A 49-year-old female patient with exacerbation of SPS was admitted to the intensive care unit (ICU) to undergo TPE. The patient was diagnosed with SPS in 2013, the first symptoms noticed were pain in the lower extremities with paroxysmal increase in muscle tone; forced, painful, upright positioning of the left limbs; and two falls due to sudden generalized stiffness triggered by external stimuli. The comorbidities included type 2 diabetes mellitus, Hashimoto’s thyroiditis, and dyslipidemia. Past medical history, along with adverse effects that the patient developed, is presented in .
In 2018 and 2019, the patient had the erector spine muscle injected with botulinum toxin A (1,000 U), what reduced spasticity and improved patient’s gait. Over the previous 6 months, despite fixed daily oral doses of diazepam and gabapentin, the patient reported progression of symptoms: nystagmus, paresis, and spasticity of the left extremities; pain in the left lower extremity; paroxysmal axial rigidity; falls; dysphagia; and dyspnea. Due to exacerbation of the disease, the patient was admitted to the department of neurology for medical stabilization. IVIG was not used as it is not reimbursed by the Polish national healthcare insurer for the treatment of immune-mediated conditions. After an unsuccessful attempt at medical stabilization (5 days), the patient was admitted to the ICU to undergo TPE.
At the time of admission to the ICU, the concentration of anti-GAD65 was >2,000 U mL−1. Following admission to the ICU, the left radial artery was cannulated (Arterial Cannula 20 G; Becton Dickinson, Poland) and continuous, invasive arterial blood pressure monitoring was started along with minimally invasive pulse contour hemodynamic monitoring (LiDCO Rapid; LiDCO, United Kingdom). The right internal jugular vein was cannulated under ultrasound guidance (M7; Mindray, People’s Republic of China) and a 13 Fr dialysis catheter (GAMCATH HighFlow Dolphin Catheter; Baxter, Poland) was inserted. A standard continuous renal replacement therapy multifiltrate system (Fresenius Medical Care, Germany) along with plasmaFlux P2dry plasma filter (Fresenius Medical Care, Germany) was used. We used unfractionated heparin for anticoagulation and 4% human albumin as substitution fluid: a mixture of 20% human albumin and multiBic solution (Fresenius Medical Care) in the 1:5 ratio. The plasma volume exchanged was 1.5. We planned and performed 5 every-other-day procedures, no complications were reported. In the ICU, further two episodes of painful (pain sensation described as worse than labor pains) stiffness with muscle contractions occurred: at the time of a dialysis catheter insertion and spontaneously on day 2 of the ICU stay. Following the fourth procedure, a noticeable reduction in paresis/dystonic posturing and improved gait were noticed. The findings from neurological examination before and immediately following the course of TPE are presented in .
The total hospital length of stay was 14 days. The concentration of anti-GAD65 stayed elevated following TPE (>2,000 U mL−1 twice after the completion of the last TPE), nevertheless improvement in clinical symptoms remained (12-month follow-up period).
Due to the noninterventional design of the study, the Bioethics Committee approval was not needed. All patients’ data were obtained in accordance with the national law regulations of personal data management, after the written informed consent was given by the patient on hospital admission. The project was approved by the head of the institution and departments within which the work was undertaken; it conforms to the provisions of the Declaration of Helsinki (as revised in Fortaleza, Brazil, October 2013).


An 81-year-old male visited our hospital with remarkable edema in both legs, particularly in his right leg. Vascular ultrasound on lower extremities revealed thrombus in the left popliteal vein; however, no thrombus was found in the right leg. Initial laboratory workup revealed mild kidney dysfunction with urea nitrogen level of 28.7 mg/dL, creatinine level of 1.27 mg/dL, and estimated glomerular filtration rate of 42 mL/min. D-dimer was elevated to 8.4 μg/L. Abdominal ultrasound revealed hyper-echoic lesion filled in the IVC from the kidney level to the right atrium. This revealed low-echoic lesion of 23.2 x 23.0 mm in the lower pole of the right kidney, which suggested tumor. Cardiac ultrasound and CT scan of the abdomen with intravenous contrast medium revealed IVC tumor protruding into the right atrium (Figures , ). However, contrast enhancement in kidneys was not clear. FDG-PET (fluorodeoxyglucose-positron emission tomography)/CT scan revealed tumor in the lower pole of the right kidney, which continued into the right renal vein through the IVC (Figure ). A right mediastinal lymph node and left hilar lymph node also showed FDG uptake. Thus, the patient was diagnosed with IVC tumor embolism possibly of RCC with mediastinal metastasis.
Transperitoneal biopsy was avoided as tumor in the right kidney was small and in the lower pole. Even if biopsy was performed to confirm the diagnosis of RCC, surgical treatment was nearly impossible due to the patient’s age. The patient and his family requested palliative care or minimally invasive treatment to preserve quality of life. CyberKnife was chosen because it is a minimally invasive short-term treatment.
Multisession SRT was performed using CyberKnife G4 system. Tumors were tracked with spine-tracking algorithm. Gross tumor volume (GTV) was defined as visible tumor on enhanced CT scan with images merged for target definition. GTV was considered the same as clinical target volume (CTV). Planning target volume (PTV) included CTV with a 1.2-mm margin.
Giant IVC tumor (GTV 211.3 cm3) was treated with a prescription dose of 40 Gy in 10 fractions and prescription isodose line 89%. Second CyberKnife treatment was performed four months afterward for left hilar lymphadenopathy (GTV: 22.6 cm3) with a prescription dose of 40 Gy in five fractions and prescription isodose line 57%. Twelve months after initial treatment, FDG uptake was not observed in IVC or left hilar lymph node. However, right mediastinal lymphadenopathy remained. The patient presented allergic reaction to the contrast medium, thereby precluding its usage. Biopsy was performed by bronchoscope, which revealed clear cell RCC (Figure ). Eleven months after the second CyberKnife treatment, the third CyberKnife treatment was performed for right mediastinal lymphadenopathy (GTV: 11.7 cm3) with a prescription dose of 45 Gy in 10 fractions and prescription isodose line 73%. Cardiac ultrasound did not reveal any mass in the right atrium, which indicated that the tumor in the IVC had shrunk and cancer cells were destroyed over time by radiotherapy.
All three treatment courses were performed on outpatient basis. Edema in both legs disappeared 18 months after initial treatment. The patient reports no symptoms thereafter. Three years and three months have passed since initial treatment, with FDG-PET indicating cancer remission for IVC tumor and mediastinal lymphadenopathy (Figure ). The patient is enjoying a normal life without any treatment-related toxicity.


We ensure our case report is compliant with the SCARE Guidelines 2020 [].
A 11-year-old girl presented severe pain during her menstruation period which was only minimally relieved with medical management, non-steroidal anti-inflammatory drugs (NSAIDs). Uterine malformation and right hematosalpinx was confirmed with magnetic resonance imaging (MRI) (ab). Pre-operative treatment with a gonadotropin-releasing hormone agonist enabled improvement in the symptoms. Elective laparoscopic surgery was planned.
During the operation, a patient was placed in a lithotomy position under general anesthesia. First, a 20 mm single vertical umbilical incision was made. The Lap-protector (alnote LapSingleTM, Applied Alfresa Pharma Coroperation, Japan) was then placed through the incision. After creating a pneumoperitoneum of 6–10 mmHg, a 5 mm, 30 degree laparoscope was inserted and three 5 mm trocars (EZ trocar®, Hakko Medical, Japan) were placed both sides of lower abdomen and left side of upper abdomen. Then, laparoscopic exploration confirmed the presence of uterine malformation () and right hematosalpinx (). The left side uterus and ovary were thought to be normal (). It could not be identified whether the RH was communicating or non-communicating. The right fallopian tube was resected laparoscopically and 3Fr feeding tube was inserted into its end cut off and injected indigo carmine in the RH (). No leakage of indigo carmine was found from the vagina, indicating the diagnosis of the uterine malformation is an unicornuate uterus with a non-communicating RH (UUNCRH) and we performed the resection of the RH safely (). The scar was very small and the patients had good cosmetic results ().


A 73-year-old Caucasian man was referred to our hospital for evaluation of a right PHEO, diagnosed two months before at another hospital, after the identification of a large retroperitoneal mass on abdominal computed tomography (CT). At that time, the patient experienced abdominal discomfort, unintentional weight loss of approximately 5 Kg within the previous 3 months, associated to sporadic episodes of watery diarrhea. At admission to our hospital, the patient was moderately dehydrated and tachypnoic. He denied any history of headache, palpitations, sweating, or hypertension. He reported episodes of watery diarrhea, up to 5-6 times a day and 2-3 times a week, without blood or mucus. He also had no relevant familial history of endocrine nor cancer diseases but only a paternal history of arterial hypertension. Physical examination showed blood pressure (BP) of 100/67 mmHg and heart rate of 88 beats/min; no significant orthostatic pressure gradient was measured. BP values, evaluated on several occasions, were 94/58 and 91/62 mm Hg. Laboratory tests showed a hypokalemia (3.3 mmol/L) with metabolic acidosis (pH 7.29, HCO3- 19 mmol/L), a serum magnesium level of 1.5 mg/dl and fasting blood glucose of 149 mg/dl. A 24-h urinary sample showed only a slight increase in normetanephrine excretion, 638 μg (normal values: 162-528/day), while metanephrine and methoxytyramine resulted within normal range. Serum chromogranin A was elevated (1028 ng/ml, normal values 20-100), as well as neuron-specific enolase level (NSE 35.7 nl/ml, normal values 1.0-13.5). Plasma cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, thyroxine, parathyroid hormone, and calcitonin were within the normal ranges. Contrast enhanced abdominal CT scan confirmed the presence of inhomogeneous right adrenal mass measuring 8.1 x 7.7 x 7.9 cm (). A 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) coupled with CT showed an area of high uptake (maximum standardized uptake value, SUV max 8.6) in the right adrenal gland, with a prevailing peripheral signal and central hypoactivity, and another area of high uptake (SUV max 9.6) in the lumbar region suspicious of lymph node localization (). In addition, 68GaDOTA-octreotate (DOTATATE) PET confirmed the peripheral high uptake (SUV max 6) in the right adrenal gland and the high uptake area (SUV max 3.7) in the lumbar region; a high uptake (SUV max 4.5) was also detected at the base of the left lung (). Based on these results, patient diagnosis was metastatic adrenal PHEO. Intravenous fluid infusion, sodium bicarbonate, potassium aspartate, magnesium sulphate supplementations were started allowing an improvement of clinical condition and blood pressure levels. Then, after 10-days pre-operative treatment with low dose alpha1-adrenergic antagonist doxazosin (given just before bed), he underwent surgical resection of the tumor. The patient had an uneventful postoperative course, except for sporadic watery diarrhea. Gross examination revealed a 10x8x6 cm brownish-yellow, friable adrenal mass. Histology showed a highly cellular tumor made up of monotonous medium-sized cells with discrete nuclear pleomorphism and mild hyperchromasia. Mitotic figures were above 3/10 high power fields, with some atypical mitoses. The cells were arranged in nests with areas of diffuse growth in more than 10% of the tumor. Confluent areas of necrosis were present. Foci of capsular and vascular invasion were noted as well as extension into periadrenal adipose tissue. The histological features were consistent with a malignant PHEO, with a PASS score (Pheochromocytoma of the Adrenal Gland Scaled Score) of 20 (), indicating a high risk of aggressive cellular behavior (PASS≥4). DNA genetic analysis of the patient with a next generation sequencing (NGS) approach using Trusight One Sequencing Panel by Illumina, revealed a synonymous single nucleotide variant of gene SDHA [rs6555055, NM_004168.2:c.619A>C, (p.Arg207=)] indicated by ClinVar database as associated to “probably benign” catecholamine-secreting PHEO (). The patient was discharged in satisfactory clinical condition. Therapy with lanreotide, a somatostatin analogue, at a dose of 60 mg once a month was initiated. At 2 months, multiple metastatic pulmonary and hepatic nodules were identified on CT scan (). The patient once again experienced abdominal discomfort, 4 kg weight loss, yet only sporadic watery diarrhea. Peptide receptor radionuclide therapy and sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, were scheduled. In the meantime, lanreotide therapy was increased to 120 mg once a month. However, after about one month, the patient was re-admitted with a 10-day history of severe watery diarrhea, up to 20 times in 24 hrs, accompanied by nausea, vomiting and occasionally quick flushing. At presentation, he was suffering and markedly dehydrated. Physical examination showed BP of 90/67 mmHg, heart rate of 120 beats/min, the pulse was fast and weak, the breath was fast and short, the skin cold and clammy, and the urination was decreased. Laboratory tests were as follows: blood urea nitrogen 96 mg/dl; serum creatinine 3.5 mg/dl; Na+ 136 mmol/l; K+ 2.5 mmol/l; Cl- 115 mmol/l; pH 7.08; HCO3
- 5.5 mmol/l; Pa CO2 30 mm Hg; Pa O2 67 mm Hg; lactate 5 mmol/l (normal values 0.5-2.2); serum anion gap 15 mmol (corrected for serum albumin levels 16 mmol); urine anion gap was negative. Serum prealbumin was 29 mg/dl (normal values 15-35) and albumin 3.9 g/dl (normal values 3.5-5.0). At that time, serum chromogranin A was 2896 ng/ml and neuron-specific enolase 49.6 ng/ml. Twenty-four hours urinary normetanephrine excretion was 920.4 μg, while metanephrine resulted at 432.6 μg (normal values 64-302 μg/day). VIP plasma levels were measured, and circulating values were more than 10 times the upper normal limit (1285 pg/ml, normal values 18-100). Cardiac ultrasound showed a reduced left ventricular ejection fraction (35%). Due to the emerging clinical picture, histological sections were re-evaluated with additional immunostainings. Sections were stained with the following primary antibodies: anti-Chromogranin A (clone LK2H10 ready to use; Ventana-Roche), Anti-Vasoactive intestinal polypeptide -VIP (rabbit 1:500; Biogenex) and anti-Somatostatin Receptor 2A -SSTR2A (rabbit 1:100; Bio-Trend). The sections were immunostained with HRP Polymer (Optiview DAB IHC Detection kit; Roche) in accordance with the manufacturer’s specifications. Negative controls consisted of substituting normal mouse serum for the primary antibodies. A set of sections adjacent to these used for single labelling with VIP, was used for double labelling with Chromogranin A. The second antibody was immunostained with AP Polymer (Ultraview Universal Alcaline Phosphatase Red Detection Kit; Roche). Permanent red chromogen was used for staining development. Immunostaining revealed strong positivity for neuroendocrine marker chromogranin A and VIP (); a large number of cells co-expressed chromogranin A and VIP (). Weak was the positivity for SSTR2A (). A diagnosis of VIP-secreting PHEO was rendered. The patient was then transferred to the intensive care unit. He was managed with intensive intravenous fluid hydration, potassium salts and bicarbonates, as well as with octreotide (0.1 mg/8 h s.c.), sunitinib 50 mg/day and loperamide. However, his diarrhea worsened with further exacerbation of metabolic acidosis (pH 6.99, HCO3
- 4.3 mmol/l), leading to hemodynamic instability and shock. He died five days later.


A 59-year-old man presented to the emergency room with worsening shortness of breath and orthopnea for two weeks. He smokes five to six cigarettes daily for 10 years, denied alcohol drinking and recreational drug use. He is a retired accountant by profession, lives home independently with unknown history of sexually transmitted infections. During the presentation to the emergency room, he was hypotensive with a blood pressure of 96/51 mm Hg, heart rate 62/min, respiratory rate 20/min saturating 90% on room air. On examination, the patient was in acute respiratory distress, with an increased work of breathing, however, no wheezing or crackles on auscultation. Cardiac examination was remarkable for a 2/6 systolic ejection murmur and 2/6 diastolic murmur at the right upper sternal border. There was no jugular venous distension, peripheral edema, or abdominal tenderness. Laboratory workup revealed elevated N-terminal pro-B-type natriuretic peptide (NT-ProBNP) 8060 pg/mL (<177 pg/mL) troponin 0.141 ng/mL (0.000-0.045 ng/mL) peaked at 0.294 ng/mL. Blood chemistry and coagulation testing were unremarkable. Electrocardiogram (EKG) showed isolated ST elevation in lead V3, which was not correlating with acute ischemic changes (Figure ). The chest radiograph revealed cardiomegaly and bilateral pulmonary infiltrates (Figure ). Computed tomography angiogram (CTA) of the chest was unremarkable for pulmonary embolism but demonstrated a large aortic root aneurysm measuring 5.9 cm (Figure ).
Transthoracic echocardiography revealed severe left ventricular dilation with reduced ejection fraction (30-35%) and severe aortic insufficiency as indicated with a large central jet sign (Figure ). There was no evidence of coronary flow limitation or obstruction on the coronary angiogram (Figure ).
Workup for the etiology of aortic root aneurysms was only remarkable for a positive syphilis screening test that was confirmed with a positive T. pallidum particle agglutination assay (TP-PA). Testing for hepatitis B, hepatitis C, and HIV was negative. The patient was diagnosed with tertiary cardiovascular syphilis without evidence of neurosyphilis. The patient was treated with three doses of 2.4 million/unit intravenous (IV) penicillin-G and underwent surgical excision of aortic root aneurysm, aortic valve, aortic root replacement with 27 mm mosaic ultra bioprosthetic valve and 30 mm gelweave graft. Inspection of excised aortic root revealed aortic dissection within the aneurysm and marked inflammation along the left lateral wall of the aneurysm extending to the normal ascending aorta. Histopathological examination of the specimen demonstrated chronic inflammatory cells including lymphocytes, plasma cells in the fibrotic adventitia, and focal calcifications with myxoid degeneration of aortic root that confirmed the diagnosis of syphilitic aortitis (Figure ).


A 65-year-old female patient was referred to our department by a dermatologist regarding a histologically proven superficial spreading basal cell carcinoma located at the right lateral lower eyelid with extensive tissue involvement. She had no significant medical history or comorbidities. Surgical excision of the lesion was carried out in two stages under general anesthesia: the first excision specimen still showed malignant cell nests in both lateral and medial section margins on histopathological examination. The second excision was effectuated five days later in a phased fashion until intraoperative frozen sections confirmed negative specimen edges. This resulted in a defect not only comprising of the anterior and posterior lamellae of the lower eyelid, which were already removed during the first stage, but also of the lateral canthus and the lateral upper eyelid including its lid margin. While awaiting the definitive pathology report, the wound was left open after each stage, protecting the eye with a tobramycine/dexamethasone ointment (Tobradex, Novartis Pharma NV, Vilvoorde, Belgium). The final histopathological examination confirmed the absence of tumour cells in the section margins, allowing reconstruction ().
The remaining periocular defect (about 40% of the upper eyelid, 75% of the lower eyelid, and the lateral canthus) was reconstructed through a two-staged procedure. Both eyelids were reconstructed separately as distinct aesthetic subunits in a bilamellar fashion. The first stage of the reconstruction took place twelve days after the first excision. To reconstruct the anterior lining of the upper eyelid a modified myocutaneous Tenzel flap was designed, superiorly based, in the lateral periorbital region. In comparison to the original technique described by Tenzel our flap was not semi-circular but angled, like a rhomboid flap.
Within this same region, a Y-shaped bifid flap from the periosteum and temporal fascia was created to reconstruct the lateral canthal ligament in order to restore the suspension of both eyelids. This Y-shaped turnover flap was hinged from lateral to medial as a sling to suture its superior component to the lateral edge of the remaining tarsal plate of the upper eyelid with an Ethilon® nylon 6-0 (Ethicon US, LLC) suture. A small palpebral conjunctiva advancement plasty was developed, which was able to reach the reconstructed upper eyelid margin, posteriorly covering the canthal sling. Then the myocutaneous Tenzel flap was advanced into the defect in de upper eyelid and was sutured subcuticular with antibacterial Monocryl Plus® poliglecaprone 25 5-0 (Ethicon US, LLC) and with Vicryl Rapide® polyglactin 910 6-0 (Ethicon US, LLC) sutures for the skin ().
Analogous to the upper eyelid, a minor palpebral conjunctiva advancement, was performed to posteriorly cover a chondral graft, which was added to reconstruct the posterior lamella of the lower eyelid. This chondral graft, with inclusion of the perichondrium to ensure ingrowth, was obtained from the concha of the right ear through a retroauricular incision. The graft was tailored to fit the defect and was sutured anterior from the conjunctiva into place with Ethilon® nylon 6-0 sutures to the lateral margin of the remaining tarsal plate of the lower eyelid and to the lateral orbital rim. Laterally, the inferior component of the Y-shaped hinged turnover flap was sutured to the cartilage as well with the same suture material, to provide suspension to the lower eyelid. In order to reconstruct the anterior lamella of the lower eyelid; an ipsilateral myocutaneous paramedian forehead flap was created, after design of a template ().
This flap, which remained vascularized via the right supratrochlear artery and contained a part of frontalis muscle, was rotated successfully into the remaining defect in the lower eyelid. To prevent devascularisation, no thinning of the flap was performed in this phase. It was sutured into place with Ethilon® nylon 6-0 (). The lateral periorbital donor site, the frontal donor site and the auricular donor site were closed in a conventional manner, whilst leaving a tie over in the concha of the right ear in order to prevent seroma and hematoma formation. On the forehead, a small defect remained which was left open for secondary healing. All wounds were covered with nitrofural ointment (Furacine, Limacom, Diepenbeek, Belgium) and a grease gauze, except in close proximity to the eye where tobramycine/dexamethasone ointment was used. The later was also applied daily into the right eye ().
The second stage of the reconstruction took place one month after the first phase when the paramedian forehead flap showed adequate ingrowth (no signs of necrosis or venous congestion). Preoperative clamping of the pedicle was not performed. The second stage consisted of release of the pedicle of the forehead flap. The glabellar donor site was closed by a V-Y plasty, advancing a small remnant of the pedicle into the remaining donor site. The lateral part of the flap was tailored to the defect and was slightly thinned by resecting a portion of the subcutaneous tissue. In order to obtain a normal eyelid aperture, a partial lateral canthotomy was performed which released the cicatrisation that arose after the previous reconstructive stage.
The lateral part of the forehead flap was then fixed into the remaining defect with subcuticular Monocryl Plus® poliglecaprone 25 5-0 sutures. It was also sutured to the lateral canthal ligament with an Ethilon® nylon 6-0 suture to provide the flap with a favourable contour and suspension. The mucosa of the lower eyelid was then partially advanced to reach the new lateral eyelid margin. All wounds were further closed with Prolene® polypropylenesutures 6-0 (Ethicon US, LLC) sutures and were covered again with nitrofural or tobramycine/dexamethasone ointment and a grease gauze ().
During the first weeks of follow-up, all flaps showed adequate ingrowth without any sings of necrosis. The remaining defect in the frontal donor site healed well secondarily. The reconstructed periocular zone healed well too, with acceptable results both functionally and aesthetically, and without changes in visual acuity. Two months after the second reconstructive stage, a minor ectropion of the lateral right lower eyelid was observed. This ectropion remained unchanged for the four next consecutive months. An ancillary corrective canthopexy was offered to the patient (). Formal approval from the Ethical Committee of AZ Groeninge Hospital Kortrijk and written consent from the patient were obtained.


A 46-year-old man with a smoking history of 15 pack-years presented with cough and dyspnea. He had been treated for a malignant mediastinal germ cell tumor, the original part of which had been surgically resected with part of the left lung and the left phrenic nerve 10 years earlier, resulting in paralysis of the left diaphragm. He had also undergone treatment for bilateral iliac metastasis with chemotherapy and heavy ion radiotherapy 5 years before and metastasis to the right lung with surgical wedge resection 6 years before. Nine months before the outpatient visit, the patient had undergone stereotactic body-radiation therapy with 56 Gy of radiation in seven fractions to treat another right lung metastasis measuring 3.5 cm in diameter and located close to the right hilum (Fig. a, b). On presentation, computed tomography revealed right bronchial stenosis over the range of previous radiotherapy (Figs. b, c; a, b). Bronchoscopy showed broad necrosis of the right bronchus, ranging from the right main bronchus to the orifices of the bronchi of the middle lobe and the superior segment of the lower lobe (Fig. a–d). Pulmonary function was low with 2.6 L of vital capacity and 1.7 L of forced expiratory volume in one second. He was repeatedly treated with bronchial debridement of the necrotic tissue, culture of which revealed infection with Aspergillus fumigatus and other various bacteria. Bronchoscopic biopsies were performed several times, showing no malignancy but only fungal hyphae. Despite intensive antibiotic therapy with voriconazole and repeated debridement, the necrosis was progressive. Neither balloon dilatation nor stenting seemed to be an option because of the fragility of the bronchial wall and serious concern regarding formation of a bronchopulmonary arterial fistula. The patient eventually developed sepsis and renal failure, which necessitated urgent surgical removal of the necrotic bronchus. However, he was unable to endure right pneumonectomy because of his low respiratory function caused by left phrenic nerve paralysis. Preoperative pulmonary perfusion scintigraphy using technetium-99m-labeled macroaggregated albumin showed moderate-to-severe decrease of blood flow into right upper lobe, and flow volume into right lung was 47%. We therefore performed right lung autotransplantation with preservation of the right basal segment, the orifice of which appeared to still be viable (Fig. d).
During the surgery, we first prepared a pedicled omental flap through an upper median laparotomy in the supine position. We continued the surgery in the left decubitus position, and right lateral thoracotomy was performed through the fourth intercostal space. Right pneumonectomy was performed with staplers placed on the right main pulmonary artery and right pulmonary vein, while the right main bronchus was trimmed to the carina because of the broad bronchial necrosis. On the back table, we removed the upper and middle lobes and the superior segment of the lower lobe, then flushed the remaining basal segment anterogradely and retrogradely using extracellular-type trehalose-containing Kyoto (ET-Kyoto) solution in the same manner as in our living-related lung transplantation protocol. Next, we implanted the basal segment by direct anastomosis of the bronchus to the carina, followed by end-to-end anastomoses of the pulmonary arteries and anastomosis of the basal pulmonary vein to the superior pulmonary vein (Fig. a). The arterial anastomosis was technically challenging because of the distance and extensive dissection of the main pulmonary artery centrally behind the superior vena cava was necessary, while the venous anastomosis was easy after dissecting the pericardium around left atrium in the same manner as regular lung transplantation. We also wrapped the bronchial anastomosis with an omental flap to facilitate bronchial healing and lower the risk of a bronchopulmonary arterial fistula (Fig. b). The operation took about 18 h due to extensive tight adhesions derived from the previous treatment, refractory bleeding from adhered regions and anastomosis of pulmonary artery, and repetitive bilateral lungs ventilation. The back table surgery took about 2 h and graft ischemic time was around 5 h. After operation, the bronchial mucosa of the transplanted basal segment appeared pale distal to the bronchial anastomosis (Fig. e).
On postoperative day 9, the patient developed left-sided pneumonia and required temporal support with extracorporeal membrane oxygenation for 2 weeks. One month later, minor bronchial dehiscence at the bronchial anastomosis was observed and was successfully treated with antibiotics and nutritional support. Three months after the operation, the right bronchial anastomosis showed stenosis due to overgrowth of granulation tissue, which was treated with repeated bronchoscopic dilatation and eventual placement of a silicone stent (Fig. f). The patient was discharged home 5 months after the operation in a stable condition. At discharge, his pulmonary function was even lower with 1.26 L of vital capacity and 0.88 L of forced expiratory volume in 1 s although he was free of supplementary oxygen.
Three months after discharge, however, the patient developed massive hemoptysis. He was resuscitated on venoarterial extracorporeal membrane oxygenation, and hemostasis was obtained. Because he had fully recovered from the condition, we started discussing further surgical intervention to segregate the bronchial anastomosis and pulmonary artery. Regrettably, however, he soon developed a second massive hemoptysis episode and died.


A 63-year-old male patient came for a follow-up visit at the Ocular Oncology Service of the Paulista School of Medicine (Federal University of São Paulo). He had been diagnosed 3 years before with choroidal melanoma in his right eye. At his initial evaluation, best-corrected visual acuity was hand motion in his right eye and 20/20 in his left eye. In the fundoscopy, he presented an inferior pigmented choroidal lesion in his right eye. His left eye was unremarkable and family history was negative. The ocular echography showed a dome-shaped lesion of 12.8 mm of thickness and a basal diameter of 15.9 mm, suggesting the diagnosis of choroidal melanoma. Enucleation of his right eye was performed. Pathology of the surgical specimen confirmed a choroidal melanoma, with the predominance of epithelioid cells, total retinal detachment, and superficial scleral invasion. Systemic evaluation showed no signs of metastasis. After that, the patient was followed-up with periodic abdominal image examinations (ultrasonography, tomography, or magnetic resonance imaging), serum liver function tests, and chest radiography, at a 6-month interval.
At his routine check-up 3 years after the enucleation, he complained of progressive visual loss. His visual acuity was 20/30 in his left eye. Slit-lamp examination revealed mild nuclear sclerosis, intraocular pressure was normal and there were no cells in the anterior chamber or vitreous. On dilated fundus examination, multiple small areas of serous retinal detachment were noted scattered throughout the posterior pole, with yellowish vitelliform lesions (Fig. ). Fundus autofluorescence (FAF) showed hyperautofluorescent material at the inferior part of the lesions, with a pseudohypopyon configuration (Fig. ). On fluorescein angiography (FA), there was a slight blockage of fluorescence and there was an absence of late staining of lesions (Fig. ). Spectral-domain optical coherence tomography (SD-OCT) showed areas of subretinal fluid, excluded choroidal involvement in all of the lesions, and showed normal choroidal thickness (Fig. ).
Abdominal magnetic resonance imaging showed two pancreatic nodules, one in the head, with 1.1 cm, and another in the uncinate process, measuring 1.5 cm (Fig. ). Both nodules presented with low signal in T1 and restriction to diffusion, suggesting secondary neoplastic involvement. Endoscopic ultrasound-guided fine-needle aspiration of these pancreatic nodules was performed, showing epithelioid cells with melanin, nuclear hyperchromatism, evident nucleoli, and karyomegaly, confirming the hypothesis of metastatic melanoma. Image examinations also showed a 0.9 cm lesion near the hepatic capsular region with rim enhancement after contrast administration, believed to be another metastatic lesion (Fig. ). The patient was referred to the Clinical Oncology Department for evaluation; however, he had a cerebrovascular accident, due to brain metastasis. His management is currently palliative.


A 72-year-old female presented to the emergency room complaining of dizziness and shortness of breath. She was found to be severely anemic and was admitted to the intensive care unit (ICU) with acute blood loss anemia. Past medical history was significant for iron deficiency anemia that was diagnosed five years prior to presentation. Upper endoscopy and colonoscopy at that time were normal. At that time, she was also diagnosed with pulmonary embolism and treated with anticoagulation for about three years which was discontinued due to persistent anemia. On presentation, physical examination was normal. Laboratory data on this admission showed hemoglobin of 4.4 gram/deciliter, mean corpuscular volume (MCV) of 56 femtoliter, red cell distribution width (RDW) of 20%, total iron of 9 microgram/deciliter, iron saturation of 1.9%, total iron binding capacity (TIBC) of 464 microgram/deciliter, and ferritin of 10.6 nanogram/milliliter. Tumor markers including carcinoembryonic antigen (CEA), cancer antigen-125 (CA-125) and CA 19-9 were all within the normal range. Celiac panel was normal. Abdomen and pelvis computed tomography (CT) scan showed bilateral pulmonary embolism (PE) which was confirmed on a chest CT scan. Lower limbs venous duplex showed bilateral deep venous thrombosis (DVT). Upper endoscopy and capsule endoscopy showed normal mucosa and no evidence of bleeding. Testing for Factor V Leiden deficiency, antithrombin and prothrombin abnormalities, protein C and S and mixing studies were inconclusive probably because of blood transfusions and active thromboses. Patient received 4 units of packed RBCs and intravenous iron. An inferior vena cava (IVC) filter was inserted due to concern for bleeding with use of anticoagulation. After the patient’s hemoglobin stabilized and active GI bleeding was ruled out, intravenous heparin was initiated and later transitioned to apixaban upon discharge from the hospital.


A 26-year-old Nigerian man presented to the emergency unit of our facility on account of difficulty urinating and abdominal pain over the past week. He was initially evaluated for urinary tract infection on account of similar symptoms at the general outpatient clinic a week before the emergency unit presentation. At this initial contact, the patient was treated for urinary tract infection empirically using PO Ciprofloxacin 500 mg bd, based on history and examination coupled with complete blood count and urinalysis findings as follows:
Complete blood count:
Packed cell volume: 40%
White blood count: 5000
Neutrophils: 40%
Lymphocytes: 59%
Eosinophils: 1%
Urinalysis:
Blood: Negative
Colour: Amber and clear
Glucose: Negative
Ketones: Negative
Leucocytes: Negative
Nitrite: Positive
pH: 6.0
Protein: Negative
Specific gravity: 1.030
Urobilinogen: Normal.
The patient presented a week later with acute urinary retention. He denied any history of urethra discharge, previous occurrence of urinary retention, urethra instrumentation, dysuria, or any recurrent urinary tract infection. He had no significant past medical or surgical history. Pertinent findings from social history are in keeping with occasional alcohol use but does not smoke or use any illicit substance. However, he reported recent ingestion of methamphetamine a few days before his symptoms began.
Physical examination findings revealed a young man in mild painful distress secondary to suprapubic discomfort. Vital signs at presentation: Temperature: 36.5 °C, Pulse rate: 78 beats per minute, Blood pressure: 128/66 mmHg.
Neurological examination revealed a conscious, alert and oriented young man. The speech was clear, fluent and coherent. All cranial nerve functions were intact. Gait is steady with normal steps and intact motor, sensory and coordination functions. Other systemic examination findings were essentially normal except for a moderate fullness noticed in the suprapubic region.
He was commenced on continuous bladder drainage via urethral catheterization using a Foley catheter with a dramatic relief of symptoms. The patient, however, found it very strange using a urethra catheter and opted to have it removed after minutes of passage. He also opted for discharge and subsequent follow-up, if need be. A day later, he presented again to the emergency unit with the same symptoms as before and in acute urinary retention. This necessitated the second urethra catheterisation for continuous bladder drainage. He agreed to have the catheter in-situ after adequate counselling on the need to do so.
Preliminary laboratory and radiological investigations were essentially normal and not suggestive of any genitourinary obstruction. Both abdominal ultrasound (KUB) and abdominal computed tomography scans done revealed an essentially normal urinary tract with preserved corticomedullary differentiation of both kidneys. No renal calculi obstructing urine flow was seen (Fig. ). However, pertinent findings from an assessment of bladder and sphincteric functions using urodynamics were in keeping with urge incontinence and mild detrusor instability with the voiding cystometrogram showing a high sphincteric pressure and significant bladder contraction.
He was subsequently referred for further evaluation and a urologist's review. Follow up done over the first two months after referral revealed intermittent visits for removal and recatheterization due to alternating resolution and recurrence of symptoms despite the complete cessation of methamphetamine use. He was commenced on α receptor antagonist and antihistamine. Thereafter, he had a gradual improvement in his symptoms and has remained symptom-free for the last 4 months.


We present the case of a 57-year-old Hispanic woman with a past medical history of alcoholic cirrhosis (MELD-Na 30 on admission, Child-Pugh Class C) complicated by Grade I esophageal varices and portal hypertensive gastropathy, as well as recently diagnosed stage I colorectal adenocarcinoma (treatment naïve), who presented to the hospital with a one-week history of fatigue, dyspnea, and dizziness. On admission, the patient was noted to be hypotensive with a blood pressure of 89/48, afebrile with a temperature of 98.4 °F, and tachycardic with a heart rate of 100 beats per minute. Physical exam was notable for appearance of weakness, although the patient was awake, alert, and oriented, with scleral icterus, jaundice, splenomegaly, ascites, and mild abdominal distension. Laboratory exams in the initial days of presentation are noted in and are significant for macrocytic anemia with a hemoglobin of 7.4 g/dL and a mean corpuscular volume of 109.4 fL. Studies were consistent with hemolysis, with an elevated LDH of 263 U/L, indirect hyperbilirubinemia of 9.2 mg/dL, undetectable haptoglobin (<10 mg/dL), and elevated reticulocyte count of 16.1% (). Her macrocytosis was most likely secondary to reticulocytosis due to hemolysis, although workup of vitamin deficiencies was initiated, demonstrating normal folate levels and elevated vitamin B12 levels, likely in the setting of severe liver disease [, ]. Peripheral smear demonstrated mostly acanthocytes (spur cells), spherocytes, rare schistocytes, target cells, and few burr cells (). The patient was resuscitated with packed red blood cells and fluids and briefly placed on vasopressors. Notably, the patient had no clinical evidence of upper or lower gastrointestinal bleeding. For this reason, the patient did not undergo endoscopy or colonoscopy during her admission.
On further workup of her hemolytic anemia, the patient was tested for paroxysmal nocturnal hemoglobinuria with FLAER, which was negative, as was direct Coombs testing. Of note, three months prior to this presentation, during a previous admission, the patient had a direct Coombs test that was positive for IgG antibody; elution testing revealed a warm autoantibody. It was speculated that perhaps the patient had a low level of antibodies, not detectable during this admission, and that she perhaps had warm autoimmune hemolytic anemia (WAIHA). However, during her previous admission, when she tested positive, she had also received a blood transfusion at that time which could have contributed to a false positive. Additional workup included CT of the abdomen and pelvis to assess for lymphadenopathy given the association of lymphoproliferative disorders and WAIHA, which was negative for lymphadenopathy although remarkable for splenomegaly of 14.4 cm. She was initially treated for WAIHA with steroids at 1 mg/kg for three days, increased to 1.5 mg/kg for five days with no clinical response in terms of her hemolysis panel; therefore, a steroid taper was started. Due to the refractory nature, she was treated with IVIG 1 mg/kg for two days. The new leading diagnosis was SCA because of findings on peripheral smear and lack of response to steroid therapy. Lipid levels, including apolipoprotein levels, were obtained, given the association with SCA and defects in lipid metabolism, and were notable for decreased total cholesterol, LDL, and apolipoproteins AI and B (). After receiving IVIG, her hemolysis panel was unchanged, except for the indirect bilirubin which continued to worsen (). Unfortunately, several days later, the patient continued to decompensate and expired from acute respiratory distress syndrome secondary to pneumonia.


A 27-year-old woman had persistent headache and amenorrhea. In addition, the size of her foot was increased by 0.5 cm for 6 months and lower jaw protrusion was observed. Thereby, she was referred to our institution. The data at that time were as follows: growth hormone (GH), 82.44 ng/ml; insulin-like growth factor-1 (IGF-1), 1,390 ng/ml; prolactin (PRL), 28.2 ng/ml. In addition, enlargement of pituitary fossa was observed in head X-ray, and thickening of heel pad was observed in foot X-ray. Based on these findings, she was diagnosed as acromegaly and hospitalized in our institution for further examination and treatment.
On admission, her height and body weight were 163.0 cm and 48.0 kg. Blood pressure and heart rate were 110/60 mmHg and 68 bpm. Body temperature was 37°C. Swelling of superciliary arch, hypertrophy of nose and lip, macroglossia, lower jaw protrusion, thickening of the plantar, enlargement of the palm and bitemporal hemianopsia were observed all of which were compatible with acromegaly. There were no abnormalities in heart and lung sound and in abdomen. The data on admission were as follows: GH, 51.12 ng/ml; IGF-1, 1,538.9 ng/ml; free triiodothyronine (FT3), 5.56 pg/ml (reference range: 2.3–4.3 pg/ml); free thyroxine (FT4), 2.52 ng/dl (0.9–1.7 ng/ml); TSH, 2.26 μU/ml. Other endocrine hormone levels were within normal range: adrenocorticotropic hormone (ACTH), 44.0 pg/ml; cortisol 8.5 μg/dl; dehydroepiandrosterone sulfate (DHEA-S), 375 μg/dl; plasma renin activity (PRA), 1.1 ng/ml/h; plasma aldosterone concentration (PAC), 29.7 pg/ml; luteinizing hormone (LH), 1.2 mU/ml; follicle stimulating hormone (FSH), 3.3 mU/ml; PRL, 26.2 ng/ml; estradiol, 26 pg/ml; testosterone 1.02 ng/ml. Thyroid-related antibodies including anti-Tg antibody, anti-TPO antibody and thyroid receptor antibody were all negative. Liver and renal function was within normal range. Inflammatory and tumor markers such as C-reactive protein (CRP), carcinoembryonic antigen (CEA) and colorectal carcinoma 19-9 (CA19-9) were also within normal range. In thyroid echography, both lobes of the thyroid gland were swelling although increase of blood flow was not observed (
). In brain magnetic resonance imaging (MRI), there was a giant tumor (51 × 34 × 22 mm) around pituitary fossa, pressuring on optic chiasm from the middle (
). Bilateral internal carotid arteries were surrounded by the tumor, and infiltration into the cavernous sinus was observed. Based on these findings, we finally diagnosed her as pituitary adenoma producing GH and TSH at the same time. After such diagnosis of GHoma and TSHoma, pituitary tumor resection was performed. Most of the tumor was resected during the pituitary surgery, although we fail to show what percentage of the tumor was resected.
In hematoxylin and eosin (HE) staining of the resected pituitary adenoma, solid proliferation of chromophobe cells was observed (). In CAM5.2 staining, many cytokeratin-producing cells were observed (). In MIB1 staining, percentage of MIB1-positive cells was about 3%, indicating that the proliferative activity was relatively low (). Based on these findings, she was pathologically diagnosed as sparsely granulated somatotroph adenoma. In GH staining, many GH-producing cells were observed () and in TSH staining, many TSH-producing cells were observed (), whereas in prolactin staining, prolactin-producing cells were not detected at all (). These findings further confirmed our diagnosis that this subject had pituitary adenoma producing GH and TSH simultaneously.
After the surgery GH level was markedly decreased although it was still higher compared to its normal range (reference range in our institution: ≤2.47 ng/ml). After the surgery, IGF-1 level was also markedly decreased and became within normal range (reference range in our institution: 141–328 ng/ml) (). About 1 year later, IGF-1 level was increased again. After then, cyber knife therapy and treatment with somatostatin analog octreotide were performed. After the cyber knife therapy together with octreotide, IGF-1 was marked decreased and became within normal range (). However, since digestive symptoms were observed after the octreotide treatment, we started a combination therapy with GH receptor antagonist and octreotide based on the previous reports (, ). After then, GH and IGF-1 levels did not increase at least for 6 years (). After the operation, since thyroid function was not sufficiently suppressed, we started anti-thyroid drug thiamazole. After then, thyroid function was normalized and we stopped thiamazole. But TSH, FT3 and FT4 levels did not increase at least for 6 years (). In addition, there were no particular abnormalities in brain MRI taken 1 month after operation (), 1 year after operation (half year after cyber knife therapy) () and 4 years after operation ().


A 65-year-old Iranian man slipped backward to the ground. He immediately felt left flank and groin pain but was able to continue walking. Approximately 4 h after falling, the pain severely increased, and the patient complaint of gross hematuria and difficulty in walking. He presented to the emergency department of Shahid Beheshti hospital affiliated to Yasuj University of Medical Sciences on the very same day because of gross hematuria. The pain was sharp, non-radiating, and worse with attempting ambulation, and better at rest. He reported no significant medical history, such as hypertension, diabetes mellitus, vascular disease or peripheral neuropathy and clotting or hemorrhagic disorders, and taking antiplatelet or anticoagulant agents. Surgical and genitourinary evaluation revealed no evidence of a hernia or any other disorder.
On physical examination, he was alert, and his vital signs were stable: temperature was 37.60C (afebrile), with a regular pulse of 72 bpm, and blood pressure of 135/70 mmHg. There was skin bruising and ecchymosis in left flank area, but abdomen was soft without tenderness. No pulsatile mass was detected and both femoral pulses were equal. There was no hernia and the scrotal contents were normal, and there was no blood at the urethral meatus. No perineal and scrotal hematoma was seen. The anal tone was good, rectal examination was normal and there was no occult blood, prostate was in normal place on examination and there was no saddle anesthesia. There was severe left CVA tenderness and mild groin tenderness, the lower back area was painful, he had some pain with the flexion of the vertebral column, and there was tenderness on the lumbar spine, but there was no tingling, paresthesia, and weakness in left lower extremity. Hip flexion was 3/5 in the left lower extremity and 5/5 in the right lower extremity. He also had pain on adduction or abduction of the left leg. The straight leg raise (SLR) and FABER tests of left leg were impaired. He was unable to bear weight on the left leg when the patient attempted ambulation. Sensory and motor examinations of the left lower extremity were normal. Ankle jerk reflex (Achilles reflex) was normal in both side, but knee-jerk reflex (patellar reflex) was 1+ in the left side, and 4+ (normal) in the right side.
At the Emergency Department (ED), initial trauma management was done according to the Advanced Trauma Life Support (ATLS) protocol and two IV accesses in the bilateral antecubital fossae were obtained, and urethral catheterization was performed in order to monitor the patient’s urine output, and patient was hydrated with 500 cc of lactated ringer at the initial stage. Focused Assessment with Sonography for Trauma (FAST) scan was done and there was no free fluid in abdomen and pelvic cavity and no solid organ damage.
Hematology revealed normal complete blood count and electrolytes. Coagulation time, prothrombin time (PT) and platelet count did not show any abnormalities. Blood urea nitrogen (BUN) and creatinine (Cr) were 19 and 8 mg/dl retrospectively. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was 7 mm/h, and 12 mg/dl retrospectively. The result of urinalysis showed 2+ protein, 3+ blood and many red blood cells (RBCs).
Radiographs of the pelvis and the lumbo-sacral spine revealed no abnormalities (Figs. and ). An ultrasound scan obtained on the day of admission revealed a hyperechoic heterogeneous area measuring 48 × 30 mm in the left psoas muscle. Left kidney was enlarged (142 mm) with multiple cortical cyst with the maximum diameter of 46 mm. The intra-abdominal solid organs and adjacent soft tissues were intact, and there was no finding indicative of vascular disorders.
The ultrasound scan was compatible with a diagnosis of organizing acute psoas hematoma. A subsequent CT scan was done and revealed multiple large cortical cysts in both kidneys, an enlarged left-sided psoas muscle, and fracture of transverse process of third vertebral spine adjacent to the psoas muscle. CT scan confirmed the presence of psoas hematoma (Figs. and ).
In order to evaluate bladder for suspected bladder rupture, a CT cystography was done (contrast was instilled retrograde into the patient's bladder, and then the pelvis is imaged with CT) and this revealed no extravasation of contrast or other abnormal pathological findings (Figs. , , and ). To evaluate kidneys, ureters, and bladder for gross hematuria, an intravenous pyelogram (IVP) was done next, and it demonstrated no abnormal findings (Figs. , , , , , , and ).
Hemoglobin levels remained stable for 3 days, thereby excluding active bleeding. Treatment was initialized after confirmation of the diagnosis. Treatment consisted of strict bed rest, conditioning activities, physiotherapy and mobilization, and IV non-steroidal anti-inflammatory drugs (NSAIDs) (Pethidine 50 mg IV every 6 h PRN, and Apotel 1000 mg by IV infusion; it is usually dissolved in 100 ml Sodium Chloride 0.9% Sterile Solution), and they all were started in the hospital, and all of them except the IV NSAIDs were continued on an out-patient basis after discharge 3 days from the injury. A 14-day course of oral analgesic tablets (naproxen sodium; 250 mg every 6 to 8 h) was prescribed. Gradually, the pain eased, and on the first and the second out-patient follow-up visit 7, and 14 days from the discharge the pain was much decreased, and the patient was able to walk without aid. On the 28 days from discharge, the patient was relatively symptom free and returned to his daily routine activities.


The reported patient was a 20-year-old male (, III2) with a family history of cancers. His mother (II6) was first diagnosed with a grade II adenocarcinoma of colon accompanied with multiple polyps at the age of 48 and received a systemic chemotherapy. Subsequently, the detailed family history of his mother was assessed. His maternal grandfather (I3) died of gastric cancer when he was 60 years old. His maternal grandmother (I4) was diagnosed with CRC at the age of 59 and died at the age of 76. Two of his maternal aunts (II7&II9) died from CRC at the age of 39 and 50, respectively. His maternal uncle (II11) died of lung cancer at the age of 59. One of his female maternal cousins (III4) was diagnosed with CRC and subsequently received surgery at the age of 30 and was still alive.
Due to the familial cancer history, in June 2018, the white blood cell sample was collected from the mother of the patient (proband, II6) and subjected to a next generation sequencing (NGS)-based genetic test using a panel consisting of 53 hereditary cancer related genes (Ugene, Burning Rock Biotech, China) with a median sequencing depth of 400x. The copy number variation analysis based on the sequencing depth revealed a copy number 1 for the exon 15 in APC gene, indicating a heterozygous loss of APC exon 15 (exon15cn_del, ). Genetic test was also performed on two of the patient’s maternal cousins (III7&III6) and revealed the same APC mutation in the male cousin (III7) but no mutation present in female cousin (III6).
NGS with the same 53-gene panel performed on the reported patient (III2) and his sister (III1) revealed existence of the germline APC exon15cn_del mutation in both (). However, in addition to APC mutation, the male patient also harbored an open reading frame shift mutation in BRAC1 (c. 5470_5477delATTGGGCA, p.lle1824AspfsX3, ). The paternal family history of the patient showed that his paternal grandfather (I1) died from gastric cancer at the age of 47. His paternal aunt (II4) was diagnosed with ovarian cancer at the age of 54 years and is still alive. We also identified a same BRAC1 (p.lle1824AspfsX3) germline mutation in her.
Taken together, the family clinical history and identified deleterious mutations were highly suggestive of FAP. The 20-year-old patient underwent a colonoscopy on Feb 21, 2019. More than ten polyps in size of 0.4-4cm with erosions on some of them were discovered. Three big polyps on the hepatic flexure of colon were biopsied which indicated high-grade intraepithelial neoplasia. The patient subsequently received a subtotal colectomy on March 25, 2019 and was diagnosed with stage T3N1bM0 colonic adenocarcinomas accompanied with more than one hundred of tubulovillous adenomas with the larger ones measuring 0.3-1cm. Immunohistochemical tests were performed with the surgical sample and revealed a status of HER2 (0), proficient DNA mismatch repair (pMMR) and BRAF (–). The patient subsequently received a modified oxaliplatin (L-OHP) with leucovorin (LV) and bolus/continuous infusion of 5-fluorouracil (5-FU) (mFOLFOX6) regimen for 12 cycles. Repeated image tests and a colonoscopy in Dec, 2019 revealed no evidence of recurrence or metastasis but the presence of multiple polyps measuring 0.3-0.8cm on the rectum, which were subsequently diagnosed with adenomatous polyps. The patient remained alive as the submission of the manuscript. The sister of the patient (III1) was also diagnosed with multiple adenomatous polyps of colon in May 2019 when she was 27 years and underwent subtotal colectomy.


A 68-year-old Hispanic man of Puerto Rican descent presented to the emergency department with a two-day history of a small amount of bright red rectal bleeding twice daily. He denied any associated symptoms like abdominal pain, nausea, vomiting, diarrhea, or constipation, shortness of breath, dizziness, or syncope. He was noted to have thrombocytopenia with a platelet count of 87 k/ul. One day prior to this event, he underwent a screening colonoscopy that showed two polyps in the ascending colon (12 and 14 mm in size) removed with hot snare polypectomy. Post-intervention hemostatic clip and epinephrine were injected. Pathology showed inflammatory polyps. He has a background history of hypertension, dyslipidemia, coronary artery disease, Hermansky Pudlak syndrome, squamous cell cancer of the skin status post-irradiation therapy eight years ago. On initial examination in the emergency department, the patient was afebrile, with stable vital signs. His abdominal examination revealed no tenderness and the rectal exam showed brown stool. The rest of the review of systems and physical examination was unremarkable.
Laboratory tests showed a decrease in his hemoglobin from a baseline of 13 gm/dl to 11.0 gm/dl and thrombocytopenia to 80k/ul, the rest of his laboratory workup was normal. Hematology service was consulted and advised to give 20 mg of 1-desamino-8-D-arginine vasopressin (DDAVP). The patient was admitted to the medicine floor for observation. He did not have any further episodes of rectal bleeding, his hemoglobin level remained stable, and he was discharged with gastroenterology follow-up.
Later, he was seen after discharge in the gastroenterology clinic, where he reported that he was symptom-free and reported no further episodes of rectal bleeding.


A 30-year-old female with no conclusive history of trauma presented with progressive complaints of pain and swelling in the proximal of the posterior region of the knee for three months. Our physical examination and subsequent imaging of the affected extremity revealed a cortex-destructing lesion located at the posterior part of the proximal tibia. Clinical examination revealed a tender palpable lump located below the popliteal area approximately 4 x 2 x 2 cm in size, with no overlying erythema. No signs of local infection were present.
The patient did not have any predisposing risk factors such as smoking or alcohol consumption. Her general well-being and vitals were stable. She was diagnosed with familial Mediterranean fever (FMF) and was prescribed colchicine. She had no surgical history and no known medication allergies.
Her laboratory test results were within normal limits: WBC: 7,800/mm3 (64% neutrophils, 29% lymphocytes, and 5% monocytes), hemoglobin: 13.6 g/dL. C-reactive protein was 3.3 mg/L (normal level: <5 mg/L), and erythrocyte sedimentation rate (ESR) was 11 mm/h (normal range: 0-20 mm/h). Alkaline phosphatase (ALP) was 93 U/L (normal range: 30-120 U/L), and lactate dehydrogenase (LDH) was 170 U/L (normal range: 125-220 U/L).
The X-ray imaging showed a solid cortex-expanding mass located at the proximal tibia (Figures , ). CT scan revealed a diffuse calcific component surrounding the bone structure, reaching dimensions of approximately 8 x 2.5 x 11 cm (Figure ). No lytic or destructive changes were detected in the fibula. Positron emission tomography (PET) scan showed blood flow increase and hyperemia in the 1/3 proximal part of the left tibia. In late static and single-photon-emission CT (SPECT)/CT images, increased osteoblastic activity was observed. These findings suggested malignant processes. A CT-assisted biopsy was performed under sedation; a local anesthetic agent was administered to the mass of the left tibia. Guided by the CT images, biopsy material was obtained using a biopsy needle (Figure ). No complications were observed after the procedure.
Materials obtained were evaluated by a specialized musculoskeletal pathologist; 9-mm tru-cut biopsy materials were processed. Histopathological features and MDM2 positivity in some of the spindle-fibroblastic cells suggested the potential for conditions such as "low-grade osteosarcoma" and "parosteal osteosarcoma".
Preoperative planning
Dual-stage reconstruction was planned. The aim of the preliminary surgery was to successfully preserve the epiphysis of the proximal tibia while attaining a tumor-free tibia. To perform the ideal resection of the tumor, 3D modeling and cut guides were created before the operation (Figure ). The aim of the second surgery was to evaluate the viability of the preserved epiphysis and reconstruction of the bone defect using the 3D-printed design, which was augmented with hydroxyapatite coating to enhance the osteointegration of the implant.
Preliminary surgery
Firstly, with the aid of radiological examinations and histopathological diagnosis of the biopsy, the lesion of the patient was staged and the indications for resection were confirmed; 3D CT scans of the bilateral lower extremities were performed to obtain a surgical margin negative wide resection. MRI scan was performed to detect tumor borders and surrounding reactive tissue. For these examinations, the parameters applied by the Dokuz Eylül University Hospital Department of Radiology (1-mm cross-section and matrix of 512 x 512) were used and scans were made accordingly with these parameters. Then, the image was saved in the Digital Imaging and Communications in Medicine (DICOM) format and transferred to the 3D Slicer software for the reconstruction of 3D geometric models. Virtual mechanical analysis of the solid model created was performed. According to the shape and structure of the tumor, and by using the Meshmixer 3.5 software (Autodesk, Inc., Mill Valley, CA), osteotomy guides were 3D-printed using polylactic acid (PLA). These guides ensured that the tumor was completely removed.
After the necessary preparations, the operation was performed. An approximately 20-cm long longitudinal incision was made at the midline of the knee, extending from the superior pole of the patella to 10 cms below the tuberositas tibia. The biopsy tract was excised during the first stage of this procedure. Arthrotomy was performed to check the viability of the anterior and posterior cruciate ligament and the menisci. Tibial tubercle osteotomy was performed. A tumor-free 5-cm segment of the bone that included the tibial tubercle and a portion of the anterior crest of the tibia was elevated. Prothesis design houses an indentation for this bone fragment to be fixated. The tumor was removed successfully using 3D-printed resection guides. To preserve the length of the limb and to avoid complications like infection, a hand-made cement spacer was used. Preserved epiphysis of the proximal tibia was then relatively stabilized onto this spacer using a conventional tibia intramedullary nail (Figure ). After the operation, the patient had no medical problem at her follow-up and was discharged with the appropriate postoperative care recommendations. Pathology later confirmed their preoperative diagnosis as ‘parosteal osteosarcoma’. Clear surgical margins were confirmed, which also confirmed the effectiveness of using 3D-printed guides for the complete removal of the tumor.
Design and production
The prosthesis was designed with the collaboration of members from the Department of Orthopedics and Traumatology and the Department of Biomechanics and Tissue Engineering at Dokuz Eylül University. Designs were then fabricated by Sayan Orthopedics, Ltd, İzmir, Turkey.
The tibial plate was designed to house and press-fit the remaining bone tissue and its attachments. Six cortical screw holes were included in the design for the fixation of bone tissue onto the prosthesis. The prosthetic body has two cortical screw locations on both sides to augment the fixation of the tibia plateau. Suture holes for fixation of the tibial tubercle were included in the prosthetic design. Thus, the continuity of the extensor mechanism will be ensured. There are two locking screw holes that fix the stem with the distal tibia. A patient-specific distal locking guide was also designed and fabricated to shorten the surgery time and minimize bone loss (Figure ). It is aimed to enrich osteointegration of both stem and prosthetic proximal with bone by hydroxyapatite coating of both the distal stem and the prosthetic body to stimulate bone ingrowth and osteointegration []. The 3D-printed prosthesis was made from titanium alloy (Ti6Al4V) (ISO 5832-3) using the computer numerical control (CNC) milling method with a diameter of 70 mm (Figure ). TI PLAZMA 280-320 micron + HA 60-90-micron coating process was done by HTI Technologies (Décines-Charpieu, France).
Custom-designed patient-specific tumor prosthesis was obtained and finite element analyzes were performed in terms of implant durability and stress effects. Virtual biomechanical evaluations, as well as finite element analysis, were performed by the Department of Biomechanics and Tissue Engineering at Dokuz Eylül University. Before clinical application, the prosthesis underwent a thorough process of cleaning and sterilization at the Dokuz Eylul University Central Sterilization Unit.
Final surgery
The final surgery was performed after the conclusion of preoperative templating (Figure ) by the Chief of the Orthopedics and Traumatology Department (Dr. Hasan Havitcioglu). Careful dissection of the key structures of the knee was carried out, and the viability of the proximal tibia and its ligamentous attachments was checked by evaluating their blood flow, before proceeding with the operation. The cement spacer was removed. The tibia plateau was press-fitted to the tibial plate of the prosthesis. The distal tibia was reamed to fit the 3D-printed prosthesis stem. All stages of the procedure and positioning of the prosthesis were checked using a C-arm fluoroscopy unit. Four cortical screws parallel to the tibia plateau were inserted to enhance the stability of primary fixation. Two cortical screws were inserted diagonally towards the eminence of the tibia from the body of the prosthesis (Figure ).
Postoperative management
The patient's knee was locked in full extension for three weeks after the operation. With physical therapy, 90 degrees of flexion was gradually achieved. Using angled immobilizers, full weight-bearing was performed four weeks after the surgery. The brace was discarded at eight weeks. By 10 months, she could walk independently without aids and pain. The follow-up X-rays showed satisfactory implant alignment. No evidence of implant loosening and tumor recurrence was seen.
Results
Hydroxyapatite coating of both the distal stem and prosthetic body and the rather unusual fixation methods allowed for better stability, which in turn allowed for a healthier extensor mechanism. The range of motion was evaluated at weekly intervals and the physical therapy plan was altered accordingly to our findings; 80 degrees of flexion was attained four weeks after the procedure. We now have 100 degrees of range of motion for the affected extremity (Figure ). No symptoms or radiological evidence of implant loosening was detected (Figure ).


The 57-year-old female patient was diagnosed with spontaneous subarachnoid hemorrhage due to a ruptured aneurysm of the right middle cerebral artery and spontaneous intracerebral hemorrhage at the right basal ganglia (Table , Fig. A). The patient underwent decompressive craniectomy and hematoma removal at the neurosurgery department of a university hospital one day after stroke onset, and C/P using auto-bone was performed seven weeks after onset. After C/P, her cognitive impairment improved seven points on MMSE (MMSE scores: 22 at 1 day before C/P → 29 at 9 days after C/P). DTT was not able to reconstruct the DLPFC in either hemisphere before or after C/P (Fig. -B). On post-C/P DTT, the FA values of the VLPFC on the OP side and the OFC on the contra-OP side were lower than on pre-C/P DTT, whereas the post-C/P MD and VN values of these neural tracts were higher. By contrast, the FA and VN values of the VLPFC on the contra-OP side were lower (Table ).


The 51-year-old female patient underwent craniectomy and removal of hematoma in the fronto-parietal lobes at the department of neurosurgery of the same university hospital (Table , Fig. A). She underwent C/P with auto-bone at 13 weeks after onset. Her MMSE score increased by eight points from the pre-C/P value (MMSE: not testable at 2 days before C/P → 8 points at 6 days after C/P). The DLPFC in both hemispheres was not reconstructed on pre-C/P DTT; in contrast, the DLPFC on the contra-OP side was reconstructed on post-C/P DTT (Fig. B). The FA value decreased, and the MD increased in the VLPFC on the contra-OP side, whereas the values of FA and MD for the OFC increased and decreased, respectively, on the contra-OP side. The VN values of the VLPFC and OFC increased on the contra-OP side (Table ).


The 63-year-old female patient was diagnosed with spontaneous intracranial hemorrhage in the right frontal lobe, as well as subarachnoid and intraventricular hemorrhages (Table , Fig. A). The patient underwent craniectomy and removal of hematoma at the neurosurgery department of the same university hospital. C/P was performed using auto-bone at seven weeks after onset. The patient's post-C/P MMSE score increased by five points compared to the pre-C/P MMSE score (MMSE: not testable at 3 days before C/P → 5 at 21 days after C/P). The DLPFC and OFC were not reconstructed in either hemisphere on pre-C/P DTT. In contrast, the DLPFC on the contra-OP side and the OFC on both sides were reconstructed on post-C/P DTT (Fig. B). On post-C/P DTT, the FA value decreased, and the MD and VN values increased on the contra-O/P side of the VLPFC compared to the pre-C/P DTT results (Table ).


The patient was a 10-year-old girl (height, 118 cm; weight, 20 kg) with recurrent right ilium osteosarcoma, which spread to the right femur. She received chemoradiation therapy for right ilium osteosarcoma 3 years before presentation. The tumor gradually invaded the right lumbar plexus (Fig. ). The spread of the tumor led to progressive lower extremity muscle weakness with throbbing pain in the right lower extremity. Metastasis of the tumor in both lungs was detected. The cancer was diagnosed as advanced, and end-of-life care was initiated. The attending pediatricians tried to manage the pain with acetaminophen, ibuprofen, pregabalin, ketamine, oxycodone, and fentanyl. The pain in the right lower extremity progressively worsened with time. The palliative care doctor gradually increased the dose of analgesics. The maximum dose of intravenous oxycodone was 1320 mg/day, which is equivalent to an oral morphine dose of 2640 mg/day. Benzodiazepines were used to mildly sedate the patient because pain control was poor. A urinary catheter was inserted due to urinary retention. The attending pediatricians estimated her life expectancy to be approximately 1–2 months. The patient and her parents expressed desire to be discharged home. However, due to intractable pain, the patient could not be discharged.
She was then referred to the Department of Pain Medicine. Because the patient was shy and rarely communicated with the medical staff, we obtained information regarding her condition from her parents. The spread of the tumor led to progressive lower extremity muscle weakness (2 to 3/5 in the manual muscle test) with severe throbbing pain (NRS 7 to 9) (Fig. a). She was not able to walk because of muscle weakness. She also complained of general fatigue, malaise, and shooting pain (NRS 10). Shooting pain appeared more than five times per hour in the same region of throbbing pain. Mild allodynia was observed in the region of pain. A tactile sensation at the innervation territory of the right thoracic (T) 12 to lumbar (L) 5 spinal nerves was decreased to 5/10 compared to the contralateral side. We diagnosed her pain as a mixed condition of neuropathic pain and somatic pain. Severe shooting pain and mild allodynia were observed in the pain region. We classified her pain as “definite neuropathic pain” using a grading system for neuropathic pain published by The International Association for the Study of Pain []. The throbbing pain was considered to be somatic pain caused by the direct expansion of the tumor. She also experienced sleep disturbances due to the pain.
We considered regional anesthesia techniques to relieve the pain since systemic analgesic therapy failed to adequately attenuate it. There was no space to perform a peripheral nerve block because the tumor had spread near the spinal canal. We had three options: first epidural infusion, second intrathecal infusion, and third intrathecal neurolytic block. Epidural analgesia might not have been able to control the pain due to its relatively wide dermatomal spread. Catheter management may have been troublesome. Although neurolytic block may cause paresis/paralysis and bladder/bowel dysfunction, she was not able to walk due to muscle weakness. She already had a urinary catheter and constipation. We considered that paresis/paralysis and bladder/bowel dysfunction were acceptable complications. After discussing the benefits and risks with the patient, parents, palliative care doctors, and attending pediatricians, we decided to try an intrathecal neurolytic block.
To evaluate the efficacy of intrathecal analgesia, we performed a test block using a fluorescence-guided intrathecal nerve block. On arrival in the procedure room, pulse oximetry, electrocardiography, and noninvasive blood pressure monitoring were established. The patient’s mother accompanied her and stayed in the room during the procedure. After applying oxygen at 7 L/min using a facemask, moderate sedation was initiated with intravenous thiamylal (75 mg). Moderate sedation with spontaneous ventilation was maintained using intermittent thiamylal (total dose, 200 mg). We selected thiamylal as a sedative because the patient already received thiamylal several times. We carefully monitored patient’s airway and ventilation. We changed the patient’s position from the supine position to the right lateral decubitus position. After local anesthesia with 1% mepivacaine, a 23 G Quincke needle was inserted into the L 3/4 intervertebral space. We confirmed adequate spread (L 2 to L 4 levels) of contrast using 24% iotrolan (0.3 mL) (Fig. b). Hyperbaric bupivacaine (0.5%, 0.3 mL) was injected intrathecally. We kept her in the right lateral decubitus position for an hour. Her vital signs were within the normal range during the procedure. The patient did not complain of any pain for 6 h. The intrathecal nerve block was considered to be effective.
Five days after the test block, we performed the intrathecal neurolytic block. The patient was mildly sedated using intravenous midazolam (2 mg) because the patient seemed anxious. Oxygen 3 L/min was applied via a facemask. Moderate sedation was maintained with intermittent thiamylal administration (total dose, 300 mg). Airway obstruction or insufficient ventilation was not observed. After local anesthesia with 1% mepivacaine, a 22 G Quincke needle was inserted into the L 3/4 intervertebral space. A 0.2 mL solution of 10% phenol-glycerol was injected. We maintained her in the right lateral decubitus position for 2 h. Her vital signs were within the normal range during the procedure. The patient reported decreased touch and pain sensation from T 12 to L 5 in the dermatome without any signs of motor block.
Over the following few days, intravenous administration of oxycodone was significantly reduced. The neurolytic block completely relieved her right lower extremity pain. Finally, she received only transdermal fentanyl patch 2 mg/day, which is equivalent to an oral morphine dose of 60 mg/day due to low back pain. The complication of neurolytic block was not observed. The patient was discharged 2 weeks after the neurolytic block. She was able to go outside using a wheelchair. Her quality of life improved and spent her last time with family. She died 3 months after the neurolytic block was performed.


We report the case of a 90-year-old woman with no haematological history who was admitted to a neurovascular intensive care unit for suspected stroke. The patient had a left sensory-motor deficit and speech impairment. The blood sample was taken 8 hours after a computed tomography angiography and thrombectomy. Serum protein electrophoresis was performed on CAPILLARYS 2 (Sebia, Lisses, France). A duplication of the β-2 globulin fraction (black arrow) with an increase in concentration to 7.4 g/L (reference interval: 2.3-4.7 g/L) and a shoulder of β-1 globulin (grey arrow) were detected compared to normal serum (). Other laboratory results were unremarkable (). An informed consent form for the publication of a case report was signed by the patient during hospitalization.


In the postanalytical phase, during verification of patient results, it was noticed that a 66-year-old male patient’s direct bilirubin (DBIL) was higher than total bilirubin (TBIL). Blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and serum electrolytes were in the reference range. Glucose concentration was slightly high, and albumin was 29 g/L (35 - 52). His haemoglobin (Hb) concentration was 70 g/L (130 – 169), whereas platelets were mildly elevated, and leukocyte count was normal (). The patient was referred to the emergency department, and DBIL was 14.2 μmol/L (0 – 3.4), while TBIL was measured 8.7 μmol/L (5.1 – 20.5). Serum indices (haemolysis, icterus, and lipaemia) were normal with photometric and visual assessment. Besides, there wasn’t any flag or warning on the analyser. The serum was not viscous, and no gel formation was present that may cause incorrect sample pipetting volume.
The sample was analysed twice in a sample cup and resulted in - 4.6 and - 19.3 μmol/L for DBIL; and 8.7 and 8.0 μmol/L for TBIL. As can be seen, there was imprecision in the repeated direct bilirubin results (). The reaction monitors of the patient’s DBIL and TBIL results were examined and then compared with the other patients’ reaction monitors analysed on the same day. An unusual absorbance curve containing sharp spikes were observed in the patient’s DBIL result ().
It was revealed from the laboratory information system (LIS) that the patient had fatigue and dyspnoea. There was not any request for radiological imaging. The patient’s diagnoses made by the doctor in the emergency department were anaemia and pain, unspecified.
Considering the patient’s age, decreased albumin level, anaemia, and the spurious direct bilirubin result, the laboratory specialist suspected a paraproteinemia, which could explain all of these findings. For eliminating suspected paraprotein interference, the serum of the patient was diluted in a 1/3 ratio. The results after dilution were TBIL = 10.3 μmol/L, DBIL = 4.6 μmol/L, and the reaction kinetics of the mentioned direct bilirubin result was normal (), so results were verified.
All biochemistry parameters, including bilirubin concentrations, were analysed with Beckman Coulter reagents on AU680 automated chemistry analyser (Beckman Coulter, Brea, USA). Direct bilirubin (REF: OSR6211) assay in our hospital is an end-point assay. The assay was based on the formation of azobilirubin at a low pH and measured bichromatically at 570/660 nm via two cuvettes (colour and blank). The reagents for DBIL assay contain hydrochloric acid, sulfuric acid, and 3,5-dichlorophenyldiazonium tetrafluoroborate as the chromogen. The chromogen is added only in the colour cuvette (reaction cuvette). For measurement of DBIL, the second cuvette is used for the sample blank, and the blank cuvette’s absorbance is subtracted from the absorbance of the reaction cuvette.
In our case, peculiar spikes appeared after the “0” (i.e., following the addition of the sample to the cuvette, which already contains sulfuric and hydrochloric acid and mixing stage) and “10” (following a stirring operation in cuvettes) photometric points (). Neither diluted sample of the patient nor other patients’ samples analysed in that day did not show any spikes, and absorbance curves were parallel in these samples’ reaction data. No unusual reaction curves were observed for the patient’s other biochemistry assays.
Simultaneously, measurement of total protein was done, as a reflective test, to check the reversed albumin/globulin ratio. Due to increased total protein and reversed albumin/globulin ratio, serum was stored, and the next day another reflective test, SPEP, was performed. The doctor in the emergency department was informed that the patient may have a disease with monoclonal gammopathy and should be referred to haematology after discharge because the patient had never applied to our hospital’s haematology department before. Also, this recommendation was added to the patient’s laboratory report as a comment. A few hours later, when the patient’s file was examined, we learnt that he left the emergency department voluntarily after 1U (one unit) of red blood cell transfusion.
The next day, SPEP analysis was performed in agarose gel (SAS-1 plus SAS-2, Helena Biosciences Europe, UK), and a monoclonal peak in the gamma region was detected (). M-protein concentration was calculated as 26.4 g/L. Another reflective test, serum IFE was performed by the Interlab G26 analyser (Interlab Srl, Rome, Italy), and a pathological band was seen in all lines (). As we saw lanes in all globulin fractions, we suspected cryoglobulinemia and/or monoclonal IgM polymerization. We could not identify the paraprotein exactly with IFE because we couldn’t repeat the analysis after treating serum with 2-mercaptoethanol (a reducing agent that breaks down disulfide bands in protein precipitates) to dissolve paraprotein precipitation (, ). Meanwhile, nephelometric quantification revealed IgM-Kappa increase (Beckman Coulter Immage 800, Brea, USA). Although the clinician had been informed and the possible paraproteinemia mentioned as a comment in the patient’s laboratory report in previous days, for patient safety, we decided to contact the patient in the light of new results obtained.
The patient was contacted by phone and asked about his previously diagnosed diseases and medications. We learnt that the patient hadn’t had any haematological diagnosis yet. He’d been taking valsartan+thiazide, metoprolol, salicylate, clopidogrel, and metformin for hypertension, coronary artery disease, and type 2 diabetes mellitus. One week ago, the patient applied to his family doctor with fatigue, dyspnoea, and weight loss (8 kg in last year). After the family doctor noticed the patient’s Hb concentration was 78 g/L in the complete blood count, she planned urinalysis, faecal occult blood test, abdomen ultrasonography, endoscopy, and colonoscopy for suspected malignancy. The patient was kindly invited to our laboratory to give him information about his reflective test results and directed him to the haematology department. We also advised him to go on all his planned requests and procedures in case of any other malignancies. A few weeks later, the patient wanted to share his results with us. Informed consent was obtained from the patient to report these findings for scientific purposes. According to the patient’s results, the faecal occult blood test was negative, urinalysis wasn’t significant, either. Abdominal ultrasonography and colonoscopy were normal; endoscopic biopsy resulted in atrophic gastritis. Cryoglobulinemia test result was negative in another laboratory. After seen by a haematologist, the patient underwent a bone marrow biopsy. The bone marrow biopsy result was reported as Waldenstrom’s Macroglobulinemia (lymphoplasmacytic lymphoma) with plasma cell differentiation expressing IgM-Kappa. The patient went on a chemotherapy protocol, and his condition has been improved in subsequent months.


The second case is a 30-year old Caucasian female with a medical history of paranoid schizophrenia (ICD-10-CM Code F20.0) Previous antipsychotics treatments were correlated with adverse effects (hyperprolactinemia with risperidone, weight gain with olanzapine and severe sedation and hypotension with quetiapine). Due to these adverse effects the compliance was poor and the paranoid symptoms persist. The PGx–CNS analysis gave information that other antipsychotics like aripiprazole and haloperidol could possibly be more suitable regarding her ADEs. The HTR2C gene (rs1414334, CG) and the MC4R gene (rs17782313, CT) are correlated with an increased risk of developing metabolic syndrome and weight gain in this patient. In line with the PGx–CNS results, the patient subsequently received a treatment with haloperidol (10 mg/day) and aripiprazole (15 mg/day) and after 4 weeks, responded well. Psychotic symptoms were decreased and the patient felt relief with enhanced functional levels. No serious adverse effects have been reported.


A 63-year-old African American male with past medical history of congestive heart failure, pulmonary sarcoidosis, non-alcoholic liver cirrhosis, chronic kidney disease, and hypertension presented with complains of shortness of breath and bilateral lower extremity swelling. He denied abdominal pain, upper respiratory tract symptoms, fever, chills, and rigor. He also denied recent exposure to pets and animals including dogs. Initial vital signs were stable. He was afebrile, normotensive, and saturated at 100% on room air. Physical examination was significant for a markedly distended abdomen, which was soft and non-tender to light and deep palpation. Jugular venous distension was evident with extensive bilateral lower extremity edema with scrotal edema. There was no jaundice on examination. Chest X-ray was unremarkable with no infiltrates and consolidations. Initial laboratory investigation revealed a white count of 4.2 cells/mm3 (4.4-11.0 cells/mm3), hemoglobin of 10.7 g/dL (13.5-17.5 g/dL), platelet of 188 cells/mm3 (150-450 cells/mm3), lactic acid of 2.3 mmol/L (0.0-2.0 mmol/L), creatinine of 1.7 mg/dL (0.6-1.2 mg/dL), B-type natriuretic peptide of 823.71 pg/mL (0.0-100.0 pg/mL), protein of 8.2 g/dL (6.4-8.4 g/dL), and albumin of 2.6 g/L (3.5-4.5 g/L). Liver function tests were mildly elevated with an aspartate aminotransferase of 43 U/L (10-36 U/L), alanine aminotransferase of 20 U/L (9-46 U/L), and alkaline phosphatase of 134 U/L (40-115 U/L). Total bilirubin was within normal limit. Coagulation profile showed slightly prolonged international normalized ratio of 1.46.
He was admitted and managed for decompensated liver cirrhosis with diuresis to relieve the edema. He had undergone similar admissions in the past and also had multiple paracentesis done, the most recent was a month earlier, for symptomatic relief. A large-volume paracentesis was done during this hospitalization with the removal of 10 L of peritoneal fluid. Following paracentesis, he became hypotensive despite resuscitative efforts with appropriate albumin. Peritoneal fluid analysis revealed a white blood cell count of 72/mm3, 49% lymphocyte differential, 44% neutrophil differential, protein of 2.6 g/dL, lactate dehydrogenase of 91 U/L, and glucose of 113 mg/dL. This analysis was consistent with a diagnosis of portal hypertension likely as a result of his liver cirrhosis, and spontaneous bacterial peritonitis was unlikely. No organism was isolated from peritoneal fluid cultures and gram stain showed no organism.
In the setting of his persistent hypotension, sepsis was considered, blood cultures were drawn, and meropenem was empirically started. Ultrasound of the abdomen was done to look for a source and showed moderate ascites with a contracted gallbladder with no evidence of cholecystitis (Figure ).
Computed tomography of the abdomen was also done which showed cirrhosis and cholelithiasis with no evidence of intra-abdominal abscess (Figure ).
A hepatobiliary iminodiacetic acid scan was done which revealed no biliary obstruction but delayed visualization of the gallbladder. Surgery was consulted and in the absence of clinical signs of cholecystitis with his multiple comorbidities, elective cholecystectomy was postponed, and ongoing antibiotic management was advised. B. bronchiseptica was isolated from blood cultures (Table ).
Echocardiogram was performed and did not show any vegetations (Figure ).
Meropenem was stopped and based on a review of the available literature, we decided to start the patient on doxycycline for the bacteremia. Blood pressure stabilized after 48 hours and repeat blood cultures were negative. The patient tolerated doxycycline and was discharged with a seven-day course of oral doxycycline.


This is a 20-year-old man from Guatemala with a history of poorly controlled type 1 D.M. and 2 hepatic abscesses: the first drained in Guatemala 6 years prior and the second drained 4 months in the US, prior to the current presentation. It is unclear what was isolated in the first event, but he was treated for Klebsiella pneumoniae liver abscess with antibiotics after the second drainage. There were no previous images for comparison. He presented with a 2-day history of altered mental status, high fever, abdominal pain, and occipital headache. He was found to be septic with diabetic ketoacidosis and acute hepatitis. C.T. of the abdomen showed a heterogeneous rounded low-attenuation lesion with irregular borders in the posterior segment of the liver's right lobe (segment 6) (Figures –) and three small nodular opacities in the right lung, which appeared infectious. Laboratory data were significant for leukocytosis with severe lactic acidosis. Blood culture was positive for Klebsiella pneumoniae. He underwent guided drainage of the abscess by interventional radiology (Figures and ), and the culture of the fluid isolated the same organism. He was treated with antibiotics, intravenous fluids, and insulin therapy with improvement in his symptoms. The patient was discharged on long-term antibiotics (7 weeks) and insulin therapy, and he was counseled on medication adherence to achieve strict glycemic control.


A 35-year-old female patient weighing 47 kg experienced swelling and pain in the left thigh 1 week ago with no obvious cause, and could not be relieved after rest. The ultrasound was performed at the local hospital 3 days ago, indicating the left iliac vein thrombosis. Symptoms had not improved after anticoagulation treatment. Then she was transferred to our hospital for further treatment and computed tomography (CT) showed May-Thurner syndrome with deep vein thrombosis of left lower extremities (Fig. ). The patient had no history of lower extremity disease, and she had no personal or family history of hypercoagulable disorder, but she had taken contraceptive pills for 3 years and D-dimer was 2.14 mg/L on admission.
The patient accepted enoxaparin sodium (4000 AXa IU every 12 h) for anticoagulant therapy in the perioperative period. Then the patient received a right femoral vein puncture in the supine position (the delay between the thrombotic event and the procedure was 11 days). Firstly, a filter was implanted in the inferior vena cava; then the patient was changed to the prone position and left popliteal vein puncture was performed for venography of left lower extremity. After thrombus aspiration, the significant narrow left common iliac vein was exposed (Fig. b). Then urokinase (1 million u/day) was pumped for thrombolytic treatment after procedure. 3 days later, the result of venography showed that the thrombus was almost completely dissolved and the severe stenosis in left common iliac vein was exposed (Fig. c). Then a 12 mm*40 mm PTA balloon was used to expand it (Fig. d-e). Further venography showed the inferior vena cava was visible (Fig. f). Considering that the thrombolytic efficacy was satisfactory and the patient was young, we did not perform stent implantation for her. 10 days later, the patient discharged and the D-dimer was 2.07 mg/L. The patient was given rivaroxaban for anticoagulant therapy (15 mg two times a day in the first three weeks, then 20 mg one time a day orally) and graduated compression stockings (30–40 mmHg) for at least one year after admission. 2 weeks later, we removed the filter from the patient.
A 37-year-old male patient weighing 64 kg worked in front of a computer for more than 7 h a day. The patient experienced swelling and pain in his right lower limb 3 days ago, so he came to our hospital for treatment. The symptoms of left lower limb were not obvious. Computed tomography indicated thrombosis of the right iliac vein, thrombosis of the left iliac vein and inferior vena cava, and stenosis due to compression of the left iliac vein by right iliac artery. May-Thurner syndrome along with DVT was diagnosed. (Fig. a) The patient had no history of trauma, surgery and lower extremity disease, and he had no personal or family history of hypercoagulable disorder, The D-dimer was 10.3 mg/L on admission.
The patient accepted enoxaparin sodium (6000 AXa IU every 12 h) for anticoagulant therapy in the perioperative period. The venography of the lower extremity showed complete occlusion of the left common iliac vein (Fig. b). The lower end of the right iliac vein was visible and the middle and upper segments were filled with a large amount of thrombus (Fig. ). The time between the thrombotic event and the procedure was 9 days. Firstly, a filter was placed in the inferior vena cava. A thrombolytic catheter was placed and urokinase (1 million u/day) was pumped for thrombolytic therapy. Three days later, we used a 14 mm*4 mm XXL balloon to expand the stenosis segment of right iliac vein after thrombolytic therapy (Fig. e), the patient complained of pain in right waist during the procedure. The balloon could not be fully opened. We considered it was caused by local old lesions. We insisted on expanding it for 2 min. The angiography showed that the stenosis of the right iliac vein and inferior vena cava was quite relieved (Fig. f). In addition, complete occlusion of left common iliac vein was showed. Because the tissue of occluded segment was tough and the guide wire could not pass through, the further procedure was stopped to prevent possible blood vessel rupture and bleeding. At the time of discharge, the D-dimer had dropped to 1.77 mg/L. Treatment was the same as case 1 after admission. Outpatient examination after 6 weeks, the swelling of both lower limbs disappeared completely, and the D-dimer had dropped to 0.2 mg/L. Sixty-four days later, we removed the filter from the patient, and the D-dimer was 0.31 mg/L.


A 57-year-old female patient underwent surgical treatment for varicose veins 10 days ago at the local hospital. She experienced swelling and discomfort in her left lower extremity 3 days ago. She was not able to walk easily and could not be relieved after rest, then she was transferred to our hospital for further treatment. Computed tomography indicated deep venous thrombosis in the left lower extremity and significant stenosis of the left common iliac vein and compression by right iliac artery. May-Thurner syndrome with deep vein thrombosis was diagnosed (Fig. a). The patient had a varicose vein in the left lower extremity for more than 10 years and had a great saphenous vein high ligation and exfoliation at the referring local hospital 10 days ago. and she had no personal or family history of hypercoagulable disorder, The D-dimer was 8.3 mg/L on admission.
The patient received enoxaparin sodium (6000 AXa IU every 12 h) for anticoagulant therapy immediately. We performed lower extremity angiography for the patient. The delay between the thrombotic event and the procedure was 9 days. A filter was placed in the inferior vena cava. Then urokinase (1 million u/day) was pumped. The venography after 2 days showed that the residual amount of thrombus decreased significantly. Three days later, venography showed that the stenosis in left common iliac vein was exposed clearly. Then a 12 mm*40 mm XXL balloon was used for expanding the stenosis two times, but the stenosis in left common iliac vein recurred due to elastic retraction (Fig. e). So, stent implantation was decided and two 14 mm*60 mm and 12 mm*60 mm stents were placed in the left iliac vein (Fig. f-g). The venography showed that the stenosis was completely relieved and the blood flow was unobstructed. The filter was taken out and the angiography showed that the inferior vena cava had smooth blood circulation. The CT showed that the stenosis of iliac vein was relieved (Fig. h) and the D-dimer had dropped to 0.25 mg/L. Treatment was the same as case 1 after discharge. 2 weeks later, we removed the filter from the patient. No symptoms of lower extremities appeared during follow-up after 1 year and recent result of D-dimer was 0.32 mg/L.