Aspects to consider regarding breast cancer risk in trans men: A systematic review and risk management approach.

BACKGROUND: The risk of breast cancer in trans men is currently a poorly understood subject and trans men likely carries a different level of risk from that of cis women. AIM: This review aims to review several aspects that affects breast cancer risk in trans men and to apply the Swiss cheese model to highlight these risks. The study takes its cue from a systematic review of all described breast cancer cases in trans men following medical or surgical intervention because of gender dysphoria. METHODS: PubMed was systematically searched on the 14th of March 2023 to find all published cases of breast cancer following chest contouring surgery in trans men. Included articles had to involve trans men, the diagnosis of breast cancer had to be preceded by either a medical or surgical intervention related to gender dysphoria, and cases needed to involve invasive breast cancer or ductal carcinoma in situ. Articles were excluded if gender identity in the case subject was unclear and/or a full English version of the report was unavailable. Quality and risk of bias was evaluated using the GRADE protocol. A literature review of specific risk altering aspects in this population followed. The Swiss cheese model was employed to present a risk analysis and to propose ways of managing this risk. RESULTS: 28 cases of breast cancer in trans men have been published. The Swiss cheese model identified several weaknesses associated with methods of preventing breast cancer in trans men. CLINICAL IMPLICATIONS: This study may highlight the difficulties with managing risk factors concerning breast cancer in trans men to clinicians not encountering this patient group frequently. CONCLUSION: This review finds that evidence for most aspects concerning breast cancer in trans men are inadequate, which supports the establishment of a risk-management approach to breast cancer in trans men.

Fixation of the Compressive Dressing for Nipple-areola Complex Graft during Double Incision Chest Contouring Surgery for Assigned-female-at-birth Persons with Diagnosis of Gender Dysphoria: Sutures or Staples?

Background: When transplanting skin grafts, a compressive dressing is usually used to hold the skin graft in place. Dressing fixation can be achieved with either sutures or staples. The purpose of this study was to compare sutures and staples as a method of fixation for the compressive dressings of the nipple-areola complex (NAC) grafts, during double incision chest contouring surgery in assigned-female-at-birth persons with diagnosis of gender dysphoria. The two methods of fixation were compared according to pain at removal, time consumption, difficulty of removal, costs, and sustainability. Methods: Forty patients were randomized to dressing fixation with either sutures or staples. Timing for dressing fixation during surgery and removing the dressing was measured. Pain during removal was measured using vNRS-11. Difficulty of removal was measured with VAS-100. Costs of materials were compared. Results: All NAC grafts survived, and no complications such as infection or bleeding occurred. Staples were significantly more painful to remove when compared to sutures [mean vNRS-11 2.98 (SD ± 2.43) versus 1.25 (SD ± 0.92), P < 0.001]. Fixation with staples was faster than fixation with sutures (5.3 versus 94.6 s). No difference in removal time was found. Nurses found staples easier to remove. Sutures were slightly less costly (18 SEK) compared to staples (30 SEK). Finally, sutures produce less material waste. Conclusion: Being that all other outcomes are similar or insignificant, the less-pain experienced at removal of sutures makes this the preferable method for fixation of the compressive dressing for NAC grafts during double incision chest contouring surgery.

Liver Inclusion Appears to Be Protective Against Graft Loss-Due-to Chronic But Not Acute Rejection Following Intestinal Transplantation.

In intestinal transplantation, while other centers have shown that liver-including allografts have significantly more favorable graft survival and graft loss-due-to chronic rejection (CHR) rates, our center has consistently shown that modified multivisceral (MMV) and full multivisceral (MV) allografts have significantly more favorable acute cellular rejection (ACR) and severe ACR rates compared with isolated intestine (I) and liver-intestine (LI) allografts. In the attempt to resolve this apparent discrepancy, we performed stepwise Cox multivariable analyses of the hazard rates of developing graft loss-due-to acute rejection (AR) vs. CHR among 350 consecutive intestinal transplants at our center with long-term follow-up (median: 13.5 years post-transplant). Observed percentages developing graft loss-due-to AR and CHR were 14.3% (50/350) and 6.6% (23/350), respectively. Only one baseline variable was selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to AR: Transplant Type MMV or MV (p < 0.000001). Conversely, two baseline variables were selected into the Cox model indicating a significantly lower hazard rate of developing graft loss-due-to CHR: Received Donor Liver (LI or MV) (p = 0.002) and Received Induction (p = 0.007). In summary, while MMV/MV transplants (who receive extensive native lymphoid tissue removal) offered protection against graft loss-due-to AR, liver-containing grafts appeared to offer protection against graft loss-due-to CHR, supporting the results of other studies.

Ethical Considerations in Surgery for Single-suture Craniosynostosis.

Singe-suture craniosynostosis (SSC) describes the premature fusion of one cranial suture, which restricts cranial growth and consequently results in unaffected regions presenting a compensatory expansion. Surgery can redistribute intracranial volume, reduce the risk of elevated intracranial pressure, and improve head shape, potentially leading to improved neurocognitive function and social acceptance. However, there is limited evidence that surgery for SSC improves neurocognitive function and social acceptance. Given the inherent surgical risks and uncertainty of outcomes, the conditions under which this surgery should be allowed remain uncertain. Here, we discuss ethical questions regarding the permissibility of surgery, value of neurocognitive function and social acceptance, research ethics associated with SSC, patient autonomy and parental roles, and the process of recommending surgery and obtaining consent. Because surgery for SSC has become a routine procedure, its practice now presents a relatively low risk of complications. Furthermore, having acquired an understanding of the risks associated with this surgery, such knowledge fulfils the principle of non-maleficence although not beneficence. Thus, we advocate that surgery should only be offered within Institutional Review Board-approved research projects. In these situations, decisions concerning enrollment in scientific research involves health care providers and parents or guardians of the child, with the former acting as gate-keepers upon recognition of a lack of coping skills on the part of the parent or guardian in dealing with unforeseen outcomes. To minimize associated surgical risks and maximize its benefits, there exists a moral obligation to refer patients only to highly specialized centers.

The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.

Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Cell-Free DNA as a Surveillance Tool for Hepatocellular Carcinoma Patients after Liver Transplant.

The liver is the world's sixth most common primary tumor site, responsible for approximately 5% of all cancers and over 8% of cancer-related deaths. Hepatocellular carcinoma (HCC) is the predominant type of liver cancer, accounting for approximately 75% of all primary liver tumors. A major therapeutic tool for this disease is liver transplantation. Two of the most significant issues in treating HCC are tumor recurrence and graft rejection. Currently, the detection and monitoring of HCC recurrence and graft rejection mainly consist of imaging methods, tissue biopsies, and alpha-fetoprotein (AFP) follow-up. However, they have limited accuracy and precision. One of the many possible components of cfDNA is circulating tumor DNA (ctDNA), which is cfDNA derived from tumor cells. Another important component in transplantation is donor-derived cfDNA (dd-cfDNA), derived from donor tissue. All the components of cfDNA can be analyzed in blood samples as liquid biopsies. These can play a role in determining prognosis, tumor recurrence, and graft rejection, assisting in an overall manner in clinical decision-making in the treatment of HCC.

Clinical characteristics and outcomes in CMV infection in intestinal transplant recipients: A single-center experience.

BACKGROUND: Cytomegalovirus (CMV) infection is one of the most common posttransplantation infections and has been associated with increased rejection and mortality. Data in intestinal transplants recipients are limited. METHODS: This is a single-center, retrospective cohort study of all intestinal transplants performed between January 1, 2009, and August 31, 2020. We included recipients of all ages who were at risk of CMV infection. To identify the risk factors, we conducted at first univariate and multivariate analysis. For the multivariate analysis, we developed a logistic regression model based on the result of univariate analysis. RESULTS: Ninety five patients with a median age of 32 (interquartile range [IQR] 4, 50) were included. CMV donor seropositive/recipient seronegative were 17 (17.9%). Overall, 22.1% of the recipients developed CMV infection at a median time of 155 (IQR 28-254) days from transplant, including 4 CMV syndrome and 6 CMV end-organ disease. Overall, 90.4%, (19/21) developed DNAemia while on prophylaxis. Median peak viral load and time to negativity was 16 000 (IQR 1034-43 892) IU/mL and 56 (IQR 49-109) days, respectively. (Val)ganciclovir and foscarnet were utilized in 17 (80.9%) and 1 (4.76%) recipients, respectively. Recurrences of CMV DNAemia and graft rejection were observed in three and six recipients, respectively. Younger age was identified as a risk factor (p = .032, odds ratio 0.97, 95% confidence interval 0.95-0.99) to develop CMV DNAemia. CONCLUSION: A significant proportion of intestinal transplant recipients developed CMV infection while on prophylaxis. Better methods such as CMV cell mediated immunity guided prophylaxis should be used to prevent infections in this population.

The importance of avoiding time-dependent bias when testing the prognostic value of an intervening event - Two acute cellular rejection examples in intestinal transplantation.

In testing the prognostic value of the occurrence of an intervening event (clinical event that occurs posttransplant), 3 proper statistical methodologies for testing its prognostic value exist (time-dependent covariate, landmark, and semi-Markov modeling methods). However, time-dependent bias has appeared in many clinical reports, whereby the intervening event is statistically treated as a baseline variable (as if it occurred at transplant). Using a single-center cohort of 445 intestinal transplant cases to test the prognostic value of first acute cellular rejection (ACR) and severe (grade of) ACR on the hazard rate of developing graft loss, we demonstrate how the inclusion of such time-dependent bias can lead to severe underestimation of the true hazard ratio (HR). The (statistically more powerful) time-dependent covariate method in Cox's multivariable model yielded significantly unfavorable effects of first ACR (P < .0001; HR = 2.492) and severe ACR (P < .0001; HR = 4.531). In contrast, when using the time-dependent biased approach, multivariable analysis yielded an incorrect conclusion for the prognostic value of first ACR (P = .31, HR = 0.877, 35.2% of 2.492) and a much smaller estimated effect of severe ACR (P = .0008; HR = 1.589; 35.1% of 4.531). In conclusion, this study demonstrates the importance of avoiding time-dependent bias when testing the prognostic value of an intervening event.

Early United States experience with liver donation after circulatory determination of death using thoraco-abdominal normothermic regional perfusion: A multi-institutional observational study.

Mortality on the liver waitlist remains unacceptably high. Donation after circulatory determination of death (DCD) donors are considered marginal but are a potentially underutilized resource. Thoraco-abdominal normothermic perfusion (TA-NRP) in DCD donors might result in higher quality livers and offset waitlist mortality. We retrospectively reviewed outcomes of the first 13 livers transplanted from TA-NRP donors in the US. Nine centers transplanted livers from eight organ procurement organizations. Median donor age was 25 years; median agonal phase was 13 minutes. Median recipient age was 60 years; median lab MELD score was 21. Three patients (23%) met early allograft dysfunction (EAD) criteria. Three received simultaneous liver-kidney transplants; neither had EAD nor delayed renal allograft function. One recipient died 186 days post-transplant from sepsis but had normal presepsis liver function. One patient developed a biliary anastomotic stricture, managed endoscopically; no recipient developed clinical evidence of ischemic cholangiopathy (IC). Twelve of 13 (92%) patients are alive with good liver function at 439 days median follow-up; one patient has extrahepatic recurrent HCC. TA-NRP DCD livers in these recipients all functioned well, particularly with respect to IC, and provide a valuable option to decrease deaths on the waiting list.

A pilot retrospective CT angio study of the internal pudendal arteries in male bodies, for the purpose of penis transplantation to trans men.

Literature reports four successful cases where penile transplantation has been performed for cis men. To date, no penis transplantation has ever been attempted for trans men. Modern surgical techniques for penis reconstruction for (trans) men with gender incongruence present multiple drawbacks, and sometimes fail to meet patients' expectations. Penis transplantation could represent an alternative solution. With the aim of planning penis transplantation to trans men, a previous study from our same group suggested a surgical technique for explantation of penis and associated vessels, nerves and urethra en-bloc from a cadaver: further radiographic imaging of vascular anatomy was recommended. To measure length and diameter of the internal pudendal arteries at three set points in biological males, in order to confirm its viability for transplantation. A retrospective examination of existing CT images visualizing the internal pudendal arteries in 12 bodies, assigned male at birth, was performed. Diameters were measured in three points: 1. the take off of the artery; 2. distal to its rectal branch; and, 3. at the bifurcation of the two terminal branches of the artery, i.e. the bulbourethral artery and the dorsal artery of the penis. Mean diameters of the selected points were 2.4 mm, 1.9 mm, and 1.5 mm on both sides. Mean lengths of internal pudendal arteries were 111.2 mm on the left, and 120.1 mm on the right side. Diameters of the internal pudendal artery is sufficient for arterial anastomosis at all measured points. Lengths are sufficient to reach recipient vessels.

Pilot study to determine the safety and feasibility of deceased donor liver natural killer cell infusion to liver transplant recipients with hepatocellular carcinoma.

Liver transplantation (LT) is a viable treatment option for cirrhosis patients with hepatocellular carcinoma (HCC). However, recurrence is the rate-limiting factor of long-term survival. To prevent this, we conducted the phase I study of the adoptive transfer of deceased donor liver-derived natural killer (NK) cells. Liver NK cells were extracted from donor liver graft perfusate and were stimulated in vitro with IL-2. The patient received an intravenous infusion of NK cells 3-5 days after LT. Eighteen LT recipients were treated. There were no severe cell infusion-related adverse events or acute rejection episodes. One patient withdrew from the study because the pathological observation revealed sarcoma instead of HCC. All patients who received this immunotherapy completed the follow-up for at least 2 years without evidence of HCC recurrence (median follow-up, 96 months [range, 17-121 months]). Considering that 9 (52.9%) of the 17 patients pathologically exceeded the Milan criteria, liver NK cell infusion is likely to be useful for preventing HCC recurrence after LT. This is the first-in-human immunotherapy study using deceased donor liver-derived NK cells to prevent HCC recurrence after LT. This treatment was well tolerated and resulted in no HCC recurrence after LT.Clinical trial registration www.clinicaltrials.gov ; NCT01147380; registration date: June 17, 2010.

Heterologous Type I Collagen as an Add-on Therapy to Narrowband Ultraviolet B for the Treatment of Vitiligo: A Pilot Study.

BACKGROUND: There is still an unsatisfied need for new treatments for vitiligo with more rapid onset and long-term sustainability of repigmentation. OBJECTIVE: We sought to evaluate the possible efficacy of heterologous type I collagen as an add-on therapy to narrowband ultraviolet B (NB-UVB) for the treatment of vitiligo. METHODS: Five patients with non-segmental vitiligo older than 18 years with bilateral and approximately symmetrical vitiligo lesions that did not evolve in size for at least six months were included. All vitiligo lesions were treated with NB-UVB therapy according to the Vitiligo Working Group recommendations. Two selected nonfacial lesions of each patient were also treated with intradermal injections of heterologous type I collagen (HTIC) every two weeks. Repigmentation of HTIC plus NB-UVB-treated lesions and their symmetrical counterparts treated just with NB-UVB was evaluated at baseline and Week 12. RESULTS: Repigmentation of the HTIC-injected lesions started after the first treatment session in three cases and after the second session in two cases. After six sessions (Week 12), the mean repigmentation rate was 70.5 percent (95% confidence interval:0.569-0.841) in the NB-UVB plus HTIC treatment group versus 16.5 percent (95% confidence interval: 0.137-0.192) in NB-UVB treatment group (p=0.0006, paired t-test). CONCLUSION: Although the number of patients treated with the combination treatment was limited in our study, our results suggest that the addition of HTIC to NB-UVB therapy might offer a more rapid onset of repigmentation in patients with vitiligo.

Intestinal Autotransplantation and In-Situ Resection of Recurrent Pancreatic Head Intraductal Tubulopapillary Neoplasm with Portal Cavernoma: A Case Report.

BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a new entity of a rare premalignant pancreatic neoplasia, and a radical curative resection is indicated. As with other tumors of the root of the mesentery, the proximity of the lesion to large splanchnic vessels, abdominal aorta, and inferior vena cava poses major risks of a massive hemorrhage and visceral ischemia using conventional surgical techniques. At times, these lesions are amenable for resection using novel techniques developed from organ transplantation. Multivisceral (allo-) transplantation should be considered when radical resection of a benign tumor is likely to compromise portal flow and possibly precipitate acute liver failure, but it may be associated with a long waitlist time and tumor progression. Autotransplantation offers a safe and curative resection of otherwise inoperable tumors in a bloodless field, an excellent exposure, and prevention of warm ischemic injury to the affected viscera, which are then autotransplanted. METHODS: We describe the en bloc resection of a large and recurrent ITPN of the pancreas, distal stomach, proximal duodenum, transverse colon, superior mesenteric vein, and portal cavernoma, followed by intestinal autotransplantation. RESULTS: A complete tumor resection was achieved with negative margins, adequate cold preservation of the reimplanted intestine, and without significant hemorrhage. The patient was discharged from the hospital 10 days later. The histopathologic examination revealed free-margin resection of ITPN with an associated invasive carcinoma. The patient received adjuvant chemotherapy with folinic acid, fluorouracil, and oxaliplatin and remains disease-free 20 months after surgery. CONCLUSIONS: Autotransplantation offers curative resection of otherwise unresectable lesions of the root of the mesentery.

No Benefit of Prophylactic Surgical Drainage in Combined Liver and Kidney Transplantation: Our Experience and Review of the Literature.

Background: Contrasting results have emerged from limited studies investigating the role of prophylactic surgical drainage in preventing wound morbidity after liver and kidney transplantation. This retrospective study analyzes the use of surgical drain and the incidence of wound complications in combined liver and kidney transplantation (CLKTx). Methods: A total of 55 patients aged ≥18 years were divided into two groups: the drain group (D) (n = 35) and the drain-free group (DF) (n = 20). Discretion to place a drain was based exclusively on surgeon preference. All deceased donor kidneys were connected to the LifePort Renal Preservation Machine® prior to transplantation, in both simultaneous and delayed technique of implantation of the renal allograft. The primary outcome was the development of superficial/deep wound complications during the study follow-up. Secondary outcomes included the development of delayed graft function (DGF) of the transplanted kidney, primary non-function (PNF) and early allograft dysfunction (EAD) of the transplanted liver, graft failure, graft and patient survival, overall post-operative morbidity rate and length of hospital stay. Results: With a median follow-up of 14.4 months after transplant, no difference in the incidence of superficial/deep wound complications, except for hematomas, in collections size, intervention rate, PNF, EAD, graft failure and patient survival, was observed between the 2 groups. Significantly lower level of platelets, higher INR values, DGF, morbidity rates and length of hospital stay were reported post-operatively in the D group. Pre-operative hypoalbuminemia and longer CIT were included in the propensity score for receiving a drain and were associated with a significantly higher rate of developing a hematoma post-transplant. Conclusions: Absence of the surgical drain did not appear to adversely affect wound morbidity compared to the prophylactic use of drains in renal transplant patients during CLKTx.

Describing universal Strongyloides serologic screening among pediatric intestinal and liver transplant recipients.

BACKGROUND: Strongyloides spp hyperinfections are a worldwide phenomenon that proves fatal for solid organ transplant recipients. Screening protocols to guide prophylaxis management vary institution to institution from universal to epidemiology driven. Our institution initiated a universal screening protocol regardless of travel history and exposure to ensure no cases were missed. METHODS: In this study, we describe the outcomes of three Strongyloides sero-positive children whom underwent intestinal or liver transplantation and the experience of universal screening at a tertiary care county hospital in South Florida. RESULTS: Among the 66 intestine and liver pediatric transplant recipients who were screened for Strongyloides antibodies, only three were identified to be sero-positive via the screening mechanism. Two of three had significant epidemiology risk factors. None of the patients reviewed were found to have developed hyperinfection. However, reflecting on the experience represented by our series of pediatric patients, the risk of any complication related to Strongyloides status appears low. Even among this South Florida population whom come from or travel to endemic regions are in contact with sero-positive individuals, very few illustrate sero-positivity. CONCLUSION: While institutions continue to analyze the cost-benefit of universal testing vs. universal prophylaxis vs. targeted screening, the decision must encompass the patient population, rolling cumulative incidence, and morbidity and mortality related to this disease.

Intestinal transplantation.

PURPOSE OF REVIEW: Intestinal transplantation has evolved to be a viable treatment option for patients with intestinal failure. This review shows the most current tendencies and practices of intestinal transplant centers and an overall comparison to intestinal rehabilitation. RECENT FINDINGS: This review outlines that timing for referral and advances in preoperative and postoperative care of intestinal and multivisceral transplant candidates are crucial to achieve results comparable to intestinal rehabilitation. SUMMARY: Current practices have shown that intestinal transplantation continues to improve overall results and could be considered in patients with permanent home parenteral nutrition. Timing for referral and preoperative and postoperative management are crucial to optimize long-term results.

Does pediatric hand transplantation undermine a child's right to an open future?

To date, pediatric hand transplantations have only been performed twice. The ethical issue most often discussed in the literature on this surgery concerns the risks of immunosuppression. While these risks are significant, they can be at least partially mitigated by selecting for patients who are already immunocompromised. Nevertheless, as we will argue, pediatric hand transplantation raises ethical issues that go beyond the risks of immunosuppression. In this paper, we focus on three additional ethical issues: the fact that pediatric hand transplantation aims to improve, rather than save life; the fact that it is an experimental surgery; and the fact that it will be performed on non-autonomous patients whose 'right to an open future' may potentially be undermined by the surgery. Taken together, we think that these considerations suggest that transplantation should be postponed until a child is mature enough to make their own decision about it.

The Aesthetically Ideal Position of the Nipple-Areola Complex on the Breast.

BACKGROUND: Several studies have attempted to identify an objective description of the aesthetically ideal breast, but they have all suffered in their reliability because of having several intrinsic limitations. It is therefore essential to design a template of ideal breast features in order to predict and evaluate aesthetic outcomes in both reconstructive and cosmetic breast surgery. The aim of this study was to determine the aesthetically preferred position of the nipple- areola complex on the breast. METHODS: A questionnaire was sent by regular mail to 1000 men and 1000 women aged between 16 and 74 years. They were asked to rank the attractiveness of a series of breasts of women in images with different NAC positions. The images showed breasts from two different angles: 12 frontal-view images with both breasts shown, and five sideview images with only one breast shown. All of the breasts had equal dimensions and proportions, with the same areola size but different NAC positions. Statistical analysis of data was carried out. RESULTS: Eight hundred and thirteen of 2000 participants completed the questionnaire. The NAC placement preferred by both genders had a ratio of 40:60 x and 50:50 y, which means that it was best situated in the middle of the breast gland vertically and slightly lateral to the midpoint horizontally. Significant differences were found between the age and gender subgroup preferences. CONCLUSIONS: This study identified the preferred position of the nipple-areola complex on the female breast in the general population. This is an important information when planning breast reconstructive and cosmetic surgery. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .