Endoscopic submucosal dissection for the treatment of a large inflammatory fibroid polyp in the gastric antrum prolapsing into the duodenum: A case report.

RATIONALE: Inflammatory fibroid polyp (IFP), also known as Vanek tumor, is a rare, benign gastrointestinal lesion characterized by its inflammatory and fibroid histological features. IFP is often discovered incidentally during endoscopic examinations. It is exceedingly rare for an IFP to prolapse into the duodenum and results in incomplete obstruction of the pylorus. PATIENT CONCERNS: A 64-year-old male patient was admitted to the hospital with recurrent episodes of melena over a 6-month period, along with complaints of dizziness and fatigue in the past 10 days. DIAGNOSES: Gastroscopy showed a giant polypoid mass on the posterior wall of the gastric antrum, prolapsing into the duodenum. Abdominal computer tomography (CT) confirmed the tumor protruding into the duodenum. Pathologic examination of the resected specimen confirmed the IFP diagnosis. INTERVENTIONS: The giant tumor was completely and successfully excised using endoscopic submucosal dissection (ESD). After the surgery, the patient underwent acid suppression and fluid replenishment therapy. OUTCOMES: The patient responded well to ESD and was discharged in stable condition. As of the submission of the case report, there has been no recurrence of the tumor after a 5-month follow-up, and the patient is still under follow-up. LESSONS: While IFPs have traditionally been managed surgically, ESD demonstrates promising treatment outcomes, avoiding the need for surgical distal gastrectomy, and emerges as a safe and effective treatment option.

[Gastric hamartomatous inverted polyps: a clinicopathological analysis of five cases].

Objective: To investigate the endoscopic and histopathological features, diagnosis and differential diagnosis of gastric hamartomatous inverted polyp (GHIP). Methods: Five cases of GHIP were collected at the University Town Hospital of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China, from May 2021 to May 2023. The endoscopic, pathological and immunohistochemical features of the 5 GHIP cases were analyzed. The relevant literature was reviewed. Results: There were 3 males and 2 females, aged from 49 to 60 years, with a mean age of 56 years. The lesions were located in the fundus and body of the stomach, and presented as polyps or masses under endoscopy. Microscopically, the lesions were mainly in the submucosa and consisted of lobulated or clustered gastric glandular epithelium surrounded by hyperplastic smooth muscle. In some areas, there were differentiated glandular elements mimicking the normal gastric mucosa. The irregularly dilated glandular elements in the center were lined by hyperplastic foveolar epithelium, while the glands in the periphery were fundic or pyloric glands. In addition, in some areas, the glands showed cystic expansion, disordered arrangement and lack of differentiation. The hyperplastic glandular epithelium included foveolar epithelium, fundic gland and pyloric gland. There were scattered neuroendocrine cells and smooth muscle bundles in the stroma. Immunohistochemically, the tumor cells were positive for MUC5AC, MUC6, Pepsinogen Ⅰ and H+/K+ ATPase ß, but negative for MUC2. The scattered neuroendocrine cells were positive for synaptophysin, and the desmin stain highlighted hyperplastic smooth muscle bundles. One case was classified as type 2 gastric inverted polyp, and 4 cases were classified as type 3. Conclusions: GHIP is a rare gastric polyp with unique histological features. It should be distinguished from inverted hyperplastic polyp, gastritis cystica profunda, adenomyoma, hyperplastic polyps and well-differentiated gastric tubular adenocarcinoma, etc. Improving the understanding of its pathogenesis and diagnostic features can help avoid misdiagnoses.

Manually driven versus motor driven hysteroscopic tissue removal system for polypectomy: Long-term results.

OBJECTIVE: The aim of this follow-up study is to compare a manually driven hysteroscopic tissue removal system (ResectrTM 9 Fr) with a motor driven system (TruclearTM) in terms of long-term clinical outcomes such as abnormal uterine bleeding and polyp recurrence. STUDY DESIGN: This is a follow-up of a multicenter randomized controlled trial comparing a manually and motor driven hysteroscopic tissue removal system for polypectomy. This prospective cohort study was performed at Ghent University Hospital (Ghent, Belgium) and Catharina Hospital Eindhoven (Eindhoven, the Netherlands). The trial was registered at Clinicaltrials.gov (Trial ID = NCT05337605, April 2022). Seventy-five women with abnormal uterine bleeding who participated in the randomized controlled trial and had pathological confirmation of the diagnosis of an endometrial polyp, were contacted. Fifty-five women (70.67 %) were willing to participate in this follow-up study. The primary outcome was the recurrence and/or persistence of abnormal uterine bleeding and the time to the recurrence of abnormal uterine bleeding. Secondary outcomes were polyp recurrence and time to polyp recurrence, symptom relief, satisfaction score regarding symptom relief and general satisfaction score regarding the surgical procedure. RESULTS: In the manually driven group, the mean time to the recurrence or persistence of abnormal uterine bleeding was 26 months (95 % CI 20 - 32). In the motor driven group, the mean time to the recurrence or persistence of abnormal uterine bleeding was 29 months (95 % CI 23- 34). A log-rank test showed a non-significant difference between both groups (P =.77). There was no significant difference in polyp recurrence (P =.22) or symptom relief between the two groups (P =.67). Additionally, the groups did not differ in satisfaction scores regarding symptoms or polypectomy (P =.16 and P =.61, respectively). CONCLUSION: This long-term follow-up study showed no statistically significant difference in the recurrence and persistence of abnormal uterine bleeding between a manually and motor driven hysteroscopic tissue removal system for polypectomy.

Large vulvar fibroepithelial polyp and review of differentials.

Vulval fibroepithelial polyps (FEPs) are a rare type of vulval fibroblastic tumour commonly found in premenopausal women. It is important to obtain an accurate pathological diagnosis because, despite being benign, the condition shares some characteristics with malignant vulva lesions in its differential diagnosis. We present a case of young woman in her 20s with a giant FEP. After surgical excision, the patient did not manifest any signs of recurrence after 1-year follow-up. Our review focuses on the distinguishing characteristics of these rare neoplasms as we explore their differential diagnosis.

Evaluation of whether there is residual polyp tissue after hysteroscopic morcellation at Cam and Sakura City Hospital: a retrospective cohort study.

BACKGROUND: In polypectomy with mechanical hysteroscopic morcellators, the tissue removal procedure continues until no polyp tissue remains. The decision that the polypoid tissues were removed completely is made based on visual evaluation. In a situation where the polyp tissue was visually completely removed and no doubt that the polyp has been completely removed, short spindle-like tissue fragments on the polyp floor continue in most patients. There are no studies in the literature on whether visual evaluation provides adequate information at the cellular level in many patients in whom polypoid tissues have been determined to be completely removed. The aim of the present study was to analyze the pathological results of the curettage procedure, which was applied following the completion of polyp removal with operative hysteroscopy, and to evaluate whether there was residual polyp tissue in the short spindle-like tissue fragments that the mechanical hysteroscopic morcellator could not remove. The secondary aims of this study were to compare conventional loop resection hysteroscopy with hysteroscopic morcellation for the removal of endometrial polyps in terms of hemoglobin/hematocrit changes, polypectomy time and the amount of medium deficit. METHODS: A total of 70 patients with a single pedunculate polypoid image of 1.5-2 cm, which was primarily visualized by office hysteroscopy, were included in the study. Patients who had undergone hysteroscopic polypectomy were divided into two groups according to the surgical device used: the morcellator group (n = 35, Group M) and the resectoscope group (n = 35, Group R). The histopathological results of hysteroscopic specimens and curettage materials of patients who had undergone curettage at the end of operative hysteroscopy were evaluated. In addition, the postoperative 24th hour Hb/HCT decrease amounts in percentage, the polypectomy time which was measured from the start of morcellation, and deficit differences were compared between groups. RESULTS: In total, 7 patients in the morcellator group had residual polyp tissue detected in the full curettage material. The blood loss was lower in the morcellator group than in the resectoscope group (M, R; (-0.07 ± 0.08), (-0,11 ± 0.06), (p < 0.05), respectively). The deficit value of the morcellator group were higher (M, R; (500 ml), (300 ml), (p < 0.05), respectively). The polypectomy time was shorter in the morcellator group (M, R; mean (2.30 min), (4.6 min), (p < 0.05)). CONCLUSIONS: Even if the lesion is completely visibly removed during hysteroscopic morcellation, extra caution should be taken regarding the possibility of residual tissue. There is a need for new studies investigating the presence of residual polyp tissue.

Analysis of the Therapeutic Efficacy of Laparoscopic Treatment for Fibroepithelial Polyps of the Ureter in Children.

Objective: The aim of this study is to assess the efficacy and safety of laparoscopic surgery in the treatment of pediatric ureteral fibroepithelial polyp (FEP) patients. Our hypothesis is that laparoscopic surgery can effectively treat FEPs while minimizing patient discomfort and complications. Our research aims to evaluate the clinical outcomes of the surgery, including postoperative symptom relief, improvement in kidney function, and risk of postoperative complications. Methods: The clinical records of 34 patients who underwent ureteral polyp surgery at the Department of Urology at Anhui Provincial Children's Hospital between May 2014 and February 2023 were retrospectively analyzed. All patients underwent laparoscopic surgery. Among the 34 pediatric patients, there were 31 males and 3 females, with 2 on the right side and 32 on the left side. Of these cases, 24 polyps were located at the ureteropelvic junction, while seven were found in the upper segment of the ureter and three in its middle segment. Patients' ages ranged from 4 years and 3 months to 15 years, with a median age of 8 years and 6 months. All children presented with varying degrees of hydronephrosis, and preoperative clinical symptoms included ipsilateral flank or abdominal pain, hematuria, and other discomfort. Preoperative examinations mainly comprised ultrasound, intravenous pyelography, CT, or magnetic resonance urography imaging studies, as well as diuretic renography. All pediatric patients underwent laparoscopic excision of the polyp segment of the ureter, followed by renal pelvis ureteroplasty or ureter-to-ureter anastomosis. Results: All patients underwent surgery without conversion to open surgery. The surgical duration ranged from 72 to 313 minutes, with an average of 179.5 minutes. The average intraoperative blood loss was 14 mL. Postoperatively, one patient experienced leakage at the anastomotic site; however, no other significant complications occurred during or after the procedure. Postoperative histopathology confirmed the presence of FEPs in the ureter for all cases. All patients experienced a favorable postoperative recovery, with hospitalization periods ranging from 3 to 16 days and an average stay of 8.6 days. A Double-J stent was inserted in all patients for a duration of 1 to 2 months after surgery, and upon removal, follow-up color Doppler ultrasound revealed reduced hydronephrosis within 1 to 3 months. Follow-up examinations were conducted at intervals ranging from 3 to 108 months postsurgery, with an average follow-up time of 42.2 months, during which no recurrence of ureteral polyps or symptoms such as pain and hematuria was observed. Conclusions: The findings of this study demonstrate that laparoscopic excision of the polyp segment of the ureter, renal pelvis ureteroplasty, and ureter-to-ureter anastomosis represent safe and effective treatment modalities for pediatric FEPs in the ureters. This technique offers several advantages, including minimal invasiveness, rapid recovery, and definitive therapeutic efficacy, which effectively alleviate clinical symptoms and improve hydronephrosis.

Office-based blue laser therapy for vocal fold polyps and Reinke's edema: a case study and review of the literature.

PURPOSE: To report the efficacy of blue laser in the treatment of vocal fold polyps and Reinke's edema in an office setting. METHODS: The medical records and video-recordings of patients who underwent office-based blue laser therapy in a tertiary referral center for vocal fold polyps and/or Reinke's edema were reviewed. The primary outcome measures were the Voice Handicap Index-10 (VHI-10) score and disease regression. Acoustic and aerodynamic parameters were also analyzed. RESULTS: Thirty-five patients (21 with vocal fold polyps and 14 with Reinke's edema) were included and a total of 47 lesions were treated. Out of the 35 patients, 7 patients were lost for follow-up. The mean VHI-10 score dropped significantly after surgery by 17.41 ± 8.67 points (p < 0.001). The endoscopic examinations of 38 lesions were reviewed (17 vocal fold polyps and 21 Reinke's edema) before and up to 6 months after laser therapy. In the subgroup with vocal fold polyps (N = 17), there was complete disease regression in 13 and partial in 4. In the subgroup with Reinke's edema (N = 21), there was complete disease regression in 7 and partial disease regression in 14. For patients with vocal fold polyp, there was a significant decrease in shimmer and a significant increase in maximum phonation time postoperatively. For patients with Reinke's edema, there was a significant decrease in shimmer and noise-to-harmonic ratio following treatment. CONCLUSION: Office-based blue laser therapy is an effective treatment for vocal fold polyps and Reinke's edema leading to complete or partial disease regression. All patients had improvement in voice quality.

Advances in the management of gallbladder polyps: establishment of predictive models and the rise of gallbladder-preserving polypectomy procedures.

Gallbladder polyps are a common biliary tract disease whose treatment options have yet to be fully established. The indication of "polyps ≥ 10 mm in diameter" for cholecystectomy increases the possibility of gallbladder excision due to benign polyps. Compared to enumeration of risk factors in clinical guidelines, predictive models based on statistical methods and artificial intelligence provide a more intuitive representation of the malignancy degree of gallbladder polyps. Minimally invasive gallbladder-preserving polypectomy procedures, as a combination of checking and therapeutic approaches that allow for eradication of lesions and preservation of a functional gallbladder at the same time, have been shown to maximize the benefits to patients with benign polyps. Despite the reported good outcomes of predictive models and gallbladder-preserving polypectomy procedures, the studies were associated with various limitations, including small sample sizes, insufficient data types, and unknown long-term efficacy, thereby enhancing the need for multicenter and large-scale clinical studies. In conclusion, the emergence of predictive models and minimally invasive gallbladder-preserving polypectomy procedures has signaled an ever increasing attention to the role of the gallbladder and clinical management of gallbladder polyps.

Minimally Invasive Surgical Therapies for Ureteral Polyps: A Systematic Review.

Background: Ureteral polyps are rare benign ureteral tumor. No guideline recommends that open or minimally invasive surgery is best for treating ureteral polyps. This article aims to provide a comprehensive review of the minimally invasive techniques currently available for treating ureteral polyps. Materials and Methods: We performed a comprehensive search of articles published in PubMed, using the keywords "ureteral" and "polyp," or "polyps." Results: A total of 275 studies were obtained from the literature search but 96 articles were excluded. Conclusions: Several minimally invasive approaches were developed with the advancement of medical technology, including endoscopic, laparoscopic, and robotic approaches; however, the best surgical technique was yet to be decided. Due to the advantages and disadvantages of these approaches, the best surgical approach should be tailored to each patient's needs and the surgeon's preferences and experience.

Preoperative prediction model for non-neoplastic and benign neoplastic polyps of the gallbladder.

BACKGROUND: Gallbladder adenoma represents a precancerous lesion of gallbladder cancer. However, distinguishing it from cholesteryl polyps of the gallbladder before surgery is challenging. Thus, we aimed to comprehensively explore various risk factors contributing to the formation of gallbladder adenoma to facilitate an informed diagnosis and treatment by clinicians. METHODS: We conducted a retrospective analysis of patients who had undergone cholecystectomy at the Affiliated Hospital of Qingdao University between January 2015 and December 2022. Following postoperative pathological examination, patients were categorized into cholesterol polyp and adenoma groups. We analyzed their baseline characteristics, ultrasound imaging variables, and biochemical data using logistic, lasso, and stepwise regression. Subsequently, we constructed a preoperative prediction model based on the independent risk factors. RESULTS: Regression analysis of 520 gallbladder polyps and 288 gallbladder adenomas in the model group revealed that age, gallbladder wall thickness, polyp size, echogenicity, pedunculation, and adenosine deaminase (ADA) levels were independent predictors of gallbladder adenoma, all with P < 0.05. Using these indicators, we established a regression equation: Logistic (P) = -5.615 + 0.018 ∗ age - 4.64 ∗ gallbladder wall thickness + 1.811 ∗ polyp size + 2.855 ∗ polyp echo + 0.97∗ pedunculation + 0.092 ∗ ADA. The resulting area under the curve (AUC) value was 0.894 (95 % CI: 0.872-0.917, P < 0.01), with a sensitivity of 89.20 %, specificity of 79.40 %, and overall accuracy of 84.41 % for adenoma detection. CONCLUSION: Age, polyp size, gallbladder wall thickness, polyp echogenicity, pedunculation, and ADA levels emerge as independent risk factors for gallbladder adenoma.

Ultrasound-guided percutaneous microwave ablation of gallbladder polyps: A case report.

RATIONALE: Gallbladder polyps are a general term for localized lesions in which the gallbladder wall protrudes into the gallbladder cavity, and benign lesions are common. Although current guidelines recommend cholecystectomy for gallbladder polyps ≥ 10 mm in size, the probability of finding cancer in postoperative pathological specimens is low. We should avoid unnecessary cholecystectomy and treat polyps with gallbladder preservation. Microwave ablation is safe and effective for the treatment of solid lesions, and can inactivates polyps while preserving gallbladder. Hence, we report a case of ultrasound-guided percutaneous microwave ablation of gallbladder polyps. PATIENT CONCERNS: A 72-year-old female patient had previously diagnosed a gallbladder polyp, but it was not taken seriously. Recently, the patient had occasional right upper abdominal discomfort and a desire to preserve gallbladder. DIAGNOSES: Ultrasound showed a medium hyperechoic papillary protrusion in the gallbladder without echo behind, and the changed position did not move. Contrast-enhanced ultrasound (CEUS) showed no malignant signs. The diagnosis was a gallbladder polyp. INTERVENTIONS: The bile is drained and the drainage tube is fixed under real-time ultrasound guidance, then the gallbladder cavity is flushed and filled. Saline was injected between the serous and mucosal layers of the gallbladder to form an "edema band" to protect the gallbladder wall. Then, ultrasound-guided biopsy of gallbladder polyps was performed and sent for histological examination. Finally, the microwave needle was inserted into the target area under real-time ultrasonic guidance, and ablation was performed for 3 minutes (20 W). Postoperative CEUS: No significant enhancement was observed in the lesion. OUTCOMES: Within 6 months of follow-up, the patient's gallbladder systolic function was normal, and there was no discomfort and no recurrence. The lesion reduction rate reached 100% at 1 week after surgery. LESSONS: Ultrasound guided percutaneous microwave ablation of gallbladder polyps not only preserves the gallbladder but also inactivates the polyps without affecting the systolic function of the gallbladder, which provides a new idea for the treatment of gallbladder polyps.

A case of an inverted appendiceal stump with dysplastic mucosa mimicking cecal polyp managed by a combined endoscopic laparoscopic approach / Un caso de muñón apendicular invertido con mucosa displásica que imita Pólipo cecal tratado mediante un abordaje laparoscópico endoscópico combinado

Endoscopic finding of invaginated appendiceal stump mimicking polyp is very rare. We present a case of patient with appendiceal stump mimicking cecal polyp covered with dysplastic mucosa which makes it even more rare. Polypoid lesions involving the appendiceal area represent a specific diagnostic-therapeutic dilemma. In these situations simple colonoscopic polypectomy poses increased risk for perforation. In our case biopsy of the polypoid cecal lesion revealed dysplastic mucosa. Due to the non-lifting sign and increased risk of perforation from simple polypectomy, polyp was removed by cecal wedge resection using combined endoscopic laparoscopic approach. Histopathology of the specimen confirmed medium dysplastic epithelium covering lymphoid follicles specific for appendix. In our case, decision on the need to remove the polyp, based on biopsy histology, was quite clear; however, the question is what should we have done if the biopsy finding was negative? In such a situation, conservative approach with endoscopic follow-up of the polyp and regular biopsy specimen analysis, or a more active approach of polyp removal should be considered. This issue can be discussed, however, we do believe that decision on approaching such patients should be made individually, based on the patient's age, comorbidities, general condition and operative risk.(AU)

[Hybrid laparo-endoscopic access for giant fibrovascular esophageal polyp: a case report]. / Gibridnyi laparo-endoskopicheskii dostup ­ novyi podkhod k udaleniyu gigantskogo fibrovaskulyarnogo polipa pishchevoda. Klinicheskii sluchai.

Fibrovascular polyp is a rare non-epithelial esophageal tumor arising from submucosal layer and consisting of connective and adipose tissue, as well large number of vessels. Large tumors can cause dysphagia, vomiting, chest pain, shortness of breath and/or asthma, while giant neoplasms are potentially life threatening. Despite active introduction of minimally invasive treatment of patients with non-epithelial gastrointestinal tumors, there are still difficulties in surgical treatment of fibrovascular polyps. The patient with a giant fibrovascular esophageal polyp presented with cough, discomfort in the throat, impaired swallowing and episode of tumor migration into oropharynx. Examination confirmed giant highly vascularized esophageal fibrovascular polyp. A novel hybrid surgical technique (endoscopic submucosal dissection with laparoscopic removal of tumor) was applied. Eight-month follow-up revealed no complications. Favorable clinical result was achieved. A hybrid laparo-endoscopic approach in the treatment of patients with large fibrovascular polyps minimizes perioperative risks and improves postoperative outcomes.

Analysis of the clinical efficacy and voice outcomes of CO2 laser resection versus laryngeal microsurgery for vocal cord polyps.

OBJECTIVE: To compare CO2 laser resection and laryngeal microsurgery for vocal cord polyps and provide evidence for the optimal surgical method. METHODS: This was a retrospective cohort study that included 74 patients with vocal cord polyps who underwent either CO2 laser resection or laryngeal microsurgery in our hospital from August 2018 to December 2021. According to their preference, 77 patients were divided into two groups: a CO2 laser resection group (n = 35) and a laryngeal microsurgery group (n = 39). Patients were evaluated two days before surgery, and follow-ups were conducted one, two and four weeks after surgery. The voice handicap index (VHI-10) score, voice acoustic analysis results and electronic laryngoscopy results were collected for each patient, and the differences between the two groups were evaluated. RESULTS: The basic demographic characteristics of the 74 patients were comparable, and all patients completed postoperative follow-up observations. A total of 30 (85.71%) patients in the CO2 laser resection group and 22 (56.41%) patients in the laryngeal microsurgery group were healed. The total effectiveness rate of the CO2 laser resection group (94.29%) was significantly higher than that of the laryngeal microsurgery group (82.05%), and the difference between the two groups was statistically significant (p = .037). Both surgical methods had a positive effect on reducing VHI-10 scores with the effect of CO2 laser resection being more obvious. The difference between the two groups in this regard was statistically significant (p < .001). The effects of each surgical method on the average fundamental frequency perturbation (jitter), amplitude perturbation (shimmer), maximum phonation time and dysphonia severity index were not statistically significant (p > .05). CONCLUSION: CO2 laser resection and laryngeal microsurgery have similar effects on voice quality, but CO2 laser resection has higher clinical efficacy.

Pregnancy Rates after Hysteroscopic Endometrial Polypectomy versus Endometrial Curettage Polypectomy: A Retrospective Study.

Background and Objectives: A relationship between endometrial polypectomy and in vitro fertilization (IVF) pregnancy outcomes has been reported; however, only a few studies have compared polyp removal techniques and pregnancy rates. We investigated whether different polypectomy techniques with endometrial curettage and hysteroscopic polypectomy for endometrial polyps affect subsequent pregnancy outcomes. Materials and Methods: Data from 434 patients who had undergone polypectomy for suspected endometrial polyps using transvaginal ultrasonography before embryo transfer in IVF at four institutions between January 2017 and December 2020 were retrospectively analyzed. Overall, there were 157 and 277 patients in the hysteroscopic (mean age: 35.0 years) and curettage (mean age: 37.3 years) groups, respectively. Single-blastocyst transfer cases were selected from both groups and age-matched to unify background factors. Results: In the single-blastocyst transfer cases, 148 (mean age: 35.0 years) and 196 (mean age: 35.9 years) were in the hysteroscopic and curettage groups, respectively, with the 148 cases matched by age. In these cases, the pregnancy rates for the first embryo transfer were 68.2% (odds ratio (OR): 2.14) and 51.4% (OR: 1.06) in the hysteroscopic and curettage groups, respectively; the resulting OR was 2.03. The pregnancy rates after up to the second transfer were 80.4% (OR: 4.10) and 68.2% (OR: 2.14) in the hysteroscopic and curettage groups, respectively, in which the OR was 1.91. The live birth rates were 66.2% (OR: 1.956) and 53.4% (OR: 1.15) in the hysteroscopic and curettage groups, respectively, in which the odds ratio was 1.71. These results show the effectiveness of hysteroscopic endometrial polypectomy compared to polypectomy with endometrial curettage. No significant difference was found regarding the miscarriage rates between the two groups. Conclusions: Hysteroscopic endometrial polypectomy resulted in a higher pregnancy rate in subsequent embryo transfer than polypectomy with endometrial curettage. Therefore, establishing a facility where polypectomy can be performed hysteroscopically is crucial.