Neoadjuvant S-1 and oxaliplatin plus bevacizumab therapy for high-risk locally advanced rectal cancer: A prospective multicenter phase II study.

Aim: We report the short/mid-term results of surgery for high-risk locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (NAC, four courses of S-1 + oxaliplatin+ bevacizumab) without radiotherapy with the primary aim of ypT0-2. Methods: High-risk LARC was defined as cT4b, mesorectal fascia (MRF) ≤1 mm (MRF+), or lateral lymph node metastasis (cLLN+) on high-resolution MRI. The planned 32 cases from April 2018 to December 2021 were all included. Results: There were 10 patients at cT4b (31.2%), 26 MRF+ (81.3%), and 22 cLLN+ (68.8%). Thirteen (40.6%) underwent NAC after a colostomy for stenosis. NAC was completed in 26 (81.2%) cases. Grade 3 or higher adverse events occurred in six (18.7%). One patient developed progressive disease (3.2%). Eleven were ycT0-3MRF-LLN- (34.3%). Curative-intent surgery was performed on 31, with sphincter-preserving surgery in 20, abdominoperineal resection in nine, total pelvic exenteration in two, and lateral lymph node dissection in 24. Two had R1/2 resection (6.4%). A Grade 3 or higher postoperative complication rate occurred in 3.2%. Pathological complete response and ypT0-2 rates were 12.9% and 45.1%. Three-year disease-free survival rates (3yDFS) for ypT0-2 and ypT ≥3 were 81.2%, 46.6% (p = 0.061), and 3-year local recurrence rates (3yLR) were 0%, 48.8% (p = 0.015). 3yDFS for ycT0-3MRF-LLN- and ycT4/MRF+/LLN+ were 87.5%, 48.0% (p = 0.031) and 3yLR were 0%, 42.8% (p = 0.045). Conclusion: NAC yielded a clinically significant effect in about half of high-risk LARC patients. If NAC alone is ineffective, radiotherapy should be added, even if extended surgery is intended.

[A Case of Pancreatic Cancer That Was Radically Resected after Chemotherapy and Radiation Therapy, but Recurred Early and Followed a Rapid Course].

A 71-year-old man presented to our hospital with abdominal pain. He was diagnosed with acute pancreatitis and pancreatic cancer. Peritoneal washing cytology(CY)was positive, and laparotomy findings revealed severe inflammatory changes of pancreatitis, suggesting a high likelihood of the need for combined resection of other organs. Therefore, following the exploratory laparotomy, mFOLFIRINOX was initiated as chemotherapy. After 24 courses of mFOLFIRINOX, he developed drug-induced pneumonia. Therefore, chemotherapy was interrupted, and a steroid was started. Radiotherapy was administered during steroid tapering. There was no evidence of local progression or distant metastasis. A radical resection that included pancreaticoduodenectomy and right hemicolectomy was performed 23 months after the exploratory laparotomy. CY was negative and R0 resection was achieved. However, 5 months after the operation, he developed liver abscesses and cholangitis and was suspected to have liver metastasis. He underwent PTAD and PTCD, but died due to liver failure 8 months postoperatively. The early recurrence of this case might have been caused by the lack of postoperative chemotherapy due to his frailty. Surgical indications should be carefully judged if there is a high risk of recurrence after NAC and a high possibility that ACT cannot be performed after radical surgery.

[Ischemic Colitis after Closure of Temporary Ileostomy for Low Anterior Resection of Rectal Cancer in a Dialysis Patient-A Case Report].

Dialysis patients are at increased risk of ischemic colitis and are likely to develop irreversible ischemic colitis. We report a rare case of ischemic colitis after the closure of a temporary ileostomy for low anterior resection(LAR)of rectal cancer in a dialysis patient. A 77-year-old man undergoing maintenance dialysis was diagnosed as having colorectal cancer with a type 2 tumor at the anastomosis site of high anterior resection performed for sigmoid colon cancer 14 years ago. After undergoing excision which included the anastomosis site of the previous operation, LAR with anastomosis in the transverse colon and rectum and temporary ileostomy were performed. Seven months later, closure of the temporary ileostomy was performed, which resulted in ileus and septic shock. Computed tomography(CT)revealed inflammation in the colon on the oral side of the anastomosis, which was diagnosed as ischemic colitis. Ischemic colitis did not improve with conservative treatment, and fever reoccurred at each maintenance dialysis session. Therefore, ileostomy was performed again, but multiple organ failure due to disseminated intravascular coagulopathy(DIC)progressed and he died. It is considered that Hartmann's operation should be selected for dialysis patients with serious underlying diseases, and if ischemic colitis is observed after closure of the stoma temporary colostomy in such patients, the lesion site of ischemic colitis should be excised promptly and colostomy should be performed again.

Combination therapy with gemcitabine and nab-paclitaxel for locally advanced unresectable pancreatic cancer.

The aim of the present study was to investigate the early treatment outcomes of combined gemcitabine and nab-paclitaxel treatment for locally advanced unresectable pancreatic cancer (LURPC). The subjects comprised 7 patients with LURPC receiving the abovementioned combination therapy at the Hirosaki University Hospital (Hirosaki, Japan) between January and September, 2015. The clinicopathological factors, adverse events and response to treatment were investigated. To determine whether the cases were unresectable, the National Comprehensive Cancer Network guidelines, version 2. 201,) were applied. The patients underwent a median of 4 (range, 2-7) courses of treatment. The response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors. The subjects included 1 male and 6 female LURPC patients, with a median age of 71 years (range, 59-78 years). The tumor was located in the head and body of the pancreas in 6 and 1 patients, respectively. No patients achieved a complete response, 5 achieved a partial response, 2 had stable disease, and none exhibited progressive disease. The response rate was 71%. The mean tumor diameter decreased significantly from 35 mm (range, 24-60 mm) prior to treatment to 22 mm (range, 20-35 mm) following treatment. Two patients were downstaged. The mean carbohydrate antigen (CA) 19-9 values decreased significantly from 767 U/ml (range, 14-1,977 U/ml) prior to treatment to 35 U/ml (range, 14-123 U/ml) following treatment. Adverse events classified as grade ≥3 occurred in 4 patients (57%): 3 patients (43%) suffered from neutropenia and 1 patient (14%) developed bilateral cellulitis of the lower extremities. No patients experienced an increase in disease severity, and all were able to continue treatment following temporary withdrawal or dosage reduction. Therefore, combined treatment with gemcitabine and nab-paclitaxel had favorable tumor-reducing effects and was not associated with severe adverse events, suggesting that this is a useful therapeutic strategy for patients with LURPC.

[Postoperative Bile Leakage Following Liver Resection Due to Stenosis of a Choledochojejunostomy Anastomosis after Pancreaticoduodenectomy - A Case Report].

We report a rare case of intractable bile leakage after liver resection due to stenosis of the anastomosis of a choledochojejunostomy after pancreaticoduodenectomy. A 65-year-old woman was diagnosed with pancreatic and right breast cancer, and underwent pancreaticoduodenectomy and right mastectomy with simultaneous axillary lymph node dissection. Adjuvant chemotherapy and follow-up were performed in our department. After 18 months, computed tomography revealed a liver metastasis of 2.5 cm in segment 8. Because the primary nest of liver metastasis was unknown and performing a biopsy was difficult due to the location, partial resection of the liver was performed. Pathological examination confirmed liver metastasis from the breast cancer. She was rehospitalized due to a right subdiaphragmatic abscess 33 days post-surgery. Abscess drainage revealed bile leakage, and the cause was believed to be stenosis of the anastomosis created by the choledochojejunostomy. Percutaneous transhepatic cholangiographic drainage was performed, and the bile leakage disappeared immediately. However, it was difficult to release the anastomotic stenosis by choledochoscopy; therefore, a retrograde drainage tube was placed in the hepatic duct using enteroscopy, and it formed an internal fistula. The patient has continued to undergo chemotherapy for recurrence in the remnant liver that was observed 16 months after the hepatectomy. In conclusion, when hepatic resection is performed after pancreaticoduodenectomy, attention should be paid to the possible occurrence of bile leakage.

[Successful Resection of the Peritoneal Dissemination Recurrence of Colon Cancer, Including Metastasis to the Inguinal Hernia Sac--A Case Report].

We report a case of aggressive resection of synchronous and asynchronous peritoneal dissemination of colon cancer, including metastasis to the inguinal hernia sac. A 68-year-old man who was examined for anemia was diagnosed with ascending colon cancer. He underwent right hemicolectomy and resection of the disseminated tumors at the omentum and peritoneum near the Treitz ligament (moderately differentiated tubular adenocarcinoma, pT4a [SE] N0M1P2H0, stageⅣ). After 1 year 6 months, he was readmitted for intestinal obstruction due to the recurrence of peritoneal dissemination, and underwent partial resection of the ileum, liver, and right kidney. In the CT scan examination before surgery, right inguinal hernia and tumor were identified, and hernioplasty with resection of the inguinal tumor was subsequently performed after intestinal obstruction resolution. All tumors were identified as peritoneal dissemination of the colon cancer tumors by pathological examination. After surgery, he was treated with mFOLFOX6 for 6 months and survived without signs of recurrences despite the absence of treatment. Even in cases of peritoneal recurrence of colon cancer, aggressive resection may improve the prognosis in some cases.

[A case of cancer in the dilated jejunal pouch after total gastrectomy].

We report a case of cancer in the dilated jejunal pouch after total gastrectomy, in which we resected the jejunal pouch. The patient was a man in his 60s and had a history of total gastrectomy with jejunal pouch ρ-interposition for mucosa-associated lymphoid tissue (MALT) lymphoma in 1994. In late July 2012, he presented to the emergency department with a protracted ileus-like symptom and was admitted to the gastroenterological department after the diagnosis of a dilated jejunal pouch. He was managed conservatively; however, the same symptom recurred. Examinations showed a duodenal carcinoma and cancer in the jejunal pouch; therefore, he was referred for digestive surgery in early August. Endoscopic mucosal resection( EMR) was performed on the duodenal carcinoma, and we resected the jejunal pouch with Roux-en-Y reconstruction for the jejunal cancer. He recovered from postoperative wound infection and was discharged 15 days after the second operation.

[Two cases of bleeding from locally advanced esophageal cancer successfully treated by transcatheter arterial embolization].

UNLABELLED: Case 1: A man in his 60s presented with a type 1 tumor of the middle thoracic esophagus that almost blocked the esophageal lumen. On the day of tumor biopsy, the patient developed massive melena and hemorrhagic shock. Hemostasis could not be achieved endoscopically, and therefore, transcatheter arterial embolization( TAE) was performed. Shock was resolved in the patient, thus avoiding the need for emergent surgery. The patient was diagnosed as having esophageal cancer, and standard elective surgery was performed. Case 2: A man in his 50s with cancer of the middle and lower thoracic esophagus underwent surgery after neoadjuvant chemotherapy. However, we were unable to resect the tumor because it had invaded the left main bronchus and the lower lobe of the right lung. We initiated chemoradiotherapy on postoperative day 42; however, the patient developed massive hematemesis. We could not achieve hemostasis endoscopically and therefore performed TAE. The hematemesis stopped following TAE, and the patient was able to undergo chemoradiotherapy. CONCLUSION: We successfully treated 2 cases of bleeding associated with locally advanced esophageal cancer by TAE. Our experience suggests that TAE is effective for controlling bleeding associated with locally advanced esophageal cancer.

[Two cases of stage IV gastric cancer treated by resection of the primary tumor after chemotherapy combined with trastuzumab].

We report 2 cases of stage IV gastric cancer in which the primary tumor was resected after chemotherapy combined with trastuzumab was administered. Case 1: A 57-year-old man who reported epigastric discomfort was diagnosed as having gastric cancer with Virchow's lymph node metastasis. Because his gastric cancer was human epidermal growth factor receptor( HER)-2-positive, he was treated with trastuzumab+capecitabine and CDDP( XP therapy). After 2 courses of this treatment, he underwent distal gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with capecitabine+trastuzumab, and the residual lymph node shrank. Case 2: A 62-year-old man examined for weight loss was diagnosed as having gastric cancer with peritoneal metastases. Because his gastric cancer was HER2-positive, he was treated with trastuzumab+S-1 and CDDP( SP therapy). After 5 courses of this treatment, he underwent total gastrectomy because of advanced pyloric stenosis. He was treated postoperatively with trastuzumab+SP therapy, and his condition remained stable. Chemotherapy combined with trastuzumab could allow resection of the primary tumor and thereby improve the prognosis.

[A case of mixed adenoneuroendocrine carcinoma of the esophagogastric junction treated with neoadjuvant chemotherapy].

We present a case of a 63-year-old man who was admitted to another hospital because of abdominal distension and body weight loss. Gastric endoscopy revealed a type III tumor at the posterior wall of the upper gastric body. The tumor had invaded into the esophagogastric junction. On the basis of the pathology of the biopsy specimen, the tumor was diagnosed as neuroendocrine carcinoma of the esophagogastric junction. Computed tomography (CT) scans showed regional lymph node swelling. Cisplatin( CDDP) +irinotecan( CPT-11) therapy was selected and administered to the patient. After 2 courses, the patient received S-1+CDDP. He was considered to have stable disease. We performed partial resection of the lower esophagus, total gastrectomy, splenectomy, and cholecystectomy. On pathology, the tumor was immunohistochemically positive for chromogranin A, AE1/AE3, neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), and p53. The Ki-67 index was 80%. The tumor was diagnosed as a mixed adenoneuroendocrine carcinoma (MANEC) of the esophagogastric junction. The patient was treated with S-1 and CDDP. Neuroendocrine cell carcinoma of the esophagogastric junction is rare and usually has a very poor prognosis. We herein report a case of mixed adenoneuroendocrine carcinoma of the esophagogastric junction that was curatively resected and resulted in patient survival without recurrence.

[A case of rapidly fatal gastric cancer with disseminated carcinomatosis of the bone marrow].

A 50-year-old man underwent thorough examination for a chief complaint of melena. Gastric cancer and right kidney cancer were diagnosed. The gastric cancer was in the antrum, and poorly differentiated adenocarcinoma was diagnosed by biopsy. The right kidney cancer was diagnosed as clear cell carcinoma by computed tomography-guided biopsy. We performed right nephrectomy and distal gastrectomy. The final diagnosis of the gastric cancer was por2, pT3( ss), pN3b( 46/ 61), M0, pStage IIIB, R0, and that of the kidney cancer was clear cell carcinoma, pT3a, pN0, pM0. The patient reported lower back pain approximately 2 months after surgery. Several examinations revealed that the patient had multiple bone metastases, disseminated carcinomatosis of the bone marrow, and disseminated intravascular coagulation (DIC).We treated the bone metastasis with denosumab and palliative radiation therapy and the gastric cancer with weekly paclitaxel (PTX). The DIC subsided during the first course but recurred during the discontinuation period. We attempted additional trastuzumab treatment but did not achieve a curative effect, and the patient died. It is necessary to provide appropriate medical care while taking into consideration the possibility of disseminated carcinomatosis of the bone marrow in cases with a high likelihood of lymph node metastasis.

VIP and calcitonin-producing pancreatic neuroendocrine tumor with watery diarrhea: clinicopathological features and the effect of somatostatin analogue.

CONTEXT: Pancreatic neuroendocrine tumor (pNET) secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial. CASE REPORT: A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0-100 pg/mL), and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL). There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR) subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable. CONCLUSION: From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

Treatment of polypoidal choroidal vasculopathy with photodynamic therapy combined with intravitreal injections of ranibizumab.

PURPOSE: To evaluate the 1-year efficacy and safety of photodynamic therapy (PDT) combined with intravitreal injections of ranibizumab for polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective chart review. METHODS: We retrospectively reviewed the medical records of 63 consecutive patients (66 eyes) with subfoveal PCV who were treated with PDT combined with intravitreal injections of ranibizumab. Of the 66 eyes, 29 had no history of treatment for PCV, 10 had been treated previously with only intravitreal injections of anti-vascular endothelial growth factor agents, and 27 had been treated previously with PDT. All eyes had a minimal follow-up of 12 months. RESULTS: The combined therapy reduced substantially the exudative change immediately after initiation of treatment. In treatment-naïve eyes, mean VA before treatment (0.47 ± 0.37 logarithm of the minimal angle of resolution [logMAR]) improved to 0.32 ± 0.30 (P < .01) at 3 months and to 0.29 ± 0.29 (P < .01) at 12 months. Polypoidal lesions were reduced in all eyes and disappeared completely in 79.1% of cases. In eyes treated previously with only anti-vascular endothelial growth factor therapy, some visual improvement was achieved, but in eyes treated previously with PDT, mean visual acuity (0.61 ± 0.45) deteriorated to 0.68 ± 0.52 at 12 months. Of all 66 eyes, 5 showed extensive postoperative subretinal hemorrhage, in 2 of which a vitreous hemorrhage developed, necessitating pars plana vitrectomy. CONCLUSIONS: PDT combined with ranibizumab led to significant visual recovery in treatment-naïve eyes with PCV, but not in eyes with PCV that had demonstrated recurrence after previous PDT. PDT in combination with ranibizumab still has a risk of the postoperative hemorrhagic complications.

Profiling of somatostatin receptor subtype expression by quantitative PCR and correlation with clinicopathological features in pancreatic endocrine tumors.

OBJECTIVES: Pancreatic endocrine tumor (PET) presents variable clinical features. Five subtypes of somatostatin receptor (SSTR) are involved in hormone secretion and cell proliferation. In this paper, we explore the correlation between the SSTR subtype messenger RNA (mRNA) expression and clinicopathological features of PET. METHODS: Twenty-one cases of PET and 5 cases of pancreatic adenocarcinomas (AC) were studied. Using total RNA extracted from paraffin sections and fresh tissues, SSTR subtype mRNA was quantified by real-time polymerase chain reaction. The hormones and MIB1 index were examined using immunohistochemical techniques. RESULTS: The mRNA levels of SSTR1, SSTR2, SSTR3, and SSTR5 were high in PET compared with AC, whereas the expression of SSTR4 was low in PET and AC. Levels of each subtype did not vary with histological grades. Somatostatin receptor 2 levels in functioning tumors were slightly low compared with nonfunctioning tumors. Four distinct groups of PET were identified by hierarchical cluster analysis, and two of these groups showed reduced SSTR5 with elevation of MIB1 index. CONCLUSIONS: The study showed a heterogeneous expression profile of SSTR subtype mRNA and the association of reduction in SSTR5 with high proliferative activity. Such profiling of SSTR subtypes may provide useful information on tumor biology and treatment of PET.

Atrophy of the multifidus muscle in patients with lumbar disk herniation: histochemical and electromyographic study.

A histochemical and electromyographic study of the lumbar multifidus muscle in 17 patients with L4-L5 lumbar disk herniation was performed. Electromyography (EMG) was recorded preoperatively with a needle electrode according to Haig's method. Biopsy specimens were obtained intraoperatively from the L5 band of the multifidus muscle on the affected and unaffected sides. Patients with lumbar disk herniation showed atrophy of type 1 and type 2 fibers with structural changes in the multifidus muscle at the involved level. Furthermore, patients with abnormal EMG results had severe muscle atrophy compared with patients with normal EMG results.

The effects of age and sex on chondroitin sulfates in normal synovial fluid.

OBJECTIVE: To examine how age and sex influence chondroitin sulfates (CS) in normal synovial fluid, we measured the concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and hyaluronic acid (HA) in healthy subjects of different ages. METHODS: Synovial fluid samples were obtained from 82 healthy volunteers, ages 20-79 years. RESULTS: The concentrations of CS and HA and the C6S:C4S ratio varied with age. Their values were highest between 20 and 30 years of age, and thereafter they showed a tendency to decrease. Statistically, the C6S concentration and the C6S:C4S ratio at ages 60-70 years were significantly lower than those at 20-30 years of age. There was also a clear between-sex difference, in which the CS concentrations and the C6S:C4S ratio in women were significantly lower than those in men (P = 0.0003 for C6S, P = 0.02 for C4S, P = 0.002 for C6S:C4S ratio). In sharp contrast, little between-sex difference was found in the HA concentration. In multiple regression analysis, age correlated strongly with the C6S concentration and the C6S:C4S ratio (r = -0.521 and r = -0.617, respectively), weakly with the C4S concentration (r = -0.202), and moderately with the HA concentration (r = -0.483). Sex showed a weak correlation with the concentrations of C6S and C4S and the C6S:C4S ratio (r = 0.307, r = 0.225, and r = 0.237, respectively), and little correlation was seen between sex and the HA concentration. CONCLUSION: The CS concentrations and the sulfation patterns in normal synovial fluid vary with age and sex, and these physiologic variations need to be taken into account when using synovial fluid CS as markers for arthritic conditions.

A report of two cases of volar and dorsal fractures of the middle phalanx caused by a basketball.

We present two rare cases of volar and dorsal fractures of the middle phalanx at the proximal interphalangeal joint (PIPJ). The first case was a 16-year-old girl. She hurt her middle finger while playing basketball. A lateral radiograph revealed volar and dorsal fractures of the middle phalanx. She underwent external immobilization of the PIPJ in 30 degrees of flexion with a splint for 3 weeks. The fractures healed 7 weeks after the injury with neither tenderness nor limitation of range of motion. The second case was a 16-year-old boy. He injured his index finger while playing basketball, and underwent immobilization of the PIPJ for 3 weeks. At 10 weeks after the injury, the dorsal fracture was almost healed, but the displacement of the volar fragment had worsened. At a 3-year follow-up, the dorsal fragment was healed, but the volar fragment remained in a site of nonunion. However, there was neither residual deformity nor restriction of movement.

A dislocation of the inner head in bipolar prosthesis with a self-centering system: a case report.

We present a case of inner head dislocation 11 years after the replacement of a bipolar prosthesis with a self-centering system. An 84-year-old woman with osteoarthritis of the left hip underwent a replacement of the Bateman UPF-II bipolar prosthesis in 1987. She fell off a chair on April 19 1998, and felt a sudden sharp pain in the left hip. Roentgenograms revealed that the inner head was dislocated from the outer head. Moreover, on June 19, when she stood up from the floor, the dislocation recurred. On July 23, a revision surgery was carried out. When the outer head was removed from the acetabulum, the bearing insert was markedly worn by the impingement of the femoral stem neck. Because there was no evidence of loosening of the femoral stem, a cemented replacement of the acetabular component was performed. At a 2-year follow-up, she had mild hip pain, but had returned fully to daily living. Our review of current published studies reveals that most inner head dislocations occurred in osteoarthritic patients. Thus, the occurrence of dislocations may be more dependent on patient selection than on failure of the bipolar prosthesis itself.

Significance of chondroitin sulfate isomers in the synovial fluid of osteoarthritis patients.

To test whether chondroitin sulfate (CS) isomers in synovial fluid are related to the radiographic severity of osteoarthritis (OA) and the age and sex, we investigated the concentrations of chondroitin 6-sulfate (C6S) and chondroitin 4-sulfate (C4S) in patients with OA of the knee joint and age-matched healthy controls. Synovial fluid was obtained from 133 patients with OA of the knee and 27 volunteers (controls). Twenty-seven patients were radiographically classified as grade 1, 59 as grade 2, 34 as grade 3, and 13 as grade 4 according to a modified version of the Kellgren and Lawrence scale. Compared with findings in the controls, values for the concentrations of C6S and C4S, and the C6 : C4S ratio, were significantly higher in the grade 1 patients, whereas in grade 3 and 4 patients, the C6S concentration and the C6 : C4S ratio were lower. There was an obvious sex difference, and all values for the women were significantly lower than those for the men in both the control and the patient groups. In the control group, multiple regression analysis showed a moderate inverse correlation between age and all three of the above biochemical variables, and sex was moderately associated with the C6S concentration and the C6S : C4S ratio. In the patient group, age and sex showed a poor correlation with any of the three variables. However, the radiographic severity of OA showed a relatively strong inverse correlation with the C6S concentration and the C6S : C4S ratio, and a weak inverse correlation with the C4S concentration.