P3 Flap: Technique for Fingertip Reconstruction.

Fingertip amputations represent an important spectrum of injuries, and most are avulsions or crush trauma. There is no consensus about one single standard treatment, and a wide number of techniques are available. The authors present the P3 flap as an option for covering fingertip defects with bone exposure, avoiding painful scars in the pulp area, without a donor site. This study included 12 fingertips with amputated segment not available for replantation. Volar oblique fingertip defects and transverse amputations with bone exposure, not more proximal than Hirase Zone IIB, were included. Defects were less than 2 cm. The patients were followed up for an average of 6 months. The aesthetic and functional outcomes and fingertip discrimination recovery were evaluated at 6 months by the static two-point discrimination (2-PD) test and DASH score (quick version). The average postoperative 2-PD test at 6 months was 5.9 mm (range from 5 to 8 mm). The mean healing time of the fingertip was 4 weeks. Nail deformity was reported in three cases with level IIB of amputation. None of the P3 flaps failed, and local infection was not reported. The average DASH score at 6 months was 1.1. The mean time to return to work was 38 days (range from 30 to 53). The P3 flap proposed in this study demonstrates a reliable single-stage technique, performed under local anesthesia, for fingertip defect reconstruction, avoiding skin incision and scars in the pulp region and preserving digital length and nail bed.

Shape-modified radial forearm flap: does it still have a role in upper extremity reconstruction?

OBJECTIVES: To carry out a radial forearm flap, the radial artery is usually harvested, incurring severe donor site morbidity. Advances in anatomical knowledge discovered constant radial artery perforating vessels, enabling the subdivision of the flap into smaller components suitable for a wide range of differently shaped recipient sites, with marked reduction of downsides. MATERIAL AND METHODS: Eight pedicled or free shape-modified radial forearm flaps were used to reconstruct upper extremity defects between 2014 and 2018. Surgical technique and prognosis were examined. Skin texture and scar quality were assessed on the Vancouver Scar Scale while function and symptoms on the Disabilities of the Arm, Shoulder and Hand score. RESULTS: At a mean follow-up of 39 months, no cases of flap necrosis, impaired hand circulation or cold intolerance were found. CONCLUSION: The shape-modified radial forearm flap is not a new technique, but is poorly known by hand surgeons; in contrast, our experience showed it to be reliable, with acceptable functional and esthetic outcomes in selected cases.

Open release of stiff wrist: a medium to long term case series and literature review.

BACKGROUND AND AIM OF THE WORK: The authors reported a personal case series of open release of stiff wrists performed after previous internal osteosynthesis of distal radius fractures. METHODS: From a series of 16 patients operated by a single surgeon, 12 were evaluated at a mean 7.1 years follow-up (range 2.25 to 19 years), while 4 were lost at follow-up. The ROM in flexion-extension achieved at the final control was measured with a goniometer and compared to that recorded before surgery. The PRWHE questionnaire was administred at the last follow-up. RESULTS: The mean flexion improved from 25.5° to 42.3° and the extension from 15.75° to 43°. The mean PRWHE value was 32.9. CONCLUSIONS: Although arthroscopic release is increasingly used in clinical practice for its minimal invasinevess and warranty of fast recovery, open arthrolysis in post-traumatic stiff wrists appears to be an effective procedure, adaptable to all types of stiffness, that lets get good long lasting functional results.

Update on Peripheral Nerve Sheath Tumors in Upper Extremity: A Descriptive Review.

Peripheral Nerve Sheath Tumors (PNSTs) are extremely uncommon and it is almost certain that no individual upper limb surgeon will gain great experience in a lifetime with these lesions. Benign and malignant PNSTs are separately analyzed in this descriptive review and discussed focusing the attention towards the most important features. A comprehensive and summarized overview of this topic is offered to the reader in order to improve the complex management of these tumors from diagnosis to treatment. A systematic search in PubMed was carried out using the keywords (and synonyms) written below in order to find relevant and most cited papers. Reckoning the rarity of the pathology, few selected case reports were taken into account. A compendium of each PNST was created to sum up the personal experience of the Authors who wrote the articles, critically inspected and analyzed. Every section of the paper is meant to provide useful tips to the reader.

Vascularized bone grafts for post-traumatic defects in the upper extremity.

Vascularized bone grafts (VBGs) are widely employed to reconstruct upper extremity bone defects. Conventional bone grafting is generally used to treat defects smaller than 5-6 cm, when tissue vascularization is adequate and there is no infection risk. Vascularized fibular grafts (VFGs) are mainly used in the humerus, radius or ulna in cases of persistent non-union where traditional bone grafting has failed or for bone defects larger than 6 cm. Furthermore, VFGs are considered to be the standard treatment for large bone defects located in the radius, ulna and humerus and enable the reconstruction of soft-tissue loss, as VFGs can be harvested as osteocutaneous flaps. VBGs enable one-stage surgical reconstruction and are highly infection-resistant because of their autonomous vascularization. A vascularized medial femoral condyle (VFMC) free flap can be used to treat small defects and non-unions in the upper extremity. Relative contraindications to these procedures are diabetes, immunosuppression, chronic infections, alcohol, tobacco, drug abuse and obesity. The aim of our study was to illustrate the use of VFGs to treat large post-traumatic bone defects and osteomyelitis located in the upper extremity. Moreover, the use of VFMC autografts is presented.

Fingertip defect reconstruction with a modified pivot flap.

The pivot flap can treat volar oblique defects of the fingers distal to the distal interphalangeal joint. We present our experience in 11 fingers (11 patients) using this flap, including some modifications that optimize flap harvesting, mobilization, inset, and vascular supply and outcomes. The flaps harvested had an average size of 2.4 × 2.0 cm. The patients were followed for an average of 21 months (range 12 to 36) after surgery. Sensitivity of the flap was evaluated with the Semmes-Weinstein monofilaments test and static two-point discrimination test. Cold intolerance was also evaluated. The pivot flap with the modifications demonstrates a reliable technique for fingertip defect reconstruction. The results, in terms of sensitivity and functional recovery, seem promising.Level of evidence: IV.

Personalized Risk-Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID-19 Outbreak.

Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer-related outcome. In this article, we attempt to estimate the individual risk-benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID-19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID-19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID-19-related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients' and health workers' psychological distress.

PD-1 Inhibitors-Related Neurological Toxicities in Patients with Non-Small-Cell Lung Cancer: A Literature Review.

The advent of immune checkpoint inhibitors gave rise to a new era in oncology and general medicine. The increasing use of programmed death-1 (PD-1) inhibitors in non-small cell lung cancer and in other malignancies means clinicians have to face up to new challenges in managing immune-related adverse events (irAEs), which often resemble autoimmune diseases. Neurological irAEs represent an emerging toxicity related to immunotherapy, and it is mandatory to know how to monitor, recognize, and manage them, since they can rapidly lead to patient death if untreated. Guidelines for the diagnosis and treatment of these irAEs have been recently published but sharing some of the most unusual clinical cases is crucial, in our opinion, to improve awareness and to optimize the approach for these patients. A literature review on the diagnosis and treatment of immune-related neurotoxicity's has been conducted starting from the report of four cases of neurological irAEs regarding cases of polyneuropathy, myasthenia gravis, Bell's palsy, and encephalopathy, all of which occurred in oncological patients receiving PD-1 inhibitors (pembrolizumab and nivolumab) for the treatment of non-oncogene addicted advanced non-small cell lung cancer. The exclusion of other differential diagnoses and the correlation between the suspension of immunotherapy and improvement of symptoms suggest that immunotherapy could be the cause of the neurological disorders reported.

Reconstruction of Traumatic Dorsal Loss of the Thumb: Four Different Surgical Approaches.

BACKGROUND: This article outlines our methods for thumb reconstruction following dorsal skin loss injury located between the metacarpophalangeal joint (MPj) and the entire nail affecting skin, nail, tendon, and bone in different combinations but with intact sensate palmar skin. METHODS: Between 1990 and 2015, 24 patients were treated for dorsal thumb defects using 4 different surgical techniques. Five cases of dorsal compound traumatic loss were reconstructed by custom-made dorsal great toe transfer. Four patients with dorsal skin and nail loss located at the distal phalanx level were covered with the homodigital flap with reverse flow vascularization. In 9 patients presenting skin defects between the MPj and the nail, reconstruction was achieved by means of the kite flap. Six cases suffered extensive dorsal skin loss, and reconstruction was performed using different types of radial forearm flaps (cutaneous, tendineocutaneous, osteocutaneous, and fascial). RESULTS: Flap survival was obtained in all cases. No vascular complications occurred with free vascularized compound toe transfer. CONCLUSIONS: Reconstruction of dorsal thumb defects is imperative and its approach is strictly correlated to type of defect, patient's requests, and flap alternatives. For defects with nail involvement, the free osteo-onychocutaneous flap harvested from the great toe provides the best aesthetic result in selected young and well-motivated patients. An alternative is represented by the dorsoulnar flap, when the defect is located distally, or the fascial pedicle radial forearm flap, for major dorsal thumb defects, in patients refusing microsurgical reconstruction. The kite flap still represents a feasible solution for medium-size defects with an intact nail.

Invasive Pulmonary Aspergillosis Complicated by Carbapenem-Resistant Pseudomonas aeruginosa Infection During Pembrolizumab Immunotherapy for Metastatic Lung Adenocarcinoma: Case Report and Review of the Literature.

The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs. These observations lead experts' opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for ≥ 4 weeks. Few data on invasive fungal infections in this context are available. We report here a case of probable invasive pulmonary aspergillosis (p-IPA) complicating first-line immunotherapy with pembrolizumab for metastatic lung cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa superinfection of fungal cavities; the patient received concurrent systemic corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and PDL1-targeted agents, we found three cases of invasive aspergillosis and one case of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab treatment; to the best of our knowledge, this is the first report of p-IPA complicating pembrolizumab immunotherapy. Briefly, in this new setting of biological/targeted drugs, waiting for growing clinical experience, we recommend a high level of alertness in diagnosing any infectious complications.

Effect of Diabetes on Survival after Resection of Pancreatic Adenocarcinoma. A Prospective, Observational Study.

AIM: To investigate the effect of diabetes mellitus (DM) on disease-free and overall post-resection survival of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Prospective observational study on patients admitted for pancreatic disease from January 2008 to October 2012. DM was classified as recent-onset (<48 months before PDAC diagnosis), longstanding (≥48 months before PDAC) or new onset (after surgery). RESULTS: Of 296 patients, 140 had a diagnosis of DM prior to surgery (26 longstanding, 99 recent-onset, 15 with unknown duration). Median follow-up time was 5.4 ± 0.22 years. Patients with recent onset DM had poorer postoperative survival than patients without DM: disease-free survival and overall survival were 1.14±0.13 years and 1.52±0.12 years in recent onset DM, versus 1.3±0.15 years and 1.87±0.15 years in non-diabetic patients (p = 0.013 and p = 0.025, respectively). Longstanding DM and postoperative new onset DM had no impact on prognosis. Compared to cases without DM, patients with recent onset DM were more likely to have residual disease after surgery and to develop liver metastases during follow-up. Multivariate analysis confirmed recent onset DM was independently associated with PDAC relapse (hazard ratio 1.45 [1.06-1.99]). CONCLUSION: Preoperative recent onset DM has an impact on survival after the resection of PDAC.

Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma.

AIMS: To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis. METHODS: Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression. RESULTS: Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival. CONCLUSIONS: Insulin resistance is associated with the aggressiveness of PDAC.

Diabetes associated with pancreatic ductal adenocarcinoma is just diabetes: Results of a prospective observational study in surgical patients.

BACKGROUND: Identification of a specific diabetes signature associated to pancreatic ductal carcinoma (PDAC) could be a key to detect asymptomatic, early stage tumors. We aim to characterize the clinical signature and the pathogenetic factors of the different types of diabetes associated with PDAC, based on the time between diabetes and cancer diagnosis. METHODS: Prospective observational study on 364 PDAC patients admitted to a referral center for pancreatic disease. Hospital and/or outpatient medical records were reviewed. Blood biochemical values including fasting blood glucose, insulin and/or C-peptide, glycosylated hemoglobin and anti-islet antibodies were determined. Diabetes onset was assessed after surgery and during follow-up. RESULTS: The prevalence of diabetes in patients was 67%. Considering 174 patients (47.8%) already having diabetes when diagnosed with PDAC (long duration, short duration, concomitant), the clinical and biochemical profile was similar to that of patients with type 2 diabetes (T2D). Diabetes was associated with known risk factors (i.e., age, sex, family history for diabetes and increased BMI) and both beta-cell dysfunction and insulin resistance were present. Considering 70 patients (19.2%) with onset of diabetes after PDAC diagnosis (early and late onset), the strongest predictor was the loss of beta-cell mass following pancreatectomy in patients with risk factors for T2D. CONCLUSION: Different types of diabetes according to the time between diabetes and PDAC diagnosis are clinical entities widely overlapping with T2D. Therefore, the success of a strategy considering diabetes onset as a marker of asymptomatic PDAC will largely depend on our ability to identify new diabetes-unrelated biomarkers of PDAC.

Diabetes after pancreatic surgery: novel issues.

In the developed world, pancreatic surgery is becoming more common, with an increasing number of patients developing diabetes because of either partial or total pancreatectomy, with a significant impact on quality of life and survival. Although these patients are expected to consume increasing health care resources in the near future, many aspects of diabetes after pancreatectomy are still not well defined. The treatment of diabetes in these patients takes advantage of the therapies used in type 1 and 2 diabetes; however, no specific guidelines for its management, both immediately after pancreatic surgery or in the long term, have been developed. In this article, on the basis of both the literature and our clinical experience, we address the open issues and discuss the most appropriate therapeutic options for patients with diabetes after pancreatectomy.

Sexual function and endocrine profile in fertile women with type 1 diabetes.

OBJECTIVE: Aims of this study were 1) to assess sexual function and endocrine profile among fertile type 1 diabetic women during the follicular and luteal phases of the menstrual cycle, 2) to compare these results with those obtained among healthy fertile women who served as control subjects, and 3) to explore the correlations between sexual function and endocrine milieu among patients and control subjects during the follicular and luteal phases of the menstrual cycle. RESEARCH DESIGN AND METHODS: Fifty fertile women with type 1 diabetes and 47 healthy control subjects completed a semistructured medical interview and filled in self-administered validated instruments to evaluate sexual function, depression, and sexual distress. Venous blood samples were drawn to measure glycated hemoglobin and an endocrine profile during either the follicular or the luteal phase of the menstrual cycle. RESULTS: Type 1 diabetic women had decreased sexual function and increased sexual distress compared with control subjects during the luteal, but not the follicular, phase of the menstrual cycle. During the follicular phase, patients had lower estrogenic basal tone, lower "weak" androgen (namely Delta4-androstenedione and dehydroepiandrosterone sulfate) production, and lower free-triiodothyronine and free-thyroxine levels compared with control subjects. During the luteal phase, total testosterone levels were higher in patients than control subjects, while 17beta-estradiol and progesterone levels were lower in patients than control subjects. CONCLUSIONS: Among type 1 diabetic women, sexual function and sexual distress vary according to the phase of the menstrual cycle. This finding may have implications on the clinical assessment of sexual function in type 1 diabetic women.