Conservative Management of Gestational Hypercalcemia Due to Primary Hyperparathyroidism with Lack of Complications.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is rare in pregnancy. PHPT and hypercalcemia are associated with negative maternofetal outcomes. Therefore, an early diagnosis and adequate treatment are essential. CASE PRESENTATION: We described the case of a pregnant woman complaining of nausea, vomiting and weight loss. Diagnosis of gestational PHPT (GPHPT) was made based on elevated serum calcium and parathyroid hormone levels (3.4 mmol/L and 41.6 pmol/L). Neck ultrasound documented a nodule suggestive of enlarged parathyroid, whereas the abdomen ultrasound revealed renal microlithiasis. Conservative treatment was started with oral hydration and a low-calcium diet. Clinical and biochemical monitoring was weekly and multidisciplinary. Despite our suggestion, the patient refused parathyroidectomy in the second trimester. Additional intravenous fluid rehydration from the 15th to the 25th week of gestation ameliorated the symptoms rapidly, and reduced calcium levels progressively from the 23rd week. At week 40, the woman gave birth to a healthy girl. At month 8 postpartum, calcemia and PTH were still elevated, and accompanied by osteoporosis and nephrocalcinosis. Surgery was accepted, and a parathyroid adenoma was removed. CONCLUSION: In the absence of guidelines for GPHPT management, its treatment should be individualized. In our case, despite high calcium levels, conservative treatment with strict monitoring led to a positive outcome of pregnancy.

Gastric GIST and prognostic models. Which is the best to predict survival after surgery?

BACKGROUND: Gastrointestinal Stromal Tumours (GIST) are the most frequent mesenchymal tumour of the alimentary tract. Their prognosis is largely variable as are their size, mitotic rate and site, the stomach being mostly affected. Several risk classifications have been proposed: two developed by the NIH, one proposed by the AFIP and one presented by the AJCC in 2010. The objective of this study is to compare the accuracy of the three prognostic models (AJCC, NIH and AFIP) with regard to survival after surgery, also based on the different surgical approaches. METHODS: A retrospective review of all cases of gastric GIST's performed at the General and Breast Surgery Unit of the Department of General Surgery the University of Catania and at the "Gemelli" General Surgery Unit of Taormina Hospital, Italy between 2001 and 2016 was conducted. The cases were reviewed and re- classified according to the three prognostic models. Analysis of data, including Kaplan-Meyer survival curves, was performed using SPSS version 21.0. RESULTS: Among a total of 1,625 gastrectomies and gastric resections were found 25 primary GIST's patients, 13 females, and 12 males, with a mean age 63 years. Cancer size varied between 1.5 cm and 37 cm and number of mitosis between 2 and 50/50 HPF. A total of 12 (48%) underwent sub-total gastrectomy (STG), seven (28%) underwent a wedge resection (WR), and 6 (12%) total Gastrectomy (TG). Twenty-three patients (92%) are currently alive at a follow up of 18 months to 17 years, and only two patients died during the long term follow-up. Both patients were AFIP high risk (6b), AJCC stage IV, already metastatic at the time of surgery. Both patients underwent total extended gastrectomy and therapy with imatinib, but died 8 and 9 years after surgery. Recurrences have been observed in 2 patients (8%), with high risk according to AFIP (6a) with AJCC stage IIIa disease. CONCLUSIONS: In localized GISTs R0 surgical resection is the standard therapy as it leads to excellent outcomes. Our findings suggest that all the three classifications considered are adequate to achieve a correct prognostic evaluation. KEY WORDS: GIST, Prognostic factors, Prognostic models.

Turbulence-Driven Ion Beams in the Magnetospheric Kelvin-Helmholtz Instability.

The description of the local turbulent energy transfer and the high-resolution ion distributions measured by the Magnetospheric Multiscale mission together provide a formidable tool to explore the cross-scale connection between the fluid-scale energy cascade and plasma processes at subion scales. When the small-scale energy transfer is dominated by Alfvénic, correlated velocity, and magnetic field fluctuations, beams of accelerated particles are more likely observed. Here, for the first time, we report observations suggesting the nonlinear wave-particle interaction as one possible mechanism for the energy dissipation in space plasmas.

Predictivity of clinical, laboratory and imaging findings in diagnostic definition of palpable thyroid nodules. A multicenter prospective study.

PURPOSE: To assess the role of clinical, biochemical, and morphological parameters, as added to cytology, for improving pre-surgical diagnosis of palpable thyroid nodules. METHODS: Patients with a palpable thyroid nodule were eligible if surgical intervention was indicated after a positive or suspicious for malignancy FNAC (TIR 4-5 according to the 2007 Italian SIAPEC-IAP classification), or two inconclusive FNAC at a ≥3 months interval, or a negative FNAC associated with one or more risk factor. Reference standard was histological malignancy diagnosis. Likelihood ratios of malignancy, sensitivity, specificity, negative (NPV), and positive predictive value (PPV) were described. Multiple correspondence analysis (MCA) and logistic regression were applied. RESULTS: Cancer was found in 433/902 (48%) patients. Considering TIR4-5 only as positive cytology, specificity, and PPV were high (94 and 91%) but sensitivity and NPV were low (61 and 72%); conversely, including TIR3 among positive, sensitivity and NPV were higher (88 and 82%) while specificity and PPV decreased (52 and 63%). Ultrasonographic size ≥3 cm was independently associated with benignity among TIR2 cases (OR of malignancy 0.37, 95% CI 0.18-0.78). In TIR3 cases the hard consistency of small nodules was associated with malignity (OR: 3.51, 95% CI 1.84-6.70, p < 0.001), while size alone, irrespective of consistency, was not diagnostically informative. No other significant association was found in TIR2 and TIR3. CONCLUSIONS: The combination of cytology with clinical and ultrasonographic parameters may improve diagnostic definition of palpable thyroid nodules. However, the need for innovative diagnostic tools is still high.

Molecular-targeted therapy for elderly patients with advanced non-small cell lung cancer.

Lung cancer is the most common cause of cancer-related mortality in men and women. Non-small cell lung cancer (NSCLC) represents close to 90% of all lung cancers. When diagnosed, >50% of patients are >65 years old. Through an improved understanding of the molecular mechanisms involved in lung oncogenesis, molecular-targeted approaches have become an essential element for the treatment of patients with NSCLC. As the toxicity profiles of the techniques are definitely more favorable compared with chemotherapy, they are particularly attractive for use in elderly patients, who are potentially more susceptible to the toxicity of systemic oncological therapies. However, studies on the activity of molecular-targeted agents in this aged patient setting are much more limited compared with those in their younger counterparts. In the present review, the literature on molecular-targeted therapy for elderly patients with advanced NSCLC is discussed. It is concluded that bevacizumab should be reserved only for highly select elderly patients with advanced NSCLC when the clinician deems it useful in the face of acceptable toxicities. In elderly patients with advanced epidermal growth factor receptor mutation-positive NSCLC, erlotinib and gefitinib appear to repeat the same favorable performance as that documented on a larger scale in the overall population of patients with activating mutations. A good toxicity profile is also confirmed for active molecules on different pathways, such as crizotinib.

Managing the incidentally detected gallbladder cancer: algorithms and controversies.

INTRODUCTION: Gallbladder cancer (GBC) is the fifth most common neoplasm of the gastrointestinal tract and the most common cancer of the biliary tract. GBC is suspected preoperatively in only 30-40% of patients. The other 60-70% are discovered incidentally (IGBC) by the pathologist on a gallbladder specimen following cholecystectomy for benign diseases such as polyps, gallstones, and cholecystitis. MATERIALS AND METHODS: Between 1995 and 2011, 30 cases of GBC, who underwent resection with curative intent in our institutions, were retrospectively reviewed. They were analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. Overall survival, disease-free survival (DFS) and the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention were analyzed. The authors also present a systematic review to evaluate the role of extended surgery in the treatment of the incidental GBC. RESULTS: GBC was diagnosed in 30 patients, 16 women and 14 men. The M/F ratio was 1:1.14 and the mean age was 69.4 years (range 45-83 years). A preoperative diagnosis was possible only in 14 cases; fourteen of the incidental cases were diagnosed postoperatively after the pathological examination; two were suspected intraoperatively at the opening of the surgical specimen and then confirmed by frozen sections. The ratio between incidental and nonincidental cases was 1, 14/1, with twelve cases discovered after laparoscopic cholecystectomy. Eighty-one per cent of the incidental cases were discovered at an early stage (≤II). The preoperative diagnosis of the 30 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases); gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case); porcelain gallbladder (three cases); gallbladder adenoma (four cases); and chronic cholecystolithiasis (thirteen cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphoadenectomy. One patient refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. Nine of the sixteen patients with incidental diagnosis reached 5-year DFS (56.25%) and eight of them are recurrence free. Surprisingly, one patient reached 38 mo survival despite a port-site recurrence (the only one in our experience) 2 years after the original surgery requiring further resection. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5 years DFS (Tables 2 and 3). CONCLUSION: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.

Is there still a role for mitomycin-based combination chemotherapy in treating patients with nonsmall cell lung cancer? A single institution experience.

BACKGROUND: Mitomycin and irinotecan are widely used in the treatment of colorectal cancer, furthermore both of these drugs are active agents against nonsmall cell lung cancer and their combination has shown synergism in preclinical studies. The aim of the study was to evaluate the efficacy and safety of mitomycin- and irinotecan-based chemotherapy combination in patients with advanced nonsmall cell lung cancer progressing after previous antineoplastic therapies. METHODS: Thirty-one consecutive patients suffering from nonsmall cell lung cancer, who underwent mitomycin- plus irinotecan-based chemotherapy as salvage treatment after failure of at least two previous systemic treatments, were retrospectively identified in our database. Between September 2003 and March 2011, 31 patients with histologically proven stage IIIB or IV nonsmall cell lung cancer, received mitomycin 5 mg/m(2) on day 1 followed by irinotecan 150 mg/m(2) on day 2. Cycles were repeated at 2-week interval. RESULTS: A total of 164 cycles of treatment were given with a median of five per patient (range 1-10). The objective responses included partial response in 6 patients (19.3%), stable disease in 4 (13%), and progressive disease in 21 (67.7%). Median time to disease progression was 4 months, and median survival was 9+ months. Twelve patients (38%) reached 1-year survival. Grade 3-4 toxicities occurred in seven patients (22.5%), mainly myelosuppression (neutropenia, anemia, and thrombocytopenia), mucositis, and diarrhea. No treatment-related death was recorded. CONCLUSION: The mitomycin- and irinotecan-based combination chemotherapy seems to be tolerated and active in this subset of heavily pretreated patients with advanced nonsmall cell lung cancer. However, evaluation or recruitment of a larger number of patients would be needed to provide more adequate data on safety and activity of the described combination.

Incidental gallbladder cancer during laparoscopic cholecystectomy: managing an unexpected finding.

AIM: To evaluate the impact of incidental gallbladder cancer on surgical experience. METHODS: Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery, one university based and one at a public hospital, were retrospectively reviewed. Gallbladder pathology was diagnosed by history, physical examination, and laboratory and imaging studies [ultrasonography and computed tomography (CT)]. Patients with gallbladder cancer (GBC) were further analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. The primary endpoint was disease-free survival (DFS). The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention. RESULTS: Nineteen patients (11 women and eight men) were found to have GBC. The male to female ratio was 1:1.4 and the mean age was 68 years (range: 45-82 years). Preoperative diagnosis was made in 10 cases, and eight were diagnosed postoperatively. One was suspected intraoperatively and confirmed by frozen sections. The ratio between incidental and nonincidental cases was 9/19. The tumor node metastasis stage was: pTis (1), pT1a (2), pT1b (4), pT2 (6), pT3 (4), pT4 (2); five cases with stage Ia (T1 a-b); two with stage Ib (T2 N0); one with stage IIa (T3 N0); six with stage IIb (T1-T3 N1); two with stage III (T4 Nx Nx); and one with stage IV (Tx Nx Mx). Eighty-eight percent of the incidental cases were discovered at an early stage (≤ II). Preoperative diagnosis of the 19 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases), gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case), porcelain gallbladder (one case), gallbladder adenoma (one case), and chronic cholelithiasis (eight cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy. One patient with stage T1b GBC refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone. Six of the nine patients with incidental diagnosis reached 5-year DFS. One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS. CONCLUSION: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.

Initial experience with hepatic intraarterial fotemustine and interferon alpha 2b combination for treatment of liver tumors.

BACKGROUND: Locoregional treatments represent a good option for patients suffering from hepatocellular carcinoma (HCC) not eligible for resection or transplantation. Locoregional approaches include a wide spectrum of therapeutic methods and hepatic intra-arterial drug infusion is also considered. Fotemustine is a chemotherapy drug usually administered intravenously according to standard administration schedules. Interferon alpha 2b (IFNα2b), a biological response modifier conventionally administered by a systemic route, has been employed in the treatment of both virus-related hepatitis and HCC. Nonetheless, both drugs can also be infused into the hepatic artery. PATIENTS AND METHODS: We report on five patients with liver cancer, not suitable for conventional therapies, treated with hepatic intra-arterial administration of fotemustine in combination with IFNα2b. They received fotemustine at a dose of 30 mg/m(2) and IFNα2b at a starting dose of 2,000,000 IU (increasing up to 3,000,000 IU for subsequent administrations) weekly for three consecutive weeks, followed by two weeks of rest. RESULTS: Among the patients suffering from HCC, the first patient showed a partial response, two patients had almost stable disease and one patient was not assessable. A patient with an intrahepatic biliary tract cancer experienced disease progression. CONCLUSION: The therapeutic regimen used showed acceptable tolerability profiles and lack of life-threatening side-effects. Further evaluation with a larger patient cohort will be required to clarify if fotemustine and IFNα2b administered into the hepatic artery could be beneficial in treating patients with HCC.

Hepatic intra-arterial interferon alpha 2b-based immunotherapy combined with 5-fluorouracil (5-FU)-based systemic chemotherapy for patients with hepatocellular carcinoma (HCC) not responsive and/or not eligible for conventional treatments: a pilot study.

BACKGROUND: Surgery (partial hepatic resection or orthotopic liver transplantation) remains the mainstay for treatment of hepatocellular carcinoma (HCC). Unfortunately, most patients have HCC that cannot be removed either as a result of its size, multiple tumors, location, proximity to major vessels or ducts within the liver, and comorbidity, such as a not well-compensated cirrhosis. For patients who cannot be treated surgically, systemic chemotherapy is frequently limited by unacceptable toxicity, poor response and low survival rates, so that locoregional approaches may be considered as alternatives. PATIENTS AND METHODS: Nine patients with HCC, not eligible for conventional treatments, were treated with interferon alpha 2b-based locoregional, hepatic intra-arterial, immunotherapy and concomitant 5-fluorouracil (5-FU)-based systemic chemotherapy. Interferon was administered at a starting dose of 2,000,000 IU, which could be escalated to 9,000,000 IU, adding 1,000,000 IU weekly, depending on toxicity. 5-Fluorouracil was infused continuously over 28 days, administered as an endovenous protracted infusion weekly at a dose of 250 mg/m2/day for 4 weeks followed by a 2-week break. Eight out of nine patients were evaluable for response and toxicity. The median patient age was 68 years (range 51-77 years). All patients were suffering from cirrhosis. RESULTS: A total of 29 cycles of treatment were administered with a median of 3.6 per patient (range 1-11 per patients). A partial response was observed in 3 out of 8 patients; 1 had stable and 4 progressive disease. The main toxicities were: grade 3 hepatic toxicity (1 patient), grade 3 flu-like syndrome (1 patient) and grade 3 abdominal pain (1 patient). Moreover, one patient developed fatal ischemic stroke and another a fatal central venous catheter infection. CONCLUSION: The preliminary data, show that an interferon-based hepatic intra-arterial immunotherapy combined with low doses of 5-fluorouracil (5-FU)-based systemic chemotherapy, can represent a tolerable combination to apply in the palliative treatment of patients with hepatocellular carcinoma.