Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection.

Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with 'skip lesions' in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.

Combined Ab interno viscocanaloplasty (ABiC) in open-angle glaucoma: 12-month outcomes.

PURPOSE: The aim of this study was to analyse the safety profile and efficacy of ab interno viscocanaloplasty (ABiC) through to 12 months post-operatively. METHODS: In this retrospective study, the medical records of all patients who underwent ABiC between September 2015 and December 2019 were analysed. Complete success was defined as a 12-month reduction in intraocular pressure (IOP) ≥ 20% from baseline with no concomitant medications. Qualified success criteria were identical, with no more medications than at baseline. RESULTS: In all, 54 eyes of 41 patients were analysed. Mean IOP decreased from 23.6 ± 7.4 mmHg preoperatively to 14.2 ± 2.9 mmHg (-39.8%; p < 0.001) after 12 months. Concomitantly, the number of anti-glaucoma treatment dropped from 2.9 ± 1.0 to 0.6 ± 1.1 (-79.3%; p < 0.001). Amongst patients with a baseline MD < -12.0 dBs, mean IOP decreased from 22.8 ± 9.8 mmHg to 13.8 ± 4.4 mmHg (p = 0.049), with a concomitant reduction of medications from 2.8 ± 1.3 to 1.2 ± 1.3 (p < 0.001). Complete success at 12 months was achieved in 46% of eyes, and qualified success was achieved in 65% of eyes. Amongst eyes with a baseline MD < -12.0 dBs, 50% achieved complete success, and 83.3% achieved qualified success. A total of 19 eyes (35.2%) were considered surgical failure, all due to uncontrolled IOP. Of them, 7 eyes (13.0%) required further filtering surgery. Twelve post-operative adverse events were observed, with early post-operative IOP spikes being the most common (22.2%). CONCLUSIONS: ABIC achieved a statistically significant reduction in IOP and anti-glaucoma medications through 12 months, while maintaining a favourable safety profile in mild-to-severe open-angle glaucoma.

Radiation and depression associated with complications of tissue expander reconstruction.

PURPOSE: Rates of implant failure, wound healing delay, and infection are higher in patients having radiation therapy (RT) after tissue expander (TE) and permanent implant reconstruction. We investigated pretreatment risk factors for TE implant complications. PATIENTS AND METHODS: 127 breast cancer patients had TE reconstruction and radiation. For 85 cases of bilateral TE reconstruction, the non-irradiated breast provided an internal control. Comparison of differences in means for continuous variables used analysis of variance, then multiple pairwise comparisons with Bonferroni correction of p value. RESULTS: Mean age was 53 ± 10.1 years with 14.6% African-American. Twelve (9.4%) were BRCA positive (9 BRCA1, 4 BRCA2, 1 Both). Complications were: Grade 0 (no complication; 43.9%), Grade 1 (tightness and/or drifting of implant or Baker Grade II capsular contracture; 30.9%), Grade 2 (infection, hypertrophic scarring, or incisional necrosis; 9.8%), Grade 3 (Baker Grade III capsular contracture, wound dehiscence, or impending exposure of implant; 5.7%), Grade 4 (implant failure, exchange of implant, or Baker Grade IV capsular contracture; 9.8%). 15.3% (19 cases) experienced Grade 3 or 4 complication and 9.8% (12 cases) had Grade 4 complication. Considering non-irradiated breasts, there were two (1.6%) Grade 3-4 complications. For BMI, there was no significant difference by category as defined by the CDC (p = 0.91). Patients with depression were more likely to experience Grade 3 or 4 complication (29.4 vs 13.2%; p = 0.01). Using multiple logistic regression to predict the probability of a Grade 3 or 4 complications in patients with depression were found to be 4.2 times more likely to have a Grade 3 or 4 complication (OR = 4.2, p = 0.03). CONCLUSIONS: Higher rates of TE reconstruction complications are expected in patients receiving radiotherapy. An unexpected finding was that patients reporting medical history of depression showed statistically significant increase in complication rates.

Supernumerary lacrimal puncta: case series and review of the literature.

We report a case series of supernumerary puncta-canaliculi, a very rare congenital anomaly, and describe different clinical presentations and new treatment options. This is a retrospective chart review of patients diagnosed with supernumerary lacrimal puncta during the time between June 2015 and December 2021 at the Research Institute of Ophthalmology, Giza, Egypt. Four patients (two females and two males) with a mean presenting age of 54 ± 14 years had unilateral double puncta. Of those four patients, three had double puncta on the right lower eyelid whereas one had double puncta on the left upper and lower eyelid. In one of the three patients, the double puncta anomaly was an incidental finding, and the patient was asymptomatic. The other three patients had associated epiphora. All four patients were found to have patent double puncta with no mechanical obstruction. No surgical interventions were necessary for all four patients as one resolved after discontinuing the topical eye drops. Another patient resolved after the diagnostic probing of the puncta, and the third asymptomatic patient required no interventions. Epiphora in the fourth patient resolved with botulinum toxin injection in the lacrimal gland. Accessory lacrimal puncta can present in patients as an incidental asymptomatic finding or patients may present with epiphora. Patients who present with unilateral epiphora, dry eye, or canaliculitis should be carefully evaluated with a detailed slit-lamp examination using lid eversion to appreciate potentially easily missed supernumerary lacrimal puncta.

An All-Digital, Binocular, Indirect Virtual Video Ophthalmoscope: A Novel Approach to Retinal Examination and Photography.

Purpose: We describe a novel method of digital, virtual-reality based binocular indirect ophthalmoscopy which allows for simultaneous stereoscopic recording of the examination with the potential of real-time anatomic correction of the retinal view. Materials and Methods: A provisional prototype of the all-digital, binocular, indirect virtual stereo video ophthalmoscope was designed consisting of a generic LED light source and two synchronized closely spaced side-by-side minicameras which are connected to a processor, storage media (a Samsung note-9 android smartphone in the current provisional prototype), and a virtual reality set (VISIONHMD Bigeyes H1 3D Video Glasses, in the current prototype). A custom designed android application was developed to capture the examination media and allow optional real-time anatomical correction of the examination view. Binocular stereoscopic indirect ophthalmoscopy was attempted on 15 eyes of 15 patients without and with digital real-time anatomic correction of the examination view. Results: Binocular, video, stereo ophthalmoscopic media could be successfully obtained in all 15 patients. Anatomic correction of the examination view as well as a collateral observer's view could be achieved in all 15 patients. Conclusion: An all-digital, binocular, stereo, video indirect ophthalmoscopy is a feasible alternative for conventional binocular indirect ophthalmoscopy and provides stereoscopic video documentation identical to what the examiner sees. The examination video can be streamed in the real-time of the examination for educational or telemedicine purposes.

A Novel Cost-Effective Simulation Model for Continuous Curvilinear Capsulorhexis.

Introduction: We describe and validate a low-cost simulation model for practicing anterior lens capsule continuous curvilinear capsulorhexis (CCC). Methods: A simulation model for CCC was developed from widely available low-cost materials. Ophthalmologists attending the annual scientific meeting of the Research Institute of Ophthalmology, Giza, Egypt, were asked to perform a five CCC model task and then anonymously answer a questionnaire that assessed the realism and training utility of the model using a five-point Likert scale (1 = unacceptable, 2 = poor, 3 = acceptable, 4 = favorable and 5 = excellent). Results: Twenty-seven ophthalmologists completed the task and the anonymous questionnaire. Overall, participants felt that the model simulated CCC step in cataract surgery well (mean: 3.5) and was comparable to other kinds of CCC simulation models (mean: 3.3). The model scored highly for its overall educational value (mean: 4.00) and for enlarging a small CCC (mean:3.7), while the feasibility of this model in practicing the management of a runaway leading edge of CCC scored 2.9. Conclusion: This model may provide an alternative method for training for CCC and other anterior lens capsule-related maneuvers. This option may be particularly helpful for residency training programs with limited access to virtual reality simulators or commercially available synthetic eye models.

Deep Sclerectomy With Intrascleral Versus Suprachoroidal Collagen Implant: A Randomized Control Trial.

PRCIS: Deep sclerectomy with intrascleral collagen implant (DSCI) was less effective in lowering intraocular pressure (IOP) than with suprachoroidal implantation. Further studies are needed to establish the potency and safety of deep sclerectomy with suprachoroidal collagen implant (DSSCI). PURPOSE: The purpose of this study was to analyze the safety and IOP-lowering effect of DSSCI in comparison with DSCI. SETTING: Geneva University Hospitals, Geneva, Switzerland. METHODS: This is a prospective, randomized, controlled study involving 13 patients (26 phakic eyes) with bilateral medically uncontrolled primary or secondary open-angle glaucoma. Bilateral deep sclerectomy was performed with each patient being randomly assigned to receive a collagen implant in the intrascleral space in one eye, and a suprachoroidal collagen implant in the other. Follow-up visits were performed at day 1; at week 1; and at months 6, 9, 12, 18, 30, 48, 54, and 60. RESULTS: Mean preoperative IOP was 24.1±4.2 mm Hg for DSCI group and 25.3±5.3 mm Hg for DSSCI group (P=0.1). The mean postoperative IOP was 14.8±4.0 mm Hg (DSCI) versus 9.8±3.7 mm Hg (DSSCI) at month 60 (P=0.01). Mean preoperative best-corrected visual acuity for the DSCI group was 0.76±0.22 and 0.74±0.23 for the DSSCI group (P=0.001), while the mean postoperative best-corrected visual acuity was 0.82±0.17 (DSCI) and 0.80±0.17 (DSSCI) at month 60 (P=0.004). CONCLUSIONS: DSSCI demonstrated a greater IOP-lowering effect than deep sclerectomy with intrascleral implantation. The safety profile of both methods was similar. More patients with a longer follow-up are required to comprehensively assess the safety and efficacy of this new approach.

Lumpectomy followed by radiation improves survival in HER2 positive and triple-negative breast cancer with high tumor-infiltrating lymphocytes compared to mastectomy alone.

OBJECTIVE: The goal was to compare the 5-year DFS and 5-year OS in patients with early-stage human epidermal growth factor receptor 2 breast cancer (HER2+ BC) and triple-negative breast cancer (TNBC) in relation to the amount of stromal tumor-infiltrating lymphocytes (TILs) after locoregional management by either mastectomy without radiation or lumpectomy and whole-breast radiotherapy (RT). METHODS: This was a retrospective review of HER2+ BC and TNBC patients' charts and histopathology slides with clinical stage of T1-T2 N0 who presented at our facility between January 2009 and December 2019. Locoregional treatment included either mastectomy without RT (M) or lumpectomy with RT (L+R). TILs were assessed by three pathologists using the guidelines of the 2014 TILs working group. A competing risk model and Kaplan-Meier analysis were used to analyze correlations between TILs levels and clinical outcome. RESULTS: We reviewed 211 patients' charts. Of them, 190 proceeded to the final analysis. Patients were split into groups of "low TILs" and "high TILs" based on a 50% TILs cut-off. Of them 26% had high TILs, 48% received RT, 97% received chemotherapy, all HER2+ BC patients received HER2-directed therapy and all HER2+ BC that were also hormone receptor positive (HR+) received endocrine therapy (ET). In patient with low TILs, L+R did not improve outcomes compared to M. Moreover, patients with high TILs had a significant improvement of their DFS and OS with L+R when compared to M. CONCLUSION: The results of our study reflect that a selected group of HER2+ BC and TNBC with elevated TILs, L+R is associated with improvement of 5-year DFS and 5-year OS.

Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of surveillance, epidemiology, and end results data.

PURPOSE: Noninvasive lesions involving the lobules of the breast are increasingly diagnosed as incidental microscopic findings at the time of lumpectomy or core-needle biopsy. We investigated the incidence rates of invasive breast cancer (IBC) after a diagnosis of lobular carcinoma-in-situ (LCIS) by using Surveillance, Epidemiology, and End Results (SEER) data. PATIENTS AND METHODS: Patients (N = 4,853) having a diagnosis of primary LCIS in the time period of 1973 to 1998 were identified using the SEER Public Use CD-ROM data. The database was then searched for patients with subsequent primary IBC occurrences (n = 350). The clinical and pathologic characteristics of patients with subsequent primary IBCs were compared with the characteristics of patients with primary IBCs attained during the same time period (N = 255,114). RESULTS: The incidence of IBC increased over time from diagnosis of LCIS, with 7.1% +/- 0.5% incidence of IBC at 10 years. IBCs detected after partial mastectomy occurred in either breast (46% ipsilateral and 54% contralateral); however, after mastectomy, most IBCs were contralateral (94.7%). IBCs occurring after LCIS more often represented invasive lobular histology (23.1%) compared with primary IBCs (6.5%). The standardized incidence ratio (the ratio of observed to expected cases) for developing IBC was 2.4 (95% CI, 2.1 to 2.6) adjusted for age and year of diagnosis. CONCLUSION: LCIS is associated with increased risk of subsequent invasive disease, with equal predisposition in either breast. The minimum risk of developing IBC after LCIS is 7.1% at 10 years.

Sarcoma as a second malignancy after treatment for breast cancer.

BACKGROUND: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer. METHODS: Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973-1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method. RESULTS: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27-35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer. CONCLUSIONS: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.

Design considerations for a computer controlled multileaf collimator for the Harper Hospital fast neutron therapy facility.

The d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron is collimated using a unique multirod collimator (MRC). A computer controlled multileaf collimator (MLC) is being designed to improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. For the current study the use of focused or unfocused collimator leaves has been studied. Since the engineering effort associated with the leaf design and materials choice impacts significantly on cost, it was desirable to determine the clinical impact of using unfocused leaves in the MLC design. The MRC is a useful tool for studying the effects of using focused versus unfocused beams on beam penumbra. The effects of the penumbra for the different leaf designs on tumor and normal tissue DVHs in two selected sites (prostate and head and neck) was investigated. The increase in the penumbra resulting from using unfocused beams was small (approximately 1.5 mm for a 5 x 5 cm2 field and approximately 7.6 mm for a 25 x 25 cm2 field at 10 cm depth) compared to the contribution of phantom scatter to the penumbra width (5.4 and 20 mm for the small and large fields at 10 cm depth, respectively). Comparison of DVHs for tumor and critical normal tissue in a prostate and head and neck case showed that the dosimetric disadvantages of using an unfocused rather than focused beam were minimal and only significant at shallow depths. For the rare cases, where optimum penumbra conditions are required, a MLC incorporating tapered leaves and, thus, providing focused collimation in one plane is necessary.

Three-dimensional visualization and dosimetry of stranded source migration following prostate seed implant.

PURPOSE: Computed tomographic (CT) imaging was used to determine the displacement of stranded seeds between day 0 and day 30 following prostate seed implants. Post-plan dosimetry was used to assess the dosimetric consequence of strand displacement. METHODS AND MATERIALS: Between March 2006 and December 2009, 86 prostate seed implant patients had day 0 and day 30 post-plan CT imaging. Migrated strands were first identified by inspection of day 0 and day 30 scans. The exact distance of displacement was measured using 3-dimensional fusion software. Post-plan dosimetric analysis was performed using CMS software. RESULTS: Of the 1550 strands placed, 23 strands exhibited substantial movement and these displacements occurred in 21 of the 86 cases. The measured distance of strand movement ranged from 0.31 cm to 3.44 cm, with mean displacement of 2.75 cm. Of the displaced strands, 15 strands moved away from the implant center while 8 strands moved toward the implant center. A comparison of changes in dosimetric parameters between day 0 and day 30 revealed expected increases in D90 related to resolution of prostate edema. When cases of strand displacement were compared with cases without displacement, there were no differences in D90 or V100 at day 0. At day 30, however, statistically significant decreases in D90 (96.8% vs 89.5%; P = .0061) and V100 (85.9% vs 82.2%; P = .046) were noted for cases with strand displacement. When the data were analyzed by looking at the change in dosimetric parameters over time for each individual case (eg, comparing the difference in D90 from day 0 to day 30 per patient) there was a trend toward decrease in D90 with displacement of the strands but this did not achieve statistical significance (P = .09). CONCLUSIONS: Stranded seeds show unexpected spatial instability in the craniocaudal dimension. Strand displacement may occur in approximately 1.5% of stranded sources placed and about 25% of cases. One may expect mean decreases in D90 and V100 of about 7% and 3%, respectively, among cases exhibiting strand migration in the first month following seed implant. Resolution of prostate edema during the same time period accounts for an approximately 30% increase in D90 and V100.