A case of postoperative pancreatitis in patients with renal cell carcinoma with an inferior vena cava tumor thrombus treated by presurgical lenvatinib plus pembrolizumab.

Pancreatic injury is a rare, but noted complication of nephrectomy. We report a case involving a 56-year-old man who presented with cT3bN0M0 left locally advanced renal cell carcinoma with an inferior vena cava thrombus. Nephrectomy with thrombectomy was performed given the remarkable shrinkage of the primary tumor and thrombus following lenvatinib plus pembrolizumab administration. The patient developed postoperative pancreatitis associated with unrecognized minor pancreatic injury, which was treated conservatively. To our knowledge, this has been the first case that underwent nephrectomy for RCC with an IVC thrombus after presurgical lenvatinib plus pembrolizumab and received conservative treatment for postoperative pancreatitis.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios alone or combined with prostate-specific antigen for the diagnosis of prostate cancer and clinically significant prostate cancer.

Objective: We evaluated whether the blood parameters before prostate biopsy can diagnose prostate cancer (PCa) and clinically significant PCa (Gleason score [GS] ≥7) in our hospital. Methods: This study included patients with increased prostate-specific antigen (PSA) up to 20 ng/mL. The associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) alone or with PSA with PCa and clinically significant PCa were analyzed. Results: We included 365 patients, of whom 52.9% (193) had PCa including 66.8% (129) with GS of ≥7. PSA density (PSAD) and PSA had better the area under the curve (AUC) of 0.722 and 0.585, respectively with p=0.001 for detecting PCa compared with other blood parameters. PSA combined with PLR (PsPLR) and PSA with NLR (PsNLR) had better AUC of 0.608 and 0.610, respectively with p<0.05, for diagnosing GS≥7 population, compared with PSA, free/total PSA, NLR, PLR, and PsNPLR (PSA combined with NLR and PLR). NLR and PLR did not predict PCa on multivariate analysis. For GS≥7 cancer detection, in the multivariate analysis, separate models with PSA and NLR (Model 1: PsNLR+baseline parameters) or PSA and PLR (Moder 2: PsPLR+baseline parameters) were made. Baseline parameters comprised age, digital rectal exam-positive lesions, PSA density, free/total PSA, and magnetic resonance imaging. Model 2 containing PsPLR was statistically significant (odds ratio: 2.862, 95% confidence interval: 1.174-6.975, p=0.021) in finding aggressive PCa. The predictive accuracy of Model 2 was increased (AUC: 0.734, p<0.001) than that when only baseline parameters were used (AUC: 0.693, p<0.001). Conclusion: NLR or PLR, either alone or combined with PSA, did not detect PCa. However, the combined use of PSA with PLR could find the differences between clinically significant and insignificant PCa in our retrospective study limited by the small number of samples.

Hard bilateral syphilitic testes with vasculitis: a case report and literature review.

BACKGROUND: We report the case of a patient with syphilitic testicular gumma and vasculitis with adrenal failure due to chronic steroid use. CASE PRESENTATION: A 63-year-old male presented with hard right eye swelling and very firm bilateral testes on palpation, which he had for 2 years. Testicular tumor markers were negative; syphilis test was positive. Radiological examination suggested aortitis and bilateral testicular malignancy. The patient received ampicillin for the infection and prednisolone for vasculitis. Left orchidectomy was performed to confirm the presence of testicular tumor; histological examinations revealed granulomatous orchitis. The prednisolone doses were adjusted because of relapses and adverse effects of steroid use. Unfortunately, the patient died in the intensive care unit because of uncontrolled blood pressure and pneumonia. CONCLUSIONS: This is a rare case of syphilis with testicular involvement and vasculitis. This report shows the importance of broadening the differential diagnoses of testicular firmness.

Estimation of the potential of landfill mining and exploration of metal-enriched zones.

Since the Industrial Revolution, people have exploited natural resources to manufacture products. Many of the products have later been disposed of in landfills and the like. The aim of this study was to determine the contents and chemical forms of valuable rare metals in landfills and to identify the metal-enriched zones in landfills using non-destructive prospecting methods. Box experiments were performed using four mixtures of sand and iron sulfide particles, and excavated waste samples. Field prospecting studies were performed at an industrial landfill site. As a result, it is possible to establish a grading system for elements based on the maximum contents in the fill, and the condition in the fill is found to potentially affect the metal distribution. In addition, investigations for rare metals coexisting with iron sulfide were performed at each target site. This allowed zones with high rare metal contents in the fill to be identified in a non-destructive manner. Based on the above approach, a basic evaluation of a landfill site that could be used as an "urban mine" was accomplished.

Induction of action-at-a-distance mutagenesis by 8-oxo-7,8-dihydroguanine in DNA pol λ-knockdown cells.

INTRODUCTION: In DNA, 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) is one of the most pivotal oxidatively damaged bases and induces G:C → T:A transversion mutations. DNA polymerase λ preferentially inserts dCTP opposite G(O) in vitro, and this error-free bypass function is considered to be important after A base removal from G(O):A pairs by the MUTYH DNA glycosylase. To examine the effects of reduced levels of DNA polymerase λ on the G(O)-induced mutations, the polymerase was knocked-down in human U2OS cells, and a shuttle plasmid DNA containing a G(O):C pair at position 122 in the supF gene was transfected into the cells. The plasmid DNA replicated in the cells was introduced into an Escherichia coli indicator strain, to measure the supF mutant frequency. RESULTS: The knockdown of DNA polymerase λ significantly enhanced the mutant frequency of the G(O) plasmid DNA. Contrary to our expectations, the knockdown did not promote the targeted G:C → T:A transversion. Instead, substitution mutations at G:C sites other than position 122 were enhanced in the cells. CONCLUSIONS: These results suggested that the knockdown of DNA polymerase λ induced action-at-a-distance mutagenesis in human cells when the G(O):C pair was present in the DNA.

Mutagenic bypass of 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) by DNA polymerase κ in human cells.

The formation of 8-oxo-7,8-dihydroguanine (G(O), 8-hydroxyguanine) in DNA and in the nucleotide pool results in G:C→T:A and A:T→C:G substitution mutations, respectively, since G(O) can pair with both C and A. In this study, the role of DNA polymerase κ in the mutagenicity of G(O) was investigated, using a supF shuttle plasmid propagated in human U2OS cells. This translesion synthesis DNA polymerase was knocked down by siRNA, and plasmid DNAs containing G(O):C and G(O):A pairs were transfected into the knock-down cells. The supF plasmid DNAs replicated in the cells were then introduced into Escherichia coli. Mutation analyses indicated that the knock-down of DNA polymerase κ by siRNA decreased the frequency of G:C→T:A mutation caused by G(O):C, although no effects of the DNA polymerase κ reduction were observed for the A:T→C:G substitution induced by G(O):A. These results suggested that DNA polymerase κ is involved in the mutagenic bypass of G(O) in living human cells, when the damaged base is generated by direct DNA oxidation.

Evaluation of low back pain using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire for lumbar spinal disease in a multicenter study: differences in scores based on age, sex, and type of disease.

BACKGROUND: The Japanese Orthopaedic Association (JOA) has investigated the JOA Back Pain Evaluation Questionnaire (JOABPEQ) to evaluate several aspects of low back pain in patients. The score includes five categories (25 items) selected from the Roland Morris Disability Questionnaire and Short Form 36, and a visual analogue scale. Japanese physicians have recently used these scores to evaluate back pain; however, the efficacy has not been fully explored in large-scale studies. In the current study, we used the JOABPEQ to evaluate lumbar spinal disease in 555 patients (with lumbar disc herniation, lumbar spinal stenosis, and lumbar disc degeneration/spondylosis) in multiple spine centers and compared the results based on age, sex, and type of disease. METHODS: A total of 555 patients who had low back or leg pain were selected in 22 hospitals in Chiba Prefecture. Spine surgeons diagnosed their disease type based on symptoms, physical examination, radiography images, and magnetic resonance imaging. In all, 486 patients were diagnosed with spinal stenosis (239 patients), disc degeneration/spondylosis (143 patients), or disc herniation (104 patients). The other 69 patients were diagnosed with spondylolysis (16 patients) or other diseases (53 patients). The pain score in all patients was evaluated using the JOABPEQ (from 0 to 100, with 0 indicating the worst pain). RESULTS: The age of the patients was 56.1 +/- 13.3 years (mean +/- SD); the age of patients in the disc herniation and disc degeneration/spondylosis group was significantly lower than that in the spinal stenosis group. The average JOABPEQ scores in all patients were, for low back pain, 47.1; lumbar function, 53.6; walking ability, 54.8; social life function, 48.7; and mental health, 48.3. The low back pain score in men was significantly worse than that in women. In contrast, the mental health score in women was significantly higher than that in men. The low back pain score in patients <40 years old and the walking ability score in patients >65 years old were significantly lower than those scores in other patients. Based on the disease type, low back pain, lumbar function, social life function, and mental health scores for patients with disc herniation were significantly worse than for those with spinal stenosis. CONCLUSION: JOABPEQ scores were evaluated for several lumbar diseases. The average of five categories of JOABPEQ scores in all patients was similarly distributed. However, the average scores in the five categories were significantly different depending on age, sex, and type of disease. Compared with prior mass data (baseline data on the observational cohort of the Spine Patient Outcomes Research Trial in the United States), many data were similar based on the type of disease in the current study. Furthermore, the JOABPEQ is easy to use compared with the SF-36. Hence, we concluded that the JOABPEQ could be used worldwide as a tool for evaluating low back pain.

Sensory innervation of the lateral portion of the lumbar intervertebral disc in rats.

BACKGROUND CONTEXT: An annular tear extending to the outer one-third of the annulus is thought to be one of the causes of low back pain. However, some patients have bilateral low back symptoms, even if the annular tear is localized in the lateral disc. Because nociceptive information from the lateral disc is transmitted by the dorsal root ganglion (DRG) neurons innervating the lateral disc, we investigated the distribution of the DRG neurons innervating the lateral portion of the disc. PURPOSE: To clarify the distribution and pathway of the DRG neurons innervating the lateral portion of the L5-L6 disc in rats. STUDY DESIGN/SETTING: Using the retrograde tracing method, we studied the innervation pattern of the lateral portion of the L5-L6 intervertebral disc in rats. METHODS: The retrograde transport of Fluoro-Gold (F-G; Fluorochrome, Denver, CO) was used in 22 rats. Subjects included a nontreated group (n=16) and a sympathectomized group (n=6). Seven days after the application of F-G crystals to the left lateral portion of the L5-L6 disc, bilateral T12-L6 DRGs were observed by fluorescent microscopy. RESULTS: In the nontreated group, of all the F-G-labeled neurons, 93.1% were present in the left DRGs and 6.9% were in the right DRGs. The number of labeled neurons was largest in the left L2 DRGs. In the sympathectomized group, the numbers of labeled neurons in the T13, L1 and L2 DRGs were significantly lower than the numbers in the nontreated group. CONCLUSION: Results of this study indicate that DRG neurons innervating the lateral portion of the disc are distributed mainly in the ipsilateral side but also in the contralateral side. The DRG neurons in T13, L1 and L2 innervate the lateral portion of the L5-L6 disc through the paravertebral sympathetic trunks.

Stereoscopic structure of sensory nerve fibers in the lumbar spine and related tissues.

STUDY DESIGN: Neurotracer was applied to various sites in the rat lumbar spine and related tissues. The segmental distribution of labeled neurons in dorsal root ganglia (DRG) was investigated. OBJECTIVES: To clarify the stereoscopic structure of afferent fibers innervating the lumbar spine and related tissues. SUMMARY OF BACKGROUND DATA: Afferent fibers in the rat L5-L6 lumbar intervertebral disc are reported to originate from neurons in L1 and L2 DRG. However, anatomic studies determined that each dorsal ramus of the spinal nerve sends nerves to dorsal elements of the corresponding lumbar vertebra. METHODS: Fluorescent neurotracer DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) was applied to various sites of the lumbar spine and related tissues in the L2, L5, and L6 levels in rats. DRG were sectioned 3 weeks after DiI application. Rostrocaudal distribution of DiI-labeled neurons was investigated. RESULTS: At L5, DiI-labeled neurons were prominent in DRG L3 for the lamina, L2 for the spinous process, L2 for the back muscle fascia, and L1 for the skin. Dorsal elements are therefore innervated by neurons in more rostral DRG. In the transverse plane, the more distant from the DRG a site was, the more rostral the DRG innervating the site. This structure suggested a concentric innervation pattern in the transverse plane. CONCLUSION: Stereoscopically, the peripheral innervation territory of a lumbar DRG is conical, with the apex at the ganglion and the base circumference located on the dermatome. The lumbar spine itself is involved in the conical innervation territories of DRG.

Dermatomes and the central organization of dermatomes and body surface regions in the spinal cord dorsal horn in rats.

Dermatomes and the associated central projection fields were studied with the application of fluorescent neurotracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), to 21 reference points on rat trunk and hindlimb skin. Segmental distribution and rostrocaudal central level of dorsal root ganglion (DRG) neurons innervating reference points were examined and DiI-induced fluorescent areas were mapped in the horizontal plane through lamina II of the dorsal horn. Segmental levels of DRG neurons innervating reference points were generally identical to the level determined using dye-extravasation methods. However, innervation of the first digit was situated in the L4 dermatome, not the L3 reported previously using those methods. Generally, afferents from a reference point projected to a single field in the ipsilateral dorsal horn. Reference points on ventral and dorsal median lines of the trunk were represented bilaterally. Afferents from reference points located on the ventral median line of the hindlimb projected to two separate fields: one on the medial margin of spinal cord segments L2-L5 and the other on the medial half of spinal cord segment L5. From the distribution of central projection fields of reference points, central projection fields of dermatomes were revealed as even in shape and located within corresponding spinal cord segments. The arrangement of peripheral and central fields of dermatomes and body surface regions suggests that peripheral and central projection fields of cutaneous afferent fibers are reshaped from the common prototypical pattern that exhibits an orderly and evenly sequenced arrangement.

Organization of cutaneous ventrodorsal and rostrocaudal axial lines in the rat hindlimb and trunk in the dorsal horn of the spinal cord.

The somatotopic organization of cutaneous primary afferents projecting to the dorsal horn of the rat spinal cord was investigated. The fluorescent neurotracer, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was applied to cutaneous incisions made along ventrodorsal axial lines (VDALs) or rostrocaudal axial lines (RCALs) of the trunk and hindlimb. DiI-induced fluorescent zones appeared in laminae I-III of the dorsal horn in the transverse section. Several fluorescent zones appeared at different mediolateral portions after tracer application to VDALs. After tracer was applied to RCALs, a single zone of fluorescence was observed. Serial transverse sections were used to reconstruct fluorescent zones in lamina II and to illustrate the rostrocaudally elongated band-like projection fields in a horizontal plane. In the horizontal plane, the fluorescent zones of VDALs were reconstructed to band-like projection fields. These fields were arranged mediolaterally and extended rostrocaudally for approximately the length of one spinal cord segment or less. The fluorescent zones of RCALs were reconstructed to one band-like projection field. This field extended rostrocaudally over several spinal cord segments. Cutaneous afferents from the ventral median line of the trunk, tail, hindlimb, sole, and ventral side of the digits projected to the medial margin of the dorsal horn. Cutaneous afferents from the dorsal median lines projected to the lateral margin of the dorsal horn. By analyzing the pattern of the body surface regions and the VDALs and RCALs, the central projection fields of body surface regions could be hypothesized, based on the central projection fields of the individual VDAL and RCAL afferents. Thus, we established a detailed dorsal view map of the central projection fields of cutaneous primary afferents.