Renzo Mazzarotto

Identification of the Nonrecurrent Laryngeal Nerve during Thyroid Surgery: 20-Year Experience

The nonrecurrent laryngeal nerve, which is rarely observed during thyroidectomy, is at high risk for damage. During a 20-year period 6000 thyroidectomies were performed at our institution, and during these operations inferior laryngeal nerves were routinely identified in all the patients with a standard procedure based on the usual anatomic landmarks. A nonrecurrent laryngeal nerve was observed on the right side in 31 cases (0.51%), with no anatomic anomalies found on the left side. The nerve anomaly was diagnosed preoperatively in five patients. A vocal cord deficit, caused by a nerve lesion, was observed in four cases (12.9%). Our results suggest that the best way to avoid morbidity is routine identification of the nerve. This can be done by carefully identifying all the thyroid structures and being suspicious of the presence of the abnormality when the inferior laryngeal nerve is not found in a classic position.

Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake

Objective  Papillary thyroid cancers (PTCs) with no iodine uptake have an aggressive behaviour and a poor prognosis. The aim of our study was to characterize, at molecular level, a subset of PTC with no 131 iodine (131I) uptake.

Early Biochemical Relapse After Radical Prostatectomy: Which Prostate Cancer Patients May Benefit from a Restaging 11C-Choline PET/CT Scan Before Salvage Radiation Therapy?

The aim of the study was to assess which factors may influence 11C-choline PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients listed for salvage radiation therapy (S-RT) in an early phase of biochemical relapse, to select which patients could obtain the most benefit by performing restaging 11C-choline PET/CT before S-RT. Methods: The study comprised 605 patients, treated with radical prostatectomy (RP) with curative intent for PCa who showed rising PSA levels after primary therapy and listed for S-RT. Prostate-specific antigen (PSA) values were >0.2 ng/mL and <2 ng/mL (mean, 1.05 ng/mL; median, 1.07 ng/mL; range, 0.2–2 ng/m; SD, ±0.59). All patients were classified as N0 after RP. Seventeen of 605 patients received adjuvant RT together with RP, whereas 148 of 605 patients received androgen-deprivation therapy (ADT) at the time of PET/CT. PSA, PSA kinetics, Gleason score, age, time to biochemical relapse, ADT, and initial tumor stage were statistically analyzed to assess which factor could influence PET/CT positivity and the detection of local versus distant relapse. Results: 11C-choline PET/CT was positive in 28.4% of patients (172/605). Eighty-three of 605 patients were positive in the pelvis (group A), distant metastasis (group B) were detected in 72 of 605 patients, and local and distant sites of relapse were detected in 17 of 605 patients (group C). At multivariate analysis, PSA, PSA doubling time (PSAdt), and ongoing ADT were significant predictors for positive scan results, whereas PSA and PSAdt were significantly related to distant relapse detection (P < 0.05). At the receiver-operating-characteristic analysis, a PSA value of 1.05 ng/mL and PSAdt of 5.95 mo were determined to be the optimal cutoff values in the prediction of a positive 11C-choline PET/CT scan, with an area under the curve (AUC) of 0.625 for PSA and 0.677 for PSAdt. Conclusion: 11C-choline PET/CT may be suggested before S-RT during the early phase of biochemical relapse, to select patients who may benefit from this aggressive treatment. Particularly, patients showing fast PSA kinetics or PSA increasing levels despite ongoing ADT should be studied with 11C-choline PET/CT before S-RT, considering the higher probability to detect positive findings outside the pelvis.

The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery

Abstract.The aim of this study was to investigate the possible role of technetium-99m methoxyisobutylisonitrile (MIBI) scan in planning post-surgical therapy and follow-up in patients with differentiated thyroid carcinoma (DTC). Four groups of DTC patients were considered: Group 1 comprised 122 patients with high serum thyroglobulin (s-Tg) levels and negative high-dose iodine-131 scan during follow-up who had previously undergone total thyroidectomy and 131I treatment. Group 2 consisted of 27 patients who had previously undergone total thyroidectomy and 131I treatment but were now considered disease-free; this group was considered as controls. Group 3 comprised 49 patients studied after total thyroidectomy but prior to 131I scan. Finally, group 4 consisted of 21 patients who had previously undergone partial thyroidectomy alone. MIBI scan, neck ultrasonography (US), and s-Tg measurements during suppressive hormonal therapy (SHT) were obtained in all patients. Neck and chest computed tomography (CT) or magnetic resonance imaging (MRI) was also performed in group 1 patients. In group 1, MIBI scan and US were very sensitive in detecting cervical lymph node metastases (93.54% and 89.24%, respectively). Furthermore, MIBI scan and US played a complementary role in several patients, yielding a global sensitivity of 97.84%. In contrast, CT/MRI sensitivity for cervical lymph node metastases was very low (43.01%). MIBI scan also showed a higher sensitivity than CT/MRI in detecting mediastinal lymph node metastases (100% vs 57.89%). Regarding distant metastases, MIBI scan provided results similar to those of conventional imaging (CT, MRI, 99mTc-methylene diphosphonate bone scan). In group 2, no false-positive cases were observed with MIBI scan (100% specificity). In group 3, MIBI scan correctly identified all the 131I-positive metastatic foci, except in two patients with micronodular pulmonary metastases that were visualised with 131I scan. In contrast, both MIBI scan and US showed low sensitivity (46.15% and 61.53%, respectively) compared with 131I scan in detecting thyroid remnants. s-Tg was increased in all patients with distant metastases but only in 56% of those with lymph node metastases. Furthermore, s-Tg was increased in 21.42% of patients with thyroid remnants alone (false-positive results). In group 4, MIBI scan was the only examination capable of detecting at an early stage a mediastinal lymph node metastasis in one patient. We conclude that the integrated MIBI scan/neck US protocol: (a) can be proposed as a first-line diagnostic procedure in the follow-up of DTC patients with high s-Tg levels and negative high-dose 131I scan, and (b) may be helpful in the follow-up of DTC patients who undergo partial thyroidectomy alone. Moreover, the combined MIBI scan/neck US/s-Tg protocol appears to be highly sensitive in identifying patients with metastatic disease after total thyroidectomy and prior to 131I scan; consequently, it may play a prognostic role in distinguishing high-risk from low-risk DTC patients. However, due to the low sensitivity of MIBI scan and neck US in detecting thyroid remnants, this diagnostic approach cannot be used as a predictor of 131I scan results. Lastly, because of the high sensitivity of MIBI scan and neck US in revealing both functioning and non-functioning metastases, this integrated protocol might be helpful in the follow-up of high-risk DTC patients, particularly for the early detection of lymph node metastases in patients with undetectable s-Tg during SHT.

A multimodality therapeutic approach in anaplastic thyroid carcinoma: Study on 39 patients

The aim of this study was to investigate the role of multimodality treatment in patients with anaplastic thyroid carcinoma. From 1992 to 1999, 39 consecutive patients with a histologically or cytologically proven anaplastic thyroid carcinoma were referred to the Thyroid Center of Padua General Hospital. There were 28 females and 11 males with a median age of 69 years (range 39–88 years). About one-third of patients had a history of preceeding nodular goiter. Two patients had areas of differentiated thyroid carcinoma at histological examination. Local disease was present in 26 patients while distant metastases, mainly to the lung, were present in 22 at diagnosis or quickly developed during the observation period in all the others except one. Thirty-two patients were previously untreated: 9 of them were in good general condition, 1 had limited lung metastases, and the tumor mass was considered resectable by the surgeon. These 9 patients were treated with cisplatin once a week and radiotherapy (RT) 36Gy in 18 fractions over three weeks, followed by total thyroidectomy (TT) and by further chemotherapy (CHT) with adriamycin and bleomycin in 4 patients. Seven patients, 3 with lung metastases at diagnosis, had undergone TT, followed by RT in 5, in another hospital and were subsequently referred to our center due to the presence of distant metastases. Therefore, a total of 16 patients (Group 1) was treated with TT, RT and CHT in various order. Nine patients with distant metastases at diagnosis (Group 2) received CHT; one of them had a disappearance of lung metastases and was then treated by TT and further CHT. Group 3 consisted of 14 elderly patients in poor general conditions; 4 of these received local RT, while the remaining did not receive any treatment. Four complete responses were seen in patients from Group 1, and 1 from Group 2. One patient without distant metastases at diagnosis is alive and free of disease 6 months after TT and adjuvant CHT, and 12 months after diagnosis. Three had long-term survival (14, 24, 27 months) with a disease-free interval of 6-8-10 months. The patient from Group 2 who was treated in a second time by TT is alive without disease after 60 months. Median survival rate was 11 months for Group 1, 5.7 months for Group 2 and 4 months for Group 3. In some patients multimodality treatment (TT, RT and CHT) is associated with increased survival. Nine out of 16 patients, who underwent surgery and complementary treatment, had no local progression. In all but one distant metastases developed, mainly in the lung, during or after post-surgical CHT. The best results were obtained in younger patients with less advanced disease. Early diagnosis is mandatory. Only a few patients responded to CHT, confirming that anaplastic thyroid carcinoma is often resistant to anticancer drugs. Our experience with combination modalities suggests that aggressive and appropriate combinations of RT, TT and CHT may provide some benefit in patients with anaplastic thyroid carcinoma. Preoperative CHT and RT may enhance surgical resectability of the primary tumor.

The role of external beam radiotherapy in the management of differentiated thyroid cancer

Well differentiated thyroid cancers (DTC), usually having an indolent course, are generally treated by surgery, i.e., total or near total thyroidectomy, followed by radioiodine and TSH suppressive therapy with thyroid hormone. The beneficial effect of external beam radiotherapy (EBRT) in the treatment of selected metastatic sites (i.e., brain and bone) or for palliation in cases of locally advanced inoperable disease is widely accepted. In contrast, its efficacy in improving postoperative locoregional disease control is still controversial. A better definition of subgroups of patients at high risk of local failure is mandatory. At present, patients older than 40-45 years affected by papillary cancers with macro- or microscopic postoperative residual disease and with extensive extrathyroid invasion appear to benefit from EBRT performed in addition to surgery and radioiodine. The role of EBRT in patients with radioiodine non-responsive progressive disease will also be discussed.

Follicular Thyroid Carcinoma with Metastases to the Pituitary Causing Pituitary Insufficiency

BACKGROUND Pituitary metastases are found in about 1% of all pituitary resections. They often derive from breast, lung, and gastroenteric tract adenocarcinomas, very rarely from thyroid carcinoma. Presenting symptoms of thyroid carcinoma metastatic to the pituitary gland are usually chiasmatic with central neurological impairment due to space-occupying expansion in the parasellar region. Hypopituitarism is more often associated with papillary and medullary rather than follicular thyroid carcinoma (FTC). Here we describe a patient with pituitary metastasis from FTC who had hypopituitarism with thyrotropin (TSH) deficiency. SUMMARY A 61-year-old woman, who presented with visual deficits and pain to the right orbit, was found on magnetic resonance imaging to have a large mass involving the pituitary gland. She was found to have pituitary insufficiency based on corticotropin-releasing hormone and TSH-releasing hormone testing. Transnasopharyngeal biopsy of the mass revealed metastases from FTC. After total thyroidectomy, which confirmed widely invasive FTC, the patient underwent external beam radiation therapy of the metastases for progressive neurological symptoms and an increase in orbit pain. Since endogenous TSH production was insufficient, we used recombinant human TSH (rhTSH) as preparation for a series of radioiodine treatments. rhTSH administration, followed by 7.4 GBq of (131)I, was repeated seven times over a 10-year period. This was associated with a marked decrease in serum thyroglobulin levels accompanied by substantial clinical improvement, but after 7 years disease progression occurred. CONCLUSIONS Seven patients with pituitary metastases from FTC have been reported. In all cases, some neurological signs and symptoms related to mass effect were reported, but no pituitary insufficiency was described. This may be the first case of FTC with metastases to the pituitary causing hypopituitarism. It seems likely that management of such cases could be limited to biopsy to confirm thyroid carcinoma, rather than more extensive surgery, and that this could be followed by multiple treatments with rhTSH followed by (131)I.

Stanford V Regimen plus Consolidative Radiotherapy Is an Effective Therapeutic Program for Bulky or Advanced-Stage Hodgkin’s Disease

Since September 1996, 48 untreated patients with bulky or advanced-stage Hodgkin’s disease received the 12-week Stanford V chemotherapy regimen followed by consolidation radiotherapy at a dose of 36 Gy to bulky mediastinal disease and 30.6 Gy to the initial sites of disease ≧3 cm in transverse diameter. After the combined therapy, 46 of 48 (96%) achieved complete remissions. With a median follow-up of 48 months, the 5-year overall survival was 95% and freedom from progression 86%.There were no treatment-related deaths. All but one premenopausal female patient (who received pelvic and inguinal irradiation) recovered normal menses. Until now no case of secondary leukemia or myelodysplasia was observed. Our results confirm that the Stanford V regimen with consolidation radiotherapy is safe and effective in patients with bulky or advanced-stage Hodgkin’s disease, achieving very high remission and overall 5-year survival rates. Longer follow-up is necessary to evaluate the extent of all complications.

Pretherapeutic dosimetry in patients affected by metastatic thyroid cancer using 124I PET/CT sequential scans for 131I treatment planning.

Purpose This study evaluates the use of sequential 124I PET/CT for predicting absorbed doses to metastatic lesions in patients with differentiated thyroid cancer undergoing 131I therapy. Methods From July 2011 until July 2013, 30 patients with metastatic differentiated thyroid cancer were enrolled. Each participant underwent PET/CT at 4, 24, 48, and 72 hours with 74 MBq of 124I. Blood samples and whole-body exposure measurements were obtained to calculate blood and red marrow doses. Activity concentrations and lesion volumes obtained from PET/CT were used to evaluate tumor doses with medical internal radiation dose formalism and spheres modeling. Mean administered 131I therapeutic dose was 5994 MBq (range, 1953–11,455 MBq). Results 124I PET/CT demonstrated all lesions detected by posttherapy 131I whole-body scans. Mean dose rates for blood, red marrow, and lesions were as follows: 0.07 ± 0.02 mGy/MBq, 0.05 ± 0.02 mGy/MBq, and 46.5 ± 117 mGy/MBq, respectively. Despite the high level of thyroid-stimulating hormone and CT detectable lesions, 15 of 30 patients did not show any abnormal 124I uptake. Conclusions The quantitative value of 124I PET/CT allows simple and accurate evaluation of lesion dosimetry following medical internal radiation dose formalism. Negative 124I PET/CT predicts absence of iodine avidity, potentially allowing avoidance of therapeutically ineffective 131I administration.

Fatal HBV-related liver failure during lamivudine therapy in a patient with non-Hodgkin's lymphoma.

.Wereportthecaseofa59-year-oldmanadmittedtoourdepartmenton2August2006withfever,fatigueandjaundice.InDecember2005thepatientwasfirstdiagno -sedwithstageIIBbulkydiffuselargeBcelllymphoma,CD20+withanaaIPIof1.Atthetimeofdiagnosis,hehadsplenomegalyandhepatomegaly;laparoscopicspleenandliverbiopsyresultedinahistologicaldiagnosisofsplenicinfiltrationofnon-Hodgkin’slymphoma(NHL)inacontextofchronichepatitis(withmildactivity,gradeG2),suggestiveofviralinfection.Stagingwascompletedwiththoracicandabdomi-nalCTthatevidencedaspleniclesionof13x14x16cmalongwithliverinvolvementwithsmallnodulesinthefourthsegmentandseveralmesenteric,hepatichilumandparaaorticinvolvedlymphnodes.SerologyrevealedthepatienttobeachronicHBVcarrier(HbsAgpositive).ThepatientwasHbeAgnegativeandanti-HBcpositivewithahighHBVDNAtiterof5,017,954IU/mL.CoexistinghepatitisCorhepatitisDviruswasexcludedbeforechemotherapy.Thelevelofaspartateaminotransferase(AST)was60U/L(normal10-45U/L),alanineaminotransferase(ALT)was50U/L(normal10-50U/L),whiletheremainingroutinebiochemicalexaminationsincludingbiliru -bin,albumin,plateletandWBCcountswerewithinnormalranges.ViralsequencingoftheHBVstraindidnotrevealthepresenceofmutationsassociatedwithresistanceto lamivudine. Lamivudine treatment 100 mg/day was started together with achemotherapyregimenconsistingofcyclophosphamide,doxorubicin,vincristine,prednisoneandrituximab(CHOP-R)givenfor8cycles.PETCTafterchemotherapyshowedremissionoftheneoplasticdiseasebutasplenicresidual,sothepatientwasgivenadditionalradiotherapytothesplenicarea(lastcourseon7July2006).Athisadmissiontoourdepartment,thepatient’shematologicalpanelwasnormalbutliverbiochemistryrevealedserumASTtobe3,878U/L,ALT4,364U/L,totalbilirubin137.1 mol/L,alkalinephosphatase138U/L,andalbumin35.5g/L.Othernonviralcausesofacutehepatitiswereexcluded.HBVDNAwas95,528IU/mL.Thepatientwasstillonlamivudinetreatment.ViralsequencingoftheHBVstrainrevealedthepresenceofacombinedL180MandM204Imutation,whichisassociatedwithre -si tan ce o lmv ud