[A Case of Locally Advanced Pancreatic Cancer Successfully Resected after S-1 Therapy in an Elderly Patient].

We report a case of locally advanced pancreatic body cancer, accomplishing R0 resection following preoperative chemotherapy. An 80-year-old female patient was admitted to our hospital because of high CA19-9 levels.Based on computed tomography images, she was diagnosed with locally advanced cancer of the pancreatic body.We started S-1 chemotherapy (100mg/day, 2 weeks administration 1 week rest)because the tumor was suspected to have invaded the celiac trunk and the common hepatic artery.The tumor decreased in size, and the encasement of the celiac trunk and the common hepatic artery were released, following 6 months of chemotherapy.Subsequently, distal pancreatectomy with D2 lymph node dissection was performed.The patient was healthy and showed no signs of recurrence 5 years and 9 months after surgery.

[A case of angiosarcoma of the spleen with intraperitoneal bleeding].

A 56-year-old man was admitted to our hospital with a history of abdominal discomfort and loss of appetite. Six days later, he suddenly went into shock; despite repeated blood transfusions, he died. Autopsy revealed the cause of death to be a ruptured splenic angiosarcoma, which had metastasized to multiple sites in the liver and bone. Splenic angiosarcoma is rare, and its pathophysiology is unclear. When presented with splenic angiosarcoma or suggestive symptoms, including splenic bleeding, splenomegaly, abdominal discomfort, and abdominal pain, we should carefully monitor the patient for signs of coagulopathy and prepare for the possibility of rapid progression to disseminated intravascular coagulation. In general, patients with angiosarcoma have a poor prognosis. Therefore, we hope this report will help in improving the prognosis of patients suffering from angiosarcoma by contributing to the limited clinical experience.

ß-Catenin-activated inflammatory hepatocellular adenoma with pigmentation and atypical features: a case report.

Hepatocellular adenomas are rare diseases, defined as benign liver neoplasms composed of cells with hepatocellular differentiation. Differential diagnosis of hepatocellular adenoma from other lesions, including focal nodular hyperplasia and hepatocellular carcinoma, is crucial to determine treatment strategy. We describe a case of ß-catenin-activated inflammatory hepatocellular adenoma with malignant transformation. A 50-year-old man with a suspected liver tumor, based on abdominal ultrasonography findings, was referred to our hospital. Contrast-enhanced computed tomography and magnetic resonance imaging revealed a liver tumor in S2 which was enhanced in the arterial phase to the delayed phase. Based on diagnostic imaging findings, hepatocellular adenoma or focal nodular hyperplasia was suspected. We considered the possibility of malignant potential because of the enlargement of the lesion. Thus, we performed a laparoscopic hepatectomy. Histological examination showed pigment deposition in the hepatocytes, which was determined to be lipofuscin. Mild nuclear swelling and atypia in the tumor area indicated nodular growth. Based on the histological and immunohistochemical findings, the diagnosis was ꞵ-catenin-activated inflammatory hepatocellular adenoma with atypical features. The imaging features of hepatocellular adenoma and focal nodular hyperplasia are similar, but if the tumor tends to grow, surgical treatment should be performed because of the possibility of malignant hepatocellular adenoma.

Potential of exogenous cartilage proteoglycan as a new material for cartilage regeneration.

BACKGROUND: Although proteoglycan (PG) is one of the major components of cartilage matrices, its biological function is not fully elucidated. METHODS: The objectives of this study were to investigate the proliferation and differentiation of chondrocytes embedded in atelocollagen gel with exogenous cartilage PG (PG-atelocollagen gel) in vitro, and also to evaluate the repair of cartilage defects by PG-atelocollagen gel in vivo. In the in vitro study, rabbit chondrocytes were cultured in the PG-atelocollagen gel. Cell proliferation and mRNA expression levels were measured, and gels were histologically evaluated. In the in vivo study, cultured PG-atelocollagen gel containing chondrocytes were transplanted into full-thickness articular cartilage defects in rabbit knees, and evaluated macroscopically and histologically. RESULTS: For the in vitro study, chondrocyte proliferation in 5.0 mg/ml PG-atelocollagen gel was enhanced, and the gene expression of Col2a1 and Aggrecan were decreased. In contrast, chondrocyte proliferation in 0.1 and 1.0 mg/ml PG-atelocollagen gel was not enhanced. The gene expression of Aggrecan in 0.1 and 1.0 mg/ml PG-atelocollagen gel was increased. For the in vivo study, the histological average total score of the 0.1 mg/ml PG-atelocollagen gel was significantly better than that of the group without PG. CONCLUSIONS: Although the appropriate concentration of PG has not been defined, this study suggests the efficacy of PG for cartilage repair.

Conversion surgery following gemcitabine plus cisplatin therapy for initially unresectable gallbladder cancer with peritoneal carcinomatosis: a case report.

BACKGROUND: Conversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer. CASE PRESENTATION: A 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy. CONCLUSIONS: This case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.

Widespread occurrence of eosinophilic neuronal cytoplasmic inclusions in an asymptomatic adult: a novel ubiquitin-negative filamentous inclusion.

We describe a 67-year-old woman without apparent neurological symptoms, in whom postmortem examination revealed widespread occurrence of eosinophilic neuronal cytoplasmic inclusions in the central and peripheral nervous systems. The inclusions were round, oval or rod-like in shape. Immunohistochemically, the inclusions were negative for ubiquitin and not labeled with any other antibodies, except for a partial and weak immunoreactivity with anti-neurofilament occurring rarely. Ultrastructurally, the inclusions revealed two different forms. The common form was entirely composed of bundles of wavy granule-coated filaments (20-30 nm in diameter). The other form consisted of a core containing linear filaments (12-15 nm in diameter) with electron-dense ribosome-like granules and an outer zone with wavy filaments as seen in the former. This inclusion seems to represent a new type of neuronal cytoplasmic inclusion.

The actual tendon-bone interface strength in a rabbit model.

PURPOSE: The purpose of this study was to evaluate the strength of the interface throughout the entire integration process by use of tendon graft reinforced with a suture material compared with nonreinforced tendon graft. METHODS: Using 60 skeletally mature female Japanese white rabbits, we performed biomechanical testing and histologic evaluation to compare tendon grafts reinforced with a suture material (suture group) and nonreinforced grafts (control group). The tendon graft was drawn through a bone tunnel measuring 2.5 mm in diameter and was tightly fixed. For biomechanical testing, the tendon graft was tested in tensile loading along the axis of the bone tunnel at a crosshead speed of 100 mm/min. RESULTS: On biomechanical testing, at 4, 6, 8, and 12 weeks, tendon grafts had pulled out of the bone tunnel in the suture group. In the control group all tendon grafts had pulled out at 4 and 6 weeks, and rupture at the midsubstance was seen at 8 and 12 weeks. The failure load-to-tunnel length ratio was significantly larger in the suture group compared with the control group at 8 and 12 weeks. On histologic evaluation, both groups had similar findings with direct attachments to bone by 12 weeks. CONCLUSIONS: In this study of the healing characteristics of augmented and nonaugmented tendon grafts placed in a bone tunnel, we found that the suture-augmented tendons had superior failure load-to-tunnel length ratios at 8, 12, and 16 weeks compared with nonaugmented tendons. The failure mode in the augmented grafts was tendon pullout at all time points except 16 weeks, whereas the nonaugmented grafts failed by midsubstance rupture after 8 weeks. Histologically, both groups had similar findings with direct attachments to bone by 12 weeks. CLINICAL RELEVANCE: The tendon graft has the potential to be pulled out of the bone tunnel after complete integration.

Basic-helix-loop-helix (bHLH) transcription factor DEC2 negatively regulates vascular endothelial growth factor expression.

DEC1 (BHLHB2/Sharp2/Stra13) and DEC2 (BHLHB3/Sharp1) are basic-helix-loop-helix (bHLH) transcription factors, involved in cellular differentiation, responses to hypoxia and circadian rhythms. We recently showed that the expression of DEC1 and DEC2 was up-regulated by hypoxia; however, the functions of these two factors under hypoxic conditions have not been elucidated in detail. It is well established that the expression of vascular endothelial growth factor (VEGF) is up-regulated by hypoxia, and the expression of VEGF in response to hypoxia depends on transcriptional activation by a heterodimer comprising hypoxia-inducible factor 1alpha (HIF-1alpha) and arylhydrocarbon receptor nuclear translocator 1 (ARNT1). In the present study, we showed that DEC2, but not DEC1, suppressed VEGF gene expression under hypoxic conditions. DEC2 protein was co-immunoprecipitated with HIF-1alpha but not with ARNT1. The binding of HIF-1alpha to the hypoxia response element (HRE) in the VEGF promoter was decreased by DEC2 over-expression, and increased by DEC2 knockdown. We also showed that the circadian expression of VEGF showed a reciprocal pattern to that of DEC2 in cartilage. DEC2 had a circadian oscillation in implanted Sarcoma 180 cells. We conclude that DEC2 negatively regulates VEGF expression and plays an important role in the pathological conditions in which VEGF is involved.

Passage-affected competitive regulation of osteoprotegerin synthesis and the receptor activator of nuclear factor-kappaB ligand mRNA expression in normal human osteoblasts stimulated by the application of cyclic tensile strain.

Mechanical stress application is a unique method for bone studies. We have reported regulation via the p38 mitogen-activated protein kinase (MAPK) pathway in osteoblasts under application of cyclic tensile strain (CTS), among many reports on the extracellular signal-regulated kinase (ERK) 1/2 pathway during mechanical stress, and questions remain as to the differences between our findings and those of others regarding types of MAPK activation. In the present study, osteoblasts were used after the third passage and stimulated by the application of 7%, 0.25 Hz CTS for 3 days, 4 h/day. CTS-induced osteoprotegerin (OPG) synthesis in osteoblasts increased at the third passage and decreased at the fifth passage, whereas CTS-induced receptor activator of nuclear factor-kappaB ligand (RANKL) mRNA expression decreased in osteoblasts at the third passage and increased at the fifth passage. Increases in CTS-induced osteopontin (OPN) synthesis, cyclooxygenase-2 (Cox-2) mRNA expression, and nitric oxide (NO) production by osteoblasts did not change at the third and fifth passages. Furthermore, p38 MAPK at the third passage and ERK1/2 at the fifth passage were found to be competitively activated in osteoblasts by the application of CTS. Based on these results, osteoblasts were shown to be affected by the number of passages. It was suggested that the examination of passage-affected characteristics of osteoblasts might not only be pertinent to the analysis of cellular senescence and in vivo models of bone remodelling with aging but could also be useful in the development of bone tissue engineering.

An aggressive course of Xp11 translocation renal cell carcinoma in a 28-year-old man.

Cases of renal cell carcinoma (RCC) associated with Xp11 translocations are rare and are reported predominantly in children. We report a case of a young man who developed an aggressive Xp11 translocation RCC. A 28-year-old man presented with back pain, fever and macroscopic hematuria. Computed tomography of the abdomen showed a heterogeneous mass in the left kidney. Left radical nephrectomy was performed. Hematoxylin-eosin staining revealed nested and papillary architecture, clear and eosinophilic cytoplasm and vesicles with prominent nucleoli. Immunohistochemical evaluation revealed that the tumor cells showed nuclear labeling for TFE3 protein. On the basis of these findings, the case was diagnosed as Xp11 translocation RCC. This tumor massively recurred and led to the patient's death 2 years after the initial diagnosis. The utility of immunohistochemistry using antibodies against TFE3 in RCC occurring in young adults may be necessary for accurate diagnosis.

Claudin-1 expression is induced by tumor necrosis factor-alpha in human pancreatic cancer cells.

Claudin-1 is a membrane protein with four transmembrane domains, that is exclusively localized at cellular tight junctions. Recent studies have reported that claudin-1 plays an important role in cancer invasion and metastasis. However, the significance of claudin-1 in pancreatic cancer is still unknown. In the present study, we investigated the role of claudin-1 expression in pancreatic cancer growth using the PANC-1 human pancreatic cancer cell line. Treatment with tumor necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, resulted in increased detection of 89 kDa products of poly-(ADP-ribose) polymerase (PARP), a marker of apoptosis, and decreased PANC-1 cell proliferation by 23%. Expression of claudin-1 was up-regulated by TNF-alpha in a concentration-dependent manner in PANC-1 cells. PANC-1 cells treated with TNF-alpha and siRNA against claudin-1 showed a 15% increase in proliferation; i.e. the cells transfected with siRNA against claudin-1 showed resistance to TNF-alpha-induced apoptosis. These results suggest that claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells.

Establishment of transplantable murine osteosarcoma cell line with endochondral ossification.

Osteosarcoma is defined as a malignant mesenchymal tumor in which tumor cells produce bone matrix. Osteosarcoma cell line (Nishi-Hirosaki osteosarcoma, NHOS) from a spontaneous soft tissue tumor in an athymic mouse was established. The cultured NHOS cells formed a monolayer consisting of spindle to polygonal cells without extracellular matrix formation or mineralization. In contrast, the transplanted NHOS tumor in immunodeficient mice consisted of short spindle and pleomorphic cells, associated with networks of calcified bone and osteoid matrices, as well as small foci of chondroid matrix. Pulmonary metastasis was detected in 22 (42.3%) out of the 52 tumor-bearing mice when NHOS cells were transplanted into the murine flanks. Pulmonary metastasis was detected in all mice (6/6) at post-injection days 21-49 when the cells were injected into the murine tail veins. The NHOS transplantable osteosarcoma cell line with ossifying ability would be useful to clarify the mechanisms of aggressive metastatic potential, as well as for studying the ossification process involved in cell-to-matrix interactions.

Immunohistochemical detection of carcinoma in radical prostatectomy specimens following hormone therapy.

Following hormone therapy, residual carcinoma is frequently difficult to identify on HE-stained prostatectomy specimens. The aim of the present study was therefore to investigate whole-mounted specimens obtained by radical prostatectomy from patients who had undergone hormone therapy. Formalin-fixed and paraffin-embedded specimens were immunostained with prostate secretory cell markers including prostate-specific antigen (PSA), P504S (alpha-methylacyl-coenzyme A racemase, AMACR), P501S (prostein), and prostate-specific membrane antigen (PSMA). Residual carcinoma was detected in 250 histological slides of 42 patients in a total of 497 slides from 45 patients. In five of 250 slides (2%), carcinoma was not able to be recognized on HE-stained slides, but was found on the immunohistochemistry slides. PSMA had reacted positively beyond a moderate degree in carcinoma from all patients. PSA was positive for carcinoma in most of the patients, while negative or minimal staining was observed in a small number of patients. Carcinoma was positively reactive with P504S and P501S in most of the patients, but was negatively reactive in a few. The Gleason score for a pretreatment needle biopsy correlated with P504S staining of the prostatectomy specimens. P504S and P501S had limited ability to identify degenerated carcinoma. PSMA was the most useful marker to identify carcinoma after hormone therapy.

Vimentin-positive gastric adenocarcinoma arising in a hyperplastic polyp.

We report a case of vimentin-positive early gastric adenocarcinoma arising in a hyperplastic polyp (HP). A 72-year-old Japanese man was admitted for the detailed examination of a gastric polyp. He had a subtotal gastrectomy due to acute abdomen 12 years ago. Upper endoscopy revealed a pedunculated polyp measuring approximately 2 cm on the greater curvature of upper body of the remnant stomach. Magnifying endoscopy revealed that the microsurface pattern was irregular and partially absent accompanied with irregular microvessels at the upper end of the polyp. We speculated that the lesion was an adenocarcinoma arising in the HP. Endoscopic submucosal dissection (ESD) was performed. Histological examination of the ESD specimen revealed that the lesion consisted of well- to poorly differentiated adenocarcinoma at the protruding lesion and foveolar hyperplastic epithelia at the base of the polyp. Immunohistochemically, most of tumor cells that comprised poorly-differentiated adenocarcinoma were positive for both cytokeratin and vimentin. Although carcinomas have occasionally been found in HPs, the histological features of the present case are considered extremely unusual. To the best of our knowledge, this is the first case of vimentin-positive early gastric carcinoma arising in a HP.

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma.

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Decreased expression of claudin-1 correlates with recurrence status in breast cancer.

Claudins (CLDNs) constitute the major transmembrane proteins of tight junctions. It may be hypothesized that changes in or loss of expression of tight junctional proteins such as CLDNs can lead to cellular disorientation and detachment, which is commonly seen in neoplasia. Recent studies have suggested that claudin-1 (CLDN1) plays an important role in invasion and metastasis and claudin-4 (CLDN4) has a particular role in mammary glandular cell differentiation and carcinogenesis. In this study, we examined 83 breast cancer cases and demonstrated immunohistochemical expression patterns of CLDN1/CLDN4 in recurrent and non-recurrent groups. We found significant results between the recurrent and non-recurrent group for expression of CLDN1/CLDN4. The recurrent group (26 cases) showed decreased expression patterns of CLDN1 (p<0.001), compared to the non-recurrent group (57 cases). Decreased expression of CLDN1 (p<0.0001) correlated with short disease-free interval. The lymph node metastasis-positive group showed decreased expression patterns of CLDN1 (p=0.001). However, there was no significance between the recurrent group and non-recurrent group in CLDN4 expression. There was no significance between histological factors and CLDN4 expression. The results indicated that CLDN1 expression correlated with the recurrence status and malignant potential of breast cancer.

Total Calcium and Albumin Are Decreased in the Deeper Epidermis of Patients with Chronic Kidney Disease-Associated Pruritus.

BACKGROUND/AIMS: In our earlier studies, we reported high concentrations of intra- and extracellular calcium ions (Ca2+) in the deeper epidermis of patients with chronic kidney disease (CKD) and associated pruritus. To determine the cause of this phenomenon, we measured total calcium (TCa) concentrations in the deeper epidermis and performed immunostaining of epidermal albumin, which binds to Ca2+. METHODS: This study included 45 patients with CKD-stage 5, which was defined as severely reduced kidney function (i.e., estimated glomerular filtration rate less than 15 mL/min or on dialysis). Subjects were divided into the pruritus group, consisting of patients with mild, moderate, or severe uremic pruritus, and the non-pruritus group, consisting of patients with no or slight pruritus. The particle-induced X-ray emission method was used to measure elements including TCa. Furthermore, we have immunostained epidermal albumin using anti-albumin antibodies and compared the results in the pruritus and non-pruritus groups. RESULTS: The TCa concentration in the spinous layer of patients with CKD with CKD-associated pruritus was lower than in patients with CKD without pruritus (median [range], 395 [235-1,063] vs. 476 [342-1,243] µg/g). The intensity of epidermal albumin expression in the spinous layer was weaker in patients with CKD with CKD-associated pruritus than in those without. CONCLUSION: Patients with CKD with CKD-associated pruritus demonstrated higher Ca2+ concentrations but lower TCa concentrations than patients without CKD-associated pruritus. This could be in part due to low concentrations of epidermal albumin, which binds to Ca2+, in those with CKD-associated pruritus. These results clarify the pathophysiology of CKD-associated pruritus, providing a valuable foundation for the future development of treatments for this condition.

DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects.

Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component.

57Arg in the bHLH transcription factor DEC2 is essential for the suppression of CLOCK/BMAL2-mediated transactivation.

The basic helix-loop-helix (bHLH) transcription factors, DEC2 and DEC1, play critical roles in the circadian rhythm of the suprachiasmatic nucleus (SCN). It is known that mammalian circadian rhythms are regulated by molecular clockwork systems based on a negative-feedback loop, and CLOCK/BMAL1 and CLOCK/BMAL2 enhance DEC2 transcription via CACGTG E-boxes. To understand the role of arginine 57 ((57)Arg) within the basic region of DEC2, we examined the effect of substituting this residue into DEC2 on CLOCK/BMAL2-mediated transactivation. A luciferase assay showed that substituting (57)Arg for Ala or Lys in DEC2 diminished the suppressive activity of wild-type DEC2 on CLOCK/ BMAL2-mediated transactivation, while substituting (48)Pro for Ala in DEC2 did not alter it, and the same was true for wild-type DEC2. We also showed that proteins which were wild-type and substitution mutants of DEC2 were expressed at nearly equivalent levels by Western blotting. These findings demonstrate that (57)Arg in the basic region of DEC2 is essential for its activity in suppressing CLOCK/BMAL2-mediated transactivation.

Pretibial cyst formation after anterior cruciate ligament reconstruction with a hamstring tendon autograft.

We report a case of pretibial cyst formation, which is a rare complication, after anterior cruciate ligament (ACL) reconstruction. The patient had undergone ACL reconstruction at age 18 and complained of pain and swelling localized on the anteromedial aspect of the ipsilateral proximal tibia 2 years postoperatively. Magnetic resonance imaging showed a multilocular fluid-filled cyst arising from the outlet of the tibial bone tunnel. Open resection of the cyst was performed and communication between the tibial tunnel and the joint space was confirmed arthroscopically. The cavity of the tibial tunnel was packed with cancellous bone to seal off a water channel. The laboratory examination revealed slightly concentrated chondroitin sulfate in the cyst fluid compared with the articular fluid, despite histologic observation of no glycosaminoglycan synthesis in the cells of the cyst wall. These findings indicated that leakage of the articular fluid via the tibial tunnel might have caused the pretibial cyst after ACL reconstruction.