The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) has an intermediate prognosis between indolent well-differentiated thyroid carcinoma (TC) and anaplastic carcinoma. Herein, we present a case report with a PDTC component, along with a systematic review of the literature. CASE REPORT: We report a case of a 45-year-old man diagnosed with a PDTC component, along with hobnail and tall-cell variant features positive for BRAFV600E mutation, after a total thyroidectomy and neck dissection. Radioactive iodine (RAI)-131 therapy was applied, but an early recurrence led to complementary surgeries. The anti-Tg rise, the presence of new lymph nodes, and the negative whole-bodyradioiodine scan were suggestive of a radioiodine-resistant tumor. Lenvatinib, sorafenib, dabrafenib/trametinib, cabozantinib and radiotherapy were all administered, controlling the tumor for a period of time before the patient ultimately died post-COVID infection. Systematic Review: We searched PubMed, Scopus, and WebofScience to identify studies reporting clinicopathological characteristics, molecular marker expression, and management of non-anaplastic TC with any proportion of PDTC in adult patients. Of the 2007 records retrieved, 82were included in our review (PROSPERO-ID545847). CONCLUSIONS: Our case, together with the systematic review, imply that a combination of molecular-targetedtreatments may be safe and effective in patients with RAI-resistantBRAF-mutated advanced PDTC when surgery has failed to control tumor progression.

Laparoscopic approach to a large adrenocortical oncocytoma: A case report and review of the literature.

INTRODUCTION: Adrenocortical oncocytomas are extremely rare tumors, considered to be non-functional and of low malignant potential. Despite the great advance in laparoscopic techniques, there are extremely limited reports of laparoscopic approach of adrenocortical oncocytomas. Herein is presented a challenging case of laparoscopic approach to a large adrenocortical oncocytoma, underlining the safety and feasibility of laparoscopy in the surgical management of these extremely rare adrenal tumors. PRESENTATION OF CASE: A 34 year-old male was referred for surgical evaluation after the incidental discovery of a large right adrenal mass, during ultrasound examination due to renal colic. Further imaging evaluation revealed a well circumscribed capsule around the mass was demonstrated, with no evidence of infiltration of the neoplasm to periadrenal tissues. The patient was scheduled for laparoscopic right adrenalectomy, running an uneventful postoperative period. Histopathology revealed the presence of an adrenal oncocytoma. DISCUSSION: Recent studies have demonstrated that approximately one third of adrenocortical oncocytomas are associated with hormonal hypersecretion, as well as that one fifth of them demonstrate malignant biological behavior. From this point of view, there is emerging evidence in favor of the necessity of surgical excision as the treatment of choice. In spite of the progress of laparoscopic surgery, only three cases of laparoscopic excision of these tumors have been reported up to date. CONCLUSION: Laparoscopic surgery offers a safe alternative in confronting adrenocortical neoplasms, even when the biological behavior of the tumors cannot be pre-operatively evaluated in a definite way.

Laparoscopic resection of an adrenal schwannoma.

BACKGROUND AND OBJECTIVES: Schwannomas are tumors originating from Schwann cells of the peripheral nerve sheath (neurilemma) of the neuroectoderm. Rarely, schwannomas can arise from the retroperitoneum and adrenal medulla. We describe a case of a 71-y-old woman who presented with an incidentally discovered adrenal tumor. METHODS: Ultrasound and computed tomography scans revealed a lesion with solid and cystic areas originating from the left adrenal gland. The patient underwent complete laparoscopic resection of the tumor and the left adrenal gland. RESULTS: Histopathological examination and immunohistochemical staining of the excised specimen revealed a benign schwannoma measuring 5.5×5 3.7 cm. To our knowledge, few other cases of laparoscopic resection of adrenal schwannomas have been reported. CONCLUSION: Because preoperative diagnosis of adrenal tumors is inconclusive, complete laparoscopic excision allows for definitive diagnosis with histological evaluation and represents the treatment of choice.

Thyroid surgery with the new harmonic scalpel: a prospective randomized study.

BACKGROUND: Despite their safety and effectiveness in thyroid surgery, the previous harmonic scalpel instruments are considered large and cumbersome by several surgeons. An innovative technical improvement of the device has been made available since 2008. The objective of this study was to compare the results of total thyroidectomy using the new harmonic scalpel (FOCUS) with that with the previously available device (HARMONIC ACE). METHODS: A prospective randomized study of all total thyroidectomies between February and July 2008 was conducted. Patients (n = 90) were randomized to undergo total thyroidectomy with FOCUS (group A, n = 45) or HARMONIC ACE (group B, n = 45). RESULTS: No significant differences were identified between the 2 groups in terms of demographics, reoperative thyroid surgery, thyroid gland weight and diameter, pathologic diagnosis, preoperative and postoperative serum PTH and calcium levels, postoperative complications, duration of hospital stay, and final outcome. The mean operative time was less in group A than group B (63 ± 7 min vs 76 ± 8 min, P = .009). CONCLUSION: The new harmonic scalpel is a useful adjunct to the armamentarium of the thyroid surgeon. It is safe, effective, and hand friendly, offering great capabilities for delicate tissue grasping and dissection. Use of this device decreased operative time compared with the previously available instrument.

Primary cavernous hemangioma of the thyroid gland.

A 78-year-old euthyroid patient presented for evaluation of a symptomatic, slowly growing neck mass. Ultrasound scan revealed a multinodular goiter and a hypoechoic nodule of the right thyroid lobe. Total thyroidectomy was performed and the lesion was completely excised. Definite diagnosis was obtained after histological examination of the surgical specimen. Cavernous hemangiomas of the thyroid gland are infrequent lesions which may escape diagnosis preoperatively. An effort should be made not to rupture these lesions in order to ensure a bloodless procedure.

Undifferentiated giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation: a case report and review of the literature.

INTRODUCTION: Undifferentiated gallbladder carcinoma is a rare entity. Among unusual types of undifferentiated gallbladder carcinoma, giant cell type carcinoma is infrequent and, moreover, very few cases of such neoplasms with osteoclast-like giant cells have been documented. We report a case of undifferentiated gallbladder carcinoma presenting an unusual immunophenotype that was shown to be of giant cell type with sarcomatoid dedifferentiation infiltrated by osteoclast-like multinucleated cells. CASE PRESENTATION: An 84-year-old Greek man presented with right upper quadrant pain, high fever, rigors, anorexia and weight loss during the past month. Clinical examination revealed tenderness in the right upper abdominal quadrant and a palpable gallbladder. Blood tests showed elevated white blood-cell count and transaminases. Abdominal ultrasound and computed tomography demonstrated a markedly distended gallbladder, measuring 16 cm x 8 cm, with oedema and pericholecystic fluid, consistent with gallbladder empyema. After an open cholecystectomy and an uneventful recovery, the patient was discharged on the 4(th) postoperative day. On cut surface, a 2cm solid mass was identified, obstructing the lumen in the neck of the gallbladder. Histopathology and immunohistochemistry offered the diagnosis of an undifferentiated, giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation infiltrated with osteoclast-like giant cells. CONCLUSIONS: Undifferentiated, giant cell type carcinoma of the gallbladder with sarcomatoid dedifferentiation infiltrated with osteoclast-like giant cells is a very infrequent neoplasm. Controversy exists over its nature, as related knowledge remains incomplete. Thorough histopathological and immunohistochemical evaluation is imperative for diagnosis. Due to their rarity, the biological behaviour and prognosis of these tumours remain unclear.

A novel laparoscopic approach to lesions related to the posterior aspect of the pancreatic head.

The posterior aspect of the pancreatic head has proven to be a technically demanding region to approach laparoscopically. Previously, this region was approached through the gastrocolic ligament with the patient in a left semilateral position. We believe that this makes the laparoscopic approach to the posterior pancreatic head extremely difficult. In the technique presented here, which has been successfully used in 4 patients, the patient was in full left lateral position, and Nathanson retractors were used to retract the liver and right kidney. This allowed full exposure of the second part of the duodenum before any major dissection. The duodenum was then Kocherized, and the posterior aspect of the pancreatic head, along with the inferior vena cava, left renal vein, and aorta, was exposed. We describe here a safe and feasible laparoscopic method for access to and management of lesions related to the posterior aspect of the pancreatic head.

Novel hemostatic devices in thyroid surgery: electrothermal bipolar vessel sealing system and harmonic scalpel.

Accurate and efficient hemostasis is one of the first priorities of the thyroid surgeon to prevent or minimize complications, including injury to the laryngeal nerves or parathyroid glands, perioperative hemorrhage and the potentially life-threatening hematoma. Means to prevent and control intra- or postoperative bleeding therefore remain a topic of utmost importance. Although thyroidectomy is one of the most common surgical procedures, the safest, most efficient and cost-effective way to achieve hemostasis is debated by endocrine surgeons and otorhinolaryngologists. In our opinion, there is no substitute for meticulous surgical technique and hemostasis, while experience in such operations is essential for the best outcome with the fewest complications. Ties, suture-ligations, monopolar/bipolar diathermy, clips, and hemostatic agents/sealants or tissue adhesives have been used. Over the last 10 years, innovative hemostatic devices, such as the electrothermal bipolar vessel sealing system and ultrasonically activated shears, have been developed and have been welcome adjuncts to the thyroid surgeon's armamentarium. In this review we aim to cover both novel and well-established traditional techniques of hemostasis in thyroid surgery, with specific focus on the bipolar vessel sealer and harmonic scalpel.

A symptomatic cyst of the ligamentum teres of the liver: a case report.

Cysts of the liver ligaments are extremely rare and cysts of the ligamentum teres of the liver have been sporadically reported in the literature during the last century. The present report describes a case of a symptomatic patient with a cyst of the ligamentum teres of the liver. The patient presented with right upper quadrant pain and indigestion during the last 2 years. Ultrasound and computed tomography scans revealed a water-density mass attached to the anterior abdominal wall, but definite diagnosis could not be reached. The cyst was completely excised during laparotomy. Cysts of the ligamentum teres of the liver, although infrequent, may produce clinical symptoms and require excision. Ultrasound and computed tomography scan preoperatively cannot rule out malignancy, thus exploratory laparotomy and total resection of these lesions are necessary.

Splenic rupture as the presenting manifestation of primary splenic angiosarcoma in a teenage woman: a case report.

INTRODUCTION: Primary splenic angiosarcoma is a rare neoplasm of vascular origin carrying a very poor prognosis, partly due to its high metastatic potential. This disease presents frequently with splenic rupture and hemorrhage. We report the case of a 17-year-old woman who presented with rupture of a primary splenic angiosarcoma. CASE PRESENTATION: The patient presented with diffuse abdominal pain and distention. Clinical examination revealed severe tenderness in the left upper abdominal quadrant, a palpable abdominal mass, and hemodynamic instability with a systolic arterial blood pressure of 75 mmHg and heart rate of 135 beats per minute. Blood tests revealed anemia (hemoglobin 7.0 g/dl) and thrombocytopenia (platelets 70 x 109/liter). After initial fluid resuscitation and stabilization, abdominal ultrasound and computed tomography were performed, revealing a large quantity of intraperitoneal free fluid, an enlarged spleen, and a heterogeneous low-density signal within the splenic parenchyma, which showed varying degrees of contrast enhancement. At laparotomy a huge (weight 1530 g, diameter 19 cm) actively bleeding spleen was identified and splenectomy was performed. Histopathology showed a primary splenic angiosarcoma. After an uneventful recovery, the patient was discharged on the sixth postoperative day. CONCLUSION: Primary splenic angiosarcoma is rare. Although this malignancy is usually encountered in advanced age, there have been a few reported cases among younger patients. The case reported here presented with splenic rupture, was treated by laparotomy and splenectomy, and the patient is disease free 16 months after surgery.

Thyroid surgery: comparison between the electrothermal bipolar vessel sealing system, harmonic scalpel, and classic suture ligation.

BACKGROUND: This study was conducted to compare the outcome of total thyroidectomy using the electrothermal bipolar vessel sealing system, the harmonic scalpel, and the classic suture ligation technique. METHODS: This was a retrospective study of prospectively collected data from 382 consecutive total thyroidectomies from September 2004 to August 2006. Patients were divided into 3 groups: group SL patients (n = 90) underwent total thyroidectomy with the classic suture ligation technique, group L (n = 148) with the electrothermal bipolar vessel sealer, and group U (n = 144) with the harmonic scalpel. The main outcomes measured were surgical and hospitalization time, intraoperative and postoperative bleeding, postoperative hypocalcemia, and superior and inferior laryngeal nerves injuries. RESULTS: The 3 groups were similar in terms of demographics, thyroid gland weight and pathology, perioperative complications, and hospital stay. Compared with the classic technique, surgical time was reduced significantly by about 20% when the bipolar vessel sealer or harmonic scalpel was used (93.3 +/- 12.5 vs 74.3 +/- 14.2 and 73.8 +/- 13.8 min, P = .001, and P = .001, respectively). CONCLUSIONS: Both the bipolar vessel sealer and harmonic scalpel are safe, useful, and time-saving alternatives to the traditional suture ligation technique for thyroid surgery. Because no differences were observed regarding these 2 devices, the choice should be made based on the surgeon's preferences and experience.

Unintentional parathyroidectomy during total thyroidectomy.

BACKGROUND: Unintentional parathyroidectomy during thyroidectomy has been evaluated in a few studies. Moreover, the impact of the surgeon's experience and operative technique has not been evaluated. Our aim was to identify the incidence of unintentional parathyroidectomy during total thyroidectomy, its clinical consequences, and factors affecting its occurrence. METHODS: We reviewed all total thyroidectomies during a 2-year period. Patients were categorized into 2 groups: those with unintentional parathyroidectomy (parathyroidectomy group) and those without unintentional parathyroidectomy (no-parathyroidectomy group). RESULTS: Incidental parathyroidectomy occurred in 100 (19.7%) of the 508 patients. The groups were comparable in age, thyroid weight and pathology, operative time, surgeon experience (high/low volume), operative technique (suture-ligation, LigaSure, or Ultracision), postoperative calcium, and transient hypocalcemia. No permanent hypocalcemia occurred. However, 11% of the parathyroidectomy group was men compared with 22% of the no-parathyroidectomy group (p =.002). CONCLUSIONS: Unintentional parathyroidectomy, although common, has no clinical consequences. Unlike surgeon's experience and operative technique, patient sex was the only factor affecting its occurrence.

Sepsis: prognostic role of apoptosis regulators in gastrointestinal cells.

BACKGROUND: Intestinal epithelial cell apoptosis has been reported in sepsis as a mechanism of organ failure. The aim of this study was to clarify the role of apoptosis-regulating proteins (bcl-2, bax, cytochrome-c, and caspase-8) in septic rats by studying their expression in gastric and intestinal epithelial cells. METHODS: Adult Wistar rats were subjected to the cecal ligation and puncture (CLP) model of sepsis and randomly divided into two study groups. Sixty-two animals were sacrificed 6, 12, 24, 36, 48, and 60 h post-procedure, and 50 animals served as the survival study group. Sham-operated animals (n = 40) were used as controls. Gastric and intestinal tissue was excised, and immunohistochemical detection of bcl-2, bax, cytochrome-c, and caspase-8 protein expression was performed. RESULTS: In gastric mucosa, sepsis induced upregulation of bax and downregulation of caspase-8 expression (p = 0.053 and p = 0.05, respectively). Both bax and caspase-8 were upregulated as early as 6 h post CLP and progressively decreased (p = 0.001, p = 0.004 respectively). In contrast, the expression of the anti-apoptotic bcl-2 was upregulated progressively during the sepsis syndrome (p = 0.03). In intestine, sepsis induced a fourfold upregulation of the cytoprotective bcl-2 (p = 0.0001), accompanied by a remarkable increase in bax (p = 0.002) and caspase-8 (p = 0.0001) expression and a decrease in cytochrome-c expression (p = 0.02). The time distribution of the apoptosis regulators followed the same pattern as in gastric tissue, showing an upregulation of the proapoptotic bax and cytochrome c (p = 0.04) during the early phases and a progressively increased expression of bcl-2 during the late phases (p = 0.0001). Bax expression in gastric epithelium of subjects with septic syndrome was detrimental to survival (p = 0.0001), whereas the expression of the cytoprotective bcl-2 in intestinal epithelium appeared to favor a good prognosis (p = 0.0001). CONCLUSIONS: Sepsis results in alterations of apoptosis regulators in gastrointestinal cells. Alterations of bax and bcl-2 expression in gastric and intestinal epithelial cells may predict the outcome in septic rats.

Prospective study of the incidence and risk factors of postsplenectomy thrombosis of the portal, mesenteric, and splenic veins.

HYPOTHESIS: Splenectomy is recognized as a cause of portal, mesenteric, and splenic vein thrombosis. The exact incidence of the complication and its predisposing factors are not known. DESIGN: Prospective observational cohort study. The median follow-up time of the patients was 22.6 months. SETTING: University surgical clinic in a teaching hospital. PATIENTS: A total of 147 consecutive patients who underwent splenectomy in a 4-year period were enrolled in the study. INTERVENTIONS: Preoperative and postoperative evaluation included ultrasonography with color Doppler flow imaging of the portal system, results of blood coagulation tests, fibrinogen levels, D-dimer levels, and complete blood counts. Operative sheets were recorded and reviewed. When portal system thrombosis (PST) was diagnosed, a complete control for acquired and congenital thrombophilia disorders was obtained. MAIN OUTCOME MEASURES: Primary end points of the study were the assessment of the incidence of postsplenectomy PST and the identification of risk factors for its occurrence. RESULTS: Portal system thrombosis occurred in 7 (4.79%) of 146 patients who underwent splenectomy. The age, sex, type or length of the operation, and use of preoperative and postoperative thromboprophylaxis with low molecular weight heparin did not prove to be significant factors in the occurrence of PST. Platelet count of more than 650 x 10(3)/microL and greater spleen weight (>650 g) was associated with the development of PST (P = .01, P = .03). Normal D-dimer levels on diagnosis of the complication showed a negative predictive value of 98%. Two of the affected patients were diagnosed with thrombophilia disorders. In a median follow-up period of 22.6 months, no other case of PST was recorded. CONCLUSIONS: Postsplenectomy PST occurs in approximately 5% of patients. Possible risk factors are thrombocytosis, splenomegaly, and congenital thrombophilia disorders.

Electrothermal bipolar vessel sealing system is a safe and time-saving alternative to classic suture ligation in total thyroidectomy.

BACKGROUND: Total thyroidectomy is associated with minimal morbidity. The electrothermal bipolar vessel sealing system is an adjunct to the surgical technique, recently made available to thyroid surgery. METHODS: This is a prospective randomized trial of total thyroidectomies performed in single unit from July 2003 to May 2004. Patients were randomly assigned in two groups: group A (n = 90), total thyroidectomy with the classic suture ligation technique; and group B (n = 94), total thyroidectomy with the use of the electrothermal bipolar vessel sealing system. RESULTS: Operative time was significantly reduced in group B by 14 minutes (mean difference, 14.3 +/- 4.2 minutes, 95% CI, 5.88-22.6 minutes). No statistically significant differences were found in postoperative complications, postoperative serum calcium measurements, or hospital stay between the two groups. CONCLUSIONS: The electrothermal bipolar vessel sealing system is a safe and useful, time-saving adjunct for total thyroidectomy.

Laparoscopic placement of Oreopoulos-Zellerman catheters in CAPD patients.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is widely accepted for the management of end-stage renal disease. Various techniques have been described for the insertion of peritoneal dialysis catheters. Lately, with the evolution of laparoscopic surgery, different laparoscopic techniques have also been presented, suggesting the technique is preferable to the open and percutaneous methods. OBJECTIVE: To introduce and evaluate a new laparoscopic technique for insertion of Oreopoulos-Zellerman catheters in CAPD patients. SETTING: The study was carried out in the First Department of Propaedeutic Surgery, Athens University Medical School, Hippokration Hospital. PATIENTS AND METHODS: Between November 2000 and March 2002, the technique was applied in 20 consecutive patients (mean age 62 years, range 54 - 70 years) with end-stage renal disease. During this technique, a 10-mm trocar is placed just below the umbilicus for the optics and a 5-mm trocar is placed in the right lower quadrant. With the help of a 10-mm trocar, a tunnel is formed in the standard paramedian position on the left side, 2 - 3 cm below the plane of the umbilicus, for the insertion of the peritoneal catheter. A laparoscopic needle (GraNee needle; R-Med, Oregon, Ohio, USA) is used for the closure of the 10-mm trocar-induced peritoneal and fascia defect using a purse-string suture. The catheter is advanced into the abdomen under direct vision and guided toward the Douglas pouch. The subcutaneous tunnel and the patency test of the catheter are performed as the last main steps in our procedure. One surgeon undertook all procedures. RESULTS: All procedures were completed laparoscopically. The mean operative time was 30 minutes (range 25 - 40 minutes). There was no intraoperative complication or surgical mortality. One patient developed leakage at the catheter exit site 3 days after surgery; it was corrected under local anesthesia. During a mean follow-up time of 17 months (range 12 - 28 months), 1 patient required catheter removal due to fungal peritonitis. CONCLUSION: Laparoscopic insertion of the Oreopoulos-Zellerman catheter is a simple, quick, and safe method. We believe future experience will encourage the laparoscopic technique as the method of choice.

Epstein-Barr virus-associated lymphoepithelial carcinoma in the pancreas.

Lymphoepithelial carcinoma is a relatively common malignancy in the nasopharyngeal region, but it rarely occurs at other sites. We report a lymphoepithelial carcinoma in the pancreas of a 65-year-old male patient operated on for a gastric stump carcinoma 7 years previously. The solitary tumor in the pancreas presented as a circumscribed lesion and measured 5.5 cm in diameter. The tumor was densely infiltrated by lymphocytes, and the neoplastic cells fulfilled all criteria for a lymphoepithelial carcinoma. Several peripancreatic lymph node metastases were observed. Marked reactivity for Epstein-Barr virus (EBV) early RNA (EBER) was detected in the majority of tumor cells using in situ hybridization. Nuclear EBER signals were also detected in the previously operated gastric stump adenocarcinoma, which also exhibited focal lymphocytic infiltration but otherwise displayed a histology different from lymphoepithelial carcinoma and did not show local recurrence. Even though an unusually late metastasis of the gastric carcinoma cannot be ruled out, we favor the hypothesis that this patient developed an EBV-related pancreatic lymphoepithelial carcinoma as a second primary tumor, based on the considerable delay of this tumor manifestation, the unusual site, the pathologic presentation, the exclusively peripancreatic nodal spread, and the different histology of the lesion.

Pancreatic polypeptide in pancreatitis.

Pancreatitis is a disease with increasing incidence which can be divided into an acute and a chronic form. In both acute and chronic pancreatitis, changes in plasma concentration of pancreatic polypeptide (PP) and its regulation have been reported. In daily clinical work a serologic test for the precise diagnosis and staging of acute and chronic pancreatitis is still desirable. Therefore, many studies have investigated plasma concentrations of PP in acute and chronic pancreatitis as a diagnostic marker and as a therapeutic option to treat pancreatogenic diabetes mellitus. Although the study results are presently inconclusive and potentially contradictory, the findings are nevertheless encouraging, and indicate that PP might have a role in diagnosis, grading and estimation of the prognosis of pancreatitis. Further data and prospective controlled studies are needed to judge whether PP is of clinical value for diagnosing, staging and predicting long-term outcome in acute and chronic pancreatitis.