Robotic resection of choledochocele in an adult with intracorporeal hepaticojejunostomy and Roux-en-Y anastomosis: encouraging progress for robotic surgical treatment of biliary disease.

BACKGROUND: Robotic surgery offers three-dimensional visualization and precision of movement that could be of great value to hepatobiliary surgeons. Previous reports of robotic choledochocele resections in adults have detailed extracorporeal jejunojejunostomies. We describe a total robotic excision of a choledochal cyst with hepaticojejunostomy and intracorporeal Roux-en-Y anastomosis. METHODS: A 58-year-old woman underwent a robotic excision of a small choledochocele with hepaticojejunostomy and intracorporeal Roux-en-Y. RESULT: Port placement was determined via collaborative surgical discussion and previously reported robotic right hepatectomies. Total operative time was 386 min and total robot working time was 330 min. The hepaticojejunostomy was performed using 5-0 PDS suture with parachute-style back wall and running front wall sutures. The jejunojejunostomy was a stapled anastomosis. Estimated blood loss was less than 100 mL. The patient was ambulating and tolerating oral intake on post-operative day 1, and was discharged home on post-operative day 2. CONCLUSIONS: Robotic resection of choledochal cyst with intracorporeal Roux-en-Y anastomosis is feasible, with advantages over open surgery such as superior visualization, precision, and post-operative patient recovery.

Radiobiology of ultrasoft X rays. V. Modification of cell inactivation by dimethyl sulfoxide.

The effects of the radioprotector dimethyl sulfoxide (DMSO) were investigated for carbon-K (0.28 keV) and aluminum-K (1.47 keV) X rays compared with 60Co gamma rays for inactivation of mouse C3H 10T1/2 cells. The protection factor for 2 M DMSO was found to be 2.8 for both of the ultrasoft X-ray energies, which is not significantly different from the protection factor of 2.6 found for gamma rays. The results indicate that the proportion of scavengeable lethal damage from gamma and X rays does not depend on the proportion of the total energy that is deposited by low-energy electrons of relatively high ionization density.

Radiobiology of ultrasoft X rays. III. Normal human fibroblasts and the significance of terminal track structure in cell inactivation.

Ultrasoft characteristic X rays from carbon (0.28 keV) are severely attenuated as they pass through biological material, causing a nonuniform distribution of dose to cell nuclei. Complications of studying ultrasoft X rays can be minimized in this context by using cells with very thin cytoplasm and nuclei (e.g., less than the attenuation length of the X rays), and which exhibit a more nearly exponential dose response to cell killing, such as normal human fibroblasts compared with V79 cells. Using this cell system, we report the relative biological effectiveness (RBE) of A1-K and C-K X rays to be near unity. Previous studies of cell inactivation by characteristic carbon X rays gave RBEs of 3 to 4, supporting the idea that localized energy depositions from secondary electrons and primary track ends represent the principal mode of biological action for other low-LET radiations. In part, the reported high RBEs result from the use of mean dose to describe energy deposited within the cell nuclei by these poorly penetrating radiations. Implicit in the use of mean dose is that cellular damage varies linearly with dose within a critical target(s), an assumption that is of questionable validity for cells that exhibit pronounced curvilinear dose responses. The simplest interpretation of the present findings is that most energy depositions caused by track-end effects are not necessarily more damaging than the sparsely ionizing component.

Radiobiology of ultrasoft X rays. I. Cultured hamster cells (V79).

Ultrasoft X rays (approximately less than keV) provide a useful probe for the study of the physical parameters associated with the induction of biological lesions because the spatial scale of their energy depositions is of nanometer dimensions, comparable to that of critical structures within the cell. We report on cell-killing experiments using cultured hamster cells (V79) exposed to carbon K (0.28 keV), aluminum K (1.5 keV), copper K (8.0 keV), and 250 kVp X rays, under oxic and hypoxic conditions, and as a function of cell-cycle phase. Our principal results are: RBE increases with decreasing X-ray energy; OER decreases with decreasing X-ray energy; and cell-cycle response is similar for all X-ray energies. Our RBE results confirm earlier observations using ultrasoft X rays on mammalian cells. The shapes of fitted curves through the data for each energy are statistically indistinguishable from one another, implying that the enhanced effectiveness is purely dose modifying. The results reported herein generally support the view that single-track effects of radiation are predominantly due to very local energy depositions on the nanometer scale, which are principally responsible for observed radiobiological effects.

Mutational extinction induced by sequential X irradiation and actinomycin D treatments in Chinese hamster ovary cells.

The interactions of sequential X irradiation and actinomycin D (AMD) treatments for mutagenesis to 6-thioguanine resistance were investigated in CHO cells. Cells were exposed to single doses of X rays followed immediately by 1-h treatments with 0.1 or 1 microgram/ml AMD. X Rays alone induced mutagenesis which increased monotonically with dose to at least 8 Gy. AMD-treated control cultures showed slight to moderate cytotoxicity and little induced mutation. X Rays followed by AMD treatment produced bell-shaped mutagenesis dose-response curves with maximal mutation at approximately 5 or 4 Gy for 0.1 or 1.0 microgram/ml AMD, respectively. Induced mutation frequencies then fell to a negligible level at fractional survival levels below 0.10 for either combination treatment. Application of a stochastic Poisson distribution model to these data led to the prediction that two possible components govern induced mutation frequencies. First, X ray +AMD induced mutations may be depleted progressively with dose from the surviving populations by selective lethality, which we term mutational extinction. Second, X ray +AMD treatments were calculated to induce potentially much greater than additive mutagenesis. However, due to the overriding mutational extinction effect, most of these mutations are not recovered as viable colonies. These studies suggest that AMD binding to DNA immediately following irradiation may cause considerably enhanced mutagenic and often lethal DNA damage, and that mutational extinction may occur because these types of damage are statistically correlated in a sensitive subpopulation of exponentially growing CHO cells.

Effect of neon ions on synchronized Chinese hamster cells.

The variation in radiosensitivity across the cell cycle after exposure to neon ions and 60Co gamma-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G1/S boundary by treatment with 10(-3)M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G1/S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for 60Co gamma-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G1/S boundary.

Cell-cycle distributions and radiation responses of Chinese hamster cells cultured continuously under hypoxic conditions.

Cell-cycle distributions were measured by flow cytometry for Chinese hamster (CHO) cells cultured continuously under hypoxic conditions. DNA histograms showed an accumulation of cells in the early S phase followed by a traverse delay through the S phase, and a G2 block. During hypoxic culturing, cell viability decreased rapidly to less than 0.1% at 120 h. Radiation responses for cells cultured under these conditions showed an extreme radioresistance at 72 h. Results suggest that hypoxia induces a condition similar to cell synchrony which itself changes the radioresistance of hypoxic cells.

Flow cytometric determination of radiation-induced chromosome damage and its correlation with cell survival.

Chinese hamster M3-1 cells were irradiated with several doses of X rays or alpha particles from 238Pu. Propidium iodide-stained chromosome suspensions were prepared at different times after irradiation; cells were also assayed for survival. The DNA histograms of these chromosomes showed increased background counts with increased doses of radiation. This increase in background was cell-cycle dependent and was correlated with cell survival. The correlation between radiation-induced chromosome damage and cell survival was the same for X rays and alpha particles. Data are presented which indicate that flow cytometric analysis of chromosomes of irradiated cell populations can be a useful adjunct to classical cytogenic analysis of irradiation-induced chromosomal damage by virtue of its ability to express and measure chromosomal damage not seen by classical cytogenic methods.

Residual radiation damage in the mouse foot after exposure to argon ions and retreatment with X rays.

The results of radiation treatment as visible residual damage are reported for acute skin reaction and foot deformity in mice exposed to argon ions. Two groups of 40 mice each were exposed to argon ions at the plateau and peak center of a 10-cm-wide Bragg peak to a fixed dose of 1200 and 1300 rad, respectively. A third group of 40 mice was exposed to 1750 rad of 250-kVp X rays while the fourth group was kept as controls. The acute skin reactions were scored for 60 days and foot deformity at 8 months after exposure. These mice were reexposed 8 months after the first exposure to graded doses of X rays ranging from 1200 to 2500 rad. Acute skin reactions were scored again for 60 days and foot deformity 8 months after the second exposure to graded doses of X rays. The results showed that no significant visible residual damage of the first treatment of either argon ions or X rays was observed after a second irradiation with X rays for acute skin reaction. For the end point deformity, however, residual damage of the first treatment was observed. The residual damage for foot deformity for argon ions does not seem to be higher than for X rays when the doses of first treatment with argon ions and X rays were matched to produce nearly uniform effect. The results also suggest a threshold dose to show the residual damage of the first treatment.

Biological response across a ridge filter carbon ion Bragg peak.

The dose distribution of carbon ion beams was modified to cover 14 cm peak width using a ridge filter suitable for clinical application. The results of cell survival as a function of depth of penetration of carbon ions and the mouse skin (foot) response at the proximal-, mid-, and distal-peak positions using four daily fractions are reported. The objective of these studies is to verify whether the dose distribution in the peak region is properly compensated to produce uniform biological effect. The implications of the shape of the dose distribution in the peak region to radiotherapy application are discussed.

Biological effects of pion therapy beams: I. Cultured cells.

The results of cell killing by pion beams of different peak widths, ranges and sizes used in therapy are reported. Cultured hamster cells (V79) suspended in gelatin were used. The results indicate that: 1) there are no significant differences in cell-killing between pion beams of different ranges but of the same peak width; 2) there is a slight decrease in biological effectiveness with increasing peak width; and 3) the range-modulation functions used to produce uniform cell-killing are satisfactory for intermediate-range pion beams, but slight corrections may be required for shorter- and longer-range pion beams.

Residual radiation damage in the mouse foot after exposure to heavy particles.

Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the "memory" of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin rection. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.

OER and RBE for negative pion beams of different peak widths.

Experimental data on survival curves for pion because of different peak widths under aerobic and hypoxic conditions are reported. Metabolic depletion of oxygen by the Chinese hamster cells (line V79) was used to obtain hypoxia. The results indicate that the RBE at the beam entrance (plateau) is approximately 1.0. When the Bragg peaks were broadened to widths of 1.3, 7.8, and 10.5 cm (at the 80% dose level), the RBE (50% cell survival) at the peak centres was 1.7, 1.6, and 1.2, respectively. The OER at the entrance was 2.4 compared with about 2.9 for X rays. The OER was independent of the survival level at which it was measured. The OER at the peak centres at widths of 1.3, 7.8, and 10.5 cm was 2.1, 2.4, and 2.2, respectively. These results indicate that, although the RBE at the centre of the 10.5 cm wide peak was significantly lower than at the centres of the 1.3 and 7.8 cm peaks, the OER values are similar for all peak widths used in this study.

A heavy particle comparative study. Part II: cell survival versus depth.

Cell-survival measurements with depth of penetration were made for a series of incident doses of proton, helium, carbon, neon, argon, negative pion, neutron, and 60Co photon beams. Cultured human cells (T1) suspended in a gel-containing medium were used, and the measurements were found to be very useful in facilitating the design of ridge filters to produce iso-effects in the region of interest. Heavy charged particle beams (proton, helium, carbon, neon, and negative pion) were found to produce similar cell killing with depth of penetration. Because of saturation effects at higher LET, argon ions were less effective in killing aerated cells at depth, compared with other heavy charged-particle beams. Cell killing at depth in the region of interest, compared with that at the entrance, was not significantly different for single-field exposures when the Bragg peaks were broadened to cover a width of 10 cm. However, when two opposed fields with overlapping peaks were used, a large enhancement in killing was obtained in the peak region.

A heavy particle comparative study. Part III: OER and RBE.

The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part III, cell-survival measurements under aerobic and hypoxic conditions were made for various heavy particle beams. For heavy charged-particle beams, the measurements were made at the beam entrance (plateau), peak centre (10 cm wide peaks), and distal peak (1 cm from dose fall-off). Chinese hamster cells (V79) were used. Metabolic depletion was used to obtain hypoxia. The results indicate that the differences in RBE between the entrance region and peak are not very large when the Bragg peaks are broadened to 10 cm. The RBE for argon ions remains the same at the entrance and peak centre, and the RBE at the distal side of the Bragg peak is significantly reduced compared to the peak centre and entrance region because of saturation effects at high LET. The OER for protons is not significantly different from that for X rays. The OER for helium ions, carbon ions, and negative pions is larger, for neon ions is similar, and for argon ions is smaller when compared with fast neutrons. The OER values for heavy ions are higher than expected and could be due to a large delta-ray penumbra associated with the energy deposited by energetic heavy ions. The oxygen effect may depend upon energy deposition over distances of the order of nanometers.

A heavy particle comparative study. Part IV: acute and late reactions.

The results of a comparative study of heavy particles of interest in radiotherapy are reported in four parts. In this Part IV, early skin reactions and late reactions (foot deformity) in mice for various heavy particles are reported. For heavy charged particles, the exposures were made at the entrance region (plateau) and centre of the peak (10 cm wide peaks). For 60Co gamma rays and fast neutrons (50 MeV D leads to Be), the exposures were made at the peak of the depth-dose curve. The time-course of development of skin reaction and subsequent healing after exposure to heavy ions or 60Co gamma rays were remarkably similar, suggesting that skin damage and subsequent epithelial repopulation after exposure to heavy ions are not different from 60Co gamma rays. When the Bragg peaks were broadened to 10 cm, the RBE at the peak, compared with the entrance region, was significantly higher for carbon ions but nearly the same or even lower for neon and argon ions because of saturation effects at high LET. The RBE for fast neutrons was comparable to that at the peak for carbon ions. The correlation between early skin reaction and foot deformity remained the same for all particles.