Exosomal marker CD63 expression pattern using immunohistochemistry (IHC) in patients with rectal adenocarcinoma in comparison with left-sided colon cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16096-e16096
Author(s):  
Pranitha Prodduturvar ◽  
Ben McCormick ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Daisy E Escobar ◽  
...  

e16096 Background: Adenocarcinomas arising from the distal one third of the transverse colon, splenic flexure, descending colon, sigmoid colon and rectum are often grouped together due to their hindgut embryologic origin and referred to as left-sided colorectal cancer (CRC). Rectal cancer represents a subset of CRC that has distinct differences in anatomical location, clinical behavior, prognosis and molecular background. In patients with left sided colon cancer (LSCC), the expression of exosomal marker CD63 was reported to be higher in the adjacent normal mucosa (ANM) compared to the tumor (224 vs 154, p = 0.0001). Here, we explored the pattern of CD63 expression using immunohistochemistry in patients with rectal cancer in comparison with patients with LSCC. Methods: Between 2015 and 2018, 53 patients underwent rectal cancer biopsy/resection and had available tissues for CD63 IHC staining. Two pathologists independently scored CD63 expression in the tumor and ANM. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Paired t test was used for statistical analysis. Results: Median age was 60 (range 34-80). Females represented 26%. Caucasians and African Americans represented 74% and 26%, respectively. In patients with rectal cancer, the mean CD63 expression was higher in ANM compared to their expression in the tumor (147 vs 113, p = 0.0012). Compared to patients with LSCC (N = 30), the mean CD63 expression in patients with rectal cancer was lower in the ANM (224 vs 147, p < 0.0001) and in the tumor (154 vs 113, p = 0.01). Conclusions: In our cohort of patients with rectal cancer, exosomal marker CD63 expression was lower in tumor compared to ANM. This observation was similar to our previously reported findings in patients with LSCC. Compared to patients with LSCC, patients with rectal cancer had lower expression of CD63 in the tumor and ANM. To our knowledge, this is the first study to explore exosomal marker CD63 expression using IHC in patients with rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 101-101
Author(s):  
Moh'd M. Khushman ◽  
Pranitha Prodduturvar ◽  
Shalla Akbar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
...  

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p < 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15119-e15119
Author(s):  
Pranitha Prodduturvar ◽  
Ben McCormick ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Leander Grimm ◽  
...  

e15119 Background: Embryologically, the right colon (cecum, ascending colon, hepatic flexure and proximal two-thirds of the transverse colon) is derived from the midgut, whereas the left colon (sigmoid colon, descending colon, splenic flexure and distal third of the transverse colon) is derived from the hindgut. There are clinical, pathological and molecular differences between patients with right-sided colon cancer (RSCC) and left-sided colon cancer (LSCC). Exosomes mediate intercellular communications and interactions and have pivotal roles in cancer behavior. CD63 and CD9 are widely accepted exosomal markers. Here we explored CD63 and CD9 expression using immunohistochemistry (IHC) in patients with RSCC and LSCC. Methods: Between 2015 and 2018, 63 patients underwent colon surgical resection for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Unpaired t test was used for statistical analysis. Results: Median age was 64 (range 33-78). Females represented 60% of our cohort. Caucasians, African Americans and other Ethnicities represented 55%, 40% and 5% respectively. The sidedness was designated as RSCC in 52% and as LSCC in 48%. The ANM and Tumor CD63 Q scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC respectively. The ANM and Tumor CD9 Q scores are 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q score is 191 vs 154 (p = 0.024), while the mean ANM CD63 Q score is 225 vs 224 (p = 0.920). The mean Tumor CD9 Q score is 152 and 154 (p = 0.883) and the mean ANM CD9 Q score is 134 vs 135 (p = 0.926). Conclusions: In our cohort of patients with RSCC and LSCC, the exosomal marker CD63 expression is lower in the tumor compared to the ANM. While ANM CD63 expression was similar between RSCC and LSCC, tumor CD63 expression was higher in RSCC compared to LSCC. The exosomal marker CD9 was not found to have significant differential expression between ANM and tumor and between RSCC and LSCC. To our knowledge, this is the first study to explore exosomal markers expression using IHC in patients with RSCC and LSCC.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 182-182
Author(s):  
Ben McCormick ◽  
Pranitha Prodduturvar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
Leander Grimm ◽  
...  

182 Background: Exosomes play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. Their pattern of expression and prognostic significance in patients with RSCC and LSCC is unknown. This study explored CD63 and CD9 expression and prognostic significance in patients with RSCC and LSCC using immunohistochemistry (IHC). Methods: Between 2015 and 2018, 63 patients underwent surgical resection of colon cancer for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored the CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (intensity X percentage of staining) was calculated. Results: RSCC and LSCC represented 52% and 48% of the patients respectively. The ANM and Tumor CD63 Q-scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC, respectively. The ANM and Tumor CD9 Q-scores were 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC, respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q-score was 191 vs 154 (p = 0.024), while the mean ANM CD63 Q-score was 225 vs 224 (p = 0.920). The mean Tumor CD9 Q-score was 152 and 154 (p = 0.883), and the mean ANM CD9 Q-score was 134 vs 135 (p = 0.926). In our cohort, there was no difference in progression free survival (PFS) between patients with RSCC and LSCC (p = 0.2349). In all patients, there was no difference in PFS in patients with CD63 expression < 100 and ≥100 (p = 0.8284). Among patients with RSCC, there was a significantly lower PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.0259). However, among patients with LSCC, there was no difference in PFS in patients with CD63 expression < 100 vs. ≥100 (p = 0.3494). Conclusions: To our knowledge, this is the first study to show a difference in exosomal marker (CD63) expression pattern and its prognostic significance in patients with RSCC and LSCC. There was a significant positive correlation between progression free survival in patients with RSCC and higher exosomal expression.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS144-TPS144
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4117-TPS4117
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Barbara Sarholz ◽  
Mirjam Kuipers ◽  
...  

TPS4117 Background: Preoperative chemo-radiotherapy with or without sequential chemotherapy, followed by surgical intervention, is standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. During open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) are due to receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50 Gy), 5 days/week. Peposertib 50 mg once daily (QD) is the starting dose. Additional dose levels will be between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D]) or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). One patient has received peposertib 50 mg QD and six patients have received peposertib 100 mg QD. Patients are currently receiving peposertib 150 mg QD. Clinical trial information: NCT03770689 .


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15730-e15730
Author(s):  
Moh'd M. Khushman ◽  
Arun Bhardwaj ◽  
Girijesh K. Patel ◽  
Javier Laurini ◽  
Kelly Roveda ◽  
...  

e15730 Background: Exosomes are important mediators of intercellular communication, and play pivotal roles in cancer progression, metastasis and chemoresistance. Exosomal membranes are enriched in endosomes-specific tetraspanins (CD63 and CD9). In patients with PDAC, positive correlation between CD9 expression and overall survival (OS) was reported. However, CD63 expression was conserved in all patients without reported prognostic significance. Here, we explored the prognostic significance of CD63 expression using IHC in patients with PDAC of mixed gender and racial background. Methods: Between 2012 and 2016, 49 patients with PDAC treated at Mitchell Cancer Institute had available tissue (pancreatic resected tissue/biopsy [N = 29] or metastatic site biopsy liver, omentum or bone (N = 20)) for CD63 staining using IHC. Two pathologists independently scored the expression of CD63. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean Quick-score (Intensity X Percentage of staining) was calculated. Unpaired t test was used for statistical analysis. Results: Median age was 64 years (range 42-85). 53% are males. 67% white, 27% African Americans (AA) and 6% are other ethnicities. 41% had stage IV disease while 49% had stage I, II and III. Tumor involved the head (51%), body (20%) and tail (29%). The mean CD63 Q score is slightly higher in AA compared to white (157 vs 149, P = 0.76). The mean CD63 Q score is higher in the pancreatic tissues compared to metastatic sites tissues (185 Vs 102, P = 0.0002). In our cohort, patients with mean CD63 Q score > = 140 had longer median OS compared to patients with mean Q score of < 140 (19 months Vs 3 months, P = 0.0003) and progression free survival (PFS) (12 months vs 1 month, P = 0.0043). Conclusions: In our cohort of patients with PDAC, there was no racial difference in CD63 expression between white and AA. The expression of CD63 is higher in the pancreas compared to metastatic sites (liver, omentum and bone). There is positive correlation between CD63 expression and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC.


2004 ◽  
Vol 18 (7) ◽  
pp. 435-440 ◽  
Author(s):  
Joseph Romagnuolo ◽  
Josée Parent ◽  
Té Vuong ◽  
Mélanie Bélanger ◽  
René P Michel ◽  
...  

BACKGROUND AND STUDY AIMS:A novel brachytherapy (BT) protocol evaluated at McGill University has shown promise in terms of downstaging and achieving high tumour sterilization rates in rectal cancer. Endoscopic ultrasound (EUS) has emerged as the imaging modality of choice for local staging of rectal cancer. However, external beam radiotherapy appears to decrease the accuracy of EUS from 85% to 40%. The aim of the present study was to prospectively evaluate the accuracy of EUS in assessing the response of rectal cancer to BT.PATIENTS AND METHODS:Thirty-three patients with locally advanced (stage T2 or T3) operable rectal carcinomas were included in an experimental protocol involving a novel conformal technique, using three-dimensional planning, to administer high-dose rate preoperative BT. The 18 patients who were able to have a post-BT EUS exam arranged within two weeks before surgery (eg, four to eight weeks post-BT) were included in this study. Tumour (T)- and lymph node (N)-staging on radial EUS, as well as interpretation of the residual tumour, were assessed prospectively. Pathologists were blinded to the post-BT EUS results.RESULTS:The mean age was 70 years (SD ±11; range, 52 to 93 years) and 78% of the patients were male. Pre-BT EUS indicated that 16 patients (89%) were stage T3, and two were stage T2. Five patients (28%) had positive nodes (N1) by ultrasound. With BT, the mean maximal wall thickness on EUS decreased from 14 mm to 9.4 mm (PÃ0.001). At the time of surgery, seven of the 18 patients (39%) had no detectable tumour in the resected specimen; one had carcinoma in situ, one was stage T1, one was stage T2, and eight were stage T3. Eleven patients (61%) underwent an abdominoperineal resection, including four of the 11 (36%) with no ultimate evidence of residual carcinoma. Eight patients (44%) were node-positive. The sensitivity, specificity, and positive and negative predictive values of post-BT EUS in predicting residual tumour were 82%, 29%, 64% and 50%, respectively. The post-BT EUS accurately predicted the T-stage in eight (44%) patients; most errors were due to overstaging.CONCLUSIONS:Rectal cancer T-staging by EUS post-BT is inaccurate, and although it appears sensitive in predicting the presence or absence of residual tumor in rectal adenocarcinoma after preoperative BT, the low predictive values in this setting limit its utility at this time.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 651-651 ◽  
Author(s):  
Kazutake Okada ◽  
Sotaro Sadahiro ◽  
Toshiyuki Suzuki ◽  
Akira Tanaka ◽  
Hiroko Okamura ◽  
...  

651 Background: For accurate staging of colon cancer, 12 or more LNs are recommended to be explored. Although the total number of LNs in rectal cancer was reported to be decreased after CRT, the number of LNs to be explored is not yet clear. We investigated the number of retrieved LNs, number of metastatic LNs, and the LN sizes within the radiation field in comparison with those outside the radiation field, to clarify the influence of CRT. Methods: The subjects were 211 patients with cStage II/III rectal adenocarcinoma who underwent radical surgery between 1991 and 2010. Of these, 111 patients underwent surgery alone (S group) and 100 patients also received preoperative CRT (40 or 45Gy) with concurrent oral UFT or S-1 (RT-group). The numbers of LNs were reviewed by pathological chart, and HE-stained specimens were examined with a digitizer to evaluate the LN sizes (short-axis, long-axis and area). Results: A total of 2049 LNs were retrieved, of which 230 were metastatic LNs. The average number of retrieved LNs was significantly higher in the S group (16±11) than that in the RT group (9±7) (P < 0.0001). The number of LNs inside the radiation field was significantly higher in the S group (6±6) than that in the RT group (4±4) (P = 0.001), whereas outside the radiation field, there was no significant difference between the two groups (5±4 in the S group vs. 5±4 in the RT group). The short-axis of the retrieved LNs was significantly larger in the S group (within the radiation field: 3.5±2.1 mm in the S group vs. 3.0±1.9 mm in the RT group, P < 0.0001; outside the radiation field: 4.3±2.6 in the S group vs. 3.8±2.4 in the RT group, P = 0.05). Conclusions: Preoperative CRT significantly decreased the total number of LNs compared to the surgery alone, attributable to the decrease in the number of LNs inside the radiation field. CRT reduced the size of the LNs and the degree of reduction was larger in the nodes within the radiation field than in those outside. And it was suggested that CRT also had an effect on the LNs outside the radiation field.


2021 ◽  
Vol 73 (2) ◽  
pp. 495-502
Author(s):  
Francesco Bianco ◽  
Paola Incollingo ◽  
Armando Falato ◽  
Silvia De Franciscis ◽  
Andrea Belli ◽  
...  

AbstractDespite advances in coloanal anastomosis techniques, satisfactory procedures completed without complications remain lacking. We investigated the effectiveness of our recently developed ‘Short stump and High anastomosis Pull-through’ (SHiP) procedure for delayed coloanal anastomosis without a stoma. In this retrospective study, we analysed functional outcomes, morbidity, and mortality rates and local recurrence of 37 patients treated using SHiP procedure, out of the 282 patients affected by rectal cancer treated in our institution between 2012 and 2020. The inclusion criterion was that the rectal cancer be located within 4 cm from the anal margin. One patient died of local and pulmonary recurrence after 6 years, one developed lung and liver metastases after 2 years, and one experienced local recurrence 2.5 years after surgery. No major leak, retraction, or ischaemia of the colonic stump occurred; the perioperative mortality rate was zero. Five patients (13.51%) had early complications. Stenosis of the anastomosis, which occurred in nine patients (24.3%), was the only long-term complication; only three (8.1%) were symptomatic and were treated with endoscopic dilation. The mean Wexner scores at 24 and 36 months were 8.3 and 8.1 points, respectively. At the 36-month check-up, six patients (24%) had major LARS, ten (40%) had minor LARS, and nine (36%) had no LARS. The functional results in terms of LARS were similar to those previously reported after immediate coloanal anastomosis with protective stoma. The SHiP procedure resulted in a drastic reduction in major complications, and none of the patients had a stoma.


2016 ◽  
Vol 124 (4) ◽  
pp. 971-976 ◽  
Author(s):  
Kristin Huntoon ◽  
Tianxia Wu ◽  
J. Bradley Elder ◽  
John A. Butman ◽  
Emily Y. Chew ◽  
...  

OBJECT Peritumoral cysts are frequently associated with CNS hemangioblastomas and often underlie neurological morbidity and mortality. To determine their natural history and clinical impact, the authors prospectively analyzed hemangioblastoma-associated peritumoral cysts in patients with von Hippel-Lindau (VHL) disease. METHODS Patients with VHL disease who had 2 or more years of follow-up and who were enrolled in a prospective study at the National Institutes of Health were included. Serial prospectively acquired laboratory, genetic, imaging, and clinical data were analyzed. RESULTS One hundred thirty-two patients (of 225 in the VHL study with at least 2 years of follow-up) had peritumoral cysts that were followed for more than 2 years (total of 292 CNS peritumoral cysts). The mean age at study entrance was 37.4 ± 13.1 years ([mean ± SD], median 37.9, range 12.3–65.1 years). The mean follow-up was 7.0 ± 1.7 years (median 7.3, range 2.1–9.0 years). Over the study period, 121 of the 292 peritumoral cysts (41.4%) became symptomatic. Development of new cysts was associated with a larger number cysts at study enrollment (p = 0.002) and younger age (p < 0.0001). Cyst growth rate was associated with anatomical location (cerebellum cysts grew faster than spine and brainstem cysts; p = 0.0002 and p = 0.0008), younger age (< 35 years of age; p = 0.0006), and development of new neurological symptoms (p < 0.0001). Cyst size at symptom production depended on anatomical location (p < 0.0001; largest to smallest were found, successively, in the cerebellum, spinal cord, and brainstem). The most common location for peritumoral cysts was the cerebellum (184 cysts [63%]; p < 0.0001). CONCLUSIONS Peritumoral cysts frequently underlie symptom formation that requires surgical intervention in patients with VHL disease. Development of new cysts was associated with a larger number of cysts at study enrollment and younger age. Total peritumoral cyst burden was associated with germline partial deletion of the VHL gene.


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