Paraesophageal hiatal hernia. Open vs. laparoscopic surgery.

BACKGROUND: paraesophageal hiatal hernia represents 5-10% of hiatal hernias. Its importance is based on the severe complications it may have, including gastric volvulus, and surgical treatment is recommended when a diagnosis is established. MATERIAL AND METHODS: a retrospective study of all patients who underwent surgery for paresophageal hernia between 1985 and 2007. RESULTS: we studied 90 cases, 68 females and 22 males with a median age of 67.6 years (37-96). Forty-five patients reported pyrosis, 34 epigastric postprandial pain, and 15 dysphagia; eight patients were diagnosed with gastric volvulus. Eighty-one patients underwent elective surgery and 9 emergency surgery. Forty-seven cases underwent an open procedure and 43 a laparoscopic one; 5 (11.6%) of them required conversion. The techniques performed were D Or fundoplication in 35 cases, Nissen in 35, Toupet in 14, simple hiatal closure in 2, Narbona in 1, and Lortat-Jakob in 1; in 10 patients a mesh was placed. The complication rate for open procedure was 10.6 and 9.5% for the laparoscopic one (p > 0.05). Median hospital stay was 9.1 days for the open procedure and 3.4 for the laparoscopic one (p < 0.05). As follow-up, we analyzed 84 patients. After a median follow-up of 12 years (1-19), 15 patients were still symptomatic (17.8%), with recurrence in 8 cases (5 required reoperation). The satisfaction rate was 95.5%. CONCLUSION: equivalent results were observed after laparoscopic and open surgery and a significant shorter hospital stay in the laparoscopic one. Therefore, we think that laparoscopic surgery should be considered as the election procedure for paraesophageal hiatal hernia.

Injury to the infrapatellar branch of the saphenous nerve in ACL reconstruction with the hamstrings technique: clinical and electrophysiological study.

The incidence of IBSN injury to the infrapatellar branch of the saphenous nerve (IBSN) in ACL surgery using the hamstrings technique has been reported to be between 30 and 59%. The purpose of this study was to evaluate the incidence of IBSN injury in ACL surgery with the hamstrings technique through clinical and electrophysiological evaluation, and also to evaluate potential risk factors of IBSN injury related to the surgical incision. Between November 2003-September 2004, 21 consecutive patients (22 knees) with an acute ACL rupture suitable for reconstruction were included. Patients with previous surgeries or scars around the knee and those with any degree of osteoarthritis were excluded. Clinical and electrophysiological evaluations were performed in all the cases. Hypoesthesia of the IBSN territory was found in 17 knees (77%) with an average area of 36 cm(2) (1-120 cm(2)). Injury to the IBSN was electrophysiologically detected in 15 knees (68%). Two patients also had an injury to the saphenous nerve (9%). The presence of sensory loss associated with damage to the IBSN did not correlate with the size of the incision or the distance to the tibial tubercle. This injury probably occurs during tendon harvesting as found by an injury to the saphenous nerve in two of our patients. However the sensory loss does not impair normal daily activities in these patients.

Bipolar radiofrequency in the human meniscus. Comparative study between patients younger and older than 40 years of age.

PURPOSE: To morphohistologically evaluate the effect of four increasing intensities of bipolar radiofrequency (RF) on the human meniscus and to compare the changes seen in the menisci from patients younger and older than 40 years old. METHODS: Thirty fresh menisci were divided in two groups. Group 1: 12 menisci from patients younger than 40 y.o.; Group 2: 18 menisci from patients older than 40 y.o. Groups 1 and 2 were divided in four zones and subjected in vitro, for 3 s, to four intensities of bipolar RF energy. The samples were studied macroscopically, and microscopically. RESULTS: Thermal changes were present between 0 and 4000 microm from the meniscal surface, with an average of 1699 microm (S.D. 740), and was significantly higher on the ablation than the coagulation group (p<0.001). We found a significant difference between the depth of thermal changes in the menisci from patients younger and older than 40 years old at medium intensities of RF energy (p=0.038 and p=0.044). CONCLUSIONS: Although bipolar RF can cause deep thermal changes (up to 4000 microm) on the human meniscus, this effect depends on the magnitude of the energy applied. When comparing the effect between younger and older patients, the changes were deeper in the older group when RF was applied at medium intensities. CLINICAL RELEVANCE: Based on our findings, we recommend to exert precaution when applying RF energy at medium intensities in the degenerative meniscus, due to a deeper thermal effect in this group.

Efficient nucleotide excision repair of cisplatin, oxaliplatin, and Bis-aceto-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216) platinum intrastrand DNA diadducts.

Tumors exhibit a spectrum of cellular responses to chemotherapy ranging from extreme sensitivity to resistance, either intrinsic or acquired. These variable responses are both patient and tumor specific. For platinum DNA-damaging agents, drug resistance depends on the carrier ligand of the platinum complex and is due to a combination of mechanisms including DNA repair. Nucleotide excision repair is the only known mechanism by which bulky adducts, including those generated by platinum chemotherapeutic agents, are removed from DNA in human cells. In this report, we show that the types of DNA lesions generated by three platinum drugs, cisplatin, oxaliplatin, and (Bis-aceto-ammine-dichloro-cyclohexylamine-platinum(IV) (JM216), are repaired in vitro with similar kinetics by the mammalian nucleotide excision repair pathway.

The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts.

Defects in mismatch repair are associated with cisplatin resistance, and several mechanisms have been proposed to explain this correlation. It is hypothesized that futile cycles of translesion synthesis past cisplatin-DNA adducts followed by removal of the newly synthesized DNA by an active mismatch repair system may lead to cell death. Thus, resistance to platinum-DNA adducts could arise through loss of the mismatch repair pathway. However, no direct link between mismatch repair status and replicative bypass ability has been reported. In this study, cytotoxicity and steady-state chain elongation assays indicate that hMLH1 or hMSH6 defects result in 1.5-4.8-fold increased cisplatin resistance and 2.5-6-fold increased replicative bypass of cisplatin adducts. Oxaliplatin adducts are not recognized by the mismatch repair complex, and no significant differences in bypass of oxaliplatin adducts in mismatch repair-proficient and -defective cells were found. Defects in hMSH3 did not alter sensitivity to, or replicative bypass of, either cisplatin or oxaliplatin adducts. These observations support the hypothesis that mismatch repair defects in hMutL alpha and hMutS alpha, but not in hMutS beta, contribute to increased net replicative bypass of cisplatin adducts and therefore to drug resistance by preventing futile cycles of translesion synthesis and mismatch correction.

Revascularisation pattern of ruptured flexor tendon grafts in anterior cruciate ligament reconstruction: A histological study. / Patrón de revascularización de injertos de tendones flexores rotos en reconstrucción de ligamento cruzado anterior: un estudio histológico.

INTRODUCTION: For successful anterior cruciate ligament (ACL) reconstruction, revascularisation and histological maturation are necessary, as their failure can cause graft rupture. PURPOSE: The purpose of this study was to describe differences in the histological maturation of early failed plasty (less than 12 months after surgery) and late failed plasty (more than 12 months after surgery) in patients with re-rupture after ACL reconstruction with hamstring tendons. MATERIAL AND METHODS: A descriptive observational study was conducted on a consecutive series of 20 patients whose ACL reconstruction had failed. Graft biopsy samples were obtained during the revision surgery from the proximal, medial, and distal graft remnants. The samples were evaluated by light microscopy, and the vascularity and maturation of the samples were established by histological scoring. RESULTS: The most common aetiology of reconstruction failure (86.6%) was a specific event with non-contact mechanism. The patients with re-rupture of their ACL plasty less than 12 months after surgery had substance vessels that were less deep. The distal segment of the graft in those patients showed a delay in histological maturation with fewer collagen fibres. CONCLUSION: In patients whose ACL grafts failed less than 12 months after surgery, a lower distribution of blood vessels and collagen fibres was found that were less ordered in the distal graft. These results indicate a delay in maturation, which leads to a higher risk of graft failure.

A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer.

We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. Considering the carboplatin doses administered (two to three times those generally achieved with growth factor support), toxicity has been relatively modest. The median duration of grade 4 neutropenia and thrombocytopenia was not significantly different between the AUCs of 8 and 18, which proved to be the maximum tolerated carboplatin dose. Twelve courses were associated with hospitalization for neutropenic fever or catheter-related thrombophlebitis. One treatment-related death occurred, and severe toxicity caused withdrawal of two patients treated at the AUC of 20. Peripheral neuropathy was the most common serious nonhematologic complication. Pharmacokinetic analysis showed significantly lower measured versus predicted AUC values. Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.

DNA damage inducible-gene expression following platinum treatment in human ovarian carcinoma cell lines.

PURPOSE: DNA damage-inducible genes, such as gadd153, gadd45, p21 and c-jun, have previously been shown to be induced by the chemotherapeutic agent cisplatin. One of these genes, gadd153, has previously been reported to be differentially expressed in cisplatin-resistant cell lines and, therefore, to be a potential prognostic indicator for tumor response to cisplatin-based chemotherapy. It is not currently known whether such damage-inducible genes are turned on by the DNA damage itself (e.g. by the formation of Pt-DNA adducts) or by the downstream biological consequences of that damage. It is also not known whether the increased expression of these DNA-damage-inducible genes is related to immediate protective responses such as DNA repair or to more delayed responses such as cell cycle arrest or apoptosis. These experiments were initiated to characterize more fully the nature of the DNA damage-inducible response to cisplatin treatment and to determine whether any of these genes might be useful prognostic indicators of tumor response to cisplatin chemotherapy. METHODS: The dose-response and time-course for the induction of the DNA damage-inducible genes gadd153, gadd45, p21 and c-jun were examined by Northern analysis in the human ovarian carcinoma cell line 2008 and its resistant subclone C13* following treatment with platinum anticancer agents. The extent of gene expression was correlated with cytotoxicity determined by growth inhibition assay, Pt-DNA adducts determined by atomic absorption spectrometry and inhibition of DNA synthesis determined by 3H-thymidine incorporation. RESULTS: All four genes were induced maximally in both sensitive and resistant cell lines at lethal cisplatin doses (> or = ID90). Induction was maximal between 24 and 48 h following exposure to the drug for all genes except c-jun which was induced by 6 h. At 24 h following cisplatin treatment the overall levels of gadd153 were less in the resistant C13* cell line than in the parental 2008 cell line, while those of gadd45 were greater in C13* than in 2008. Maximal expression of p21 and c-jun was not significantly different in the two cell lines. The dose-response of these genes correlated with the cytotoxicity of cisplatin and the inhibition of DNA synthesis by cisplatin, rather than to the actual levels of Pt-DNA adducts. The more cytotoxic platinum analog, ormaplatin, also induced gadd153 and its induction was also based on cytotoxicity. CONCLUSION: These results suggest that the regulation of gadd153 and gadd45 expression occurs thorough separate pathways in the 2008 and C13* cell lines. The DNA damage-inducible gene response for all four damage-inducible genes tested appeared to be more directly correlated with downstream biologic effects of cisplatin damage than with actual Pt-DNA adduct levels. The time-course and dose-response for induction of these genes was more consistent with delayed responses such as apoptosis rather than more immediate responses such as DNA repair. Finally, these results strengthen previous suggestions that the expression of gadd153, and possibly other DNA damage-inducible genes, may be useful indicators of tumor response to cisplatin-based chemotherapy.

Organ-specific biotransformation of ormaplatin in the Fischer 344 rat.

We examined the intracellular biotransformation products of ormaplatin [(d,l-trans)1,2-diaminocyclohexanetetrachloroplatinum(IV)] (formerly called tetraplatin) in liver, kidney, spleen, small intestine, and plasma of the adult male Fischer 344 rat. Previous studies have established that the rank order of ormaplatin toxicity in Fischer 344 rats is spleen approximately gastrointestinal tract > kidney >> liver. Animals were given tritium-labelled drug i.v. at 12.5 mg/kg, and tissues were harvested 30 min later. The kidney was found to concentrate total and cytosolic platinum to a greater extent than any of the other tissues. The absolute amount of cytosolic platinum, in micrograms per gram tissue, that was irreversibly bound to protein and/or other macromolecules was also greatest in the kidney. However, when the amount bound was expressed as a percentage of the total cytosolic platinum, the kidney was significantly lower than any other tissue. Of the various low molecular mass platinum biotransformation species characterized, by far the most abundant were complexes of platinum with the sulfur-containing molecules cysteine, methionine, and glutathione (GSH). There was more of the methionine complex in the blood plasma than in any of the tissues except for the spleen. No significant differences among the tissues were detected for the dichloro, cysteine, methionine, or the GSH complexes. The tritium-labelled diaminocyclohexane (DACH) carrier ligand appeared to remain stably bound to the platinum while in the plasma, as there was less free DACH ligand detected in plasma ultrafiltrate than in any tissue ultrafiltrate. Among the tissues, the free DACH levels were in the range of 20% of the radioactivity recovered from the HPLC column and were not significantly different. Consequently, neither biodistribution nor tissue-specific biotransformation of ormaplatin provides a ready explanation for the tissue specificity of ormaplatin toxicity in Fischer 344 rats. However, in kidney there was much less of the reactive PtCl2(DACH) species than has previously been reported for the corresponding Pt(NH3)2Cl2 species in cisplatin-treated rats. Thus, these data suggest a possible explanation for differences in nephrotoxicity induced by cisplatin versus that by ormaplatin.

Cisplatin-induced alterations in the expression of the mRNAs for UV-damage recognition protein.

Enhanced DNA repair is believed to be an important mechanism of the cisplatin-resistant phenotype. UV-damage recognition protein (UV-DRP) recognizes and binds to DNA lesions and may play a role in DNA nucleotide excision repair and/or replicative bypass (which is associated with post-replication repair). Potential alternations in the expression of mRNAs for UV-DRP were analyzed in this study. Two pairs of parental and cisplatin-resistant human ovarian carcinoma cell lines were utilized. Gene expression level was assessed by northern blot hybridization. No alterations in mRNA levels for the large subunit of UV-DRP were found following cisplatin treatment, whereas mRNA levels for the small subunit of UV-DRP were induced up to 4.5-fold. The time-course and concentration-response of this induction corresponded to the previously reported increase in the UV-DRP binding activity, as measured by gel shift assay. UV-DRP binding activity in cell extracts corresponds to expression of small subunit mRNA but not to expression of large subunit mRNA. These data suggest that the small subunit may be limiting for UV-DRP activity.

Specificity of platinum-DNA adduct repair.

Cell lines with resistance to cisplatin and carboplatin often retain sensitivity to platinum complexes with different carrier ligands (e.g., oxaliplatin and JM216). HeLa cell extracts were shown to excise cisplatin, oxaliplatin, and JM216 adducts with equal efficiency, suggesting that nucleotide excision repair does not contribute to the carrier-ligand specificity of platinum resistance. We have shown previously that the extent of replicative bypass in vivo is influenced by the carrier ligand of the platinum adducts. The specificity of replicative bypass may be determined by the DNA polymerase complexes that catalyze translesion synthesis past Pt-DNA adducts, by the mismatch-repair system that removes newly synthesized DNA opposite Pt-DNA adducts, and/or by DNA damage-recognition proteins that bind to the Pt-DNA adducts and block translesion synthesis. Primer extension on DNA templates containing site-specifically placed cisplatin, oxaliplatin, or JM216 Pt-GG adducts revealed that the eukaryotic DNA polymerases beta, zeta, gamma and HIV-1 RT had a similar specificity for translesion synthesis past Pt-DNA adducts (oxaliplatin > or = cisplatin > JM216). In addition, defects in the mismatch-repair proteins hMSH6 and hMLH1 led to increased replicative bypass of cisplatin adducts, but not of oxaliplatin adducts. Finally, primer extension assays performed in the presence of HMG1, which is known to recognize cisplatin-damaged DNA, revealed that inhibition of translesion synthesis by HMG1 also depended on the carrier ligand of the Pt-DNA adduct (cisplatin > oxaliplatin = JM216). These studies show that DNA polymerases, the mismatch-repair system and damage-recognition proteins can all impart specificity to replicative bypass of Pt-DNA adducts. Replicative bypass, in turn, may influence the carrier-ligand specificity of resistance.

[Usefulness of magnetic resonance imaging in the evaluation of patellar malalignment]. / Utilidad de la resonancia magnética en la evaluación del mal alineamiento patelar.

OBJECTIVES: The aim of this study is to evaluate the usefulness of Magnetic Resonance Imaging (MRI) at 20° of knee flexion in patients with patellofemoral pain syndrome (PFPS) caused by suspected patellofemoral malalignment (PFM). MATERIAL AND METHOD: Fifty MRIs were performed on 25 patients with PFPS secondary to suspected PFM based on clinical examination, and on 25 patients without PFPS (control group). Measurements were made of tibial tuberosity-trochlear groove distance (TTTG) and modified Laurin, Merchant and trochlear angles. The results were analyzed with ANOVA and Fischer tests. Pearson correlation coefficients were used to analyze differences between PFPS and control cases. Specificity, sensitivity, positive predictive value and negative predictive value for knee pain were documented. RESULTS: Significant differences were observed between PFPS and control groups in TTTG (11.79 mm vs. 9.35 mm; P=.002), Laurin angle (12.17° vs. 15.56°; P=.05), and trochlear angle (139° vs. 130.02°; P=.049). No differences were found between groups as regards the Merchant angle (P=.5). TTTG was 70% predictive of PFPS; however, it was only 53.33% specific, with a sensitivity of 51.61% for PFPS. Laurin angle was 77.78% predictive of PFPS, with a specificity of 92% and a sensitivity of 28%. Trochlear angle was 85.71% predictive of PFPS, with a specificity of 96% and a sensitivity of 24%. CONCLUSIONS: MRI can confirm clinically suspected PFPS secondary to malalignment. MRI determination of TTTG, patellar tilt, and trochlear angle correlates positively with clinical diagnosis of PFPS, suggesting that PFPS is caused by subtle malalignment.

[Clinical factors and findings in knee arthroscopy of patients with knee arthrosis candidates for conversion to total replacement]. / Factores clínicos y hallazgos en la artroscopia de pacientes con artrosis de rodilla que favorecen la conversión a artroplastia total.

OBJECTIVES: To identify those clinical characteristic and arthroscopic findings in patients with knee arthrosis that are associated with worsening of the disease and subsequent total knee arthroplasty (TKA). METHOD: A retrospective, descriptive study was conducted on 78 consecutive patients (88 knees) who underwent knee arthroscopy for arthrosis. The study included 44 women and 34 men, with a mean age of 58.9 years (range: 37-78 years). After a mean follow-up of 50.4 months (range: 12-96 months), those patients who progressed towards TKA were identified. A logistic regression model was applied to recognise the factors associated with deterioration of the arthrosis, with consequent progression towards a TKA. RESULTS: Twenty-four out of the 88 knees progressed towards a TKA (27.3%) within a mean time of 13.5 months after arthroscopy (range: 13-29 months). The clinical characteristics that showed a significant association with poor progression of the arthrosis were: female gender (0.02) and Ahlbäck 2 (P=.04). Arthroscopic finding that proved significant correlation with worsening of the arthrosis towards TKA were: meniscal tears of the posterior horn (P=.02), meniscectomies above 60% (P=.03), and 2nd degree chondral lesions in loading areas of the medial femoral condyle (P=.02). CONCLUSION: The variables associated with a greater chance of progressing towards a TKA after a knee arthroscopy due to arthrosis in this study were, female gender, grade 2 radiographic arthrosis, posterior horn meniscal lesions, meniscectomies over 60%, and chondral lesions in loading area of the medial femoral condyle.