Prompt gamma imaging of proton pencil beams at clinical dose rate.

In this work, we present experimental results of a prompt gamma camera for real-time proton beam range verification. The detection system features a pixelated Cerium doped lutetium based scintillation crystal, coupled to Silicon PhotoMultiplier arrays, read out by dedicated electronics. The prompt gamma camera uses a knife-edge slit collimator to produce a 1D projection of the beam path in the target on the scintillation detector. We designed the detector to provide high counting statistics and high photo-detection efficiency for prompt gamma rays of several MeV. The slit design favours the counting statistics and could be advantageous in terms of simplicity, reduced cost and limited footprint. We present the description of the realized gamma camera, as well as the results of the characterization of the camera itself in terms of imaging performance. We also present the results of experiments in which a polymethyl methacrylate phantom was irradiated with proton pencil beams in a proton therapy center. A tungsten slit collimator was used and prompt gamma rays were acquired in the 3-6 MeV energy range. The acquisitions were performed with the beam operated at 100 MeV, 160 MeV and 230 MeV, with beam currents at the nozzle exit of several nA. Measured prompt gamma profiles are consistent with the simulations and we reached a precision (2σ) in shift retrieval of 4 mm with 0.5 × 10(8), 1.4 × 10(8) and 3.4 × 10(8) protons at 100, 160 and 230 MeV, respectively. We conclude that the acquisition of prompt gamma profiles for in vivo range verification of proton beam with the developed gamma camera and a slit collimator is feasible in clinical conditions. The compact design of the camera allows its integration in a proton therapy treatment room and further studies will be undertaken to validate the use of this detection system during treatment of real patients.

Strong-interaction shifts and widths of kaonic helium isotopes.

The kaonic 3He and 4He [Formula: see text] transitions in gaseous targets were observed by the SIDDHARTA experiment. The X-ray energies of these transitions were measured with large-area silicon-drift detectors using the timing information of the [Formula: see text] pairs produced by the DAΦNE [Formula: see text] collider. The strong-interaction shifts and widths both of the kaonic 3He and 4He 2p states were determined, which are much smaller than the results obtained by the previous experiments. The "kaonic helium puzzle" (a discrepancy between theory and experiment) was now resolved.

Preliminary study of kaonic deuterium X-rays by the SIDDHARTA experiment at DAΦNE.

The study of the [Formula: see text] system at very low energies plays a key role for the understanding of the strong interaction between hadrons in the strangeness sector. At the DAΦNE electron-positron collider of Laboratori Nazionali di Frascati we studied kaonic atoms with [Formula: see text] and [Formula: see text], taking advantage of the low-energy charged kaons from Φ-mesons decaying nearly at rest. The SIDDHARTA experiment used X-ray spectroscopy of the kaonic atoms to determine the transition yields and the strong interaction induced shift and width of the lowest experimentally accessible level (1s for H and D and 2p for He). Shift and width are connected to the real and imaginary part of the scattering length. To disentangle the isospin dependent scattering lengths of the antikaon-nucleon interaction, measurements of [Formula: see text] and of [Formula: see text] are needed. We report here on an exploratory deuterium measurement, from which a limit for the yield of the K-series transitions was derived: [Formula: see text] and [Formula: see text] (CL 90%). Also, the upcoming SIDDHARTA-2 kaonic deuterium experiment is introduced.

Measurements of the strong-interaction widths of the kaonic (3)He and (4)He 2p levels.

The kaonic (3)He and (4)He X-rays emitted in the [Formula: see text] transitions were measured in the SIDDHARTA experiment. The widths of the kaonic (3)He and (4)He 2p states were determined to be [Formula: see text], and [Formula: see text], respectively. Both results are consistent with the theoretical predictions. The width of kaonic (4)He is much smaller than the value of [Formula: see text] determined by the experiments performed in the 70's and 80's, while the width of kaonic (3)He was determined for the first time.

First measurement of kaonic helium-3 X-rays.

The first observation of the kaonic (3)He 3d→2p transition was made, using slow K- mesons stopped in a gaseous (3)He target. The kaonic atom X-rays were detected with large-area silicon drift detectors using the timing information of the K+K- pairs of ϕ-meson decays produced by the DAΦNE e+e- collider. The strong interaction shift of the kaonic (3)He 2p state was determined to be -2±2(stat)±4(syst) eV.

Combined chemoradiation therapy for anal cancer. A report of 56 cases.

Fifty-six consecutive patients with primary epidermoid cancer of the anus were treated with combined chemoradiotherapy (CRT). No patient had been previously treated. There were 44 women and 12 men, with an age range of 25 to 88 years (median, 62 years). Cancer was located at the anal verge in five and at the anal canal in 51 patients. The tumor extended from the canal to adjacent sites in 37 cases. All patients had their tumors histologically assessed: 54 were squamous cell and two were basaloid carcinoma. Twelve patients had T1, 27 had T2, and 17 had T3 primaries, and eight had inguinal metastatic nodes. The protocol treatment consisted of three cycles of 5-fluorouracil (FU) (750 mg/m2/day x 5 days continuous infusion) and mitomycin C (MMC) (15 mg/m2 intravenous (I.V.) bolus on day 1 of each course) given every 6 weeks. Radiotherapy (RT) was started simultaneously: 36 Gy was given in 4 weeks to the anal region with perineum and the lower and middle pelvis, including inguinal and external iliac nodes. After 2 weeks of rest, a boost of 18 Gy was delivered to the anoperineal region in 10 fractions. Because of toxicity, the planned treatment was performed in 50% of patients: 28 patients received less than three cycles of chemotherapy, and seven patients received less than 49 Gy radiation therapy. Toxicities were mild to moderate, and no patients needed hospitalization. A complete response (CR) was observed in 49 patients (87%), eight of whom had metastatic nodes. A partial response (PR) was assessed in five patients (9%) and stable and progressive disease in 2 patients (4%). Objective response (OR) had no evident relationship with extent of primary, presence of metastatic nodes, number of cycles of chemotherapy, and doses of radiotherapy. Of 49 patients who achieved CR, 12 (24%) developed a local recurrence after a median interval of 8 months (range, 2 to 45 months); 11 of them were submitted to surgical rescue and 8 are alive without evidence of disease. Local recurrence was correlated with the main characteristics of patient and tumor and with treatment, but no clear correlation was observed. Actuarial survival rate at 5 years was 81%. Results of present study are compared with those reported by others, and crucial questions concerning combined chemoradiationtherapy are discussed. The authors conclude that chemoradiotherapy is a highly effective treatment of anal cancer, which should be employed as primary approach regardless of different characteristics of patient and tumor.

Double versus single stapling technique in rectal anastomosis.

A retrospective analysis to compare the single vs double stapled technique for rectal anastomosis was carried out on patients that underwent radical surgical resection between January 1986 and January 1989 at the Istituto Nazionale Tumori of Milan. In 143 patients anastomotic integrity had been checked both intraoperatively with air insufflation and postoperatively by water soluble contrast enema. A single stapled anastomosis (SST) was performed using the EEA instrument in 94 patients, and in 49 patients a double stapled (DST) using the EEA and TA instruments was performed. The level of the anastomosis was less than or equal to 10 cm from the anal margin in 94 patients (54 SST, 40 DST). In 52 patients it was greater than 10 cm (40 SST, 12 DST) (SST vs DST ns). The presence of anastomotic dehiscence occurred in 29 (20%) patients (17 SST, 12 DST). This was not related either to the anastomotic site or to the suture technique used. The dehiscence was located on the posterior wall in 79% of cases and in 58% the size was less than 1 cm. In 78% clinical symptoms were evident. There was no difference between SST and DST patients. Further surgery (colostomy) was necessary in six patients (2 SST, 4 DST). Two patients died through complications (1 SST, 1 DST); making an overall mortality rate of 1.0% and 2.0% in each group. There was no difference in infection rate and length of postoperative stay in the two groups. Our data demonstrate that both methods give similar results.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver hemodynamic flow balance by image-directed Doppler ultrasound evaluation in normal subjects.

Image-directed Doppler ultrasonography of main hepatic vessels (hepatic artery, portal vein, hepatic veins, and inferior vena cava (IVC)] was performed in 22 healthy volunteers, 20 years to 65 years of age. For each vessel an estimate was made of the diameter, velocity time interval (VTI), volume blood flow in relation to heart rate (stroke volume in L/min/beat), and body size (blood flow index in L/min/m2 body surface area). Moreover, a hemodynamic hepatic balance to define a range of values in normal population was described. The summation of flow of hepatic veins and IVC flow, just over renal veins, (= IVC subhepatic flow) was significantly correlated with the IVC flow rate before entrance into the atrium (R2 = 0.90). Hepatic artery flux plus portal vein flux plus subhepatic vein flux was also related to IVC flux before right atrium entrance (R2 = 0.92). This study confirms the utility and efficiency of Doppler ultrasonography in understanding liver flow hemodynamic balance.

Combined chemotherapy--radiotherapy of anal cancer.

Forty-five patients were treated from 1984 to 1988. Thirty-eight, with a minimum follow-up of 6 months, are considered evaluable: median age, 62 years (25-88); males 6, females 32; T1 = 7, T2 = 21, T3 = 10; inguinal positive nodes, 5 patients. Chemotherapy (CT) (Mitomycin C, 15 mg/sqm, bolus day 1; 5-FU, 750 mg/sqm, 24 hr infusion, days 1 to 5) and radiotherapy (RT) started the same day. A dose of 36 Gy was given to the tumor and to the pelvis including inguinal nodes, in 20 fractions. After 2 weeks a boost of RT (18 Gy) to the ano-perineal area and a second cycle of CT completed the treatment. CR (biopsy) was achieved in 32/38 patients (84.2%). Among the six patients on PR, four received a Miles operation (2 NED), and two a wide local resection (both NED). Five out of 32 CRs relapsed: 2/5 were rescued with a Miles resection, 3 died from progression. In conclusion, 32/38 patients (84.2%) are NED after a median follow-up of 22 months and 28 of them retained their anal sphincter. A longer follow-up is needed to define optimal treatment modality, but it is clear that surgery must play a minor role in the treatment of anal cancer.

Cell kinetics of hepatic metastases as a prognostic marker in patients with advanced colorectal carcinoma.

Cell kinetics was determined, as 3H-thymidine labeling index (LI), in hepatic lesions from 36 patients with primary colorectal carcinoma: LI values ranged from 0.9% to 23.5% and were normally distributed. Cell kinetics was not related to sex or age of the patient, or to liver function. For clinical studies the median LI value of 10% was used to separate slowly and rapidly proliferating lesions. Univariate analysis showed that patients radically resected and with a low LI tumor have a longer disease-free interval and a better probability of 12-month survival than those non-radically resected and with a high LI tumor. When treatment and cell kinetics were taken into consideration, the probability of 12-month survival was 100% for patients with slowly proliferating and radically resected hepatic metastases. Patients with rapidly proliferating tumors, regardless of type of treatment, had the worst prognosis.

The role of CEA and liver function tests in the detection of hepatic metastases from colo-rectal cancer.

Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyltranspeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallible imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.

Abnormal pattern of mucin secretion at the resection margin of colorectal carcinomas.

In a retrospective study, we investigated 56 consecutive patients who had undergone radical intestinal resection for colorectal adenocarcinoma and who had developed local or distant recurrences of the disease. We found that the presence of a predominant sialomucin pattern at the margins of resection of the surgical specimen was correlated with a high percentage of local, endoluminal recurrence in the anastomotic mucosa. In contrast, no correlation could be found when the recurrences occurred in the outer tissues around the anastomosis or at some distance from it.

A clinico-pathologic study of clear-cell hepatocellular carcinoma.

We reviewed the pathologic and clinical features of 7 cases of clear-cell hepatocellular carcinomas. Tumor cells had a typical clear, empty cytoplasm due to prominent accumulation of glycogen and lipid droplets, as demonstrated by ultrastructural study in one of our cases. Follow-up of the 7 patients did not confirm the better prognosis of this tumor reported by other investigators. The clinical course of our cases was more unfavorable than that of the other 130 cases of usual hepatocellular carcinomas treated at this Institute.