice, it was completely absent in the liver of these same animals. EPO mRNA expression was also absent in the bone marrow in both states of acute anemia and CRF. These results show that CRF can directly or indirectly can suppress the extrarenal production of EPO by the liver and that this effect may further aggravate the anemia of CRF.

A common pathway for p10 and calyx proteins in progressive stages of polyhedron envelope assembly in AcMNPV-infected Spodoptera frugiperda larvae.

The assembly of the polyhedron envelope in baculovirus-infected cells has been the subject of several studies, yet it is still poorly understood. We have used immunogold-labelled antibodies to two baculovirus proteins, p10 and calyx (also referred to as polyhedron envelope protein or PEP), to follow envelope assembly in AcMNPV-infected tissues of Spodoptera frugiperda larvae. We show that, in wild type virus, both proteins colocalize in fibrillar structures and associated electron-dense spacers which progress to encircle the polyhedra, as well as in completed polyhedron envelopes. In cells infected with polyhedrin-negative (PH-) viruses, an unusual proliferation of these spacers was observed suggesting a deregulatory event in the envelope assembly process. Results of Northern and Western blot analysis revealed that synthesis of P10 and calyx mRNA and proteins in PH- AcMNPV is unaffected as compared to wild type virus. Taken together, the observed physical and compositional connection between fibrillar structures, spacers and polyhedron envelopes, as well as the abnormal appearance of the spacers in PH- mutants, provide further evidence in support of a cooperative role of these structures in the assembly of the polyhedron envelope.

Photooxidation of d(TpG) by riboflavin and methylene blue. Isolation and characterization of thymidylyl-(3',5')-2-amino-5-[(2-deoxy-beta-D- erythro-pentofuranosyl)amino]-4H-imidazol-4-one and its primary decomposition product thymidylyl-(3',5')-2,2-diamino-4-[(2-deoxy-beta-D- erythro-pentofuranosyl)amino]-5(2H)-oxazolone.

The major initial product of riboflavin- and methylene blue-mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen-saturated aqueous solution has previously been identified as 2-amino-5-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino] 4H-imidazol-4-one (dlz). At room temperature in aqueous solution dlz decomposes quantitatively to 2,2-diamino-4-[(2-deoxy-beta-D-erythro- pentofuranosyl)amino]-5(2H)-oxazolone (dZ). The data presented here show that the same guanine photooxidation products are generated following riboflavin- and methylene blue-mediated photosensitization of thymidylyl-(3',5')-2'-deoxyguanosine [d(TpG)]. As observed for the monomers, the initial product, thymidylyl-(3',5')-2-amino-5-[(2-deoxy- beta-D-erythro-pentofuranosyl)amino]-4H-imidazol-4-one [d(Tplz)], decomposes in aqueous solution at room temperature to thymidylyl-(3',5')-2,2-diamino-4- [(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-5(2H)-oxazolone [d(TpZ)]. Both modified dinucleoside monophosphates have been isolated by HPLC and characterized by proton NMR spectrometry, fast atom bombardment mass spectrometry, chemical analyses and enzymatic digestions. Among the chemical and enzymatic properties of these modified dinucleoside monophosphates are: (i) d(Tplz) and d(TpZ) are alkali-labile; (ii) d(Tplz) reacts with methoxyamine, while d(TpZ) is unreactive; (iii) d(Tplz) is digested by snake venom phosphodiesterase, while d(TpZ) is unaffected; (iv) relative to d(TpG), d(TpZ) and d(Tplz) are slowly digested by spleen phosphodiesterase; (v) d(Tplz) and d(TpZ) can be 5'-phosphorylated by T4 polynucleotide kinase. The first observation suggests that dlz and dZ may be responsible for some of the strand breaks detected following hot piperidine treatment of DNA exposed to photosensitizers.

The value of computed tomography for the diagnosis of recurrent patellar subluxation in adolescents.

OBJECTIVE: To determine if computed tomography of the patellofemoral joint has any advantage over standard radiologic techniques in the evaluation of recurrent patellar subluxation. DESIGN: A case series. SETTING: A tertiary children's hospital out-patient clinic. PARTICIPANTS: Forty consecutive adolescents with a clinical diagnosis of recurrent patellar subluxation (study group) and 14 volunteers with normal knees (control group). INTERVENTIONS: A standardized radiologic protocol, including axial views of the patella at 30 degrees of knee flexion, with and without external torsion of the tibia, and computed tomography (CT) of the patella at 15 degrees of knee flexion. MAIN OUTCOME MEASURES: The lateral patellofemoral angle on the axial views and on the CT scan and patellar centralization on the CT scan. RESULTS: In the control group, no radiologic evidence of recurrent patellar subluxation was found. In the study group, an abnormal lateral patellofemoral angle was found in 25% of axial views; this rate increased to 42% with external rotation and 86% on the CT scan. Patellar centralization was abnormal in 79% of cases. CONCLUSIONS: CT of the patellofemoral joint is more sensitive than standard radiographs for the diagnosis of recurrent patellar subluxation. The use of CT is recommended when standard radiographs appear normal.

Congenital glenoid dysplasia: case report in two consecutive generations.

Congenital glenoid dysplasia is a rare congenital condition of the shoulder. We report the case of a 6-year-old girl that was referred to our institution for restricted motion of both shoulders. Radiological examination revealed bilateral glenoid dysplasia. At the time of the child's examination, her mother also complained of shoulder stiffness; radiographs of her shoulders were taken and revealed that she too had glenoid dysplasia. Congenital glenoid dysplasia results from failure of development of the inferior ossification center of the glenoid fossa. Shoulder stiffness is the primary resultant disability, although it is variable. Our case is notable because we identified the dysplasia in two successive generations of the same family, although the mother was unaware she had the condition.