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Importance: Rapid source control is recommended to improve patient outcomes in sepsis. Yet there are few data to guide how rapidly source control is required., Objective: To determine the association between time to source control and patient outcomes in community-acquired sepsis., Design, Setting, and Particpants: Multihospital integrated health care system cohort study of hospitalized adults (January 1, 2013, to December 31, 2017) with community-acquired sepsis as defined by Sepsis-3 who underwent source control procedures. Follow-up continued through January 1, 2019, and data analyses were completed March 17, 2022., Exposures: Early (<6 hours) compared with late (6-36 hours) source control as well as each hour of source control delay (1-36 hours) from sepsis onset., Main Outcomes and Measures: Multivariable models were clustered at the level of hospital with adjustment for patient factors, sepsis severity, resource availability, and the physiologic stress of procedures generating adjusted odds ratios (aOR) and 95% CI., Results: Of 4962 patients with sepsis (mean [SD] age, 62 [16] years; 52% male; 85% White; mean [SD] Sequential Organ Failure Assessment score, 3.8 [2.5]), source control occurred at a median (IQR) of 15.4 hours (5.5-21.7) after sepsis onset, with 1315 patients (27%) undergoing source control within 6 hours. The crude 90-day mortality was similar for early and late source control (n = 177 [14%] vs n = 529 [15%]; P = .35). In multivariable models, early source control was associated with decreased risk-adjusted odds of 90-day mortality (aOR, 0.71; 95% CI, 0.63-0.80). This association was greater among gastrointestinal and abdominal (aOR, 0.56; 95% CI, 0.43-0.80) and soft tissue interventions (aOR, 0.72; 95% CI, 0.55-0.95) compared with orthopedic and cranial interventions (aOR, 1.33; 95% CI, 0.96-1.83; P < .001 for interaction)., Conclusions and Relevance: Source control within 6 hours of community-acquired sepsis onset was associated with a reduced risk-adjusted odds of 90-day mortality. Prioritizing the rapid identification of septic foci and initiation of source control interventions can reduce the number of avoidable deaths among patients with sepsis.

Objective: Although the current guidelines for the management of blunt traumatic aortic injury (BTAI) have recommended intervention for grade 2 injuries or higher, a national trend has occurred for aggressive endovascular treatment of low-grade BTAIs. Little is known about the natural history of grade 1 and 2 injuries treated nonoperatively. We hypothesized that most of these low-grade injuries would remain stable with nonoperative management., Methods: We performed a review of BTAIs at a large referral level 1 trauma center from 2004 to 2020. The injuries were graded using a standard 1 to 4 scale. The outcomes of the nonoperative and thoracic endovascular aortic repair (TEVAR) management strategies were compared, including post-trauma morbidity, mortality, reinterventions, and lesion stability., Results: A total of 176 patients with BTAIs and sufficient imaging studies and follow-up data available were identified during the study period, including 36 with grade 1, 24 with grade 2, 115 with grade 3, and 1 with a grade 4 injury. Of these 176 patients, 112 had undergone TEVAR and 64 had been treated nonoperatively. Most of the patients (90.2%) who had undergone TEVAR had had grade 3 injuries. Nonoperative management was performed for 97.2% of the grade 1 injuries and 62.5% of the grade 2 injuries. Endovascular reintervention after TEVAR was rare (2.7%). The rates of post-trauma morbidity within 30 days (stroke, 3.6% vs 3.1%; myocardial infarction/arrhythmia, 8.9% vs 1.6%; respiratory failure, 31.2% vs 28.1%; acute kidney injury, 9.8% vs 12.5%; urinary tract infection, 2.7% vs 4.8%; gastrointestinal bleeding, 3.6% vs 0.0%; pulmonary embolism, 10.9% vs 4.5%) and 1-year mortality after discharge (1.8% vs 3.1%) were comparable between the operative and nonoperative groups. The median follow-up was 1501 days (interquartile range [IQR], 475.6-2804 days) for the TEVAR group and 1170.5 days (IQR, 317-2173 days) for the nonoperative group. No lesion progression had occurred in the patients with low-grade (grade 1-2) injuries managed nonoperatively. Resolution of grade 1 and 2 injury had occurred in 20% of the patients at 30 days, which had improved to 44% at long-term follow-up. Fourteen patients with grade 3 injuries (12.2% of the grade 3 injuries in our series) were also observed and did not require future intervention. These patients had generally had smaller pseudoaneurysms with minimal periaortic hematoma. None of these 14 patients had experienced progression or rupture during follow-up (median, 454.5 days; IQR, 81-1199 days) using computed tomography., Conclusions: Nonoperative management of low-grade BTAIs did not result in long-term aortic complications or the need for reintervention. We found that grade 3 injuries with smaller pseudoaneurysms and minimal periaortic hematoma can be safely observed if the patients can be appropriately followed up. Thus, the indications for treatment of select grade 3 injuries merit further consideration., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to quantify the risk of incarceration of incisional hernias., Background: Operative repair is the definitive treatment for incisional ventral hernias but is often deferred if the perceived risk of elective operation is elevated secondary to comorbid conditions. The risk of incarceration during nonoperative management (NOM) factors into shared decision making by patient and surgeon; however, the incidence of acute incarceration remains largely unknown., Methods: A retrospective analysis of adult patients with an International Classification of Diseases, Ninth Revision or Tenth Revision diagnosis of incisional hernia was conducted from 2010 to 2017 in 15 hospitals of a single healthcare system. The primary outcome was incarceration necessitating emergent operation. The secondary outcome was 30-, 90-, and 365-day mortality. Univariate and multivariate analyses were used to determine independent predictors of incarceration., Results: Among 30,998 patients with an incisional hernia (mean age 58.1 ± 15.9 years; 52.7% female), 23,022 (78.1%) underwent NOM of whom 540 (2.3%) experienced incarceration, yielding a 1- and 5-year cumulative incidence of 1.24% and 2.59%, respectively. Independent variables associated with incarceration included: age older than 40 years, female sex, current smoker, body mass index 30 or greater, and a hernia-related inpatient admission. All-cause mortality rates at 30, 90, and 365 days were significantly higher in the incarceration group at 7.2%, 10%, and 14% versus 1.1%, 2.3%, and 5.3% in patients undergoing successful NOM, respectively., Conclusions: Incarceration is an uncommon complication of NOM but is associated with a significant risk of death. Tailored decision making for elective repair and considering the aforementioned risk factors for incarceration provides an initial step toward mitigating the excess morbidity and mortality of an incarceration event., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The use of hepatitis C virus-positive (HCV+) donors has expanded the donor pool for orthotopic heart transplantation (OHT). This study evaluated center-level trends and utilization of HCV+ donors for OHT., Methods: Data were extracted from the Scientific Registry of Transplant Recipients on adults (≥18 y) undergoing OHT between January 1, 2016 and December 31, 2019. Centers performing <10 OHTs during the study period were excluded. Donor utilization rates were evaluated at the center level. Center-level characteristics were compared between centers performing HCV+ donor hepatitis C virus-negative (HCV-) recipient OHTs and those not utilizing HCV+ donors for HCV- recipients., Results: A total of 10 134 patients underwent OHT, including 613 (6.05%) HCV+ donors transplanted into HCV- recipients. The number of HCV+ OHTs increased from 15 of 2512 (0.60%) in 2016 to 285 of 2490 (11.45%) in 2019 (P < 0.001). In 2016, among 105 centers performing OHTs, 7 (6.67%) utilized HCV+ donors compared to 2019 during which 55 (52.89%) of 104 centers utilized HCV+ donors (P < 0.001). In total, 57 of 107 (53.27%) centers utilized HCV+ donors during the study period. Centers utilizing HCV+ donors had higher overall donor utilization rates (7376/24 378 [30.26%] versus 3463/15 335 [22.58%], P < 0.001) and were higher volume as compared to nonutilizing centers (mean annual OHT volume 30.72 ± 1.21 versus 16.2 ± 1.40, P < 0.001)., Conclusions: Although the use of HCV+ donors for OHT is rapidly expanding in the United States, almost half of transplant centers remain nonutilizers. Broader education and implementation of HCV+ donor protocols may be important in expanding OHT to more patients with end-stage heart failure., Competing Interests: A.K. serves on a Medical Advisory Board for Medtronic, Inc. The other authors declare no funding and conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Computed tomography (CT) is commonly performed when evaluating trauma patients with up to 55% showing incidental findings. Current workflows to identify and inform patients are time-consuming and prone to error. Our objective was to automatically identify thyroid and adrenal lesions in radiology reports using deep learning., Materials and Methods: All trauma patients who presented to an accredited Level 1 Trauma Center between January 2008 and January 2019 were included. Radiology reports of CT scans that included either a thyroid or adrenal gland were obtained. Preprocessing included word tokenization, removal of stop words, removal of punctuation, and replacement of misspellings. A word2vec model was trained using 1.4 million radiology reports. Both training and testing reports were selected at random, manually reviewed, and were considered the gold standard. True positive cases were defined as any lesions in the thyroid or adrenal gland, respectively. Training data was used to create models that would identify reports that contained either thyroid or adrenal lesions. Our primary outcomes were sensitivity and specificity of the models using predetermined thresholds on a separate testing dataset., Results: A total of 51,771 reports were identified on 35,859 trauma patients. A total of 1,789 reports were annotated for training and 500 for testing. The thyroid model predictions resulted in a 90.0% sensitivity and 95.3% specificity. The adrenal model predictions resulted in a 92.3% sensitivity and a 91.1% specificity. A total of 240 reports were confirmed to have thyroid incidentals (mean age 69.1 yrs ± 18.9, 35% M) and 214 reports with adrenal incidentals (mean age 68.7 yrs ± 16.9, 50.5% M)., Conclusions: Both the thyroid and adrenal models have excellent performance with sensitivities and specificities in the 90s. Our deep learning model has the potential to reduce administrative costs and improve the process of informing patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: The radiographic finding of pneumatosis intestinalis can indicate a spectrum of underlying processes ranging from a benign finding to a life-threatening condition. Although radiographic pneumatosis intestinalis is relatively common, there is no validated clinical tool to guide surgical management., Methods: Using a retrospective cohort of 300 pneumatosis intestinalis cases from a single institution, we developed 3 machine learning models for 2 clinical tasks: (1) the distinction of benign from pathologic pneumatosis intestinalis cases and (2) the determination of patients who would benefit from an operation. The 3 models are (1) an imaging model based on radiomic features extracted from computed tomography scans, (2) a clinical model based on clinical variables, and (3) a combination model using both the imaging and clinical variables., Results: The combination model achieves an area under the curve of 0.91 (confidence interval: 0.87-0.94) for task I and an area under the curve of 0.84 (confidence interval: 0.79-0.88) for task II. The combination model significantly (P < .05) outperforms the imaging model and the clinical model for both tasks. The imaging model achieves an area under the curve of 0.72 (confidence interval: 0.57-0.87) for task I and 0.68 (confidence interval: 0.61-0.74) for task II. The clinical model achieves an area under the curve of 0.87 (confidence interval: 0.83-0.91) for task I and 0.76 (confidence interval: 0.70-0.81) for task II., Conclusion: This study suggests that combined radiographic and clinical features can identify pathologic pneumatosis intestinalis and aid in patient selection for surgery. This tool may better inform the surgical decision-making process for patients with pneumatosis intestinalis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Incisional hernia develops in up to 20% of patients undergoing abdominal operations. We sought to identify characteristics associated with poor outcomes after acute incisional hernia incarceration., Study Design: We performed a retrospective cohort study of adult patients with incisional hernias undergoing elective repair or with acute incarceration between 2010 and 2017. The primary end point was 30-day mortality. Logistic regression was used to determine adjusted odds associated with 30-day mortality. The American College of Surgeons Surgical Risk Calculator was used to estimate outcomes had these patients undergone elective repair., Results: A total of 483 patients experienced acute incarceration; 30-day mortality was 9.52%. Increasing age (adjusted odds ratio 1.05; 95% CI, 1.02 to 1.08) and bowel resection (adjusted odds ratio 3.18; 95% CI, 1.45 to 6.95) were associated with mortality. Among those with acute incarceration, 231 patients (47.9%) had no documentation of an earlier surgical evaluation and 252 (52.2%) had been evaluated but had not undergone elective repair. Among patients 80 years and older, 30-day mortality after emergent repair was high (22.9%) compared with estimated 30-day mortality for elective repair (0.73%), based on the American College of Surgeons Surgical Risk Calculator. Estimated mortality was comparable with observed elective repair mortality (0.82%) in an age-matched cohort. Similar mortality trends were noted for patients younger than 60 years and aged 60 to 79 years., Conclusions: Comparison of predicted elective repair and observed emergent repair mortality in patients with acute incarceration suggests that acceptable outcomes could have been achieved with elective repair. Almost one-half of acute incarceration patients had no earlier surgical evaluation, therefore, targeted interventions to address surgical referral can potentially result in fewer incarceration-related deaths., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: Invasive stratified mucin-producing carcinoma (i-SMILE) represents a recently recognized subtype of cervical adenocarcinoma (AC) developing in a background of a stratified mucin-producing intraepithelial lesion (SMILE). Clinical and prognostic data on i-SMILE are limited., Methods: We report a series of five cases with histopathological, immunohistochemical (p16) and PCR analyses. The cases as well as the patients previously published in the literature were reviewed for follow-up information., Results: Thirteen cases were identified. The mean age of 47.1 years (range 34-66) was not different from the usual type of cervical AC. 10/13 cases presented with tumors > 2 cm and a polypoid-exophytic appearance. Regardless of tumor size and stage of the disease, 7 out of 11 patients developed recurrent disease after a mean of 7.8 months (range 6 weeks-36 months). Five patients developed distant metastases (three of them in the lungs). Five out of the 11 informative cases died of the disease. All reported cases were positive for high-risk HPV (mainly HPV type 18) and associated with p16-overexpression., Conclusion: i-SMILE represent a distinct subtype of invasive endocervical AC, associated high-risk HPV infection and strong p16-overexpression. Clinically, i-SMILE may represent an aggressive tumor with early recurrent disease and substantial risk of distant metastatic disease, especially to the lungs.

Background: Blogs have become a major venue of information sharing and emotional release for people worldwide. Illness blogs are a specific type of blog in which patients describe their experience with illness and coping with disease. Illness blog research has been conducted on several disorders; however, blogs by Parkinson's disease (PD) patients have been neglected., Objectives: To categorize the characteristics of PD patients from blogs and explore whether we can learn about the medical issues with which they are most concerned, as conveyed through their blog posts., Methods: Using located PD patients' blogs, we analyzed the contents of 78 blogs, and employed thematic analysis of eight arbitrarily selected blogs., Results: The majority of blog authors in our sample (N=78) were from the United States (42%). The number of blogs written by male and female authors was fairly similar: 49% and 44%, respectively, while gender was unknown for 7%. Blogs were written by both early- and late-onset PD patients. The thematic analysis revealed five major themes: diagnosis, symptoms, treatment, coping mechanisms, and information., Conclusions: Thematic analysis of blogs by PD patients provided considerable information and insight regarding the experience of these patients, which is significant to other patients and their families, as well as to medical professionals. Further qualitative studies of larger blog samples utilizing data mining techniques are needed to further explore the subjective experiences of patients.

The World Health Organization (WHO) classification from 2014 differentiates between different subtypes of mucinous adenocarcinoma of the uterine cervix. A gastric subtype was recently described that showed no association with high-risk human papillomavirus (HPV) infections, has a poor prognosis, is mainly diagnosed in women of Asian origin and can occur in patients with Peutz-Jeghers syndrome. Although no clear grading system has been recommended in the WHO classification, it is likely that grading of adenocarcinomas of the uterine cervix will partly be based on the different patterns of invasion. Deep stromal infiltration of macroinvasive carcinomas is defined as an infiltration of >66 % of the cervical stroma. In the near future a maximum tumor size of 2 cm could act as a discriminator for planning of less radical surgery. Parameters of the histopathological report that are relevant for the prognostic assessment as well as the choice of adjuvant treatment and function as quality indicators during certification are described. The histological type of an adenocarcinoma alone is of no predictive or prognostic relevance for patients undergoing primary surgical treatment, neoadjuvant chemotherapy, combined chemo-radiotherapy or treatment with angiogenesis inhibitors. Currently, molecular parameters and biomarkers are of no relevance.

Introduction: Angiomyofibroblastoma is a benign, rare mesenchymal tumor arising from the genital tract of both men and women and was first described by Fletcher and colleagues in 1992. The tumor needs to be distinguished from other, similar lesions, such as deep and superficial aggressive angiomyxoma and cellular angiofibroma, because aggressive angiomyxoma demands much more extensive treatment. The vast majority of angiomyofibroblastomas arise from the vulva and appear as solid cystic masses on ultrasound images., Case Presentation: We report a case of a 35-year-old Caucasian woman with an angiomyofibroblastoma arising from the vagina. She presented with a painless mass of about 5cm in diameter that had a rather homogeneous, hypoechoic appearance on ultrasound images. The patient underwent surgical resection of the mass, which was subsequently diagnosed as angiomyofibroblastoma. We present sonographic and magnetic resonance imaging findings, intraoperative and histologic images, and a thorough review of the literature., Conclusions: In our opinion, ultrasonography is the most valuable tool to establish a preoperative diagnosis of this tumor entity, differentiate it from other lesions of the female genital tract, and plan surgery accordingly. Even though it is a rare tumor, gynecologists should be able to recognize it and to differentiate it from other tumor entities that demand more aggressive treatment. We describe a different sonographic appearance of this tumor than previously reported.

Introduction: Although rapid response systems (RRS) have been shown to decrease the incidence of cardiac arrest (CA), there are no studies evaluating optimal staffing. We hypothesize that there are no outcome differences between ICU physician and senior resident led events., Methods: A retrospective study of the RRS database at a single, academic hospital was performed from July 1, 2006 to May 31, 2010. Surgical patients and those in the ICU were excluded. Daytime (D) was defined as 7 am-5 pm Monday through Friday, and weekends were defined as 5 pm on Friday to 6:59 am on Monday. The nurse to patient ratio is constant during all shifts. An ICU physician leads daytime events on weekdays whereas night/weekend (NW) events are led by residents. NW events were compared against D events using chi square or Fischer's exact test. Significance was defined as p<0.05., Results: A total of 1404 events were reviewed with 534 (38%) D and 870 (62%) NW events. Respiratory and staff concerns were more likely during NW compared to D (50% vs. 39% and 46% vs. 34%, p<0.001, respectively). Following RRS activation, no difference was noted between D and NW periods in the incidence of progression to CA, transfer to ICU, or hospital mortality. Invasive procedures were more common in the NW period., Conclusion: Resident-led RRS may have similar outcomes to attending intensivist led events. Prospective studies are needed to determine the ideal team composition., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods., (©2011, Wiley Periodicals, Inc.)

Objectives: The aim of this study was to determine the frequency of diaphragm involvement (DI) in cases of International Federation of Gynecology and Obstetrics (FIGO) stage IIIC and IV primary epithelial ovarian, fallopian tube, or peritoneal cancer; the frequency of use of different surgical techniques in managing diaphragm implants; and the procedure-associated morbidity., Methods: A retrospective analysis of consecutive patients undergoing primary surgery by a single surgical team between January 2005 and June 2007 was accomplished. Patients with tumors of low malignant potential and nonepithelial histologic diagnosis and those who received neoadjuvant chemotherapy were excluded., Results: Thirty-three patients met the inclusion criteria. Diaphragm involvement was found in 91% of the cases. Whereas the left hemidiaphragm is never involved alone, the right side is significantly affected more extensively (P = 0.002) and frequently (alone, 20%; both sides, 80%). The frequency of use of procedures varies considerably in the literature, whereas full-thickness diaphragm resection (DR) had to be performed in 53% of our patients with DI. Diaphragm resection at the left hemidiaphragm and bilateral DRs are very rare in primary cases. A specific histopathologic examination of the DR preparation is desirable. A simple 4-tiered classification of the infiltration depth is proposed. The most frequent complication is serothorax, but a generous indication for intraoperative chest tube placement is solely recommended in cases of DR., Conclusions: Surgical effort in achieving an optimum cytoreduction could be evaluated more precisely with parameters of DI and diaphragm-related treatment procedures. The usual quality criteria for ovarian cancer surgery, such as residual tumor state and morbidity, are more marked by subjectivity and inconsistent definitions.

Endometrial cancer (EC) is the most common malignancy of the female genital tract in the western world. Conceptually, a dualistic model of endometrial carcinogenesis exists for sporadic EC, based on molecular findings with a good correlation to the morphologic phenotype and clinical behavior. Type 1 endometrial carcinoma represents an estrogen-related tumor, which usually arises in the setting of endometrial hyperplasia, has endometrioid histology with low grade, and tends to be biologically indolent. Grade 3 endometrioid cancers, which constitute a minority of EC, also behave aggressively. The type 2 cancers are not estrogen-driven and have a higher grade, various histologies, particularly serous carcinomas and clear-cell carcinomas, and a poorer prognosis. The diagnostic criteria of endometrial hyperplasia, endometrial in situ carcinoma, and of the different histologic types of EC, according to the most recent World Health Organization classification, are given in detail. In addition, the risk of progression of endometrial hyperplasia into endometrioid type EC and their treatment modalities are discussed. Endometrial pathologies in patients with breast cancer, receiving tamoxifen, and women affected by hereditary nonpolyposis colorectal cancer syndrome are described, including their pathogenetic aspects. Finally, a short practical description for the handling of surgical specimens from fractional curetting and hysterctomies is given.

The search for better photosensitizers for photodynamic therapy of malignancies has led to the investigation of a new water-soluble, positively charged, and chemical stable tetrahydroporphyrin tetratosylat (THPTS) with a strong absorption at 760.5 nm, belonging to the bacteriochlorophyll family. THPTS undergoes a rapid uptake by human choroidal melanoma (CM) cells with a weak dark toxicity after a 24-h incubation (LD10 = 150 microM, LD50 = 6.0 mM). In response to laser light at 760+/-3 nm and doses of 10, 15 and 30 J/cm2, around 71%, 76%, and 92% of the CM cells were killed, respectively. Studies of pharmacokinetics and biodistribution in vivo (living mice) and ex vivo (excised organs) were made in a Balb/c mice bearing subcutaneously inoculated C26 colon carcinoma using fiber-optic spectrofluorimetry (FOS). Tumours were irradiated 3 h after intraperitoneal (i.p.) injection of 5.0 mg/kg THPTS with an incoherent light source at 750+/-20 nm and an intensity of 100 mW/cm2 and fluences of 60, 90 and 120 J/cm2. THPTS demonstrated preferential accumulation in C26 colon carcinoma in comparison with most normal tissues except kidneys. For the tissues of liver, colon, muscle, and spleen the tumour/normal tissue ratio (TNTR) ranged from 8.0 to 50. After irradiation with 120 J/cm2 the depth of tumour necrosis reached 15 mm. Histological examination of the tumour samples 24 h after THPTS-PDT, revealed severe stasis in the blood vessels and coagulative necrosis. These results suggest that THPTS-PDT may be of particular importance in the treatment of accessible malignancies.