Cutaneous side effects in a cohort of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: General description and further characterization, correlation with photoexposition and study of hypopigmentation as treatment's prognostic factor.

Cutaneous adverse effects (AE) related to tyrosine-kinase inhibitor (TKI) drugs have been mainly described as case reports. We have characterized their appearance and correlation with patient's photoexposition habits and, further, with treatment response, in 61 patients with chronic myelogenous leukemia (CML) treated with TKI drugs. We have found hypopigmentation in 49.2% of the cases and a statistically significant association with interferon (IFN) intake. Eyelid edema's frequency was 45.4%. Mean photo-exposure was 1.95 h/day and only 8.3% of the patients used sunscreen daily. 44.3% of the patients reported a lighter skin color with the treatment and a statistically significant relationship with conjunctival hemorrhage was also found. Concordance between patients and dermatologist was moderate (kappa index 0.41). We found xerosis (21.3%), eczematous eruptions (21.3%), melasma (4.9%) and other isolated skin problems (ie, granulomatous panniculitis) in up to 16.4% of cases. Appearance of hypopigmented macules is associated to vascular conjunctival fragility and these patients need a slightly longer time to reach a complete molecular response, but without additional changes in survival or relapse frequency. We have stablished a specific dermatologic diagnosis in all the cases and we have not found the previously published as maculopapular rashes. Hypopigmentation, the more frequent AE, was not perceived as a relevant side effect. Photosensitivity, in our cases, was not reported, although imatinib-treated patients avoided sun-exposure. In addition, we identified some nonpreviously described dermatologic conditions in patients taking TKI drugs, like granulomatous panniculitis tufted folliculitis or oral spindle cell lipoma.

Analysis of the Increase in Bone Mineral Density After Surgical Treatment of Primary Hyperparathyroidism.

AIM: To analyze the effect of the surgery in bone mineral density (BMD) and to study the value of preoperative clinical and analytical factors as predictors of bone increase. MATERIAL AND METHODS: Prospective observational study. Postmenopausal women who were operated for primary hyperparathyroidism were included. A bone densitometry of the lumbar spine and femoral neck and analytical determinations (parathyroid hormone [PTH], alkaline phosphatase, albumin, phosphate, creatinine, 25-hydroxy-vitamin D3, creatinine clearance, and calciuria) were performed previous to the intervention and after 12 months from surgery. RESULTS: Two hundred and twenty-eight patients were operated on for primary hyperparathyroidism were considered for study, 108 postmenopausal women entered in the final analysis. The mean age was 63 ± 7 yr. After the intervention, a significant increase in BMD was observed in the two locations analyzed, although this increase was significant greater at the level of the lumbar spine. In the lumbar spine, 68 patients (63%) recorded a significant postoperative increase in bone density. Median postoperative BMD was 0.860 g/cm2 (interquartile range: 0.93). The observed average percentage of density increase was 6.63 ± 17.9. In femoral neck, 61 patients (56.6%) registered a significant increase in bone density. Median postoperative BMD value was 0.741 g/cm2 (interquartile range: 0.76). The average percentage of density increase was 3.19 ± 17.9. In the lumbar spine, patients with osteoporosis before surgery increased postoperative BMD more frequently than those with osteopenia or normal density. Patients who increased BMD preoperatively presented lower bone density levels both in the lumbar spine (median: 0.775, interquartile range: 0.882) and in the hip (median: 0.655, interquartile range: 0.562) than patients in whom it was not observed postoperative increase. PTH preoperative serum was lower among patients who increased bone density in the femur (median: 141 pg/ml, interquartile range: 291) than among those who did not (median: 152 pg/ml, interquartile range: 342) (p = 0.01). In the multivariate analysis, the increase in BMD in the lumbar spine was related to preoperative BMD (odds ratio [OR] 0.084, 95% confidence interval [CI]: 0.007-0.961); in femoral neck it was related to preoperative BMD (OR 0.001; 95% CI: 0.0-0.028) and to the preoperative PTH serum concentration (OR 0.99; 95% CI: 0.98-0.99). CONCLUSIONS: After surgery, a significant increase in BMD was observed in the lumbar spine and femoral neck. In the multivariate analysis, preoperative bone density was the factor that showed the highest predictive value of the increase in BMD after surgery.

Collision of Subungual Neurofibroma and Onychomatricoma: S100 Positivity as a Clue.

We present a 41-year-old man with a hemionychodystrophy of the first toe, appearing as a longitudinal thickening of the nail plate, overcurved and with holes in its thickened free margin, thus leading to the clinical diagnosis of onychomatricoma. Complete excision showed typical nail plate of onychomatricoma and, underlying it, curvy disorganized neural-looking fascicles without atypia and with diffuse positivity for S100, interpreted as subungual neurofibroma (NF). Subungual NF is a very rare tumor, with only 12 previous cases reported. Its diagnosis is based on histopathology, as the tumor presents waves or whorls of disorganized neural-looking cells positive for S100. Regarding onychomatricoma, it is characterized by typical glove finger digitations (which were present in our case) and an underlying stroma composed by a cellular superficial layer (this layer expresses CD34 but not CD99) and a more sclerotic and deeper area. As we did not find information on S100 expression in the stroma of onychomatricoma, we have stained 4 typical cases, and all were negative with S100 and positive with CD34, as expected. In conclusion, as "subungual NF" is so rare and, in our case, seems to collide with a typical onychomatricoma, we recommend adding S100 staining to properly characterize tumors involving nail plate, to detect underlying neural tumors, as has happened in our case.

Spontaneous haematoma of the anterior rectus abdominis muscle. / Hematoma espontáneo del músculo recto anterior del abdomen.

INTRODUCTION: Spontaneous haematoma of the rectus abdominis muscle is an uncommon cause of abdominal pain. It occurs mostly in anticoagulated patients. The objective of this paper is to analyse the onset, diagnosis and treatment in patients under anticoagulant therapy. METHODS: A retrospective analysis of a prospectively maintained database of all patients with a diagnosis of spontaneous hematoma of the abdominal rectus muscle between March 2003 and December 2014. RESULTS: The study included 34 patients, of whom 28 were women, with an average age of 80 years old. All the patients showed a unilateral infraumbilical haematoma. Twenty- 8 patients had received long-term anticoagulant treatment (26 with acenocumarol and 2 low molecular weight heparin); and 6 patients were under anticoagulant prophylaxis with low molecular weight heparin. The diagnosis was performed with ultrasound in 7 cases, computed tomography angiography in 27 patients, and with both methods in 6 cases. The treatment consisted of stopping the anticoagulant drug, correcting haemostasis parameters and blood transfusion when required. Ten patients displayed active bleeding in the computed tomography angiography, and 8 underwent selective arterial embolization. The evolution was successful in 34 patients, however, 2 patients required surgery and, finally, died due to persistent haemorrhage. CONCLUSION: Spontaneous haematoma of the rectus abdominis muscle is more frequent in elderly women under oral anticoagulant treatment. Non-operative treatment is successful in most cases. Computed tomography angiography is useful to determine which patients could benefit from selective arterial embolization.

Spontaneous cervical hematoma caused by giant parathyroid adenoma in an elderly patient: A case report.

Spontaneous cervical hematoma usually occurs as a consequence of extracapsular bleeding from a parathyroid gland, generally due to the presence of an adenoma (giant adenoma), glandular hyperplasia, cystic component, or, less frequently, due to the existence of a carcinoma. The hematoma can be confined to the cervical compartment or extend to the mediastinum, potentially causing airway compression. Despite this, the recommended management in hemodynamically stable patients consists of surveillance and hospital monitoring with delayed surgery after a few weeks. On the other hand, in those patients with airway compromise and instability, emergency surgery, consisting of cervicotomy and drainage, is mandatory. The present study describes the case of a 78-year-old patient with a medical history of high blood pressure, non-insulin-dependent diabetes mellitus, dyslipidemia, moderate aortic stenosis, chronic kidney disease and sarcoidosis under pharmacological treatment who attended the emergency department due to symptoms of neck pain, an increase in soft tissue, and dyspnea on moderate exertion with an evolution leading to respiratory failure. This was secondary to a diagnosis of spontaneous cervical hematoma that required urgent surgical intervention. The results of histopathological analysis revealed that a giant parathyroid adenoma was responsible for the bleeding. The patient had a complicated post-operative period with a prolonged admission to the intensive care unit.

Effect of Tumor Regression Grade on Survival and Disease-Free Interval in Patients Operated on for Locally Advanced Rectal Cancer.

INTRODUCTION: Colorectal cancer is the fourth leading cause of cancer-related death in both men and women in our population. In this regard, rectal cancer accounts for more than half of colorectal cancer deaths, and its incidence is expected to increase in the coming years. There have been significant changes in neoadjuvant therapy regimens, with promising results, as demonstrated by the recent RAPIDO and PRODIGE23 studies. Around 40% of patients diagnosed with locally advanced rectal cancer show some degree of response to neoadjuvant treatment, with complete tumor regression observed in up to one in five patients. MATERIALS AND METHODS: Retrospective observational study. A total of 181 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were analyzed. Clinical and pathological data were collected from the patients, including assessment of tumor regression through histopathological studies after surgery. The Mandard tumor regression grading system was used to categorize tumor response into different grades. RESULTS: The results showed a significant association between the degree of tumor regression and several important clinical outcomes. Specifically, patients with higher tumor regression had significantly better disease-free survival than those with less regression (p = 0.004). In addition, tumor regression was also correlated with the incidence of local recurrence (p = 0.018) and distant metastasis (p = 0.032). These associations suggest that tumor responsiveness to neoadjuvant therapy may influence the long-term progression of the disease. Regarding tumor deposits and the presence of lymphadenopathy, these factors were also found to be significantly associated with clinical outcomes. Patients with tumor deposits had a higher incidence of local recurrence (p = 0.025) and distant metastases (p = 0.041), while the presence of lymphadenopathy increased the risk of local recurrence (p = 0.013). These findings highlight the importance of evaluating not only tumor regression but also other pathological markers to predict prognosis and guide clinical management. CONCLUSIONS: The degree of tumor regression was not an independent predictor of survival compared to other variables such as nodal stage and presence of tumor deposits. This indicates that while tumor regression is an important factor, other elements also play a crucial role in determining the prognosis of patients with locally advanced rectal cancer. This study provides additional evidence for the importance of tumor regression, tumor deposits, and lymphadenopathy as predictors of clinical outcomes in patients with rectal cancer treated with neoadjuvant chemoradiotherapy.

Single metachronous bone metastasis following rectal adenocarcinoma: A case report.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality in developed countries. While its incidence in early stages has increased due to screening programs, a significant number of patients experience the development of metastases either at the time of diagnosis or during follow-ups. Unlike certain other types of cancer, such as breast, prostate, or lung cancer, where bone tissue is a common site for secondary dissemination, CRC primarily spreads to the lymph nodes, liver and lungs. The occurrence of bone metastases from CRC is rare and usually coincides with tumor involvement in other locations. Risk factors for bone metastases include the location of the primary tumor, the age of the patients, KRAS mutations and the degree of tumor differentiation. Unlike metastases to the liver and lungs, bone metastases tend to be symptomatic, affecting the patient's quality of life and resulting in a poorer prognosis with shorter survival rates. The approach to patient management needs to be personalized. The present study describes the of a patient who underwent surgery for stage IV rectal adenocarcinoma and later developed a metastasis in the costal wall 79 months post-intervention, with no evidence of recurrence at other sites.

Malignant adipocytic tumours: A 20­year single­centre retrospective study.

Adipocytic tumours are the most common soft tissue neoplasms. Among them, liposarcoma is the most frequent malignant neoplasm. However, to the best of our knowledge, no previously published study has assessed the evolution and oncological prognosis of the different subtypes of liposarcoma at the retroperitoneal level compared with at other locations. The present study is a retrospective observational study in which all patients were operated on between October 2000 and January 2020 with a histological diagnosis of liposarcoma. Variables, such as age, sex, location, histological type, recurrence, type of treatment and mortality, among others, were analysed. The patients were divided into two groups: Group A (retroperitoneal location) and group B (non-retroperitoneal location). A total of 52 patients with a diagnosis of liposarcoma (17 women and 35 men) and a mean age of 57.2±15.9 years were assessed. A total of 16 patients were classified into group A and 36 into group B. The OR of recurrence was 1.5 (P=0.02) for R1 vs. R0 resection in group A. The OR of recurrence in group B for R1 vs. R0 resection was 1.8 (P=0.77), whereas for R2 vs. R0 resection, the OR was 69 (P=0.011). In conclusion, 52 cases of malignant adipocytic tumours collected during 2000-2020 were analysed with the new World Health Organization classification (updated 2020). Although its recurrence potential and capacity for distant metastasis depended on each histological type, surgical treatment with unaffected margins was the main prognostic factor for survival. The present study identified differences in relation to the survival of each histological subtype and its location, finding greater survival in dedifferentiated liposarcoma, myxoid liposarcoma and pleomorphic liposarcoma located at the extraperitoneal level than in the retroperitoneal location. Resectability was not influenced by liposarcoma location.

Prognostic Factors of Survival in Patients with Peritoneal Metastasis from Colorectal Cancer.

Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32−92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan−Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1−10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11−20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294−3.077), KRAS mutation (HR 1.751; 95% CI: 1.188−2.581), PCI 11−20 (HR: 9.935; 95% CI: 5.204−18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291−7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis.

Hyperthermic Intraperitoneal Chemotherapy and Recirculation with CO2: A Safe Technique.

INTRODUCTION: Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) has evolved as a treatment for peritoneal carcinomatosis in various tumors after a careful and complete cytoreductive surgery, and it demonstrated much better and longer survival than more traditional therapeutic schemas. Our objective has been to examine the safety, efficacy and survival achieved with closed technique with CO2-agitation system Combat PRS® (Peritoneal Recirculation System: PRS). To achieve this, we compared the appearance of adverse events, mortality and survival with the described using classic techniques (open, closed without CO2-agitation) for the treatment of selected patients with peritoneal carcinomatosis; Materials and methods: We studied overall survival, disease-free survival and safety (morbidity and mortality) of the administration of HIPEC through a closed method technique with CO2 recirculation (Combat PRS®) in 482 patients from 11 Spanish hospitals; Results: The mortality of our technique (1.66%) was similar to other published techniques (open, closed). Morbidity exhibited a 9.96% rate of Clavien-Dindo (CD) III/IV complications in 482 patients, which was lower than in other series. Survival (overall survival (OS) and disease-free survival (DFS)) was similar to previously published results: 86% 1y-OS, 54% 3y-OS, 77% 1y-DFS and 31% 3y-DFS; Conclusion: The procedure with closed PRS with CO2 agitation is as safe as standard open and closed procedures for the administration of HIPEC after complete cytoreductive surgery, with similar and very low mortality (1.66%) and lower morbidity (9.96% CD III and IV in our series vs range of 20-40% in the majority of different series); only Kusamura had similar results, with 12% in 205 patients, using the closed technique without CO2 agitation).

Bilateral Nipple Enlargement as a Secondary Effect of Anabolic Drugs: A Histopathological Mimicker of Smooth Muscle Hamartoma.

Smooth muscle hamartoma are usually solitary and congenital, may affect the genital area and nipples. Histopathologically, they are characterized by the presence of mature smooth muscle bundles. We present a 40 year-old male with bilateral nipple enlargement excised with clinical suspicion of bilateral leiomyoma. Skin biopsy shows mature, irregularly arranged smooth muscle bundles and lactiferous ducts between them. Immunohistochemistry is positive for smooth muscle actin, desmin and fumarase, but negative for estrogen and progestogen receptors. The presence of lactiferous ducts excludes bilateral leiomyomas. Even when, histopathologically, this can be interpreted as the nipple-type of muscular hamartoma of the breast, clinical history favors an anabolic drug-induced lesion. Bodybuilders present gynecomastia and nipple enlargement as frequent problems, but we have not found any histopathological description of these nipple lesions. We consider that dermatologists should be aware of the presence of them and dermatopathologists should know their histopathological features to avoid misdiagnosis as neoplasms.

Unusual Case of Gallbladder Adenocarcinoma Metastasis to the Abdominal Wall 11 Years Later: Synchronous Presentation with Two Malignant Colon Tumors, Coincidence or Not?

INTRODUCTION: Abdominal wall masses are a common finding in clinical practice. A high percentage of these masses are malignant. We present the case of a patient operated for a gallbladder adenocarcinoma, who consulted eleven years later for a malignant mass of the abdominal wall in synchrony with two adenocarcinomas of the left colon and sigmoid. Case Report. A 75-year-old male underwent a laparoscopic cholecystectomy with an incidental diagnosis of adenocarcinoma in situ (TisN0M0 according to AJCC 8th edition). The operative report mentioned that the removal of the gallbladder was difficult due to the inflammatory process, and the gallbladder was accidentally opened during the operation. It was not clear from the operative report whether an extraction bag was utilized to remove the specimen, but the histopathological study confirmed an open gallbladder. He presented 11 years later with an asymptomatic heterogeneous complex cystic mass involving the anterior rectus abdominis muscle. Colonoscopy showed synchronous tumors in the descending and sigmoid colon with pathology confirming adenocarcinoma. The patient underwent an elective laparotomy with resection of the anterior abdominal wall mass, left hemicolectomy, and sigmoidectomy. The histopathological results of the abdominal mass (CK7, CK20, EMA, CEA positive) were described as metastasis of adenocarcinoma of biliary origin. Discussion. Port site recurrences are rare complications following laparoscopic surgery when malignancy is unsuspected. Possible factors related to local implantation include direct seeding of spilled bile or tumor cells into the wound or shedding of tumor cells due to pneumoperitoneum-induced loss of the peritoneal barrier at the trocar site. In the absence of distant metastasis, treatment should include wide port site excision with malignancy-free surgical margins. CONCLUSION: Abdominal wall metastasis from gallbladder carcinoma is rare, and its synchronous presentation with a malignant neoplasm of the colon is exceptional. This is the first report of a patient with abdominal wall metastasis from a gallbladder adenocarcinoma operated eleven years ago that debuted synchronously with two adenocarcinomas of the left colon and sigma.

Prognostic Value of KRAS Gene Mutation on Survival of Patients with Peritoneal Metastases of Colorectal Adenocarcinoma.

OBJECTIVE: The main objective of the study was to determine the effect of the presence of mutation in the KRAS gene on the survival in patients with colorectal cancer (CRC) and peritoneal metastases (PM). MATERIALS AND METHODS: A retrospective cohort study was performed. Patients diagnosed with CRC with synchronous or metachronous PM between January 2006 and December 2019 were included. Data on the histopathological, clinical, and treatment factors were collected. The effect of each variable on survival was evaluated by Cox regression. RESULTS: A total of 149 patients were included (64 women (43%) and 85 men (57%); mean age, 63 years). The long-term survival rate at 36 months was 24% (median, 21 months). KRAS mutation was detected in 75 patients (50.3%). Kaplan-Meier analysis estimated that likelihood of survival was higher in patients with wild-type KRAS tumours (35%) than in mutated-type KRAS (14%) (median: 28 vs. 15, respectively) (P=0.001). Within the categories into which the peritoneal cancer index (PCI) was classified, survival at 36 months depended on the KRAS status. Survival in wild-type KRAS tumours with PCI 1-10 was 71% and with PCI 11-20 was 26%, while in mutant-type KRAS tumours, survival was 41% and 4%, respectively (P=0.025). In the multiple regression analysis, the KRAS mutation was revealed to have an independent prognostic value (HR: 2.144; 95% CI: 1.342-3.424). CONCLUSION: The mutational status of the KRAS gene has demonstrated a strong association with survival and prognostic utility in patients with CRC with PM.

Septic thrombosis of internal jugular vein: a rare cause of uncontrollable hiccups.

Septic thrombosis of the internal jugular vein is a possible complication related to central venous catheters. The enlargement of the diameter of the jugular vein can stimulate phrenic nerve causing hiccups and, septic thrombus can metastasize to different organs threating patient's life. Diagnosis of septic thrombosis of internal jugular vein should be confirmed with a cervicothoracic CT-scan. Its management consists of catheter's removal, antibiotic treatment and anticoagulation in high-risk patients. Surgical intervention might be considered if conservative treatment fails.