Prevalence of preoperative asymptomatic deep vein thrombosis in patients undergoing elective general surgery for benign disease.

Background: The systemic inflammatory response following surgery as well as that of malignant disease itself is associated with a hypercoagulable state, and thromboprophylaxis is thus recommended during postoperative management of cancer patients. However, limited information is available on the prevalence of preoperative deep vein thrombosis (DVT) and its risk factors in surgical candidates, especially those receiving operations for benign diseases. Methods: This is a retrospective observational study with data of all patients scheduled for elective general surgery between January 2011 and September 2020, undergoing lower extremity venous ultrasonography as preoperative screening for DVT. The prevalence of preoperative asymptomatic DVT was estimated and its associations with clinical variables were evaluated. Results: Among 1512 patients included in the study, 161 (10.6%) had asymptomatic DVT before surgery. DVT prevalence was 13.7% in patients with malignant disease, while it was 8.6% in those with benign disease. The site of the thrombus was distal type in 141 (87.6%) patients, most commonly in the soleal vein. Advanced age (>70 years), female sex, and decreased hemoglobin level were significantly associated with preoperative asymptomatic DVT by multivariate analysis. The odds ratio for advanced age was the highest and rose as age increased. Malignant disease was not an independent risk factor for preoperative DVT. Conclusion: This study showed the prevalence of asymptomatic DVT to be equal in patients with and without malignant disease undergoing elective general surgery. Preoperative DVT assessment is necessary regardless of the disease indicated for surgery, especially in patients with the risk factors identified in this study.

Intraoperative cholangiography and bile duct flushing in 47 dogs receiving laparoscopic cholecystectomy for benign gallbladder disease: A retrospective analysis.

OBJECTIVE: To describe a laparoscopic approach for performing intraoperative cholangiography (IOC) and bile duct flushing (BDF) during laparoscopic cholecystectomy (LC) in dogs. To investigate the clinical outcomes of dogs undergoing these procedures for the treatment of benign gallbladder disease, ie gallbladder mucocele (GM) or cholecystitis. STUDY DESIGN: Retrospective study. ANIMALS: Forty-seven client-owned dogs. METHODS: Medical records of client-owned dogs with benign gallbladder diseases that underwent IOC and BDF during LC between September 2016 and December 2019 were reviewed. Of these dogs, only dogs with GM or cholecystitis were included in the study. The fundus dissection first method was used for LC. Intraoperative cholangiography and BDF procedures were performed laparoscopically using a catheter inserted into the cystic duct following dissection within the subserosal layer of the gallbladder. Videos recorded during each procedure were reviewed, and data on procedure duration, completion, outcome, and technical approach were recorded. RESULTS: Forty-seven dogs were included in the study. The median procedure time for BDF and IOC was 4 min (range, 2-48 min), and no intraoperative or postoperative complications occurred. CONCLUSION: During LC, BDF and IOC were performed safely and successfully. Intraoperative cholangiography identified obstructions and strictures in the common bile duct that were not detected using BDF alone. CLINICAL SIGNIFICANCE: Our findings suggest that BDF and IOC are both safe and time effective and should be considered for routine use by surgeons during LC.

Urinary bladder fistula following laparoscopic inguinal hernioplasty: a case report.

BACKGROUND: Fistula formation due to mesh erosion into hollow viscera, such as the urinary bladder, is uncommon. To date, there have been no reports of fistula formation into the urinary bladder without evidence of mesh erosion after hernioplasty; herein, we report one such rare case, in which the clinical symptoms improved without any surgical intervention. CASE PRESENTATION: A 73-year-old man underwent a trans-abdominal preperitoneal repair for bilateral direct inguinal hernia. One month later, the patient experienced a painful induration in the right inguinal region, and computed tomography revealed fluid collection in this region. A culture of the aspirated fluid yielded no bacteria. Seven months later, he experienced another episode of painful induration in the same region. However, blood examination revealed a normal white blood cell count and C-reactive protein level. Moreover, no organisms were detected by aspirated fluid culture. Although the painful induration subsided after aspiration of the fluid collection, he developed gross hematuria and dysuria a month later. Cystoscopy revealed a fistula in the right wall of the urinary bladder that discharged a purulent fluid. Culture of the fluid revealed no bacteria, and there was no evidence of mesh erosion. Hematuria improved without therapeutic or surgical intervention. The patient's clinical symptoms improved without mesh removal. Moreover, cystoscopy revealed that the fistula was scarred 12 months after the initial appearance of urinary symptoms. No further complications were observed during a 42-month follow-up period. CONCLUSIONS: We report a rare case of a fistula in the urinary bladder without evidence of mesh erosion after laparoscopic hernioplasty. The patient's condition improved without mesh removal. Fluid collection due to foreign body reaction to meshes can cause fistula formation in the urinary bladder without direct mesh contact.

Canine idiopathic chylothorax: Anatomic characterization of the pre- and postoperative thoracic duct using computed tomography lymphography.

Surgical treatment has improved the prognosis of canine idiopathic chylothorax, although a recurrence of the disease occurs occasionally after the procedure. An improved understanding of possible causes for this recurrence would be helpful for prognosis and treatment planning in affected patients. In this retrospective case series study, we described the detailed pre- and postoperative computed tomographic lymphography (CTLG) imaging characteristics for a group of dogs with surgically confirmed idiopathic chylothorax. Preoperative CTLG was performed in 12 of 14 dogs diagnosed with idiopathic chylothorax. Thoracic ducts were present on the right side in 10 dogs, left side in one dog, and bilaterally in one dog. All the 14 dogs received a combination therapy of pericardiectomy and thoracic duct ligation (TDL) by video-assisted thoracoscopic surgery. One week after surgery, a postoperative CTLG was performed, and the thoracic ducts were apparent in seven of 14 dogs. Three dogs had an unchanged course of the thoracic duct, which could have resulted from a missed duct. Four dogs were identified as having a bypass formation: the oblique duct originated at the ligation site and connected to the duct on the other side. Our findings indicated that one of the possible causes for postoperative recurrence of chylothorax in dogs could be "invisible or sleeping" fine ducts that are collapsed and not visible in preoperative CTLG scans. After TDL causes a change in the pressure of lymphatic flow, these fine thoracic ducts may become apparent using postoperative CTLG.

Transanal minimally invasive surgery for rectal neuroendocrine tumors.

BACKGROUND: There is no literature that mainly searched for rectal neuroendocrine tumor (rNET) using transanal minimal invasive surgery (TAMIS). We report our clinical experiences of TAMIS for rectal neuroendocrine tumors to evaluate the feasibility and safety. METHODS: Between December 2010 and March 2020, the 25 consecutive patients with rectal neoplasma underwent the TAMIS procedure performed by single laparoscopic surgeon at the two hospitals. Of these, ten patients with rectal neuroendocrine tumors were reviewed retrospectively. The full-thickness excision down to the outer fatty tissues was completed using TAMIS technique. Clinicopathological findings, perioperative and postoperative complications were recorded. RESULTS: TAMIS for small rNET was successfully completed in all cases. There were seven cases with a tumor size of less than 10 mm, and three cases with a tumor size between 10 and 15 mm. Six patients underwent the primary tumor excision; the remaining four patients underwent resection for the scar after endoscopic procedure. The median surgical duration was 80.5 (53-124) minutes and the median blood loss was 1 (1-12) ml. All removed tumors in the 6 primary excisions were diagnosed as neuroendocrine tumor G1. The margins of specimens were completely free in all cases. Among the four patients after endoscopic procedure, all had no histological evidence of residual tumor. The median length of hospital stay was 7 days postoperatively. There was no post-operative mortality or severe complication. The median length of observation was 54 months. No recurrence, no local or distant metastasis and no mortality of all patients were observed. CONCLUSIONS: TAMIS is safety and feasible procedure for small rNET. Further experience and clinical trials are needed to fully define the advantages, disadvantages, and indications of TAMIS for rNET.

Comparison of Short-Term Outcomes Between Hand-assisted Laparoscopic Distal Gastrectomy and Laparoscopy-assisted Distal Gastrectomy in Gastric Cancer.

Hand-assisted laparoscopic surgery is considered to provide the benefits of laparoscopic surgery in various diseases. However, limited information is available regarding the feasibility of hand-assisted laparoscopic distal gastrectomy (HALDG)-a subset of hand-assisted laparoscopic surgery-as a gastric cancer treatment. This study aimed to evaluate the usefulness of HALDG compared with laparoscopy-assisted distal gastrectomy (LADG). Consecutive patients who underwent HALDG (n=58) or LADG (n=90) for stage I gastric cancer between 2005 and 2016 were eligible. Operative time was significantly shorter and blood loss was significantly higher in HALDG than in LADG (P<0.001, both). Postoperative aminotransferase levels were significantly lower in HALDG than in LADG (P<0.001). There was no significant difference in perioperative complications, a number of analgesics, postoperative C-reactive protein levels, and 3-year relapse-free and overall survival rates between the groups. This study suggests that HALDG is a safe and feasible approach and could become an effective option for stage I gastric cancer treatment.

Efficacy of en bloc thoracic duct ligation in combination with pericardiectomy by video-assisted thoracoscopic surgery for canine idiopathic chylothorax.

OBJECTIVE: To compare the outcomes of pericardiectomy performed with conventional clipping thoracic duct ligation (C-TDL) to those with en bloc thoracic duct ligation (EB-TDL) using video-assisted thoracoscopic surgery (VATS) for canine idiopathic chylothorax. STUDY DESIGN: Retrospective consecutive case series. ANIMALS: Thirteen client-owned dogs with idiopathic chylothorax. METHODS: Medical records of dogs treated with pericardiectomy in combination with TDL by VATS without intraoperative contrast were reviewed. Five and seven dogs underwent C-TDL and EB-TDL, respectively, and 11 dogs were evaluated by preoperative and 7- to 10-days-postoperative computed tomography-lymphography (CTLG). No clinical symptoms with absent or minimal pleural effusion was defined as clinical improvement. Long-term remission (LTR) was defined as rapid resolution of pleural effusion and no recurrence for more than 1 year. Anesthesia time, operation time, the duration of hospitalization, and time until pleural effusion resolution were compared. RESULTS: Clinical improvement was achieved in 91.7% of the cases (C-TDL, 4/5; EB-TDL, 7/7), excluding one case of intraoperative death. The LTR rate was significantly higher with EB-TDL (6/7 [85.7%]) than with C-TDL (1/5 [20%]). Anesthesia time, operation time, and time until pleural effusion resolution were significantly better with EB-TDL than with C-TDL. The rates of thoracic ducts visualization by postoperative CTLG were 100% (5/5) with C-TDL and 42.9% (3/7) with EB-TDL. CONCLUSION: En bloc TDL was an effective treatment for canine idiopathic chylothorax in this patient population. It compared favorably to C-TDL, although missed branches at the time of surgery may explain the difference between C-TDL and EB-TDL in this small population of cases. CLINICAL SIGNIFICANCE: En bloc TDL by VATS was an effective minimally invasive treatment for canine idiopathic chylothorax. Computed tomography-lymphography can be used for surgical planning and postoperative evaluation.

Tracking and clarifying differential traits of classical- and atypical L-type bovine spongiform encephalopathy prions after transmission from cattle to cynomolgus monkeys.

Classical- (C-) and atypical L-type bovine spongiform encephalopathy (BSE) prions cause different pathological phenotypes in cattle brains, and the disease-associated forms of each prion protein (PrPSc) has a dissimilar biochemical signature. Bovine C-BSE prions are the causative agent of variant Creutzfeldt-Jakob disease. To date, human infection with L-BSE prions has not been reported, but they can be transmitted experimentally from cows to cynomolgus monkeys (Macaca fascicularis), a non-human primate model. When transmitted to monkeys, C- and L-BSE prions induce different pathological phenotypes in the brain. However, when isolated from infected brains, the two prion proteins (PrPSc) have similar biochemical signatures (i.e., electrophoretic mobility, glycoforms, and resistance to proteinase K). Such similarities suggest the possibility that L-BSE prions alter their virulence to that of C-BSE prions during propagation in monkeys. To clarify this possibility, we conducted bioassays using inbred mice. C-BSE prions with or without propagation in monkeys were pathogenic to mice, and exhibited comparable incubation periods in secondary passage in mice. By contrast, L-BSE prions, either with or without propagation in monkeys, did not cause the disease in mice, indicating that the pathogenicity of L-BSE prions does not converge towards a C-BSE prion type in this primate model. These results suggest that, although C- and L-BSE prions propagated in cynomolgus monkeys exhibit similar biochemical PrPSc signatures and consist of the monkey amino acid sequence, the two prions maintain strain-specific conformations of PrPSc in which they encipher and retain unique pathogenic traits.

Short-term outcome of laparoscopic cholecystectomy for benign gall bladder diseases in 76 dogs.

Laparoscopic cholecystectomy (LC) is widely accepted as the standard treatment for benign gall bladder diseases in humans because it has proven to be less invasive and safer than are traditional methods. However, the efficacy of LC in dogs remains unclear. The present study aimed to examine the short-term outcome of LC for benign gall bladder diseases in dogs. We enrolled 76 consecutive dogs that underwent LC for benign gall bladder diseases at our hospital between April 2008 and October 2016. Dogs with jaundice, gall bladder ruptures, abdominal effusion, or extrahepatic biliary obstruction were not excluded from the indication. Factors including age, body weight, sex, clinical sign, disease, operative time, conversion to open surgery, perioperative complications, and postoperative hospital stay were investigated. The median age of the dogs was 11 years, and the median body weight was 5.4 kg. Fifty percent of the dogs exhibited no symptoms at the initial visit. Preoperative elevation of total bilirubin levels was observed in 16 dogs (21%). LC was successfully completed in 71 dogs (93%); the median operative time was 124 min. Although gall bladder ruptures were observed in 2 (2.6%) dogs, the operations were completed successfully. Three dogs (4.1%) had to be converted to open cholecystectomy and 2 (2.6%) underwent reoperation. Two dogs (2.6%) died intraoperatively and 2 (2.6%) died postoperatively. LC was a feasible, safe, and appropriate procedure considering the current operative indications for benign gall bladder diseases in dogs.

Neoadjuvant Chemoradiotherapy for Stage II or III Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The goal of this retrospective study was to investigate the efficacy and safety of neoadjuvant chemoradiotherapy (CRT) in patients with Stage II or Stage III esophageal squamous cell carcinoma (SCC). PATIENTS AND METHODS: Between January 2004 and December 2014, a total of 86 patients underwent surgical resection in conjunction with preoperative CRT for esophageal SCC in our Institute. RESULTS: A pathological complete response was achieved in 38.7% of patients with Stage II cancer and 20% of patients with Stage III. Postoperative complications were observed in 61.3% of Stage II and 76.4% of Stage III patients. The 5-year overall survival rate (OS) was 83.2% in Stage II and 22.8% in Stage III (p=0.0001). The 5-year disease-free survival (DFS) rate was 67.9% in Stage II and 29.9% in Stage III (p=0.0007). CONCLUSION: Neoadjuvant CRT may improve OS and DFS rates in patients with Stage II esophageal SCC.

Evaluation of rapid post-mortem test kits for bovine spongiform encephalopathy (BSE) screening in Japan: Their analytical sensitivity to atypical BSE prions.

A classical type of bovine spongiform encephalopathy (C-BSE), recognized in 1987, had a large impact on public health due to its zoonotic link to variant Creutzfeldt-Jakob disease by the human consumption of dietary products contaminated with the C-BSE prion. Thus, a number of countries implemented BSE surveillance using rapid post-mortem test kits that were approved for detection of the C-BSE prion in the cattle brain. However, as atypical BSE (L- and H-BSE) cases emerged in subsequent years, the efficacy of the kits for the detection of atypical BSE prions became a matter of concern. In response to this, laboratories in the European Union and Canada evaluated the kits used in their countries. Here, we carried out an evaluation study of NippiBL®, a kit currently used for BSE screening in Japan. By applying the kit to cattle brains of field cases of C-BSE and L-BSE, and an experimental case of H-BSE, we showed its comparable sensitivities to C, L-, and H-BSE prions, and satisfactory performance required by the European Food Safety Authority. In addition to NippiBL®, two kits (TeSeE® and FRELISA®) formerly used in Japan were effective for detection of the L-BSE prion, although the two kits were unable to be tested for the H-BSE prion due to the discontinuation of domestic sales during this study. These results indicate that BSE screening in Japan is as effective as those in other countries, and it is unlikely that cases of atypical BSE have been overlooked.

[Preoperative Chemoradiotherapy for Stage II or III Esophageal Squamous Cell Carcinoma].

BACKGROUND: The goal of this retrospective study was to investigate the efficacy and safety of preoperative chemoradiotherapy( NACR)in patients with Stage II or Stage III esophageal squamous cell carcinoma(SCC). METHODS: Between 2004 and 2014, a total of 86 patients underwent surgical resection in conjunction with NACR for esophageal SCC at our institute. Thirty-one patients(36.0%)had Stage II disease and 55 patients(64.0%)had Stage III disease. RESULTS: The median age was 64(43-81)years. A total of 78 patients received the full NACR regimen. The most common major Grade 3 hematologic toxic effects of NACR were leukopenia and neutropenia(48 cases), while the most common major Grade 3 non-hematologic toxic effect was anorexia(12 cases). One patient died in the hospital and no patients died within 30 days after surgery. A pathological complete response was achieved in 23 cases. Pathological staging(number of cases)was Stage 0(23), Stage I (8), Stage II (28), Stage III (25), and Stage IV (2). The 5-year overall survival rate(OS)was 51.0%, and was 83.2% in Stage II patients and 29.9% in Stage III patients. CONCLUSION: Preoperative NACR is safe and may improve OS and downstaging rates in patients with esophageal SCC.

Effect of preoperative colonic drainage for obstructing colorectal cancer.

Obstructing colorectal cancer (OCRC) is believed to indicate poorer long-term survival. The purpose of this study was to compare retrospectively perioperative safety and long-term results in patients undergoing surgery for OCRC following preoperative colonic decompression with that in those undergoing elective surgery alone for nonobstructing colorectal cancer (CRC). A total of 656 consecutive CRC patients undergoing colectomy between 2001 and 2011 at our institute were eligible for inclusion in the study. The patients were divided into an OCRC group, which included 104 patients undergoing colectomy with preoperative colonic decompression, and a CRC group, which included 552 patients undergoing colectomy alone. Morbidity, mortality, and prognosis were assessed. In the OCRC group, decompression was performed by nasointestinal tube in 42 patients (40.4%), transanal tube in 15 (14.4%), and colostomy in 47 (45.2%). The mortality rate was 0% in the OCRC group and 0.4% in the CRC group (2 of 552 patients). The morbidity rate was 44.8% in the OCRC group (48 of 104 patients) and 36.6% in the CRC group (202 of 552 patients). The 5-year overall survival rate was 69.5% in the OCRC group and 72.9% in the CRC group [hazard ratio 0.76; 95% confidence interval, 0.35 to 1.16; P = 0.48)]. No statistically significant difference in survival was observed between the 2 groups in stage II, III, or IV, or overall. No difference was observed in safety or survival between advanced OCRC patients undergoing preoperative colonic decompression and advanced non-obstructing CRC patients undergoing surgery alone.

Radiochemotherapy for esophageal squamous cell carcinoma in elderly patients.

BACKGROUND/AIMS: The goal of this retrospective study was to investigate the efficacy and safety of curative radiochemotherapy (CRT) in elderly patients with esophageal squamous cell cancer (SCC). METHODOLOGY: Between 1986 and 2011, 38 consecutive patients aged over 75 years with esophageal SCC were initially treated with a CRT regimen comprising radiation therapy at a dose of 60 Gy and two cycles of chemotherapy with 5-fluorouracil/cisplatin. RESULTS: Fourteen patients were aged over 80 and 24 under 79 years. Complete treatment compliance was obtained in 30 (78.9%) of the patients. Chemotherapy was terminated and the dose of radiation reduced in 7 and 1 patients, respectively. The overall incidence of CRT-related complications was 86.8% (33 patients). Grade 3 leukocytopenia was observed in 6 (15.8%) patients, all of whom recovered promptly. A complete response was observed in 17 patients (44.7%). The overall 3-year survival rate was 32.0%. CONCLUSIONS: Curative CRT is safe and may improve overall and progression-free 3-year survival rates in elderly patients aged more than 75 years with esophageal SCC.

Evaluation of three types of platforms in single-incision laparoscopic surgery for performing transanal endoscopic microsurgery (SILSTEM).

BACKGROUND/AIMS: Transanal endoscopic microsurgery using a platform for single-incision laparoscopic surgery (SILSTEM) is safe for excising rectal lesions. We tested three types of platforms. METHODOLOGY: Nine patients underwent SILSTEM by one surgeon. Tumors located 5­15 cm from the anal verge were eligible. After measuring their dimensions, length, and trocar channels, the platforms tested were the SILSTM port (SP), EZTM access (EA), and GelPOINTTM Path (GP). Clinicopathology, intraoperative parameters, and postoperative outcomes were recorded. RESULTS: Six men and three women (median age 63 years) underwent SILSTEM using platform SP in three patients, EA in four, GP in two. Median operation time was 128 min (range 71­313). Median blood loss was 3 ml (range 1­71). Pathology confirmed adenocarcinoma in five patients, adenoma in three, and carcinoid in one. Patients were discharged within 2­13 days postoperatively. There was no postoperative fecal incontinence or soiling. Overall median follow-up was 13.3 months (range 1.3­27.2). There were no recurrences. CONCLUSION: SILSTEM can effectively resect rectal tumors using any of three platforms. Large prospective trials are needed to define the advantages, disadvantages, and indications for each platform and to draw conclusions regarding operation time, anorectal function, and costs.

FOLFIRI plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer: a JACCRO CC-03 multicenter phase II study.

PURPOSE: The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m², and L-leucovorin 200 mg/m² as an intravenous infusion, followed by 5-FU 400 mg/m² as an intravenous bolus and then 5-FU 2,400 mg/m² as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS). RESULTS: We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively. CONCLUSION: Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer.

Species-barrier phenomenon in prion transmissibility from a viewpoint of protein science.

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal infectious neurodegenerative disorders. Their causative agents are prions, which are composed of disease-associated forms of prion protein (PrP(Sc)). Naturally occurring cases of TSEs are found in several mammalian species including humans, sheep, goats, minks, cattle and deer. Prions are also experimentally transmissible to other mammals such as mice, hamsters and monkeys, but interspecies transmission is often inefficient due to the 'species-barrier'. Studies have suggested that the barrier is not only simply determined by differences in amino acid sequences of cellular PrP (PrP(C)) among animal species, but also by prion strains which are closely associated with conformational properties of PrP(Sc) aggregates. Although the conformational properties of PrP(Sc) remain largely unknown, recent investigation of local structures of PrP(C) and, in particular, structural modelling of PrP(Sc) aggregates have provided molecular insight into this field. In this review, we discuss the species-barrier phenomenon in terms of the protein science.

Mouse prion protein (PrP) segment 100 to 104 regulates conversion of PrP(C) to PrP(Sc) in prion-infected neuroblastoma cells.

Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrP(Sc); PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrP(C)) to PrP(Sc) and the subsequent conversion of PrP(C) to PrP(Sc). We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrP(C) and PrP(Sc). Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrP(Sc) state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrP(Sc) and interfered with the conversion of endogenous MoPrP(C). The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrP(Sc). Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrP(C) reduced the accumulation of PrP(Sc) after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrP(C) plays a key role in conversion after binding to MoPrP(Sc).