A Randomized Trial of Broad Area ALA-PDT for Field Cancerization Mitigation in High-Risk Patients.

BACKGROUND: The relationship between actinic keratoses (AKs) and nonmelanoma skin cancers (NMSCs) is well established. Patients with field cancerization are at high risk of developing new lesions. A treatment to interrupt new lesion formation or progression is required. OBJECTIVE: To evaluate occurrence of AKs in high-risk patients after field aminolevulinic acid–photodynamic therapy (ALA–PDT). METHODS: In this randomized, parallel-group, evaluator-blinded, 52-week study, patients with 4–15 facial AKs (N = 166) were random-ized (ALA 2x vs ALA 3x vs vehicle [VEH]-pooled [VEH 2x+VEH 3x], 1:1:1) to receive 2 or 3 PDT treatments (1-hour incubation) following cryotherapy at screening. RESULTS: More ALA-treated patients than VEH-treated patients had no AKs at week 52 (ALA 2x, 36.0%, P=0.0102; ALA 3x, 37.5%, P=0.0089; VEH, 18.9%). Week 52 lesion recurrence rates were 7.7% (P=0.0004) and 6.1% (P<0.0001) for ALA 2x and ALA 3x, respec-tively, versus 15.5% for VEH. Therapy was well tolerated; no patient requested early termination of light treatment. ALA 3x reduced NMSC development versus VEH (5 vs 12 lesions, P=0.0014). CONCLUSION: 2 or 3 ALA–PDT treatments with 1-hour incubation can significantly reduce occurrence of AKs after 1 year in patients at high risk of NMSC versus VEH–PDT (NCT02239679). J Drugs Dermatol. 2020;19(5):452-458. doi:10.36849/JDD.2020.4930.

A Randomized, Vehicle-Controlled Phase 3 Study of Aminolevulinic Acid Photodynamic Therapy for the Treatment of Actinic Keratoses on the Upper Extremities.

BACKGROUND: Blue-light aminolevulinic acid photodynamic therapy (ALA-PDT) after broad-area application and 3-hour incubation is efficacious for actinic keratosis (AK) lesion clearance on upper extremities, with use of occlusive dressing significantly increasing efficacy. OBJECTIVE: To prove the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the spot treatment of multiple AKs on upper extremities. METHODS: Aminolevulinic acid or VEH was spot applied only to lesions on one upper extremity 3 hours before blue-light exposure. Treated extremity was covered with occlusive dressing during incubation. Identical treatment was repeated at Week 8 if AK lesions were present in the treated area. RESULTS: Thirty-one percent (42/135) of subjects treated with ALA-PDT had complete clearance at Week 12, compared with 13% (17/134) of the subjects treated with VEH-PDT (p = .0001). The mean AK lesion clearance rate for ALA-treated subjects at Weeks 8 and 12 was 53% and 69%, respectively, compared with 26% and 30% for the VEH-treated group (p < .0001, linear mixed model). Safety profile observed in this study is consistent with previous studies/reports in the literature, and the therapy was well tolerated overall. CONCLUSION: Aminolevulinic acid-PDT spot treatment using a 3-hour occluded incubation was superior to VEH-PDT for AK lesion clearance of the upper extremity.

Theranostic Uses of the Heme Pathway in Neuro-Oncology: Protoporphyrin IX (PpIX) and Its Journey from Photodynamic Therapy (PDT) through Photodynamic Diagnosis (PDD) to Sonodynamic Therapy (SDT).

ALA PDT, first approved as a topical therapy to treat precancerous skin lesions in 1999, targets the heme pathway selectively in cancers. When provided with excess ALA, the fluorescent photosensitizer PpIX accumulates primarily in cancer tissue, and ALA PDD is used to identify bladder and brain cancers as a visual aid for surgical resection. ALA PDT has shown promising anecdotal clinical results in recurrent glioblastoma multiforme. ALA SDT represents a noninvasive way to activate ALA PDT and has the potential to achieve clinical success in the treatment of both intracranial and extracranial cancers. This review describes the creation and evolution of ALA PDT, from the treatment of skin cancers to PDD and PDT of malignant brain tumors and, most recently, into a noninvasive form of PDT, ALA SDT. Current clinical trials of ALA SDT for recurrent glioblastoma and high-grade gliomas in adults, and the first pediatric ALA SDT clinical trial for a lethal brainstem cancer, diffuse intrinsic pontine glioma (DIPG), are also described.

Quality measurement in cancer care delivery.

During the past decade, increasing emphasis has been placed on defining and measuring the quality of health care delivery. The Outcomes Committee of the Society of Surgical Oncology (SSO) was established in 2008 to explore and promote emerging outcomes-related topics that are most relevant to society membership. In recognition of the importance of health care quality, a mini-symposium was held at the SSO's 63rd Annual Cancer Symposium in St. Louis, Missouri, in March 2010. The primary objective of the symposium was to define what constitutes quality measurement in cancer care. This article presents an overview of the symposium proceedings.

MR-guided Focused Ultrasound Facilitates Sonodynamic Therapy with 5-Aminolevulinic Acid in a Rat Glioma Model.

Glioblastoma multiforme (GBM) continues to have a dismal prognosis and significant efforts are being made to develop more effective treatment methods. Sonodynamic therapy (SDT) is an emerging modality for cancer treatment which combines ultrasound with sonosensitizers to produce a localized cytotoxic effect. It has long been known that ultrasound exposure can cause both thermal and non-thermal bioeffects and it remains an open question to what degree does temperature impact the efficacy of SDT. In order to optimize the ultrasound parameters of SDT, transcranial MRI-guided focused ultrasound (MRgFUS) and real-time MRI thermometry were used to monitor the therapy in a rat brain tumor model. Experiments were performed using a C6 intracranial glioma tumor model in 37 male Sprague Dawley rats. Treatments were performed about 7 days following tumor implantation when the tumor reached 1-3 mm in diameter as determined by MRI. 5-aminolevulinic acid (5-ALA) was injected at a dose of 60 mg/kg six hours before sonication. MRgFUS at 1.06 MHz was delivered continuously at an in situ spatial-peak temporal-average intensity of 5.5 W/cm2 for 20 min. MR thermometry was acquired to monitor the temperature change in the brain during sonication. The tumor growth response for animals receiving 5-ALA alone, FUS alone, 5-ALA + FUS and a sham control group were evaluated with MRI every week following treatment. During 20 min of MRgFUS at 5.5 W/cm2, the temperature within the targeted brain tumor was elevated from 32.3 ± 0.5 °C and 37.2 ± 0.7 °C to 33.2 ± 0.9 °C and 38.4 ± 1.1 °C, respectively. Both the tumor growth inhibition and survival were significantly improved in the 5-ALA + FUS group with 32 °C or 37 °C as the starting core body (rectal) temperature. 5-ALA alone and FUS alone did not improve survival. These promising results indicate that relatively low power continuous wave transcranial MRgFUS in conjunction with 5-ALA can produce an inhibitory effect on rat brain tumor growth in the absence of thermal dose. Further investigation of the ultrasound parameters is needed to improve the therapeutic efficacy of MRgFUS and 5-ALA.

Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments.

The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "ObamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons.

Neoadjuvant chemotherapy, surgery, and adjuvant intraperitoneal chemotherapy in patients with locally advanced gastric or gastroesophageal junction carcinoma: a phase II study.

A phase II trial, using neoadjuvant chemotherapy and intraperitoneal (IP) consolidation, was conducted in patients with locally advanced, potentially resectable gastric cancer or cancer of the gastroesophageal junction, both staged as T3N0, T4N0, or any TN1 or TN2 disease. Preoperative chemotherapy consisted of two cycles of irinotecan 75 mg/m(2) with cisplatin 25 mg/m(2)/week for 4 weeks followed by a 2-week break. Unless disease progression was encountered, surgery was performed and followed by two courses of adjuvant therapy with IP floxuridine 3 g x 3 days plus IP cisplatin 60 mg/m(2) on day 3. Of 32 evaluable patients, 29 (90.6%) underwent surgery, and 25 (86.2%) had R0 on resection. Evidence of primary-tumor downstaging was documented in at least one half of the patients. Toxicity of induction therapy was primarily grade 3/4 neutropenia (38.2%/8.8%), grade 3 diarrhea (20.6%), and grade 3 nausea/vomiting (14.7%). Except for three catheter complications, toxicities with IP therapy were infrequent. After a median follow-up of 28.0 months in 32 patients, 10 patients (31.3%) had no evidence of disease, 4 (12.5%) were alive with disease, 13 (40.6%) had died from disease, and 5 (15.6%) died from unrelated causes. Among 25 patients who underwent R0 resection, there were no local recurrences. Sites of first recurrences were outside the abdominal cavity in seven patients, in the liver in two, and in the abdominal cavity in four patients. Median overall survival for all 32 patients was 36.5 months from the start of treatment after median follow-up of 28 months, whereas median disease-specific survival had not been reached at the time of this analysis. For patients with R0 resection, median overall survival was 48 months after median follow-up of 35 months. The data suggest that an approach consisting of systemic induction therapy, curative surgery with high R0 resection rates, and IP adjuvant therapy has acceptable toxicity and encouraging survival outcomes.

Photodynamic therapy systems and applications.

Photodynamic therapy (PDT) is a form of photochemotherapy requiring the simultaneous presence of a photosensitiser, activating light of the proper wavelength and molecular oxygen in order to produce a localised therapeutic effect thought to be due to high-energy singlet oxygen generation. Neither drug nor light alone are effective as therapeutic agents and thus PDT treatment methods should be looked upon as true, necessary, drug and device combinations ('systems'). Selectivity of treatment is imparted by a combination of factors, including accumulation of photosensitiser by the target lesion and targeted application of activating light. The most common systemic side effect of systemically administered photosensitisers is cutaneous photosensitivity of varying periods of time. Local toxicities depend on the area of treatment. Sources of light which have been used in PDT include lasers, arc lamps, light-emitting diodes and fluorescent lamps. PDT has been used for a wide variety of clinical applications. In 1995, the first PDT system, using porfimer sodium (Photofrin, Axcan Pharma, Inc.), lasers and fibre optic light delivery methods, developed by QuadraLogic Technologies, was approved in the US for endoscopic palliation of malignant dysphagia caused by oesophageal cancer. A topical PDT system, aminolevulinic acid HCL (Levulan Kerastick) and the large-area BLU-U PDT Illuminator, was developed by DUSA Pharmaceuticals, Inc. for the treatment of actinic keratoses of the face and scalp and approved in the US in 2000. Topical PDT has applicability to a wide variety of skin cancers and precancerous conditions. In 2001, Novartis launched the systemically administered verteporfin (Visudyne) laser-based PDT system in the US as the first pharmacologic treatment for age-related macular degeneration. Development programmes are continuing to investigate PDT for the potential treatment of a variety of diseases, yielding therapeutic results with minimal toxicity.

Multiorgan resection for gastric cancer: intraoperative and computed tomography assessment of locally advanced disease is inaccurate.

Multiorgan resection of locally advanced gastric cancer has previously been associated with increased morbidity. This study was performed to determine the actual prevalence of pathologic T4 disease in multiorgan gastric resection specimens excised for presumed clinical T4 gastric cancer. A prospective oncology database was queried to identify gastric cancer patients who underwent en bloc multiorgan resection for clinical T4 lesions. Four hundred eighteen patients with gastric cancer underwent gastrectomy between 1990 and 2002. Multiorgan resection was performed in 21 of 418 (5%) patients. Multiorgan resection was not associated with a significant increase in morbidity or mortality. Pathologically confirmed T4 disease was present in only 8 of 21 (38%) patients; the pathologic T stage in all remaining patients was T3 (13 [62%]). Fifteen patients were evaluated by preoperative computed tomography scan. Preoperative computed tomography was inaccurate in assessing T4 lesions, with a positive predictive value of only 50%. Multiorgan resection was safely performed in patients with locally advanced gastric cancer. Pathologic T4 disease was present in only one third of multiorgan resections performed for en bloc excision of locally advanced gastric cancer. Improved methods for intraoperative assessment of disease extension to adjacent viscera should be investigated.

Neoadjuvant chemotherapy with CPT-11 and cisplatin downstages locally advanced gastric cancer.

We examined the role of neoadjuvant therapy in downstaging locally advanced gastric cancer. Preoperative staging was performed with a combination of CT scans, endoscopic ultrasonography and/or laparoscopy, and laparoscopic ultrasonography. Patients with T > or =3 tumors and/or node-positive disease by preoperative clinical staging were eligible for entry. Neoadjuvant therapy consisted of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)) weekly four times every 6 weeks. This was followed by resection with D2 lymph node dissection and two cycles of intraperitoneal chemotherapy with floxuridine and cisplatin. Twenty-two patients were entered into the study (4 with T3N0 disease and 18 with T3N1 disease). Induction chemotherapy was well tolerated with major toxicities being neutropenia and diarrhea. A median of 78%/75% of the planned dosage of CPT-11/cisplatin was delivered. Two patients withdrew consent during the first cycle and were lost to follow-up. One patient progressed to stage IV disease during induction chemotherapy and did not undergo surgery. Nineteen patients underwent surgery. One patient had undetected stage IV disease (liver) and underwent a palliative R2 resection. Of the 18 remaining patients, 17 had curative R0 resections and one had a palliative R1 resection. A median of 21 lymph nodes (range 1 to 121) were examined histologically. There was one postoperative death. Surgical morbidity did not appear to increase after the neoadjuvant regimen. The median postoperative length of hospital stay was 9 days (range 3 to 75 days). Postoperative pathologic staging yielded 16% T3 lesions compared to 85% before treatment based on clinical staging; postoperative American Joint Committee on Cancer staging yielded 37% stage IIIA disease compared to 70% stage IIIA before treatment. With a median follow-up of 15 months, median survival has not yet been reached. We conclude that CPT-11-based neoadjuvant therapy downstages locally advanced gastric cancer. Further follow-up is necessary to determine the ultimate impact of this combination therapy on recurrence and survival.

Complications of gastrectomy following CPT-11-based neoadjuvant chemotherapy for gastric cancer.

Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased R0 resection rate. Potential disadvantages include increased surgical complications. This study assesses postoperative morbidity and mortality by comparing patients undergoing gastrectomy with and without neoadjuvant chemotherapy. From October 1998 to July 2002, a total of 34 patients with locally advanced gastric cancer were placed on a phase II neoadjuvant chemotherapy protocol consisting of two cycles of CPT-11 (75 mg/m(2)) with cisplatin (25 mg/m(2)). Demographic, clinical, morbidity, and mortality data were compared for these patients (CHEMO) versus 85 patients undergoing gastrectomy without neoadjuvant chemotherapy (SURG). The CHEMO patients were more likely to be less than 70 years of age (P< or =0.01), have proximal tumors (P< or =0.01), and undergo proximal gastrectomy (P< or =0.025). Fifty-two percent of SURG patients had T3/T4 tumors compared to 19% of CHEMO patients, consistent with tumor downstaging. The R0 resection rate was similar (80%). Morbidity was 41% in CHEMO patients and 39% in SURG patients. There were five postoperative deaths (4.4%), two in the CHEMO group and three in the SURG group (P=NS). It was concluded that neoadjuvant chemotherapy with CPT-11 and cisplatin is not associated with increased postoperative morbidity compared to surgery alone. CPT-11-based neoadjuvant chemotherapy should be tested further in combined-modality treatment of gastric cancer.

Workforce shortage for general surgeons: results from the Society for Surgery of the Alimentary Track (SSAT) surgeon shortage survey.

BACKGROUND: Population shifts among surgeons and the general populous will contribute to a predicted general surgeon shortage by 2020. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract designed and conducted a survey to assess perceptions and possible solutions from important stakeholders: practicing surgeons of the society, general surgery residents, and medical students. RESULTS: Responses from 1,208 participants: 658 practicing surgeons, 183 general surgery residents, and 367 medical students, were analyzed. There was a strong perception of a current and future surgeon shortage. The majority of surgeons (59.3 %) and residents (64.5 %) perceived a current general surgeon shortage, while 28.6 % of medical students responded the same. When asked of a perceived general surgery shortage in 20 years, 82.4, 81.4, and 51 % said "yes", respectively. There were generational differences in responses to contributors and solutions for the impending shortage. Surgeons placed a high value on improving reimbursement, tort reform, and surgeon burnout, while residents held a strong interest in a national loan forgiveness program and improving lifestyle barriers. CONCLUSION: Our survey offers insight into possible solutions to ward off a surgeon shortage that should be addressed with programmatic changes in residency training and by reform of the national health care system.

Staying alive: strategies for accountable health care.

The Patient Protection and Affordable Care Act signed into law in March 2010, has led to sweeping changes to the US health care system. The ensuing pace of change in health care regulation is unparalleled and difficult for physicians to keep up with. Because of the extraordinary challenges that have arisen, the public policy committee of the Society for Surgery of the Alimentary tract conducted a symposium at their 52nd Annual Meeting in May 2011 to educate participants on the myriad of public policy changes occurring in order to best prepare them for their future. Expert speakers presented their views on policy changes affecting diverse areas including patient safety, patient experience, hospital and provider fiscal challenges, and the life of the practicing surgeon. In all areas, surgical leadership was felt to be critical to successfully navigate the new health care landscape as surgeons have a long history of providing safe, high quality, low cost care. The recognition of shared values among the diverse constituents affected by health care policy changes will best prepare surgeons to control their own destiny and successfully manage new challenges as they emerge.

Evaluation of surgical outcomes and gallbladder characteristics in patients with biliary dyskinesia.

INTRODUCTION: This study was designed to compare symptomatic outcomes following cholecystectomy in patients with biliary dyskinesia. MATERIALS AND METHODS: From 1999 to 2006 at New York University Medical Center, 197 adults underwent hepatobiliary scintigraphy with cholecystokinin administration to evaluate gallbladder ejection fraction (GBEF). Biliary dyskinesia was demonstrated in 120 patients based on decreased GBEF of

Results following resection for stage IV gastric cancer; are better outcomes observed in selected patient subgroups?

BACKGROUND: Patients who present with stage IV gastric cancer are not commonly managed with surgical resection as effective palliation can usually be accomplished with systemic chemotherapy, endoscopic stenting, or surgical bypass procedures. Given the inherent morbidity and mortality associated with gastrectomy, palliative resection for stage IV gastric cancer should be reserved for ideal surgical candidates who are most likely to benefit from the procedure. The purpose of this study is to review outcomes following resection for stage IV gastric cancer, and to identify criteria predictive of improved outcomes following gastrectomy in this setting. METHODS: A retrospective review of a prospective GI oncology database was conducted. Sixty-three patients with stage IV gastric cancer managed with surgical resection between 1989 and 2001 were identified. Variables including demographic data, patterns of distant spread (ex: peritoneal, lymphatic, hematogenous), location of tumor, and type of gastrectomy were utilized to conduct survival analyses. RESULTS: Actuarial survival for all patients at one and 3-year intervals was 52% and 12%, respectively. Improved survival was observed for patients of East Asian race (median survival 20 vs. 12 months, P < 0.05, students t-test) and age less than 60 years (median survival 15 vs. 12 months, P < 0.05). This trend was also illustrated by Kaplan-Meier survival analysis. Other variables including pattern of distant spread, location of tumor, and type of gastrectomy were not associated with a significant difference in survival. Both East Asian race and age less than 60 years were statistically significant predictors of improved survival when assessed by univariate regression analysis. When variables were analyzed in a multivariate regression analysis, Asian race and age <60 both lost their statistical significance as independent predictors of improved survival. CONCLUSIONS: Long-term survival for patients with stage IV gastric cancer who are managed with surgical resection is achievable. Patient specific variables including East Asian race and age less than 60 years appear to be associated with prolonged survival when assessed by comparison of means, Kaplan-Meier analysis, and univariate regression analysis. However, multivariate regression analysis failed to demonstrate these factors as independent predictors of improved outcome. In conclusion, highly selected acceptable risk surgical candidates with stage IV gastric cancer should be considered for management with surgical resection in clinically appropriate scenarios.

Acceptance of repeat esophagogastroduodenoscopy to detect gastric cancer in a Chinese immigrant cohort.

GOAL: To study the feasibility of using repeat esophagogastroduodenoscopy (EGD) to screen for Helicobacter pylori infection and gastric cancer in an Asian immigrant cohort. BACKGROUND: Immigrants in the United States (US) from countries with high per capita rates of gastric cancer remain at higher risk for gastric cancer. The existence of the possibly modifiable risk factor of H. pylori infection and the poor outcomes associated with late-stage disease make screening higher-risk groups with EGD an appealing possibility. It is unknown whether Asian immigrants in the US would accept an EGD-based strategy for gastric cancer screening. STUDY: Cross-sectional study of adult Chinese immigrants in New York City with dyspepsia who underwent EGD in an earlier gastric cancer detection study, who were offered a second EGD four years later. Our main outcome measure was acceptance or refusal of repeat EGD. RESULTS: Seventy-three of the 115 Chinese participants in the earlier study were successfully contacted for this current study. Twenty-three of 73 (32%) underwent repeat EGD. Leading reasons given for declining were lack of symptoms and lack of time. Significantly associated with acceptance of repeat EGD was the belief that EGD will find stomach cancer "nearly always" in someone who has it (P=0.0054; odds ratio=14.0, 2.1 to 94.2 95% confidence interval). CONCLUSIONS: Acceptance of repeat EGD for gastric cancer detection in a cohort of Chinese immigrants was relatively low despite the mitigation of cost and language factors, 2 major barriers to healthcare access. Relocation seemed to be a factor as well. In this population, perceptions of the benefits of EGD may influence acceptance of testing for cancer detection purposes.

Follow-up care after a diagnosis of Helicobacter pylori infection in an Asian immigrant cohort.

GOAL: To study the rate at which Helicobacter pylori infection is treated in an immigrant cohort after diagnosis by esophagogastroduodenoscopy (EGD). BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide, and is especially prevalent in East Asia; immigrants from this part of the world remain at higher risk. Infection with H. pylori is a known risk factor for gastric cancer. There have been no studies of completion of H. pylori treatment in immigrant populations. STUDY: Prospective cohort study of East Asian immigrants diagnosed with H. pylori infection who underwent EGD in a gastric cancer screening protocol. Our primary outcome was self-report or chart evidence of completion of treatment of H. pylori. RESULTS: Sixty-eight of the 126 participants (54%) tested positive for H. pylori infection on EGD. Forty-nine (72%) were seen for a follow-up visit at one of the clinics involved in the study. According to clinic records, 39 of these 49 participants (57% of all H. pylori-positive participants) were prescribed treatment. Only 31 participants (46%) completed treatment. Of possible explanatory factors, only having a "regular doctor" was significantly associated with treatment completion (odds ratio=5.6; 95% confidence interval, 1.2-25.0). CONCLUSIONS: In a sample of Asian immigrants, the rate of treatment of H. pylori infection, a potentially modifiable risk factor, was lower than expected. Having a "regular doctor" appeared to increase the likelihood of receiving appropriate follow-up care.